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Journal articles on the topic 'Fetal nerve tissue'
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1
Anagnostou, Valsamo K., Ipatia Doussis-Anagnostopoulou, Dina G. Tiniakos, Despina Karandrea, Emmanouil Agapitos, Petros Karakitsos, and Christos Kittas. "Ontogeny of Intrinsic Innervation in the Human Thymus and Spleen." Journal of Histochemistry & Cytochemistry 55, no. 8 (April 4, 2007): 813–20. http://dx.doi.org/10.1369/jhc.6a7168.2007.
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The ontogeny of the innervation of human lymphoid organs has not been studied in detail. Our aim was to assess the nature and distribution of parenchymal nerves in human fetal thymus and spleen. We used the peroxidase immunohistochemical technique with antibodies specific to neuron-specific enolase (NSE), neurofilaments (NF), PGP9.5, S100 protein, and tyrosine hydroxylase (TH) and evaluated our results with image analysis. In human fetal thymus, NSE-, NF-, S100-, PGP9.5-, and TH-positive nerves were identified associated with large blood vessels from 18 gestational weeks (gw) onwards, increasing in density during development. Their branches penetrated the septal areas at 20 gw, reaching the cortex and the corticomedullary junction between 20 and 23 gw. Few nerve fibers were seen in the medulla in close association with Hassall's corpuscles. In human fetal spleen, NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers were localized in the connective tissue surrounding the splenic artery at 18 gw. Perivascular NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers were seen extending into the white pulp, mainly in association with the central artery and its branches, increasing in density during gestation. Scattered NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers and endings were localized in the red pulp from 18 gw onward. The predominant perivascular distribution of most parenchymal nerves implies that thymic and splenic innervation may play an important functional role during intrauterine life. (J Histochem Cytochem 55: 813–820, 2007)
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Bosse, A., K. Schwarz, E. Vollmer, and H. Kresse. "Divergent and co-localization of the two small proteoglycans decorin and proteoglycan-100 in human skeletal tissues and tumors." Journal of Histochemistry & Cytochemistry 41, no. 1 (January 1993): 13–19. http://dx.doi.org/10.1177/41.1.8417108.
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The core protein of a recently described small proteoglycan, proteoglycan-100, was localized in fetal human tissues by indirect immunocytochemistry and compared with the localization of known members of the small proteoglycan family. Co-localization of decorin and proteoglycan-100 was seen in bone tissue but decorin and proteoglycan-100 exhibited a substantially divergent distribution in fetal skin, cartilage and in the mineralization zone of the growth plate. Proteoglycan-100 was also found in striated muscle, nerve fibers, and synovial tissue. Immunostaining of a chondroblastic osteosarcoma demonstrated chondroid cells selectively expressing either proteoglycan-100 or decorin. Co-expression of both small proteoglycans was observed in sections from a chordoma. In fetal bone and in the two tumors, colocalization of proteoglycan-100 and of biglycan was also found. These results provide evidence of the wide and characteristic distribution of proteoglycan-100.
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Kjær, Inger. "Nerve tissue as an initiating factor in human fetal bone formation." Cell Differentiation and Development 27 (August 1989): 196. http://dx.doi.org/10.1016/0922-3371(89)90595-9.
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Panula, P., O. Häppölä, M. S. Airaksinen, S. Auvinen, and A. Virkamäki. "Carbodiimide as a tissue fixative in histamine immunohistochemistry and its application in developmental neurobiology." Journal of Histochemistry & Cytochemistry 36, no. 3 (March 1988): 259–69. http://dx.doi.org/10.1177/36.3.3343510.
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The object of this study was to develop an immunohistochemical method that could be used to study neuronal histamine, especially in nerve fibers and terminals where most previous methods have not been applicable. Three new antisera were produced in rabbits against conjugated histamine, and the fixative used in conjugation, 1-ethyl-3(3-diamethylaminopropyl)-carbodiimide (EDCDI), was used in tissue fixation and compared to paraformaldehyde. Specificity of the antisera was established with dot-blot tests on nitrocellulose, with blocking controls and affinity-purified antibodies. EDCDI appeared to be superior to paraformaldehyde as a fixative, and histamine-immunoreactive nerve cells were visualized in developing rat brain during late fetal development from embryonal day 12. By the second postnatal week, the distribution of histamine-immunoreactive neurons in rat brain had reached the adult pattern and immunoreactive nerve fibers were seen in many areas. Posterior hypothalamic neurons from newborn rat in vitro showed strong immunoreactivity for histamine and developed long varicose fibers, which covered the culture dish by the end of the fourth week in vitro. Fixation with EDCDI also allowed detection of histamine in gastric enterochromaffin-like cells and mast cells in rat. The results suggest that the histamine-containing neuron system in rat brain develops during the late fetal and early postnatal periods, and that immunoreactive neurons develop long fibers both in vivo and in vitro.
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Stromberg, Ingrid, Lars Björklund, and Petter Forander. "The Age of Striatum Determines the Pattern and Extent of Dopaminergic Innervation: a Nigrostriatal Double Graft Study." Cell Transplantation 6, no. 3 (May 1997): 287–96. http://dx.doi.org/10.1177/096368979700600311.
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In animal models of Parkinson's disease, transplanted fetal mesencephalic dopaminergic neurons can innervate the dopamine-depleted host brain, but it is unclear why large portions of the host striatum are left uninnervated. During normal development, the dopaminergic innervation first occurs in the form of a dense patchy pattern in the striatum, followed by a widespread nerve fiber network. Using intraocular double grafts we have investigated dopaminergic growth patterns initiated when ventral mesencephalic grafts innervate striatal targets. The fetal lateral ganglionic eminence was implanted into the anterior eye chamber. After maturation in oculo, fetal ventral mesencephalon was implanted and placed in contact with the first graft. In other animals the two pieces of tissue were implanted simultaneously. Tyrosine hydroxylase (TH) immunohistochemistry revealed a pattern of dense TH-positive patches throughout the total volume of the striatal grafts in simultaneously transplanted cografts, while a widespread, less dense, pattern was found when mature striatal transplants were innervated by fetal dopaminergic grafts. To investigate which type or types of growth patterns that developed after grafting to striatum in situ of an adult host, fetal ventral mesencephalic tissue was implanted into the lateral ventricle adjacent to the dopamine-lesioned striatum. After maturation of the mesencephalic graft, the fetal lateral ganglionic eminence was implanted into the reinnervated part of the host striatum. TH immunohistochemistry revealed a few nerve fibers within the striatal graft and the growth pattern was of the widespread type. In conclusion, grafted dopaminergic neurons preferably innervate mature striatum with a widespread sparse nerve fiber network, while the innervation of the immature striatum occurs in the form of dense patches. Furthermore, when the patchy pattern is formed, the total volume of the striatal target is innervated while growth of the widespread type terminates prior to reaching distal striatal parts. Thus, the growth pattern seems essential to the final volume that is innervated. Once the widespread growth pattern is initiated, the presence of immature striatum does not change the dopaminergic growth pattern.
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Nishiura, Hayate, Shino Jou, Toru Ogata, Hiroki Kondo, Toshihiro Ichijo, Jun Sasaki, and Kenji Ochiai. "Calving-related intradural avulsion injuries of the thoracolumbar spinal nerve roots in a calf." Journal of Veterinary Diagnostic Investigation 32, no. 6 (September 15, 2020): 968–71. http://dx.doi.org/10.1177/1040638720957640.
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Calving difficulty may lead to traumatic peripheral nerve injury. A male, 8-mo-old, Japanese Black calf with a history of secondary dystocia as a result of fetal gigantism had lameness and gait disturbance. At autopsy, multifocal dural thickening with adhesions to the adjacent spinal cord was observed at T12–13 and L4–5 vertebral levels. Microscopically, numerous traumatic neuroma-like fascicles of nerve twigs were embedded in the dura mater with abundant collagenous connective tissue. By immunohistochemistry, axons and Schwann cells were confirmed in each nerve fascicle. Our observations suggest that avulsion injuries in the preganglionic fibers of the spinal nerve roots, and secondary spinal cord compression, resulted in the development of neurologic signs.
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Fitzgibbon, T., and B. E. Reese. "Organization of retinal ganglion cell axons in the optic fiber layer and nerve of fetal ferrets." Visual Neuroscience 13, no. 5 (September 1996): 847–61. http://dx.doi.org/10.1017/s095252380000910x.
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AbstractPrevious authors have hypothesized that retinotopic projections may be influenced by ‘preordering’ of the axons as they grow towards their targets. In some nonmammalian species, axons are reorganized at or near the optic nerve head to establish a retinotopic order. Data are ambiguous concerning the retinotopy of the mammalian retinal nerve fiber layer and whether fibers become reorganized at the optic nerve head. We have examined this question in fetal and newborn ferrets (Mustela putorius furo) by comparing the arrangement of axons in the retinal nerve fiber layer with that in the optic nerve. Dil or DiA crystals were implanted into fixed tissue in the innermost layers of the retinal periphery, or at a location midway between the periphery and the optic nerve head. Fluorescence labelling was examined in 100–200 μm Vibratome sections, or the eyecup and nerve were photooxidized and 1–2 μm longitudinal or transverse sections were examined. Regardless of fetal age, eccentricity or quadrant of the implant site, a segregation of labelled peripheral axons from unlabelled central ones was not detected within the nerve fiber layer. Axons coursed into the nerve head along the margin of their retinal quadrant of origin, often entering the optic nerve as a radial wedge, thus preserving a rough map of retinal circumference. However, peripheral axons were in no way restricted to the peripheral (nor central) portions of the nerve head or nerve, indicating that the optic axons do not establish a map of retinal eccentricity. Our results demonstrate that (1) the nerve fiber layer is retinotopic only with respect to circumferential position and (2) optic axons are not actively reorganized to establish a retinotopic ordering at the nerve head. The present results suggest that any degree of order present within the optic nerve is a passive consequence of combining the fascicles of the retinal nerve fiber layer; optic axons are not instructed to establish, nor constrained to maintain, a retinotopic order within the optic nerve.
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Liu, Yihe. "Molecular Biology Research on the Information Coding Mechanism of Brain Nerve Cells." Highlights in Science, Engineering and Technology 2 (June 22, 2022): 166–71. http://dx.doi.org/10.54097/hset.v2i.570.
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The function of the brain is to integrate information and make behavioral decisions accordingly. The understanding of brain function is an important part of neuroscience, and it also provides inspiration for artificial intelligence. However, how information is represented and encoded in the brain, and how it is read by other downstream tissue links, these questions have not yet been clarified. To explore the regulation of information expression by molecular biology during the in vitro development of human fetal brain neurons. These cytokines all promote the expression of neural cells at the transcriptional level, laying the foundation for analyzing the molecular mechanism of their biological effects.
The function of the brain is to integrate information and make behavioral decisions accordingly. The understanding of brain function is an important part of neuroscience, and it also provides inspiration for artificial intelligence. However, how information is represented and encoded in the brain, and how it is read by other downstream tissue links, these questions have not yet been clarified. To explore the regulation of information expression by molecular biology during the in vitro development of human fetal brain neurons. These cytokines all promote the expression of neural cells at the transcriptional level, laying the foundation for analyzing the molecular mechanism of their biological effects.
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Khmara, T. V., L. Ya Lopushniak, O. M. Boichuk, A. A. Halahdyna, L. М. Gerasym, and M. Yu Leka. "FETAL ANATOMICAL VARIABILITY OF STRUCTURES IN INFRAHYOID AREA." Актуальні проблеми сучасної медицини: Вісник Української медичної стоматологічної академії 20, no. 3 (November 12, 2020): 164–69. http://dx.doi.org/10.31718/2077-1096.20.3.164.
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When performing myoplastic operations and surgical interventions on the thyroid gland, trachea and esophagus, information on the variant anatomy of the infrahyoid muscles, the features of their innervation and blood supply are of great clinical importance. Moreover, when additional muscles are attached to the thyroid gland, intraoperative bleeding can occur resulting in hematoma and tissue scarring in the postoperative period. There are fragmentary data in the literature on the variants of the structure and topography of the human infrahyoid area muscles. The specificity of branching nerves and blood vessels, their vascular-nervous relationships in a separate part of the sternohyoid, sternothyroid, thyrohyoid, and omohyoid muscles should be taken into account when performing rational incisions in the neck, moving both the flaps and the above muscles in plastic surgery. The purpose of study was to establish the anatomical variability and features of innervation and blood supply of the infrahyoid muscles of the neck in human foetuses of 4 – 10 gestational months age. Material and methods. The study was performed on 36 human foetuses, whose parieto-coccygeal length was 81.0 – 375.0 mm, without visible signs of anatomical abnormalities or anomalies in the cervical region. Thin sections of the structures from the anterior and lateral parts of the neck were prepared under the control of binocular magnifier, vascular injection technique, and morphometry. Foetal preparations weighing over 500.0 g were studied directly at Chernivtsi Regional Paediatric Pathological Bureau. Foetal preparations were taken from the Museum of M.G. Turkevich Human Anatomy Department, Bukovinian State Medical University. Results and discussion. The study demonstrated anatomical variability of the infrahyoid area muscles during the foetal period of human ontogenesis. Human foetuses were mainly found to have loose extending intramuscular branching of the nerves of the cervical loop in the infrahyoid muscles. The only exception is the inferior belly of the omohyoid muscle, where main nerve branching is found out. The distribution of nerves in the thickness of the infrahyoid muscles is uneven. Macroscopic examination revealed the smallest number of nerve branches was found within the middle third of the sternohyoid and upper third of the sternothyroid muscles. Arteries and nerves enter the sternothyroid and thyrohyoid muscles through the anterior surface, and the omohyoid and sternohyoid muscles enter mainly through the posterior surface of these muscles. The infrahyoid muscles are characterized by the main form of intramuscular branching of the arteries. The data on the peculiarities of intramuscular branching of arteries and nerves in the infrahyoid muscles we obtained, as well as the variant anatomy of the infrahyoid area muscles must be taken into account when performing a surgical access to the neck, or when operating on in the anterior cervical region, in particular myoplastic and reconstructive operations, in order to avoid muscle injuries.
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Stein, Donald G., and Marylou M. Glasier. "Some practical and theoretical issues concerning fetal brain tissue grafts as therapy for brain dysfunctions." Behavioral and Brain Sciences 18, no. 1 (March 1995): 36–45. http://dx.doi.org/10.1017/s0140525x00037250.
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AbstractGrafts of embryonic neural tissue into the brains of adult patients are currently being used to treat Parkinson's disease and are under serious consideration as therapy for a variety of other degenerative and traumatic disorders. This target article evaluates the use of transplants to promote recovery from brain injury and highlights the kinds of questions and problems that must be addressed before this form of therapy is routinely applied. It has been argued that neural transplantation can promote functional recovery through the replacement of damaged nerve cells, the reestablishment of specific nerve pathways lost as a result of injury, the release of specific neurotransmitters, or the production of factors that promote neuronal growth. The latter two mechanisms, which need not rely on anatomical connections to the host brain, are open to examination for nonsurgical, less intrusive therapeutic use. Certain subjective judgments used to select patients who will receive grafts and in assessment of the outcome of graft therapy make it difficult to evaluate the procedure. In addition, little long-term assessment of transplant efficacy and effect has been done in nonhuman primates. Carefully controlled human studies, with multiple testing paradigms, are also needed to establish the efficacy of transplant therapy.
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Johansson, Saga, and Ingrid Strömberg. "Fetal Lateral Ganglionic Eminence Attracts One of Two Morphologically Different Types of Tyrosine Hydroxylase-Positive Nerve Fibers Formed by Cultured Ventral Mesencephalon." Cell Transplantation 12, no. 3 (April 2003): 243–55. http://dx.doi.org/10.3727/000000003108746803.
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The purpose of this study was to investigate the influence of fetal lateral ganglionic eminence (LGE) on nerve fiber outgrowth formed by fetal ventral mesencephalon (VM). Organotypic tissue cultures of fetal VM and LGE plated as single or cocultures were employed. Survival time was 3–21 days in vitro. Nerve fiber outgrowth and migration of astrocytes were analyzed using immunohistochemistry for tyrosine hydroxylase (TH) and S100. In addition, cultures were labeled with the TUNEL technique and with antibodies directed against neurofilament (NF) in order to study apoptosis and retraction of nerve fibers, respectively. The results revealed two morphologically different types of TH-positive outgrowth growing into the substrate. The initially formed TH-positive outgrowth radiated continuously without changing direction, while a second wave of TH-positive outgrowth became obvious when the initial growth already had reached a distance of approximately 1000 μm. The second wave of TH-positive outgrowth radiated from the tissue, but at a certain distance changed direction and formed a network surrounding the culture. The initially formed TH-positive growth was not associated with the presence of S100-positive astrocytes and avoided to grow into the LGE. At longer time points the first wave of TH-positive nerve fibers appeared dotted, with disrupted NF-immunoreactive fibers and in most cultures these long distance growing fibers had disappeared at 21 days in vitro. The second wave of TH-positive nerve fibers was growing onto a layer of glia and never reached the distance of the first wave. LGE became innervated by TH-positive fibers at the time point for when the second wave of TH-positive growth had been initiated, and the innervation appeared in TH-dense patches that also showed a high density of S100-positive astrocytes. Significantly increased TUNEL activity within LGE portion of cocultures was observed when TH-positive fibers entered the LGE and formed patches. In conclusion, two morphologically different types of TH-positive outgrowth were found and the initially formed fibers neither targeted the LGE nor were they guided by glial cells, but their potential to grow for long distances was high.
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Buchwalder, Lynn F., Michelle Lin, Thomas J. McDonald, and Peter W. Nathanielsz. "Fetal sheep adrenal blood flow responses to hypoxemia after splanchnicotomy using fluorescent microspheres." Journal of Applied Physiology 84, no. 1 (January 1, 1998): 82–89. http://dx.doi.org/10.1152/jappl.1998.84.1.82.
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Buchwalder, Lynn F., Michelle Lin, Thomas J. McDonald, and Peter W. Nathanielsz. Fetal sheep adrenal blood flow responses to hypoxemia after splanchnicotomy using fluorescent microspheres. J. Appl. Physiol. 84(1): 82–89, 1998.—Adrenal gland blood flow (ABF) increases during hypoxemia in fetal sheep, but regulation of ABF is poorly understood. The purpose of this study was to determine the effects of splanchnic nerve section on fetal ABF responses to hypoxemia using the fluorescent microsphere (FM) technique. At 125 days of gestation, 14 unanesthetized fetal sheep [bilateral splanchnicotomy (Splx, n = 6) and control (Cont, n = 8)] were injected with FM before and at 60 min of N2-induced hypoxemia (∼40% decrease in fetal arterial [Formula: see text]). Adrenal tissue and reference blood samples were digested and filtered, and FM dye was extracted for spectrometer analysis. Baseline whole, medullary, and cortical ABF for the Cont group were similar to published values using radioactive microspheres and did not differ from Splx values. Hypoxemia increased whole, medullary, and cortical ABF (mean ± SE) from baseline for the Cont group by 281 ± 35, 258 ± 31, and 496 ± 81% ( P < 0.05). The increase for the Splx group was attenuated compared with the Cont group ( P < 0.05) for whole and medullary ABF (139 ± 27 and 43 ± 27%) but not cortical ABF (326 ± 91%). We conclude that 1) the FM technique is valid for measuring fetal ABF and 2) in fetal sheep the splanchnic nerve is not necessary to maintain basal ABF but plays an important role in regulating the hypoxemia-induced increase in ABF through the medullary, but not cortical, ABF response.
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Schuijers, J. A., D. W. Walker, C. A. Browne, and G. D. Thorburn. "Peripheral and brain tissue catecholamine content in intact and anti-NGF-treated fetal sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 252, no. 1 (January 1, 1987): R7—R12. http://dx.doi.org/10.1152/ajpregu.1987.252.1.r7.
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Fetal lambs were treated with a single dose of anti-mouse nerve growth factor (anti-NGF) at 80 days gestational age. The catecholamine content of tissues was determined at 135 days gestational age. There was a reduction of either norepinephrine, epinephrine, or both, in the thymus, thyroid, atrium (but not ventricle), lung, liver, kidney, and jejunum when compared with age-matched control fetuses. The spleen, ileum, colon, and the adrenal glands were not affected by anti-NGF. In treated fetuses there was a reduction in catecholamine content of the thalamus, hypothalamus, hippocampus, medulla, cerebellum, and cervical spinal cord. These results show that some tissues are sensitive to, and some are refractory to, the action of anti-NGF at 80 days gestation. Also the results suggest that NGF may play a role in the development of catecholamine-containing neurons within the central nervous system.
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López-Lozano, Juan J., Gonzalo Bravo, Javier Abascal, Begoña Brera, Isabel Millan, and _. _. "Clinical outcome of cotransplantation of peripheral nerve and adrenal medulla in patients with Parkinson's disease." Journal of Neurosurgery 90, no. 5 (May 1999): 875–82. http://dx.doi.org/10.3171/jns.1999.90.5.0875.
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Object. Transplants of adrenal medulla (AM) and fetal ventral mesencephalon (FVM) are currently being tested as therapeutic alternatives in patients with Parkinson's disease (PD). At the Clínica Puerta de Hierro in Madrid, a controlled clinical trial is underway to establish which donor tissue, if any, is the best for open surgical implantation in patients with PD.Methods. Since 1987, varying degrees of clinical improvement have been achieved in Grade IV and V parkinsonian patients by implanting perfused AM and FVM into the right caudate nucleus. To investigate further whether implantation of different types of donor tissues results in qualitatively and quantitatively different degrees of recovery, four patients with Grade IV or V PD received implants of pre-coincubated autologous AM and intercostal nerve in the caudate nucleus. Four nonsurgically treated patients served as a control group. Three years posttransplantation, longer on phases (46.2% ± 10.4% of the day presurgery to 87.5% ± 10.4% of the day 36 months postsurgery) and improved symptoms in on and off phases persist in all four cases, with reduced dyskinesias (67.1% ± 9.2% of the day in on phases presurgery to 17% ± 13.8% of the day in on phases 36 months postsurgery). Progress appears to be stepwise, starting within weeks of tranplantation and becoming clinically significant in the 2nd and 3rd months (similar to our AM- and sooner than in our FVM-implanted patients), followed by a period of stability and, after a second wave of improvement 12 to 18 months posttransplantation (similar to FVM implants), has continued (87.5 ± 7 points presurgery to 46 ± 5.6 points 36 months postsurgery). In the experimental group, doses of levodopa have been reduced by more than 60% and dopamine agonist use has not resumed. In contrast, there have been no significant clinical changes in the control group.Conclusions. Implantation of tissue other than fetal tissue can promote a long-term improvement in the clinical symptomatology of seriously disabled parkinsonian patients. This finding is supported by the autopsy report of a patient with PD who had undergone grafting of AM plus peripheral nerve in which it was demonstrated that a large number of tyrosine hydroxylase—positive cells survive 1 year after implantation. In addition, there was a dense network of host dopaminergic fibers around the graft.
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Ardiani, Yessi, Defrin Defrin, and Husna Yetti. "Kajian Pustaka: Kadar Brain Derived Neurotrophic Factor Mempengaruhi Berat Badan Lahir pada Bayi." Jurnal Ilmiah Universitas Batanghari Jambi 19, no. 1 (January 22, 2019): 152. http://dx.doi.org/10.33087/jiubj.v19i1.576.
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Brain Derived Neurotrhophic Factor (BDNF) is one of the proteins needed for the growth of neurons. During its development period BDNF plays a role in nerve growth, differentiation, repair, and survival of nerve cells. In addition, researchers from certain groups found that BDNF also had an important role during the implantation period, placental development and development of fetal growth. BDNF is known to have an important role in regulating angiogenesis needed for placental development. Because of this role, BDNF deficiency will cause disruption in placental growth which will eventually cause fetal growth disorders or Intrauterine growth restriction (IUGR). In recent years studies have shown that neurotrophins play an important role in the regulation of placental development and fetal growth. BDNF has been found to be expressed in large amounts in blastocysts which indicate the potential role of BDNF in implantation and development of the placenta. BDNF is also produced in the muscle tissue of one of them in the uterus precisely in the endometrium and myometrium. The discovery of the role of BDNF, is expected to be used as an indicator to assess the occurrence of growth disorders in the fetus as well as additional information about the etiology and pathophysiology of IUGR. Keywords: BDNF; IUGR; Neurotrophin
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Cheng, Henrich, Susanne Almström, and Lars Olson. "Fibrin Glue Used as an Adhesive Agent in CNS Tissues." Journal of Neural Transplantation and Plasticity 5, no. 4 (1995): 233–43. http://dx.doi.org/10.1155/np.1994.233.
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One of the limitations of many bridging experiments in neural transplantation is that the CNS tissues cannot be sutured. Fibrin glue is a two-component system derived from whole blood which, when mixed, reproduces the final stage of blood coagulation and solidifies. Many experimental studies of humans and animals show that fibrin glue repair of peripheral nerves is almost equivalent to microsurgical sutures. In this study, we attempted to extend its use to CNS tissues and transplants. Two techniques were tried: (1) Bilateral parietal knife cuts were performed by stereotaxic technique in six rats. Fibrin glue was applied in the right-side cortical lesion. Immunohistochemistry using antisera to tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), laminin and neurofilament (NF) was essentially similar between the control and treatment groups. The immunoreactivity of each marker revealed no significant differences between the two groups on days 1, 7 and 30. There was no difference in terms of gliosis or microvascular proliferation. (2) Embryonic day 16 fetal locus coeruleus was grafted together with E16 cortex to the anterior chamber of sympathectomized eyes. In the six eyes of the glue treatment group, the parietal cortical piece and the locus coeruleus piece were joined together before grafting by immersing them in the solution of fibrin glue. In the eight eyes of the control group, pieces of parietal cortex and locus coeruleus were introduced individually and approximated by gently pressing the cornea. The sizes of double grafts showed no significant difference between groups during six weeks postgrafting. The immunohistochemical pictures using antisera against TH, GFAP and laminin were similar in both groups. Catecholaminergic fibers from the grafted locus coeruleus were found bridging over into the parietal cortical piece in both the control and treatment groups. There was no significant difference in TH-positive nerve fiber density between tissue glue joined and control double intraocular grafts. In conclusion, fibrin glue can be used as an adhesive agent in CNS tissues without hampering the outgrowth of neurites or causing adverse tissue reactions in fetal or adult nervous tissues.
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Humpel, Christian, Ingrid Strömberg, and Lars Olson. "Expression of Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Neurotrophin-3 mRNAs in Human Cortical Xenografts." Journal of Neural Transplantation and Plasticity 5, no. 4 (1995): 257–64. http://dx.doi.org/10.1155/np.1994.257.
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Trophic factors play an important role in the development of neurons and glia. In order to study the involvement of neurotrophins in human cortical development, human fetal parietal cortical tissue, obtained after early elective abortions, was transplanted to cortical cavities in immunosuppressed rats. Usingin situhybridization it was demonstrated that nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNAs are expressed in developing human cortical xenografts. We conclude that neurotrophins may play a role in human cortical development and rat-derived astroglial cells could be involved in establishing reciprocal “permissive sites”.
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Zurita, Mercedes, Jesús Vaquero, Santiago Oya, and Jesús Montilla. "Functional recovery in chronic paraplegic rats after co-grafts of fetal brain and adult peripheral nerve tissue." Surgical Neurology 55, no. 5 (May 2001): 249–54. http://dx.doi.org/10.1016/s0090-3019(01)00442-6.
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Lischer, Mirko, Pietro G. di Summa, Carlo M. Oranges, Dirk J. Schaefer, Daniel F. Kalbermatten, Raphael Guzman, and Srinivas Madduri. "Human platelet lysate stimulated adipose stem cells exhibit strong neurotrophic potency for nerve tissue engineering applications." Regenerative Medicine 15, no. 3 (March 2020): 1399–408. http://dx.doi.org/10.2217/rme-2020-0031.
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Aim: We investigated a potential strategy involving human platelet lysate (HPL) as a media additive for enhancing the neurotrophic potency of human adipose stem cells (ASC). Materials & methods: Dorsal root ganglion explants, ASC and Schwann cells were used for in vitro axonal outgrowth experiments. Results: Remarkably, HPL-supplemented ASC promoted robust axonal outgrowth, in other words, four-times higher than fetal bovine serum-supplemented ASC and even matched to the level of Schwann cells. Further, analysis of regime of growth medium additive supplementation revealed the critical play of HPL in dorsal root ganglion and stem cells co-culture system for mounting effective axonal growth response. Conclusion: HPL supplementation significantly improved the neurotrophic potency of ASC as evidenced by the robust axonal outgrowth; these findings hold significance for nerve tissue engineering applications.
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Krivova, Y. S., A. E. Proshchina, D. A. Otlyga, and S. V. Saveliev. "Application of antibodies to the vesicular transporter of acetylcholine and acetylcholinesterase in the studies of prenatal development of parasympathetic innervation of the human pancreas." CLINICAL AND EXPERIMENTAL MORPHOLOGY 9, no. 3 (September 23, 2020): 27–33. http://dx.doi.org/10.31088/cem2020.9.3.27-33.
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Introduction. Parasympathetic fibers innervating the pancreas are involved in the regulation of both exo-crine and endocrine function, in the regulation of endocrine cell proliferation, and are also implicated in the pathogenesis of type 1 diabetes. Nonetheless, data concerning the distribution of parasympathetic fibers within the human pancreas in prenatal development are absent in the literature. Our aim was to evaluate the possibility of using the markers of cholinergic neurons and nerve fibers, namely vesicular acetylcholine transporter (VAChT) and acetylcholinesterase (AChE) in studies of prenatal develop-ment of parasympathetic innervation of the human pancreas. Materials and methods. The study was performed on 10 autopsies of the fetal pancreas (gestational age 10-34 weeks) using immunoperoxidase labeling with antibodies to VAChT and AChE. Results. Immunopositive reaction to AChE was detected in bundles of nerve fibers of various diameters, networks of thin nerve fibers as well as in individual neurons of the intramural ganglia. The structures of the nervous system were immunonegative to VAChT. In the exocrine pancreas, that is, in the interlobular connective tissue, near the ducts and inside the forming lobules, thin cholinergic fibers prevailed on the studied developmental periods. In pancreatic islets, cholinergic fibers were detected less frequently and were located at the periphery.Immunopositive reaction with antibodies to AChE and mouse monoclonal antibodies to VAChT was also detected in some endocrine cells in the pancreatic islets. Conclusion. We have shown that antibodies to AChE detect cholinergic neurons and nerve fibers in the developing human pancreas. We have also demonstrated that in the fetal pancreas thin cholinergic fibers prevail in the exocrine part and rarely are detected in the pancreatic islets, which is typical in adults. The results showing the VAChT and AChE immunoreactivity in the endocrine cells of fetal pancreatic islets are in agreement with data obtained in the adult human pancreas and suggest that the endocrine cells can be a source of acetylcholine. Keywords: pancreas, human development, parasympathetic innervation, VAChT, AChE
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Frank, Pierre, Gabriela Barrientos, Irene Tirado-González, Marie Cohen, Petra Moschansky, Eva M. Peters, Burghard F. Klapp, Matthias Rose, Mareike Tometten, and Sandra M. Blois. "Balanced levels of nerve growth factor are required for normal pregnancy progression." REPRODUCTION 148, no. 2 (August 2014): 179–89. http://dx.doi.org/10.1530/rep-14-0112.
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Nerve growth factor (NGF), the first identified member of the family of neurotrophins, is thought to play a critical role in the initiation of the decidual response in stress-challenged pregnant mice. However, the contribution of this pathway to physiological events during the establishment and maintenance of pregnancy remains largely elusive. Using NGF depletion and supplementation strategies alternatively, in this study, we demonstrated that a successful pregnancy is sensitive to disturbances in NGF levels in mice. Treatment with NGF further boosted fetal loss rates in the high-abortion rate CBA/J x DBA/2J mouse model by amplifying a local inflammatory response through recruitment of NGF-expressing immune cells, increased decidual innervation with substance P+ nerve fibres and a Th1 cytokine shift. Similarly, treatment with a NGF-neutralising antibody in BALB/c-mated CBA/J mice, a normal-pregnancy model, also induced abortions associated with increased infiltration of tropomyosin kinase receptor A-expressing NK cells to the decidua. Importantly, in neither of the models, pregnancy loss was associated with defective ovarian function, angiogenesis or placental development. We further demonstrated that spontaneous abortion in humans is associated with up-regulated synthesis and an aberrant distribution of NGF in placental tissue. Thus, a local threshold of NGF expression seems to be necessary to ensure maternal tolerance in healthy pregnancies, but when surpassed may result in fetal rejection due to exacerbated inflammation.
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Rettig, W. J., and P. Garin-Chesa. "Cell type-specific control of human neuronectin secretion by polypeptide mediators and phorbol ester." Journal of Histochemistry & Cytochemistry 37, no. 12 (December 1989): 1777–86. http://dx.doi.org/10.1177/37.12.2685108.
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Neuronectin (NEC1) is a human extracellular matrix (ECM) protein expressed with a unique rostrocaudal pattern in white matter of the normal adult central nervous system. In addition, NEC1 is expressed in normal fetal and adult smooth muscle, along certain epithelial-mesenchymal junctions, and transiently in developing fetal cartilage. Region-specific induction of NEC1 is found in dermal wounds and in the reactive stroma of actinic keratoses, psoriatic skin lesions, and a range of malignant tumors. One explanation for these diverse tissue patterns is that cells capable of producing NEC1 are widely distributed in neural and mesenchymal tissues, but they become NEC1 producers only when induced by region-specific differentiation signals. In this study, we used cultured human cells to show that several regulatory polypeptides, including fibroblast growth factors, tumor necrosis factor, platelet-derived growth factor, nerve growth factor, and transforming growth factor-beta (TGF-beta), as well as 12-O-tetradecanoyl phorbol-13-acetate (TPA), modulate NEC1 secretion, with distinct patterns of inducing and inhibitory activities in different neural and mesenchymal cell types. TPA and TGF-beta act both as inducers and inhibitors of NEC1 secretion, depending on the target cell. These effects are specific for NEC1 and are not seen for several other secreted and membrane proteins studied. We suggest that NEC1 expression comes under different modes of extrinsic control in different cell lineages and in response to tissue injury and neoplasia.
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Brooks, A. N., L. A. Power, S. A. Jones, K. P. Yang, and J. R. G. Challis. "Controls of corticotrophin-releasing factor output by hypothalamic tissue from fetal sheep in vitro." Journal of Endocrinology 122, no. 1 (July 1989): 15–22. http://dx.doi.org/10.1677/joe.0.1220015.
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ABSTRACT Corticotrophin-releasing factor (CRF) is thought to be an important physiological regulator of the pituitary-adrenal axis in fetal sheep and, as such, plays a fundamental role in the initiation of parturition in this species. However, little is known of the controls of CRF secretion from the fetal hypothalamus. We looked for the presence of CRF in fetal hypothalami, and examined whether the hypothalamic CRF concentration or molecular species changed in relation to gestational age. We established an in-vitro perifusion system to examine the release of CRF from perifused hypothalami taken from fetuses at day 100 and day 140 of pregnancy, under basal conditions and in response to potassium depolarization and/or dexamethasone administration. Immunoreactive CRF was present in fetal hypothalami as early as day 100 (2·42 ± 0·99 (s.e.m.) μg/g protein, n = 9) and in similar concentrations at day 140 (2·31 ± 0·69 μg/g protein, n = 9). There was a significant (P < 0·05) increase in hypothalamic CRF content to 14·79 ± 4·09 μg/g protein (n = 16) between day 122 and day 135 of gestation. Using Sephadex G-75 chromatography, hypothalamic extracts at day 100, days 122–135 and day 140 eluted with a single peak of immunoreactivity which corresponded to synthetic ovine CRF(1–41). The basal release of CRF from perifused hypothalami at day 140 (76·6 ± 10·4 pg/fraction, n = 8) was significantly (P < 0·05) greater than at day 100 (50·1 ± 10·2 pg/fraction, n = 11). Dexamethasone significantly inhibited basal CRF release at day 140 of gestation but not at day 100. Potassium depolarization caused a rapid release of CRF in all cases, a response which was independent of gestational age or treatment with dexamethasone. We conclude that the fetal hypothalamus contains immunoreactive CRF as early as day 100 of gestation and that this material may be released when perifused in vitro under basal conditions and in response to a depolarizing agent. The basal release of CRF from perifused hypothalami of day-140 fetuses was greater than at day 100 and was inhibited by dexamethasone, suggesting maturation of negative feedback control of CRF output between days 100 and 140. Since dexamethasone had no effect on potassium-stimulated release of CRF, we suggest that its effects are at sites other than the hypothalamic CRF nerve terminals. Journal of Endocrinology (1989) 122, 15–22
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Wang, Huan, Huabin Zhu, Zhihui Hu, Nuo Heng, Jianfei Gong, Yi Wang, Huiying Zou, and Shanjiang Zhao. "Uncovering Novel Features of the Pc Locus in Horn Development from Gene-Edited Holstein Cattle by RNA-Sequencing Analysis." International Journal of Molecular Sciences 23, no. 20 (October 11, 2022): 12060. http://dx.doi.org/10.3390/ijms232012060.
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The Polled Celtic (Pc) mutation locus is a genetically simple single mutation that is the best choice for breeding polled cattle using gene editing. However, the mechanism of the Pc locus for regulating horn development is unclear, so we used gene editing, somatic cell nuclear transfer and embryo transfer to obtain polled Holstein fetal bovine (gestation time 90 days) with a homozygous Pc insertion (gene-edited Holstein fetal bovine, EH) and the wild-type 90 days Holstein fetal bovine (WH) as controls. The hematoxylin-eosin (HE) staining results showed that, compared to the WH, the EH horn buds had no white keratinized projections or vacuolated keratinocytes and no thick nerve bundles under the dermal tissue. Furthermore, DNA sequencing results showed that the Pc locus was homozygously inserted into the fetal bovine genome. A total of 791 differentially expressed genes were identified by transcriptome sequencing analysis. Enrichment analysis and protein interaction analysis results of differentially expressed genes showed that abundant gene changes after Pc insertion were associated with the adhesion molecule regulation, actin expression, cytoskeletal deformation and keratin expression and keratinization. It was also noted that the results contained several genes that had been reported to be associated with the development of horn traits, such as RXFP2 and TWIST1. This study identified these changes for the first time and summarized them. The results suggested that the Pc mutant locus may inhibit neural crest cell EMT generation and keratin expression, leading to failures in neural crest cell migration and keratinization of the horn bud tissue, regulating the production of the polled phenotype.
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Aikawa, Yuri, Takayuki Baba, Tomohiro Nizawa, Hirotaka Yokouchi, and Shuichi Yamamoto. "Worsening of Retinal Detachment after Cataract Surgery in the Eye with Persistent Fetal Vasculature." Case Reports in Medicine 2021 (February 22, 2021): 1–4. http://dx.doi.org/10.1155/2021/6641161.
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Purpose. To report a case of persistent fetal vasculature (PFV) with a retinal detachment that worsened after cataract surgery. Pars plana vitrectomy (PPV) was performed which reduced the vitreous traction and reattached the retina. Observations. A 20-year-old Myanmarese woman presented with a mature cataract, and her vision was light perception. She underwent uneventful cataract surgery with implantation of an intraocular lens. Her visual acuity improved to 20/200 immediately after the surgery. However, fibrotic tissue was observed between the optic nerve head and the posterior capsule. She was diagnosed with PFV, and she was followed without any intervention. One and a half years after the cataract surgery, she had an advanced retinal detachment which extended over the inferior two quadrants. Her vision deteriorated to 20/400. She underwent PPV, and the PFV tissue was removed which resulted in the reattachment of the retina. The visual acuity improved to 20/60. Conclusions. Surgeons should be aware that it is possible to worsen a retinal detachment after cataract surgery in the eyes with PFV. A simple technique to release the anterior-posterior traction by the PPV was sufficient to achieve the reattachment of the retina.
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Houle, John D., and Mei Kheng Ziegler. "Bridging a Complete Transection Lesion of Adult Rat Spinal Cord with Growth Factor-Treated Nitrocellulose Implants." Journal of Neural Transplantation and Plasticity 5, no. 2 (1994): 115–24. http://dx.doi.org/10.1155/np.1994.115.
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The ability of a substrate bound neurotrophic factor to promote growth of ascending sensory axons across a complete transection lesion of the rat spinal cord was examined in a transplantation model. Aspiration lesions created a 3 mm long cavity in the upper lumbar spinal cord of adult rats. Five weeks after injury two strips of nerve growth factortreated nitrocellulose, were implanted, each in a medio-lateral position, and apposed to the rostral and caudal surfaces of the cavity. Control animals received untreated nitrocellulose implants. Fetal spinal cord tissue was transplanted alongsideand between these strips. Six weeks post transplantation, animals were sacrificed and vibratome sections through the grafts were processed for immunocytochemical demonstration of ingrowing axons expressing calcitonin gene-related peptide (CGRP-IR), Immunolabeled axons were abundant at the caudal interface between host tissue and the NGF-treated nitrocellulose implants, with dense fascicles of fibers abutting the grafts. As the distance from the caudal surface increased some CGRP-IR fibers extended into the fetal tissue although most appeared to remain oriented in a longitudinal course adjacent to the nitrocellulose. Labeled axons were evident along the entire length of the nitrocellulose and appeared to aggregate at the rostral tip of the implant, with many fibers extending into the host spinal cord rostral to the lesion/transplant site. When untreated nitrocellulose was implanted, fewer labeled axons appeared to extend beyond the caudal host-graft interface. Most CGRP-IR axons displayed limited association or contact with the untreated nitrocellulose in this condition. Computer-assisted quantitative analysis indicated that NGF-treated nitrocellulose supported regrowing host axons for nearly three times the length exhibited by axons associated with non-treated nitrocellulose implants. These results indicate that substrate bound nerve growth factor has the capacity to enhance the regrowth of ascending sensory axons across a traumatic spinal cord injury site. The potential to reestablish functional contacts across such a lesion may be heightened by the ability of neurotrophic factors to promote more extensive axonal regrowth.
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Doering, Laurie C. "Transplantation of Fetal CNS Tissue Into the Peripheral Nervous System: A Model to Study Aberrant Changes in the Neuronal Cytoskeleton." Journal of Neural Transplantation and Plasticity 2, no. 3-4 (1991): 193–205. http://dx.doi.org/10.1155/np.1991.193.
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Defined regions (septum, substantia nigra) of the embryonic central nervous system (CNS) were transplanted into the sciatic nerves of young adult rats. Immunocytochemical techniques were used to examine the expression of neurotransmitter related enzymes and neuronal cytoskeletal proteins in the grafts.The origin of the septal grafts was confirmed by immunoreactivity in nenrons to choline acetyltransferase and the β-nerve growth factor receptor (192-IgG). In substantia nigra grafts, neuronal perikarya and processes were identified with an antibody directed against tyrosine hydroxylase. Typical spatial distributions of phosphorylated (Mr200,000) and non phosphorylated (Mr168,000 & 200,000) neurofilaments were observed in the short term (1-2 months) grafts with the monoclonal antibodies RT97 and SMI-32 respectively. Dense dendrite arbors and neuronal cell bodies were immunostained with an antibody that recognizes a high molecular weight microtubule associated protein (MAP2).In the long term (1 year) transplants, prominent cytoskeletal changes in the somata, axons and dendrites of neurons were evident. The cells showed a shift in phosphorylated neurofilament staining from the axon to the soma accompanied by a reduction in axonal immunoreactivity in the adjacent neuropil, Other abnormal features included swollen perikarya, hypertrophied axonal segments and Short segments of kinked axons. Regression of the dendrite trees in the long standing grafts was also apparent when sections were reacted with the MAP2 antibody.These experiments indicate that grafted fetal neurons, isolated in the peripheral nervous system, differentiate and express markers like their counterpartsin situ. After extended time periods under these circumstances, cytoskeletal modifications become apparent in the neurons. These aberrant changes are similar to morphological characteristics associated with aging and neurodegenerative disorders. This experimental paradigm offers a new approach, to study cytoskeletal disturbances in neurons and provides a unique opportunity to examine conditions that may modulate the abnormal changes.
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Csobonyeiova, Maria, Stefan Polak, Radoslav Zamborsky, and Lubos Danisovic. "Recent Progress in the Regeneration of Spinal Cord Injuries by Induced Pluripotent Stem Cells." International Journal of Molecular Sciences 20, no. 15 (August 6, 2019): 3838. http://dx.doi.org/10.3390/ijms20153838.
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Regeneration of injuries occurring in the central nervous system, particularly spinal cord injuries (SCIs), is extremely difficult. The complex pathological events following a SCI often restrict regeneration of nervous tissue at the injury site and frequently lead to irreversible loss of motor and sensory function. Neural stem/progenitor cells (NSCs/NPCs) possess neuroregenerative and neuroprotective features, and transplantation of such cells into the site of damaged tissue is a promising stem cell-based therapy for SCI. However, NSC/NPCs have mostly been induced from embryonic stem cells or fetal tissue, leading to ethical concerns. The pioneering work of Yamanaka and colleagues gave rise to the technology to induce pluripotent stem cells (iPSCs) from somatic cells, overcoming these ethical issues. The advent of iPSCs technology has meant significant progress in the therapy of neurodegenerative disease and nerve tissue damage. A number of published studies have described the successful differentiation of NSCs/NPCs from iPSCs and their subsequent engraftment into SCI animal models, followed by functional recovery of injury. The aim of this present review is to summarize various iPSC- NPCs differentiation methods, SCI modelling, and the current status of possible iPSC- NPCs- based therapy of SCI.
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Bakay, Roy A. E., Kevin L. Boyer, Curt R. Freed, and Aftab A. Ansari. "Immunological Responses to Injury and Grafting in the Central Nervous System of Nonhuman Primates." Cell Transplantation 7, no. 2 (March 1998): 109–20. http://dx.doi.org/10.1177/096368979800700206.
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Allogeneic transplantation for the therapy of human Parkinson's disease is being considered as a viable approach at several clinical centers worldwide. As an attempt to understand the basic biology of central nervous system (CNS) transplantation, our laboratory has developed an experimental nonhuman primate model for human Parkinson's disease and carried out preliminary studies directed at evaluating the potential pathology at the graft site. In addition, studies have been conducted to examine whether such transplantation procedures lead to specific and/or nonspecific immunologic sensitization of the host or results in generalized immunosuppression. Groups of rhesus macaques (Macaca mulatta) were either controls operated (n = 6), autografted with adrenal medullary and peripheral nerve tissue (n = 3), or allografted with fetal mesencephalic tissue (n = 6). Immunohistological studies demonstrated the presence of mononuclear cell infiltrates as early as 1 wk and up to 1 yr postoperatively, although the frequency of the infiltrating cells declined with time. The infiltrates consisted of variable numbers of cells which express CD2+, CD3+, CD4+, CD8+, CD19+, CD22+, CD25+, and CD68+. There appeared to be no difference in the frequency, kinetics, or phenotype of the infiltrating cells in operative controls compared with recipients of auto- or allografts. Tissue sections obtained postoperatively showed low levels of major histocompatibility complex (MHC) Class I antigens and no detectable level of MHC-Class II antigens in neural tissue. A small aliquot of tissue from the operative site was placed in vitro with media containing interleukin-2 (IL-2), which led to the exudation and growth of mononuclear cells that were predominantly CD4+ cells. Phenotypic studies of peripheral blood mononuclear cells (PBMC) from operative controls, auto- and allograft recipient monkeys performed at varying time periods postoperatively failed to show differences in the frequencies of subsets of T-cells, B-cells, NK-cells, or monocytes. Studies on aliquots of the same PBMC failed to show major functional differences in NK-cells, LAK cells, or response to polyclonal mitogens. Finally, recipients of allogeneic mesencephalic grafts failed to show evidence of donor-specific humoral or cellular sensitization. These data indicate that transplantation of autograft adrenal or allograft fetal mesencephalic tissues in the CNS of nonhuman primate did not induce detectable donor-specific sensitization nor nonspecific immunosuppression.
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Ilchenko, Viktoriia Aleksandrovna, and Yuliana Aleksandrovna Moshko. "ANTIPHOSPHOLIPID SYNDROME AND PREGNANCY." International Medical Journal, no. 4 (February 26, 2020): 20–22. http://dx.doi.org/10.37436/2308-5274-2019-4-5.
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The main issues of etiopathogenesis, clinical manifestations, diagnosis of antiphospholipid syndrome are considered. This syndrome is a state of the body whereat a thrombosis can occur, especially during pregnancy. This syndrome pathogenesis is characterized with an interaction of antiphospholipid antibodies with negatively charged phospholipids. They are the part of membranes of platelets, endotheliocytes, prothrombin−activating complex, beta−2−glycoprotein and nerve cells with impaired functions. Joining to phospholipids, the antiphospholipid antibodies lead to a sharp decrease in platelet count and impaired endothelial cell function. In nerve tissue disorders according to the structural and functional type occur, the formation and function of the humoral agents responsible for hemostasis are disrupted. The antiphospholipid syndrome in obstetrics and gynecology often manifests as spontaneous miscarriages, the effect of the "empty fetal egg", fetal growth retardation and even its antenatal death, as well as preeclampsia. In the treatment of pregnant women with antiphospholipid syndrome, mainly several protocols have been used, i.e. anticoagulants and antiplatelet agents in combination with glucocorticoids; combination of glucocorticoids with acetylsalicylic acid; monotherapy with sodium heparin or acetylsalicylic acid; anticoagulants and antiplatelet agents for hemostasis correction. The treatment protocols during pregnancy, childbirth and postpartum period have been presented. It is emphasized that the patients with antiphospholipid syndrome and vascular thrombosis should be monitored by rheumatologist, surgeon, obstetrician and gynecologist after successful child delivery. Duration of receiving antiplatelet and anticoagulant therapy has to be solved individually. Key words: antiphospholipid syndrome, antiphospholipid antibodies, cardiolipin antibodies, lupus anticoagulant, pregnancy, postpartum period.
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Treadway, Taylor A., Phoenix M. Shepherd, Christina M. Newman, Emma L. Mohr, Dawn M. Dudley, Meghan E. Breitbach, Keisuke Yamamoto, et al. "#79: Modeling Zika Virus Tissue Tropism in Rhesus Macaques to Define the Risk of Donor-derived Transmission." Journal of the Pediatric Infectious Diseases Society 10, Supplement_1 (March 1, 2021): S4. http://dx.doi.org/10.1093/jpids/piaa170.012.
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Abstract Background Almost 115,000 people in the United States are currently on a transplant waitlist, which vastly exceeds the number of organ donors every year. This discrepancy emphasizes the need for retention of all possible donors. Those who have recently traveled to an area with an active outbreak of Zika virus (ZIKV) are often disqualified as a donor because immunosuppressed recipients would be at risk of a donor-derived ZIKV infection. Therefore, we define ZIKV tissue tropism and the risk of donor-derived transmission. Methods We subcutaneously inoculated 15 Indian-origin rhesus macaques (RM) with a Puerto Rican isolate of ZIKV (PRVABC59). All RMs were inoculated in mid to early gestation. We inoculated during pregnancy because plasma viremia is typically prolonged in pregnancy and we wanted to model tissue tropism for donor-derived transmission in the worst scenario of prolonged viremia. At 30, 65, and 105 days post-infection (dpi), the animals were euthanized and comprehensive necropsies were performed, which evaluated a minimum of 60 tissues per animal. ZIKV RNA was quantified in tissues via qRT-PCR. Results Plasma viremia duration was >10 days in 13 of 15 RMs. ZIKV RNA was most commonly detected in lymph nodes, with 19/45 lymph nodes that were vRNA positive in 5 RMs at 30 dpi. There were 15/45 vRNA positive lymph nodes at 60 dpi and 8/38 at 105 dpi. Reproductive and maternal fetal-interface (MFI) tissues were the second most commonly positive tissues. Twenty-five MFI tissues, including the amniotic/chorionic membrane, decidua, placenta, uterus, and placental bed, were positive, with 10/53 positive at 30 dpi, 14/24 positive at 60 dpi and 1/47 positive at 105 dpi. Other vRNA positive tissues included the primary bronchus, femoral vein, kidney, thyroid, lung, colon, mammary gland, pericardium, hand nerve, and sciatic nerve in 1–2 RMs at one of the three timepoints. Conclusions We found ZIKV RNA most frequently within lymph nodes. Lymph nodes are included in lung and small bowel transplants, indicating that these transplants could pose a risk of donor-derived ZIKV transmission. Virus detection within other commonly transplanted tissues, such as the kidney and blood vessels was much less common. We did not determine what fraction of vRNA comes from replication-competent virus in each tissue; some tissues with vRNA might not contain virions that could initiate new infections. Donor-derived Zika virus transmission from other commonly transplanted organs, such as the liver, seems unlikely since no viral RNA was detected in this organ.
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Treadway, Taylor A., Phoenix M. Shepherd, Christina M. Newman, Emma L. Mohr, Dawn M. Dudley, Meghan E. Breitbach, Keisuke Yamamoto, et al. "#20: Modeling Zika virus tissue tropism in rhesus macaques to define the risk of donor derived transmission." Journal of the Pediatric Infectious Diseases Society 10, Supplement_2 (June 1, 2021): S1—S2. http://dx.doi.org/10.1093/jpids/piab031.003.
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Abstract Background Almost 115,000 people in the United States are currently on a transplant waitlist, which vastly exceeds the number of organ donors every year. This discrepancy emphasizes the need for retention of all possible donors. Those who have recently traveled to an area with an active outbreak of Zika virus (ZIKV) are often disqualified as a donor because immunosuppressed recipients would be at risk of a donor-derived ZIKV infection. Therefore, we define ZIKV tissue tropism and the risk of donor derived transmission. Methods We subcutaneously inoculated 15 Indian-origin rhesus macaques (RM) with a Puerto Rican isolate of ZIKV (PRVABC59). All RMs were inoculated in mid to early gestation.We inoculated during pregnancy because plasma viremia is typically prolonged in pregnancy and we wanted to model tissue tropism for donor derived transmission in the worst scenario of prolonged viremia. At 30, 65, and 105 days post-infection (dpi), the animals were euthanized and comprehensive necropsies were performed, which evaluated a minimum of 60 tissues per animal. ZIKV RNA was quantified in tissues via qRT-PCR. Results Plasma viremia duration was >10 days in 13 of 15 RMs. ZIKV RNA was most commonly detected in lymph nodes, with 19/45 lymph nodes that were vRNA positive in 5 RMs at 30 dpi. There were 15/45 vRNA positive lymph nodes at 60 dpi and 8/38 at 105 dpi. Reproductive and maternal fetal-interface (MFI) tissues were the second most commonly positive tissues. Twenty-five MFI tissues, including the amniotic/chorionic membrane, decidua, placenta, uterus, and placental bed, were positive, with 10/53 positive at 30 dpi, 14/24 positive at 60 dpi and 1/47 positive at 105 dpi. Other vRNA positive tissues included the primary bronchus, femoral vein, kidney, thyroid, lung, colon, mammary gland, pericardium, hand nerve, and sciatic nerve in 1–2 RMs at one of the three timepoints. Conclusions We found ZIKV RNA most frequently within lymph nodes. Lymph nodes are included in lung and small bowel transplants, indicating that these transplants could pose a risk of donor-derived ZIKV transmission. Virus detection within other commonly transplanted tissues, such as the kidney and blood vessels was much less common. We did not determine what fraction of vRNA comes from replication-competent virus in each tissue; some tissues with vRNA might not contain virions that could initiate new infections. Donor-derived Zika virus transmission from other commonly transplanted organs, such as liver, seems unlikely since no viral RNA was detected in this organ.
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Feng, Yuping, Jiao Wang, Shixin Ling, Zhuo Li, Mingsheng Li, Qiongyi Li, Zongren Ma, and Sijiu Yu. "Differentiation of mesenchymal stem cells into neuronal cells on fetal bovine acellular dermal matrix as a tissue engineered nerve scaffold." Neural Regeneration Research 9, no. 22 (2014): 0. http://dx.doi.org/10.4103/1673-5374.145378.
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Humpel, Christian, Marc Bygdeman, Lars Olson, and Ingrid Strömberg. "Human fetal neocortical tissue grafted to rat brain cavities survives, leads to reciprocal nerve fiber growth, and accumulates host IgG." Journal of Comparative Neurology 340, no. 3 (February 15, 1994): 337–48. http://dx.doi.org/10.1002/cne.903400305.
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Popova, I. "MORPHOLOGICAL FEATURES OF FASCIAL STRUCTURES IN INFRAHYOID NECK DURING PRENATAL HUMAN ONTOGENESIS." Clinical anatomy and operative surgery 19, no. 1 (February 27, 2020): 93–97. http://dx.doi.org/10.24061/1727-0847.19.1.2020.16.
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Fascia and fascial spaces of the neck remains a controversial morphological question, which requires in-depth study, especially in the focus of prenatal morphogenesis. We have examined specimens of human embryos, prefetuses and fetuses in order to study the development and topographic-anatomical features of the neck fascial structures at different stages of human prenatal development. For this purpose, a set of microscopic methods (three-dimensional reconstruction, series of histological sections examination) for embryos (8.0-13.0 mm PCL (parieto-coccygeal length) and prefetuses (14.0-80.0 mm PCL) was used; macroscopic examination for fetuses’ specimens (80.0-230.0 mm PCL). It was found that at the end of the embryonic period of development, there are rudiments of the larynx and pharynx, which are not delimited; precrusors of vascular and nerve trunks of the neck are already present. In the prefetal we may observe change from the bilaminar to multilaminar fascial morphology. The definitive structure of fascial structures may be found in fetal stage of human ontogenesis. It is important that at fetal stage, fascial leaves tend to fuse in areas that contact with the periosteum or in the fascial spaces that do not yet contain adipose tissue yet.
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Sinson, Grant, Madhu Voddi, and Tracy K. McIntosh. "Combined fetal neural transplantation and nerve growth factor infusion: effects on neurological outcome following fluid-percussion brain injury in the rat." Neurosurgical Focus 7, no. 3 (September 1999): E5. http://dx.doi.org/10.3171/foc.1999.7.3.6.
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This study was designed to evaluate the histological and behavioral impact of fetal neural transplantation with and without neurotrophin infusion in rats subjected to traumatic brain injury using a clinically relevant model of lateral fluid-percussion brain injury. Adult male Sprague-Dawley rats received lateral fluid-percussion brain injury of moderate severity (2.1-2.3 atm). Twenty-four hours after injury, minced fetal cortical grafts (E16) were stereotactically transplanted into the site of injury cavity formation (in 32 rats). Ten control animals received injections of saline. A third group of 29 animals that received transplants also underwent placement of a miniosmotic pump (immediately after transplantation) to continuously infuse nerve growth factor (NGF) directly into the region of graft placement for the duration of the experiment. A fourth group of eight animals underwent transplantation of fetal cortical cells that had been dissociated and placed in suspension. Animals were evaluated at 72 hours, 1 week, and 2 weeks after injury for cognitive function (using the Morris water maze), posttraumatic motor dysfunction, and transplant survival and morphology (using Nissl and modified Palmgren's silver staining techniques). Robust survival of whole-tissue transplants was seen in 65.6% of animals and was not increased in animals receiving NGF infusion. Animals receiving transplants of cell suspension had no surviving grafts. Brain-injured animals receiving transplants showed significant cognitive improvements compared with controls at the 2-week evaluation. Significantly improved memory scores were seen at all evaluation times in animals receiving both NGF and transplants compared with injured controls and compared with animals receiving transplants alone at the 72-hour and 1-week evaluations. Neurological motor function scores were significantly improved in animals receiving transplants alone and those receiving transplants with NGF infusion. Histological evaluation demonstrated differentiation of grafted cells, decreased glial scarring around transplants when compared with control animals, and the presence of neuronal fibers bridging the interface between graft and host. This study demonstrates that fetal cortical cells transplanted into the injured cortex of the adult rat can improve both posttraumatic cognitive and motor function and interact with the injured host brain.
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Sinson, Grant, Madhu Voddi, and Tracy K. McIntosh. "Combined fetal neural transplantation and nerve growth factor infusion: effects on neurological outcome following fluid-percussion brain injury in the rat." Journal of Neurosurgery 84, no. 4 (April 1996): 655–62. http://dx.doi.org/10.3171/jns.1996.84.4.0655.
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✓ This study was designed to evaluate the histological and behavioral impact of fetal neural transplantation with and without neurotrophin infusion in rats subjected to traumatic brain injury using a clinically relevant model of lateral fluid-percussion brain injury. Adult male Sprague—Dawley rats received lateral fluid-percussion brain injury of moderate severity (2.1–2.3 atm). Twenty-four hours after injury, minced fetal cortical grafts (E16) were stereotactically transplanted into the site of injury cavity formation (in 32 rats). Ten control animals received injections of saline. A third group of 29 animals that received transplants also underwent placement of a miniosmotic pump (immediately after transplantation) to continuously infuse nerve growth factor (NGF) directly into the region of graft placement for the duration of the experiment. A fourth group of eight animals underwent transplantation of fetal cortical cells that had been dissociated and placed in suspension. Animals were evaluated at 72 hours, 1 week, and 2 weeks after injury for cognitive function (using the Morris water maze), posttraumatic motor dysfunction, and transplant survival and morphology (using Nissl and modified Palmgren's silver staining techniques). Robust survival of whole-tissue transplants was seen in 65.6% of animals and was not increased in animals receiving NGF infusion. Animals receiving transplants of cell suspension had no surviving grafts. Brain-injured animals receiving transplants showed significant cognitive improvements compared with controls at the 2-week evaluation. Significantly improved memory scores were seen at all evaluation times in animals receiving both NGF and transplants compared with injured controls and compared with animals receiving transplants alone at the 72-hour and 1-week evaluations. Neurological motor function scores were significantly improved in animals receiving transplants alone and those receiving transplants with NGF infusion. Histological evaluation demonstrated differentiation of grafted cells, decreased glial scarring around transplants when compared with control animals, and the presence of neuronal fibers bridging the interface between graft and host. This study demonstrates that fetal cortical cells transplanted into the injured cortex of the adult rat can improve both posttraumatic cognitive and motor function and interact with the injured host brain.
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Tseng, V. Chia-Hsuan, Chee Ho Chew, Wan-Ting Huang, Yang-Kao Wang, Ko-Shao Chen, Szu-Yi Chou, and Chien-Chung Chen. "An Effective Cell Coculture Platform Based on the Electrospun Microtube Array Membrane for Nerve Regeneration." Cells Tissues Organs 204, no. 3-4 (2017): 179–90. http://dx.doi.org/10.1159/000477238.
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Recently, a novel substrate known as an electrospun polylactic acid (PLLA) microtube array membrane (MTAM) was successfully developed as a cell coculture platform. Structurally, this substrate is made up of one-to-one connected, ultrathin, submicron scale fibers that are arranged in an arrayed formation. Its unique structure confers several key advantages which are beneficial in a cell coculture system. In this study, the interaction between rat fetal neural stem cells (NSC) and astrocytes was examined by comparing the outcome of a typical Transwell-based coculture system and that of an electrospun PLLA MTAM-based coculture system. Compared to tissue culture polystyrene (TCP) and Transwell coculture inserts, a superior cell viability of NSC was observed when cultured in lumens of electrospun PLLA MTAM (with supportive immunostaining images). Reverse transcription polymerase chain reaction revealed a strong interaction between astrocytes and NSC through a higher expression of doublecortin and a lower expression of nestin. These data demonstrate that MTAM is clearly a better coculture platform than the traditional Transwell system.
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Rieger, F., M. Grumet, and G. M. Edelman. "N-CAM at the vertebrate neuromuscular junction." Journal of Cell Biology 101, no. 1 (July 1, 1985): 285–93. http://dx.doi.org/10.1083/jcb.101.1.285.
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We have detected the neural cell adhesion molecule, N-CAM, at nerve-muscle contacts in the developing and adult mouse diaphragm. Whereas we found N-CAM staining with fluorescent antibodies consistently to overlap with the pattern of alpha-bungarotoxin staining at nerve-muscle contacts both during development and in the adult, we observed N-CAM staining on the surfaces of developing myofibers and at much lower levels on adult myofibers. Consistent with its function, N-CAM was also detected on axons and axon terminals. Immunoblotting experiments with anti-N-CAM antibodies on detergent extracts of embryonic (E) diaphragm muscle revealed a polydisperse polysialylated N-CAM polypeptide, which in the adult (A) was converted to a discrete form of Mr 140,000; this change, called E-to-A conversion, was previously found to occur in different neural tissues at different rates. The Mr 140,000 component was not recognized by monoclonal antibody anti-N-CAM No. 5, which specifically recognizes antigenic determinants associated with N-linked oligosaccharide determinants on N-CAM from neural tissue. The relative concentration of the Mr 140,000 component prepared from diaphragm muscle increased during fetal development and then decreased sharply to reach adult values. Nevertheless, expression of N-CAM in muscle could be induced after denervation: one week after the sciatic nerve was severed, the relative amount of N-CAM increased dramatically as detected by immunoblots of extracts of whole muscle. Immunofluorescent staining confirmed that there was an increase in N-CAM, both in the cell and at the cell surface; at the same time, however, staining at the motor endplate was diminished. Our findings indicate that, in muscle, in addition to chemical modulation, cell-surface modulation of N-CAM occurs both in amount and distribution during embryogenesis and in response to denervation.
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Araissi, Ahmad Bilal, Alaa Fayed, and Youssef Helmy. "Bilateral Morning Glory Syndrome with Bilateral Persistent Fetal Vasculature in a Patient with Joubert’s Syndrome." Case Reports in Medicine 2020 (August 11, 2020): 1–5. http://dx.doi.org/10.1155/2020/5872758.
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Purpose. We report a case of a 1-year-old girl who was referred to us with a cerebellar anomaly and delayed growth and development for bilateral ptosis and poor fixation. Based on our ophthalmologic examination, we concluded that she has bilateral persistent fetal vasculature (PFV) with morning glory syndrome (MGS). A closer look into her neurologic condition revealed that she has Joubert’s syndrome. Observations. External examination revealed bilateral symmetrical ptosis with syndromic facies and her fundus examination revealed a large dysplastic optic disc with anomalous radiating vessels and a fibrous tissue tuft originating from the disc. The left eye showed similar findings in addition to a central excavation and a fibrovascular stalk extending from the optic disc. These findings were consistent with bilateral MGS and bilateral PFV. The brain imaging included a computed tomography scan and magnetic resonance imaging, both of which revealed a “molar tooth appearance” of the midbrain and an anomalous cerebellum suggestive of Joubert’s syndrome. Conclusions and Importance. This is the first case report of a case of bilateral MGS and bilateral PFV associated with Joubert’s syndrome. This case report documents the associated optic nerve disease in these patients, not previously described, which are additive causes of visual compromise in addition to the brain insult.
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Kim, Jong Joong, In Youb Chang, Yoon Young Chung, Jeong Seok Moon, Sang Pil Yoon, and Young Hoon Bai. "Immunoelectronmicroscopical Study on the Axonal Coexistence of Serotonin and Substance-P of Fetal Nerve Tissue Transplantation into the Transected Spinal Cord of Rats." Korean Journal of Physical Anthropology 12, no. 1 (1999): 55. http://dx.doi.org/10.11637/kjpa.1999.12.1.55.
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López-Lozano, Juan J., Gonzalo Bravo, Begoña Brera, Isabel Millán, Jose Dargallo, Javier Salmeán, Jose Uría, Jose Insausti, and _. _. "Long-term improvement in patients with severe Parkinson's disease after implantation of fetal ventral mesencephalic tissue in a cavity of the caudate nucleus: 5-year follow up in 10 patients." Journal of Neurosurgery 86, no. 6 (June 1997): 931–42. http://dx.doi.org/10.3171/jns.1997.86.6.0931.
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✓ Different groups worldwide have observed in recent years that stereotactic implantation of fetal tissue can ameliorate the clinical symptoms of Parkinson's disease. The authors therefore investigated whether implantation of fetal ventral mesencephalic (FVM) tissue via open surgery is also capable of producing an improvement and whether this improvement is transient or long lasting. The authors report their findings in a 5-year follow-up study in 10 patients with Hoehn and Yahr Grade IV or V Parkinson's disease in whom a single FVM graft was implanted in a cavity created in the right caudate nucleus. The results indicate that the implants improved motor function and that clinical recovery persisted in seven of the 10 patients 5 years after implantation. Amelioration was observed in both the on and off phases and was accompanied by a 64% reduction in the levodopa dose and withdrawal of the dopamine agonist. The on phase was prolonged from 39% of the waking day to 72%, with reduced intensity and duration of dyskinesias. All symptoms that were analyzed showed improvement, although they differed in intensity and time of onset. The course of improvement seemed to be stepwise, with significant improvement between 5 and 7 months postimplantation followed by two waves of progress peaking in Months 15 and 36. Withdrawal of cyclosporine in three patients after more than 2 years of administration produced a decline in the patients' clinical conditions. In conclusion, the results indicate that open surgery implantation of FVM tissue in the caudate nucleus improves the clinical condition of parkinsonian patients and that this improvement can persist for at least 5 years. In comparison with two earlier series reported by the authors, which involved implants of perfused adrenal medulla and coimplantation of adrenal medulla and peripheral nerve, the course and pattern of improvement in these implant recipients suggests that their recovery can be attributed to more than one factor.
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Baker, Christian, Miguel Xochicale, Fang-Yu Lin, Sunish Mathews, Francois Joubert, Dzhoshkun I. Shakir, Richard Miles, et al. "Intraoperative Needle Tip Tracking with an Integrated Fibre-Optic Ultrasound Sensor." Sensors 22, no. 23 (November 22, 2022): 9035. http://dx.doi.org/10.3390/s22239035.
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Ultrasound is an essential tool for guidance of many minimally-invasive surgical and interventional procedures, where accurate placement of the interventional device is critical to avoid adverse events. Needle insertion procedures for anaesthesia, fetal medicine and tumour biopsy are commonly ultrasound-guided, and misplacement of the needle may lead to complications such as nerve damage, organ injury or pregnancy loss. Clear visibility of the needle tip is therefore critical, but visibility is often precluded by tissue heterogeneities or specular reflections from the needle shaft. This paper presents the in vitro and ex vivo accuracy of a new, real-time, ultrasound needle tip tracking system for guidance of fetal interventions. A fibre-optic, Fabry-Pérot interferometer hydrophone is integrated into an intraoperative needle and used to localise the needle tip within a handheld ultrasound field. While previous, related work has been based on research ultrasound systems with bespoke transmission sequences, the new system—developed under the ISO 13485 Medical Devices quality standard—operates as an adjunct to a commercial ultrasound imaging system and therefore provides the image quality expected in the clinic, superimposing a cross-hair onto the ultrasound image at the needle tip position. Tracking accuracy was determined by translating the needle tip to 356 known positions in the ultrasound field of view in a tank of water, and by comparison to manual labelling of the the position of the needle in B-mode US images during an insertion into an ex vivo phantom. In water, the mean distance between tracked and true positions was 0.7 ± 0.4 mm with a mean repeatability of 0.3 ± 0.2 mm. In the tissue phantom, the mean distance between tracked and labelled positions was 1.1 ± 0.7 mm. Tracking performance was found to be independent of needle angle. The study demonstrates the performance and clinical compatibility of ultrasound needle tracking, an essential step towards a first-in-human study.
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Gansburgskii, A. N., A. V. Yal'tsev, A. R. Sleptsov, and D. A. Sleptsova. "Umbilical Cord Teratoma: A Rare Case Report." Journal of Anatomy and Histopathology 10, no. 1 (April 14, 2021): 9–14. http://dx.doi.org/10.18499/2225-7357-2021-10-1-9-14.
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The state of the stroma, blood vessels and the anatomical features of the umbilical cord are of direct diagnostic value, and various pathological changes can become the primary cause of fetal death. The frequency of umbilical cord tumors is not reliably known due to a very rare incidence: in the available literature there were reported about 19 cases.The aim of the study was to clinically and pathohistologically analyze a case of umbilical cord teratoma and to give an analytical review of recently reported cases.The material was obtained from a healthy 35-year-old woman with a third pregnancy. Combined ultrasound screening at the 20th week of pregnancy revealed a solid structure with cystic inclusions along the periphery on the umbilical cord. In the solid component, hyperechoic inclusions giving acoustic shadows were visualized; in the color Doppler imaging mode the neoplasm was avascular. A dead premature baby girl was born at 35th week. The cause of intrauterine fetal death was mechanical compression of the vessels of the umbilical cord by teratoma. Microscopic examination of the umbilical cord neoplasm in the area of the solid component demonstrated a pronounced development of the sebaceous glands, adipose tissue, myelinic nerve fibers, hair follicles; in the cystic component – epidermoid cysts. This evidenced about organismoid mature teratomas. Due to their rare incidence umbilical teratomas should be reported to better understand their pathomorphosis and impact on infant morbidity and mortality. Given the increased risk of concomitant malformations, the detection of an umbilical teratoma should be accompanied by a detailed and comprehensive examination of the newborn for additional pathologies.
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Peralta, O., W. Huckle, M. Martinez, J. Correa, R. Gatica, and W. Eyestone. "262 TISSUE-SPECIFIC ANALYSIS OF PRION EXPRESSION IN EARLY BOVINE FETUSES." Reproduction, Fertility and Development 18, no. 2 (2006): 238. http://dx.doi.org/10.1071/rdv18n2ab262.
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The prion protein (PrP) is best known for its mis-folded, pathogenic isoform, which is widely regarded as the infectious agent in transmissable spongiform encephalopathies. However, the role of normal, cellular PrP, a host-encoded 29-kD glycoprotein tethered to the cell membrane by a phosphatidyl-inositol glycane (GPI) anchor, is poorly understood. PrP binds copper with high affinity, has antioxidant activity and may play a role in cell adhesion and/or signaling. PrP is expressed in mouse embryos on 6.5 days post-coitum in extra-embryonic tissue and at 13.5 days in the central and peripheral nervous system, intestine, and dental lamina. Our previous data revealed PrP gene expression in bovine embryos throughout pre-implantation embryo development. As part of a larger effort to map the ontogeny of cellular PrP expression in cattle, we sought here to analyze in early bovine fetuses (1) total PrP gene expression by real-time quantitative PCR (QPCR), and (2) tissue-specific PrP expression by immunohistochemistry. Fetuses were obtained from donor cattle bred by artificial insemination (AI; Day 0) and subjected to mid-ventral laparotomy on Days 32 (n = 2) and 39 (n = 2). Immediately upon recovery, one fetus from each stage was placed in RNAlater for RNA isolation and the other fixed in 10% formalin for immunohistochemistry. RNA was isolated using an RNeasy� mini kit (Qiagen, Valencia, CA, USA). cDNA was generated by reverse transcription with random hexamer priming and used the ΔΔcT method for estimation of PrP expression by QPCR. Tissue-specific expression was determined by immunohistochemistry. Formalin-fixed fetuses were embedded in paraffin, sagittally sectioned, dehydrated, and subjected to an unmasking protocol that employed Vectorlab unmasking solution and autoclaving. Tissues were then probed with a primary anti-PrP monoclonal antibody (SAF 32; Cayman Chemical Company, Ann Arbor, MI, USA). Bound primary antibody was detected with a biotinylated horse anti-mouse secondary antibody complexed to horseradish peroxidase using the ABC kit (Vector Laboratories, Burlingame, CA, USA). Probed sections were then counterstained with hematoxolin and eosin. Neighboring sections, processed identically but to which no primary antibody was added, served as controls. PrP gene expression was detected by QPCR at both stages examined and tended to be higher in Day 39 compared to Day 32 fetuses. PrP immunoreactivity was found throughout the central and peripheral nervous systems, ganglia, nerve trunks, and neural cell populations of sensory organs in both Day 32 and Day 39 fetuses. PrP immunolabeling was also observed in the mesonephric kidney, liver, and heart in the Day 39 fetus. At both stages, immunoreactivity was most intense in the nervous system. Thus, PrP is expressed in a tissue-specific pattern in early bovine fetuses. Tissue distribution of fetal PrP expression appears similar to that of adult PrP. Moreover, PrP appears to be expressed in a developmentally regulated fashion in some tissues.
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Stiefel, Dorothea, Takashi Shibata, Martin Meuli, Patrick G. Duffy, and Andrew J. Copp. "Tethering of the spinal cord in mouse fetuses and neonates with spina bifida." Journal of Neurosurgery: Spine 99, no. 2 (September 2003): 206–13. http://dx.doi.org/10.3171/spi.2003.99.2.0206.
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Object. Tethering of the spinal cord is a well-known complication in humans with spina bifida aperta or occulta. Its pathogenesis consists of a pathological fixation of the spinal cord resulting in traction on the neural tissue which, in turn, leads to ischemia and progressive neurological deterioration. Although well established in humans, this phenomenon has not been described in animal models of spina bifida. Methods. A fetal mouse model with naturally occurring, genetically determined spina bifida was produced by generating double mutants between the curly tail and loop-tail mutant strains. Microdissection, labeling with 1,1′-dioctadecyl-3,3,3,′,3′-tetramethylindocarbocyanine perchlorate, immunohistochemistry for neurofilaments, H & E staining of histological sections, and whole-mount skeletal preparations were performed and comparisons made among mutant and normal fetuses. Normal fetuses exhibited the onset of progressive physiological ascent of the spinal cord from embryonic Day 15.5. Spinal cord ascent resulted, by embryonic Day 18.5, in spinal nerve roots that pass caudolaterally from the spinal cord toward the periphery. In contrast, fetuses with spina bifida exhibited spinal cord tethering that resulted, at embryonic Day 18.5, in nerve roots that run in a craniolateral direction from the spinal cord. The region of closed spinal cord immediately cranial to the spina bifida lesion exhibited marked narrowing, late in gestation, suggesting that a potentially damaging stretch force is applied to the spinal cord by the tethered spina bifida lesion. Conclusions. This mouse model provides an opportunity to study the onset and early sequelae of spinal cord tethering in spina bifida.
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Ferland-McCollough, David, Susan E. Ozanne, Kenneth Siddle, Anne E. Willis, and Martin Bushell. "The involvement of microRNAs in Type 2 diabetes." Biochemical Society Transactions 38, no. 6 (November 24, 2010): 1565–70. http://dx.doi.org/10.1042/bst0381565.
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T2D (Type 2 diabetes mellitus) is a major health issue that has reached epidemic status worldwide. T2D is a progressive metabolic disorder characterized by reduced insulin sensitivity, insulin resistance and pancreatic β-cell dysfunction. Improper treatment of TD2 can lead to severe complications such as heart disease, stroke, kidney failure, blindness and nerve damage. The aetiology and molecular mechanisms of T2D are not fully understood, but compelling evidence points to a link between T2D, obesity, dyslipidaemia and insulin resistance. Although T2D seems to be strongly linked to environmental factors such as nutrition and lifestyle, studies have shown that genetic factors, such as polymorphisms associated with metabolic genes, imprinting, fetal programming and miRNA (microRNA) expression, could also contribute to the development of this disease. miRNAs are small 22–25-nt-long untranslated RNAs that negatively regulate the translation of mRNAs. miRNAs are involved in a large number of biological functions such as development, metabolism, immunity and diseases such as cancer, cardiovascular diseases and diabetes. The present review examines the various miRNAs that have been identified as being potentially involved in T2D, focusing on the insulin-sensitive organs: white adipose tissue, liver, skeletal muscle and the insulin-producing pancreatic β-cells.
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Hung, Chih-Huang, Yi-Chen Li, and Tai-Horng Young. "INDUCTION OF NEURONAL DIFFERENTIATION OF EMBRYONIC RAT CORTICAL NEUROSPHERES BY NERVE GROWTH FACTOR AND FETAL BOVINE SERUM ON THE NONADHERENT AND ADHERENT SUBSTRATES." Biomedical Engineering: Applications, Basis and Communications 25, no. 01 (February 2013): 1250053. http://dx.doi.org/10.4015/s1016237212500536.
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Regulating neural stem cells will greatly aid in developing regenerative medicine for the repair purpose of central nervous system (CNS). In this study, we explored the effect of nerve growth factor (NGF) on the differentiation of neural stem cells from embryonic rat cerebral cortex on nonadherent and adherent substrates at neurosphere level. The results showed that NGF could not promote adhesion and differentiation of neural stem cells when neurospheres were cultured on nonadherent tissue culture polystyrene (TCPS) substrates under serum-free condition. However, when 10% fetal bovine serum (FBS) was added to the culture system, FBS could induce the attachment of neurospheres onto an originally nonadherent substrate and almost all of the neurosphere-forming cells would migrate away from the spheres with the protoplasmic astrocyte morphology. Furthermore, when NGF was added into the FBS-containing medium, a significant number of differentiated neurons developed and distributed on the astrocyte layer. For comparison, adherent poly-D-lysine (PDL) substrates were also used. It was found that NGF could enhance differentiation of neural stem cells into neurons on PDL under serum-free condition but neurons and astrocytes could not migrate far away from the spheres. Similar to the TCPS results were also observed on PDL that differentiated neurons migrated out from the spheres and developed on the astrocyte layer when the medium contained NGF and FBS. Since the development of neurons needs glia cells to form a cellular substratum and to support neuronal migration to appropriate location, these results provide evidences that FBS-induced glia cells, serving as an architectural support layer, are essential for the growth and migration of NGF-induced neurons.
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Ysasi, Alexandra B., Janeil M. Belle, Barry C. Gibney, A. V. Fedulov, Willi Wagner, AkiraTsuda, Moritz A. Konerding, and Steven J. Mentzer. "Effect of unilateral diaphragmatic paralysis on postpneumonectomy lung growth." American Journal of Physiology-Lung Cellular and Molecular Physiology 305, no. 6 (September 15, 2013): L439—L445. http://dx.doi.org/10.1152/ajplung.00134.2013.
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Respiratory muscle-associated stretch has been implicated in normal lung development (fetal breathing movements) and postpneumonectomy lung growth. To test the hypothesis that mechanical stretch from diaphragmatic contraction contributes to lung growth, we performed left phrenic nerve transections (PNT) in mice with and without ipsilateral pneumonectomy. PNT was demonstrated by asymmetric costal margin excursion and confirmed at autopsy. In mice with two lungs, PNT was associated with a decrease in ipsilateral lung volume ( P < 0.05) and lung weight ( P < 0.05). After pneumonectomy, PNT was not associated with a change in activity level, measureable hypoxemia, or altered minute ventilation; however, microCT scanning demonstrated altered displacement and underinflation of the cardiac lobe within the first week after pneumonectomy. Coincident with the altered structural realignment, lung impedance measurements, fitted to the constant-phase model, demonstrated elevated airway resistance ( P < 0.05), but normal peripheral tissue resistance ( P > 0.05). Most important, PNT appeared to abrogate compensatory lung growth after pneumonectomy; the weight of the lobes of the right lung was significantly less than pneumonectomy alone ( P < 0.001) and indistinguishable from nonsurgical controls ( P > 0.05). We conclude that the cyclic stretch associated with diaphragmatic muscle contraction is a controlling factor in postpneumonectomy compensatory lung growth.
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Watabe, T., M. L. Levidiotis, B. Oldfield, and E. M. Wintour. "Ontogeny of corticotrophin-releasing factor (CRF) in the ovine fetal hypothalamus: use of multiple CRF antibodies." Journal of Endocrinology 129, no. 3 (June 1991): 335—NP. http://dx.doi.org/10.1677/joe.0.1290335.
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ABSTRACT In previous studies, using one particular antibody, immunohistochemical localization of corticotrophin-releasing factor (CRF) in ovine fetal brain was not possible before 90 days of gestation (term is approximately 150 days), although radioimmunoassay of hypothalamic extracts, using a different antibody, had shown CRF to be present from 63 days. The purpose of this study was to use a variety of CRF antibodies in both immunohistochemistry and radioimmunoassay to determine the presence and concentration of the CRF peptide as early in gestation as possible, and to determine whether more than one molecular size of CRF is detectable at any time in gestation. Seven different antibodies were used on hypothalamic tissue or extracts from seven adult sheep and 37 fetuses from 48 to 140 days of gestation. With one ovine CRF antibody (provided by Dr W. Vale, Salk Institute) immunohistochemical detection of CRF-labelled neurones and nerve fibres of the paraventricular nucleus and median eminence was possible from 49 days. The antibody with the greatest sensitivity in radioimmunoassay was one raised against human CRF, Ab-code R1 (provided by Dr E. Hillhouse, University of Newcastle upon Tyne). The hypothalamic contents of CRF (ng/whole hypothalamus) were 0·28±0·06 (mean ± s.e.m.) (n = 4), 9·0±0·6 (n = 5), 14·3±0·6 (n = 5), 30·0±3·4 (n = 4) in fetuses at 48–50, 100–109 and 139–140 days of gestation and in adult sheep respectively. At all ages only one peak of CRF-like activity, which co-eluted with synthetic ovine CRF, was observed after chromatography of hypothalamic extracts, and assays performed with three different antibodies. Thus there are small amounts of CRF in the ovine fetal pituitary from very early in gestation (50 days), and there is no evidence for a larger molecular weight form, as seen in the immature human fetus. Journal of Endocrinology (1991) 129, 335–341