Academic literature on the topic 'Blood Diseases Molecular aspects'
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Journal articles on the topic "Blood Diseases Molecular aspects":
1
Schechter, Alan N. "Hemoglobin research and the origins of molecular medicine." Blood 112, no. 10 (November 15, 2008): 3927–38. http://dx.doi.org/10.1182/blood-2008-04-078188.
Abstract:
Abstract Much of our understanding of human physiology, and of many aspects of pathology, has its antecedents in laboratory and clinical studies of hemoglobin. Over the last century, knowledge of the genetics, functions, and diseases of the hemoglobin proteins has been refined to the molecular level by analyses of their crystallographic structures and by cloning and sequencing of their genes and surrounding DNA. In the last few decades, research has opened up new paradigms for hemoglobin related to processes such as its role in the transport of nitric oxide and the complex developmental control of the α-like and β-like globin gene clusters. It is noteworthy that this recent work has had implications for understanding and treating the prevalent diseases of hemoglobin, especially the use of hydroxyurea to elevate fetal hemoglobin in sickle cell disease. It is likely that current research will also have significant clinical implications, as well as lessons for other aspects of molecular medicine, the origin of which can be largely traced to this research tradition.
2
Quinlivan, Mark, and Judith Breuer. "Molecular and therapeutic aspects of varicella–zoster virus infection." Expert Reviews in Molecular Medicine 7, no. 15 (August 10, 2005): 1–24. http://dx.doi.org/10.1017/s146239940500966x.
Abstract:
Varicella–zoster virus (VZV) is a highly species-specific member of the Herpesviridae family. The virus exhibits multiple cell tropisms, infecting peripheral blood mononuclear cells and skin cells before establishing latency in sensory neurons. Such tropisms are essential both for primary infection, which manifests itself as chickenpox (varicella), and subsequent reactivation to cause herpes zoster (shingles). The highly cell-associated nature of the virus, coupled with its narrow host range, has resulted in the lack of an animal model that mimics its diseases in humans, thereby greatly hindering the study of events in VZV pathogenesis. Despite this, extensive studies both in vitro and in vivo in small-animal models have provided a fascinating insight into molecular events that govern VZV diseases. In addition, VZV has become the first human herpes virus for which a live attenuated vaccine has been developed.
3
Shperling, M. M., N. P. Tolokonskaya, N. V. Fomenko, and Ye V. Romanova. "The clinical aspects of Lyme borreliosis." Bulletin of Siberian Medicine 7 (December 30, 2008): 106–10. http://dx.doi.org/10.20538/1682-0363-2008-0-106-110.
Abstract:
The diagnosis of Lyme borreliosis is objective difficult. There are tendention of increasing of patients the age of 51 and older. The characteristics of disease, for example fever at acute time is connected to reactivity in acute diseases in general. On time antibodies detection of patients blood with suspicion of the cronical borreliosis is not criteria of proven disease.
4
Chen, Qijun, Martha Schlichtherle, and Mats Wahlgren. "Molecular Aspects of Severe Malaria." Clinical Microbiology Reviews 13, no. 3 (July 1, 2000): 439–50. http://dx.doi.org/10.1128/cmr.13.3.439.
Abstract:
SUMMARY Human infections with Plasmodium falciparum may result in severe forms of malaria. The widespread and rapid development of drug resistance in P. falciparum and the resistance of the disease-transmitting mosquitoes to insecticides make it urgent to understand the molecular background of the pathogenesis of malaria to enable the development of novel approaches to combat the disease. This review focuses on the molecular mechanisms of severe malaria caused by the P. falciparum parasite. The nature of severe malaria and the deleterious effects of parasite-derived toxins and host-induced cytokines are introduced. Sequestration, brought about by cytoadherence and rosetting, is linked to severe malaria and is mediated by multiple receptors on the endothelium and red blood cells. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is the ligand responsible for a majority of binding interactions, and the multiply adhesive features of this sticky molecule are presented. Antigenic variation is also a major feature of PfEMP1 and of the surface of the P. falciparum-infected erythrocyte. Possible mechanisms of P. falciparum antigenic variation in asexual stages are further discussed. We conclude this review with a perspective and suggestions of important aspects for future investigations.
5
Villar, M., J. M. Marimon, J. M. Garcia-Arenzana, A. G. de la Campa, M. J. Ferrandiz, and E. Perez-Trallero. "Epidemiological and molecular aspects of rifampicin-resistant Staphylococcus aureus isolated from wounds, blood and respiratory samples." Journal of Antimicrobial Chemotherapy 66, no. 5 (March 2, 2011): 997–1000. http://dx.doi.org/10.1093/jac/dkr059.
6
Vogler, Ingridt Hildegard, Anna Nishiya, Helena Kaminami Morimoto, Edna Maria Vissoci Reiche, André Luiz Bortoliero, Tiemi Matsuo, Ester Cerdeira Sabino, and Adelaide Jose Vaz. "Serological, epidemiological and molecular aspects of hepatitis C virus infection in a population from Londrina, PR, Brazil, 2001-2002." Revista do Instituto de Medicina Tropical de São Paulo 46, no. 6 (December 4, 2004): 303–8. http://dx.doi.org/10.1590/s0036-46652004000600002.
Abstract:
Serological, epidemiological and molecular aspects of hepatitis C virus (HCV) infection were evaluated in 183 subjects from Londrina, Paraná, Brazil, and adjacent areas. Serum samples which tested anti-HCV positive by microparticle enzyme immunoassay (MEIA) obtained from eight patients with chronic hepatitis C, 48 blood donors, and 127 patients infected with the human immunodeficiency virus (HIV) were submitted to another enzyme immunoassay (ELISA) and to the polymerase chain reaction (PCR). About 78.7% of samples were also reactive by ELISA, with the greater proportion (70.8%) of discordant results verified among blood donors. A similar finding was observed for HCV-RNA detection by PCR, with 111/165 (67.3%) positive samples, with higher rates among HIV-positive subjects and patients with chronic hepatitis than among blood donors. Sixty-one PCR-positive samples were submitted to HCV genotyping, with 77.1, 21.3 and 1.6% of the samples identified as types 1, 3 and 2, respectively. Finally, analysis of some risk factors associated with HCV infection showed that intravenous drug use was the most common risk factor among HIV/HCV co-infected patients, while blood transfusion was the most important risk factor in the group without HIV infection. The present study contributed to the knowledge regarding risk factors associated with HCV infection and the distribution of HCV genotypes in the population evaluated.
7
Riva, Giovanni, Mario Luppi, Patrizia Barozzi, Fabio Forghieri, and Leonardo Potenza. "How I treat HHV8/KSHV-related diseases in posttransplant patients." Blood 120, no. 20 (November 15, 2012): 4150–59. http://dx.doi.org/10.1182/blood-2012-04-421412.
Abstract:
Abstract Posttransplantation human herpesvirus-8 (HHV8)/Kaposi sarcoma herpesvirus (KSHV) primary infection and/or reactivations are associated with uncommon and sometimes fatal, neoplastic, and non-neoplastic diseases. HHV8-related clinical manifestations notably range from Kaposi sarcoma (KS) to either primary effusion lymphoma or multicentric Castleman disease B-cell malignancies, and from polyclonal HHV8-positive plasmacytic lymphoproliferative disorders to bone marrow failure and peripheral cytopenias, associated or not with hemophagocytic syndromes, and to acute hepatitis syndromes. We reviewed the patient series reported in the literature and summarized clinical management aspects, in terms of diagnosis, follow-up, and treatment. We described typical clinical presentations and histopathologic diagnostic features of these diseases, and we discussed the role of HHV8-specific serologic, molecular, and immunologic assays, particularly focusing on recent data from HHV8-specific T-cell monitoring in posttransplantation KS patients. We finally discussed actual therapeutic options, namely, the reduction or discontinuation of immunosuppressive therapy or the switch from calcineurin inhibitors to mTOR inhibitors, as alternatives to antineoplastic chemotherapy, along with the use of antiherpesvirus agents as prophylactic or therapeutic measures, and treatment with rituximab in posttrans-plantation multicentric Castleman disease patients and non-neoplastic HHV8-associated syndromes.
8
Artemenko, Yu S., M. B. Khamoshina, V. A. Ryabova, and Z. V. Zyukina. "Obesity in women: current aspects of reproductive health disorders." Meditsinskiy sovet = Medical Council, no. 5 (April 19, 2022): 32–39. http://dx.doi.org/10.21518/2079-701x-2022-16-5-32-39.
Abstract:
Obesity and overweight tend to increase in prevalence in the whole world. Obese people have a higher incidence of cardiovascular diseases, stroke, osteoarthritis, diabetes mellitus and reproductive system diseases. This is especially evident in women. Hormonal imbalances is developed among obese women in the hypothalamic-pituitary-ovarian axis, typically there are menstruation disorders, anovulation and female infertility. Adipose tissue is an endocrine organ, with an intricate role in bioactive molecules secrete, in particularly adipokines, which interact differently with a variety of molecular pathways, contribute to the development of insulin resistance, inflammation, hypertension, increased risk of cardiovascular events, disorders of blood clotting, differentiation and maturation of oocytes. In addition, women with obesity and metabolic syndrome have problems with conception at the endometrial level often, a significantly higher risk of having a miscarriage, and worse assisted reproductive technology outcomes. Obesity has negative effects on the endometrium in non-pregnant women, it is increasing the risk of abnormal uterine bleeding. Hormones derived from adipose tissue could be affected on the function of the uterus/endometrium and, consequently, affect the amount of menstrual blood loss. Contradictory results are observed in patients with endometriosis. The correlation of body mass index to the risk of endometriosis has not been proven in clinical studies, but there was a direct relationship between the severity of endometriosis and a high body mass index. The review presents possible relationships of diseases of the reproductive system with obesity and overweight, determining their development and pathogenesis of disorders of the formation of the functions of reproductive organs.
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Eelen, Guy, Lucas Treps, Xuri Li, and Peter Carmeliet. "Basic and Therapeutic Aspects of Angiogenesis Updated." Circulation Research 127, no. 2 (July 3, 2020): 310–29. http://dx.doi.org/10.1161/circresaha.120.316851.
Abstract:
All organisms growing beyond the oxygen diffusion limit critically depend on a functional vasculature for survival. Yet blood vessels are far more than passive, uniform conduits for oxygen and nutrient supply. A remarkable organotypic heterogeneity is brought about by tissue-specific differentiated endothelial cells (lining the blood vessels’ lumen) and allows blood vessels to deal with organ-specific demands for homeostasis. On the flip side, when blood vessels go awry, they promote life-threatening diseases characterized by endothelial cells inappropriately adopting an angiogenic state (eg, tumor vascularization) or becoming dysfunctional (eg, diabetic microvasculopathies), calling respectively for antiangiogenic therapies and proangiogenic/vascular regenerative strategies. In solid tumors, despite initial enthusiasm, growth factor–based (mostly anti-VEGF [vascular endothelial growth factor]) antiangiogenic therapies do not sufficiently live up to the expectations in terms of efficiency and patient survival, in part, due to intrinsic and acquired therapy resistance. Tumors cunningly deploy alternative growth factors than the ones targeted by the antiangiogenic therapies to reinstigate angiogenesis or revert to other ways of securing blood flow, independently of the targeted growth factors. In trying to alleviate tissue ischemia and to repair dysfunctional or damaged endothelium, local in-tissue administration of (genes encoding) proangiogenic factors or endothelial (stem) cells harnessing regenerative potential have been explored. Notwithstanding evaluation in clinical trials, these approaches are often hampered by dosing issues and limited half-life or local retention of the administered agents. Here, without intending to provide an all-encompassing historical overview, we focus on some recent advances in understanding endothelial cell behavior in health and disease and identify novel molecular players and concepts that could eventually be considered for therapeutic targeting.
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Łój, Magdalena, Magdalena Garncarz, and Michał Jank. "Genomic and genetic aspects of heart failure in dogs — A review." Acta Veterinaria Hungarica 60, no. 1 (March 1, 2012): 17–26. http://dx.doi.org/10.1556/avet.2012.002.
Abstract:
The most common causes of heart failure in dogs are valvular disease, predominantly endocardiosis, and myocardial disease, predominantly dilated cardiomyopathy. They are related to changes in the expression of several genes in the heart muscle and in peripheral blood nuclear cells which could be considered as prognostic or diagnostic markers of heart disease in dogs. Since many human genetic markers of heart failure have turned out to be useless in dogs, the screening for genomic markers of canine heart failure could give more insight into the molecular pathology of these diseases and aid the development of new treatment strategies.
Dissertations / Theses on the topic "Blood Diseases Molecular aspects":
1
Bianco-Miotto, Tina. "Loss of ABO antigens in haematological malignancies / Tina Bianco-Miotto." Thesis, Adelaide, S.A, 2002. http://hdl.handle.net/2440/21857.
Abstract:
"May 2002"Includes bibliographical references (leaves 229-251)
xv, 251 leaves : ill. (some col.) ; 30 cm.
Describes the investigation of the alteration of ABH antigen expression on the surface of red blood cells in patients with haematological malignancies.
Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 2003
2
Bianco-Miotto, Tina. "Loss of ABO antigens in haematological malignancies." Adelaide, S.A, 2002. http://web4.library.adelaide.edu.au/theses/09PH/09phb578.pdf.
Abstract:
"May 2002" Includes bibliographical references (leaves 229-251) Describes the investigation of the alteration of ABH antigen expression on the surface of red blood cells in patients with haematological malignancies.
3
Chopra, M. S. "Some biochemical aspects of blood in rheumatoid arthritis and vascular diseases." Thesis, University of Strathclyde, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381360.
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Jim, Jin-to, and 詹展韜. "Genetics and molecular characterization of degenerative disc disease." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B35720189.
5
Lau, Kin-chong, and 劉健莊. "Microarray-based investigations of genetic diseases." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B45894760.
6
Chan, Shun-kwan, and 陳信君. "Molecular detection of streptococcus sinensis in blood culture samplesfrom hospitalized patients in Hong Kong: aneight-year retrospective study." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46632074.
7
Lilliecreutz, Caroline. "Blood-and Injection Phobia in Pregnancy : Epidemiological, Biological and Treatment aspects." Doctoral thesis, Linköpings universitet, Hälsouniversitetet, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-59745.
Abstract:
Introduction: Blood- and injection phobia is an anxiety disorder with a prevalence of approximately 3-5% in the general population. The etiology is often a combination of genetic factors and a conditioning experience. The symptoms of blood- and injection phobia are dizziness, confusion, nausea, epigastria discomfort, anxiety and sometimes panic attacks when receiving injections, seeing blood or having a blood sample taken. Unique for this specific phobia is the high probability of fainting when the phobic situation is encountered if there is no possibility to escape or to avoid the stimuli. During pregnancy and labor, women with blood- and injection phobia are exposed to most of their fears and they therefore find themselves in anxiety-ridden situations. Stress and anxiety during pregnancy is known to be risk factors for adverse obstetric and neonatal outcomes. Studies have shown an altered hypothalamic-adrenal-pituitary axis in women with stress or/and anxiety during pregnancy and increased cortisol concentrations can imply negative consequences for the unborn child. Cognitive behavioral therapy (CBT) is known to be effective in treating specific phobias such as blood- and injection phobia. Aim: The prevalence, obstetric and neonatal consequences, impact on the hypothalamic adrenal-pituitary axis and treatment aspects of blood- and injection phobia in a pregnant population have not been investigated before. The aims of this thesis were to study each of these phenomena. Material and methods: During 2005 a total of 1606 pregnant women were approached at their first visit in an antenatal care clinic in the southeast region in Sweden. They were asked to complete the “Injection Phobia Scale-Anxiety” questionnaire. All women who scored ≥ 20 on the “Injection Phobia Scale-Anxiety” questionnaire (N=347), were interviewed and either diagnosed for blood- and injection phobia or dismissed. In total, 110 women were diagnosed as having blood- and injection phobia. Among the women who scored <20 on the “Injection Phobia Scale-Anxiety” questionnaire, 220 women were randomly stratified for age and parity as a control group. The women in the study population answered questionnaires in gestational week 25, 36 and postpartum concerning symptoms of blood- and injection phobia, depression and anxiety. Samples of cortisol in the saliva were collected in the morning and evening in gestational week 25 and 36 in both groups of pregnant women. The medical records from the antenatal care visits, the delivery and postpartum check-up was used to collect data of importance. A treatment study was conducted using a two session cognitive behavioral therapy in a group of pregnant woman with blood- and injection phobia. Results: The prevalence of blood- and injection phobia is 7 % in a pregnant population. Pregnant women with blood- and injection phobia stated more often a fear of childbirth (p<0.001) and were more frequently delivered by elective cesarean section (p=0.032). The incidence of having a baby diagnosed with a complication (p=0.001) was also higher among these women. The women with blood- and injection phobia had increased cortisol concentrations in the saliva compared to the healthy controls (p=0.014). A two-session CBT in group for pregnant women with blood- and injection phobia reduced phobic (p<0.001) anxiety (p<0.001) and depressive (p<0.001) symptoms during pregnancy. Conclusions: Blood- and injection phobia during pregnancy is rather common. Pregnant women with blood- and injection phobia are more likely to be delivered by elective cesarean section and having a baby born with a complication compared to women not suffering from this specific phobia. Untreated blood- and injection phobia during pregnancy increases salivary cortisol concentrations indicating an altered hypothalamic-adrenal-pituitary axis during these weeks of pregnancy. To enhance psychological well being in pregnant women with blood- and injection phobia a two-session program providing CBT for groups of pregnant women is valuable and produces stable results for at least 3 months after delivery.
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Chan, Cheuk-wing Wilson, and 陳卓榮. "ER stress in the pathogenesis of osteochondrodysplasia." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43085192.
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Makubalo, Zola. "Mutation screening of candidate genes and the development of polymorphic markers residing on chromosome 19q13.3, the progressive familial heart block I gene search area." Thesis, Stellenbosch : Stellenbosch University, 2000. http://hdl.handle.net/10019.1/51838.
Abstract:
Thesis (MSc)--Stellenbosch University, 2000.ENGLISH ABSTRACT: Progressive familial heart block type I (PFHBI) is a cardiac ventricular conduction disorder of unknown cause associated with risk of sudden death, which has been described in several South African families. Clinically, PFHBI is characterised by right bundle branch block on ECG, which may progress to complete heart block, necessitating pacemaker implantation. The disease shows an autosomal dominant pattern of inheritance with evidence of genetic anticipation. Using genetic linkage analysis, the PFHBI-causative gene was mapped to a 10 eentimorgan (cM) gene-rich area of chromosome (C) 19q13.3, which has, subsequently, been reduced to 7cM by fine mapping with polymorphic dinucleotide (CA)n short tandem repeat (STR) markers. Several attractive candidate genes, including muscle glycogen synthase (GSY 1) and histidine-rich calcium binding protein (HRC), lie within this region. The aim of the present study was two-fold: 1) to identify and characterise tetranucleotide (AAAT)n STRs within the PFHBI critical region that could be developed as polymorphic markers for use in genetic fine mapping and 2) to screen selected regions of GSY 1and HRC, positional candidate genes, for the presence ofPFHBI-causing mutation(s). Cosmids harbouring CI9q13.3 insert DNA were screened for the presence of (AAAT)n STRs by dot blot and Southern blot hybridisation using a radiolabelled (AAAT)lO oligonucleotide probe. To characterise the harboured (AAAT)n STRs, the positively hybridising fragments identified by Southern blot were sub-cloned, sequenced and primers designed from the unique repeat-flanking sequences. These primers were used to genotype the (AAAT)n repeat locus to assess its polymorphic nature in a panel of unrelated individuals. Alternatively, vectorette PCR, a rapid method of identifying repeat sequences and obtaining the flanking sequences in large inserts, was employed to develop polymorphic markers from the positively hybridising clones. Selected exons of GSY1 and HRC were screened for the presence of potentially disease-causing mutations by PCR-SSCP analysis and direct sequencing, respectively, in PFHBI-affected and unaffected family members. Of the available cosmid clones that gave strong signals on dot blot and Southern blot hybridisation, three, 29395, 24493 and 20381, were located within the critical PFHBI area and were used for marker development. An interrupted (AAAT)n repeat motif (n less than 5) was identified in cosmid 29395, however, the repeat locus was not polymorphic in the tested population. No (AAAT)n motif, single or repeated was observed in the partial sequence of the sub-cloned fragment of cosmid 24493. Using vectorette peR, no repeated (AAAT)n motif was identified on sequencing the generated products in either cosmid 24493 or 2038l. However, diffuse single AAAT motifs were detected in both cosmids. Exons 4, 5, 11, 12 and 16 of GSY 1, containing domains that are conserved across species, and the conserved eterminus- encoding exons 2-6 of HRC were selected for screening for potential PFHBI-causing mutation(s). However, no sequence variations were detected. The interrupted (AAAT)n repeat identified in cosmid 29395 was not polymorphic, which confirmed reports that complex repeats, especially those containing AAAT motifs of less than 6 repeats, are not polymorphic. One possible explanation for the absence of a repeated AAAT motif in cosmids 24493 and 20381, which both gave positive hybridisation signals, is that the low annealing temperature of the AfT -rich repeat-anchored primers used in vectorette peR may have resulted in transient annealing to the diffuse single AAAT motifs detected on sequencing. The screened regions of candidate genes GSYI and HRC were excluded from carrying the disease-causing mutation(s). The availability of new sequence data generated by the Human Genome Project will influence future strategies to identify the PFHBI gene. Electronic searches will allow identification of STR sequences for development of polymorphic markers and gene annotation will allow selection of new candidate genes for mutation screening.
AFRIKAANSE OPSOMMING: Sien volteks vir opsomming
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Hall, Richard James, and n/a. "Chromosome 18 and autoimmune disease." University of Otago. Department of Biochemistry, 2005. http://adt.otago.ac.nz./public/adt-NZDU20070221.141018.
Abstract:
The autoimmune diseases embody a diverse range of common human conditions that are caused by a loss of self-tolerance in the host immune system to a specific organ or tissue type. Approximately 5% of the general population are affected by autoimmune diseases which include type 1 diabetes (T1D), rheumatoid arthritis (RA) and Graves disease (GD). The majority of the autoimmune diseases are multifactorial in origin, brought about by a combination of both environmental and genetic factors. Numerous susceptibility loci have been identified for each autoimmune disease and a number of these loci have been shown to be shared amongst the autoimmune diseases. The fine-mapping of susceptibility loci to the underlying disease genes remains the current challenge facing complex disease genetics. This project aimed to further characterise the autoimmune disease susceptibility locus IDDM6 on chromosome 18q12-21. This was achieved by using a comparative mapping approach that incorporates the study of genetic association in human autoimmune disease alongside the consomic mapping of the orthologous region in the non-obese diabetic (NOD) mouse model of autoimmunity.
Deleted in colorectal carcinomas (DCC) provided a strong candidate gene at IDDM6 and the resident R201G polymorphism was identified as a functional candidate A potential mechanism for the R201G polymorphism involvement in T1D aetiology was identified where the polymorphism may affect the ability of DCC to induce apoptosis in vitro. However, no evidence for R201G association could be detected in autoimmune disease case-control datasets from the New Zealand (NZ) population (T1D n = 428, RA n = 730, autoimmune thyroid disease n = 192 (AITD); versus n = 1246 healthy controls). In addition, no evidence for R201G involvement in T1D could be provided in a transmission disequilibrium test (TDT) incorporating 382 affected sib-pair families (54.2% transmission; P = 0.15). Significant association of R201G with GD was detected in a United Kingdom (UK) dataset (P = 0.002) from the Newcastle population (423 cases vs. 393 controls) but this was not replicated in an additional dataset from the UK Birmingham population (731 cases vs 668 controls; P = 0.81). It was concluded that the R201G polymorphism may encode susceptibility to GD but is unlikely to be the sole aetiological variant that accounts for the linkage previously observed at IDDM6 in autoimmune disease. To further investigate DCC as a positional candidate at IDDM6, five SNPs were selected from a 100 kb window surrounding a DCC-resident microsatellite that had previously been associated with T1D, called "88,21". The five SNPs were genotyped in the NZ T1D dataset, and the ascertainment of estimated haplotypes in this dataset revealed association of a rare haplotype with T1D, called haplotype H (3.31% cases vs 1.17% controls; P = 0.0044), in addition to global association of all haplotypes (P = 0.018). Haplotype H was also associated in an independent case-control dataset from the UK comprised of 400 T1D subjects and 443 healthy controls (P = 0.038). Maximum support for association of haplotype H was extended when both the UK and NZ T1D datasets were combined (P = 0.0017). Association of haplotype H could not be verified in a family-based test for association using the 382 UK T1D families (P = 0.40). However, the inclusion of the DCC SNPs in a TDT analysis of the published DCC-resident microsatellites "88,21" and "55,26", that had been used to identify IDDM6, extends support for the previously-associated 2-10 haplotype (2-10 refers to the published allele nomenclature at "88,21" and "55,26" respectively; 2-10-haplotype A; 59.6% T; P = 0.0058). There was no evidence for association of the five SNPs with RA or AITD when using either individual SNP analyses or estimated haplotypes in the NZ datasets. A similar lack of association was reported for the UK Newcastle GD dataset. Taken together, these data further support DCC, or a nearby gene, as conferring susceptibility to T1D.
The human genetic data that supports IDDM6 involvement in autoimmune disease is further strengthened by consomic mapping of the orthologous region in mouse, using the non-obese diabetic mouse (NOD) model of autoimmune disease. In this thesis, the first evidence for a diabetes and thyroiditis susceptibility locus on mouse chromosome 18 is presented, which have been designated Idd21 and Sat1 respectively. This was achieved by using a chromosome-replacement strain with chromosome 18 derived from the diabetes-resistant Biozzi ABH strain on a diabetes-susceptible NOD genome, called NOD.ABH[Chr�⁸]. Mouse chromosome 18 contains orthology to both IDDM6 and the rat diabetes-susceptibility locus Iddm3. The NOD.ABH[Chr�⁸] mice showed a dramatic and significant reduction in diabetes incidence (30% of females were affected by 7 months of age versus 85% in NOD; P <0.0001) and that of thyroiditis (15.5% at 12 months compared to 37.4% in NOD; P <0.002).
The comparative mapping of the chromosome 18 autoimmune susceptibility locus IDDM6 in human and mouse presented in this thesis provides further support for this locus. This research also clearly defines the next steps required to fine-map IDDM6 to the underlying disease genes, especially in regard to the DCC gene.
Books on the topic "Blood Diseases Molecular aspects":
1
B, Provan Andrew, and Gribben John, eds. Molecular hematology. 2nd ed. Oxford: Blackwell, 2005.
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Andrew, Provan, and Gribben John, eds. Molecular hematology. 3rd ed. Chichester, West Sussex: Wiley-Blackwell, 2010.
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George, Stamatoyannopoulos, ed. The molecular basis of blood diseases. 3rd ed. Philadelphia: W.B. Saunders, 2001.
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Dunphy, Cherie H. Molecular Pathology of Hematolymphoid Diseases. Boston, MA: Springer Science+Business Media, LLC, 2010.
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Crisan, Domnita. Hematopathology: Genomic mechanisms of neoplastic diseases. New York, N.Y: Humana Press, 2010.
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Bahou, Wadie Farid. Genetics for haematologists: The molecular genetic basis of haematological disorders. London: ReMEDICA, 2000.
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Naeim, Faramarz. Hematopathology: Morphology, immunophenotype, cytogenetics and molecular approaches. Amsterdam: Elsevier/Academic Press, 2008.
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Pia, Glas-Greenwalt, ed. Fibrinolysis in disease: Molecular and hemovascular aspects of fibrinolysis. Boca Raton, Fla: CRC Press, 1996.
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Jackson, Trachette L. Modeling tumor vasculature: Molecular, cellular, and tissue level aspects and implications. New York: Springer, 2012.
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Schmid-Schönbein, G. W. Molecular basis for microcirculatory disorders. Paris: Springer, 2003.
Book chapters on the topic "Blood Diseases Molecular aspects":
1
Hamilton, John D. "Cytomegalovirus and Blood Transfusion." In Molecular Aspects of Human Cytomegalovirus Diseases, 150–61. Berlin, Heidelberg: Springer Berlin Heidelberg, 1993. http://dx.doi.org/10.1007/978-3-642-84850-6_9.
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Periquito, João S., Ludger Starke, Carlota M. Santos, Andreia C. Freitas, Nuno Loução, Pablo García Polo, Rita G. Nunes, Thoralf Niendorf, and Andreas Pohlmann. "Analysis Protocols for MRI Mapping of the Blood Oxygenation–Sensitive Parameters T2* and T2 in the Kidney." In Methods in Molecular Biology, 591–610. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-0978-1_36.
Abstract:
AbstractRenal hypoxia is generally accepted as a key pathophysiologic event in acute kidney injury of various origins and has also been suggested to play a role in the development of chronic kidney disease. Here we describe step-by-step data analysis protocols for MRI monitoring of renal oxygenation in rodents via the deoxyhemoglobin concentration sensitive MR parameters T2* and T2—a contrast mechanism known as the blood oxygenation level dependent (BOLD) effect.This chapter describes how to use the analysis tools provided by vendors of animal and clinical MR systems, as well as how to develop an analysis software. Aspects covered are: data quality checks, data exclusion, model fitting, fitting algorithm, starting values, effects of multiecho imaging, and result validation.This chapter is based upon work from the PARENCHIMA COST Action, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by two separate chapters describing the basic concept and data analysis.
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Levin, Tomer Levin T., and Judith Cukor. "Psychological Aspects of Hematological Neoplasms." In Neoplastic Diseases of the Blood, 1291–306. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-64263-5_60.
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Levin, Tomer T. "Psychological Aspects of Hematological Neoplasms." In Neoplastic Diseases of the Blood, 1387–402. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-3764-2_62.
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Van Ness, Brian. "Molecular Genetics of Myeloma." In Neoplastic Diseases of the Blood, 601–13. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-3764-2_31.
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Reitsma, P. H. "Molecular Basis of Thrombophilia." In Hereditary Diseases and Blood Transfusion, 25–30. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4615-2017-7_3.
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Spector, Logan G., Erin L. Marcotte, Rebecca Kehm, and Jenny N. Poynter. "Epidemiology and Hereditary Aspects of Acute Leukemia." In Neoplastic Diseases of the Blood, 179–95. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-64263-5_13.
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Linet, Martha S., Graça M. Dores, Clara J. Kim, Susan S. Devesa, and Lindsay M. Morton. "Epidemiology and Hereditary Aspects of Acute Leukemia." In Neoplastic Diseases of the Blood, 199–212. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-3764-2_15.
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Peake, I. R. "The Molecular Biology of Haemophilia." In Hereditary Diseases and Blood Transfusion, 3–9. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4615-2017-7_1.
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Siess, W. "Cellular Activation Mechanisms: The Blood Platelet as a Model." In Molecular Aspects of Inflammation, 49–58. Berlin, Heidelberg: Springer Berlin Heidelberg, 1991. http://dx.doi.org/10.1007/978-3-642-76412-7_5.
Conference papers on the topic "Blood Diseases Molecular aspects":
1
Antonijević, Marko, Žiko Milanović, Edina Avdović, Dušica Simijonović, and Zoran Marković. "ANOTHER LOOK AT THE BIOLOGICAL ROLES OF A PLANT ALKALOID-BERBERINE." In XXVII savetovanje o biotehnologiji. University of Kragujevac, Faculty of Agronomy, 2022. http://dx.doi.org/10.46793/sbt27.455a.
Abstract:
For millennia, berberine extracts or berberine itself has been the effective traditional drug with wide application due to its broad spectrum of antibiotic activity. A significant aspect of the berberine’s physiological activity that is often overlooked is the ability to go through the blood-brain barrier and has an impact on different processes and irregularities in the brain such as dementia and Alzheimer’s disease. Potential inhibitory activity towards enzymes for which is believed to be involved in these diseases, in this paper is confirmed by molecular docking simulations. Binding energies suggest that berberine exhibits good potential inhibitory activity and confirms that one of the aspects of suppression of Alzheimer’s disease and dementia is the inhibition of cholinesterase enzymes.
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De Luca, Amalia, Christina M. Warboys, Narges Amini, Pedro Ferreira, Peter Gatehouse, David Firmin, Justin Mason, Spencer Sherwin, and Paul C. Evans. "Image-Based Computational Hemodynamics and Microarray Analysis of the Porcine Aortic Arch Reveals a Correlation Between Shear Stress and Endothelial Cell Apoptosis." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80948.
Abstract:
Atherosclerosis is a focal disease that occurs predominantly at regions of the arterial tree that are exposed to disturbed blood flow, which generates low, oscillatory wall shear stress (WSS) at the lumen. WSS controls the spatial distribution of lesions by influencing numerous aspects of endothelial cell (EC) physiology, including inflammatory activation and viability. Of particular note, ECs in low shear, lesion-prone regions are characterized by increased apoptosis and turnover rates1 thus providing a potential explanation for the distinct spatial localization of lesion formation. Although the molecular mechanisms underlying the effects of WSS on EC physiology are poorly understood, they are known to involve transcriptional changes.
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Hill, F. G. H., C. W. Williams, S. M. Enayat, and P. J. Darbyshire. "ASYMPTOMATIC vWD VARIANT WITH ABSENT RISTOCETIN ACTIVITY BUT PRESERVED BOTROCETIN ACTIVITY AND A DAUGHTER WITH TYPE III (HOMOZYGOUS) vWD." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644109.
Abstract:
The propositus, female aged 1 year, was investigated because of severe bruising. Bleeding time (BT) was in excess of 20 mins, VIIIC <0.01 u/ml and vWF Ag and ristocetin cofactor absent. Family studies showed:-Multimeric analysis was not possible on the propositus, but was normal in the plasma of all other family members. The father of the propositus, however, had an abnormal multimer pattern on lysed platelets, in that the faint low molecular weight doublet is absent and a dense band in the position of the lower band of the doublet with anodal and cathodal trailing.The maternal grandmother and mother appear to have asynpto-matic type I vWD and the father possibly has asymptomatic type I together with an alteration in the biologically vWF site with loss of the ristocetin site. This abnormality is not seen in his parents and his daughter possibly has type III vWD. The propositus' father although having some similarities to the patient of Howard et al., is different in other aspects.1. Howard MA, Salem HH. et al. (1982) Variant von Willebrand's disease Type B - Revisited. Blood, 60: 1420-1428.
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Pshenichnaya, N. Yu, I. A. Lizinfeld, G. Yu Zhuravlev, and N. S. Morozova. "CHARACTERISTICS OF INCIDENCE RATE OF COVID-19, ACUTE RESPIRATORY DISEASES, INFLUENZA AND COMMUNITY ACQUIRED PNEUMONIA IN RUSSIA ACCORDING TO CLIMATE, GEOGRAFICAL ASPECTS AND POPULATION DENSITY." In Molecular Diagnostics and Biosafety. Federal Budget Institute of Science 'Central Research Institute for Epidemiology', 2020. http://dx.doi.org/10.36233/978-5-9900432-9-9-184.
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Priezzhev, A. V., A. E. Lugovtsov, A. N. Semenov, P. B. Ermolinskiy, Kisung Lee, Sehyun Shin, and S. Yu Nikitin. "Laser-optic methods for revealing molecular and microrheologic mechanisms of interaction of blood components and related impairment of metabolism at cardiovascular diseases." In 2020 International Conference Laser Optics (ICLO). IEEE, 2020. http://dx.doi.org/10.1109/iclo48556.2020.9285722.
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Mahmoud, Ahmed M., Daniel H. Cortes, S. Jamal Mustafa, and Osama M. Mukdadi. "High Frequency Precise Ultrasound Imaging System to Assess Mouse Hearts and Blood Vessels." In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-192836.
Abstract:
Genetically modified mice provide a powerful tool for understanding the molecular mechanisms and pathogenesis of human cardiovascular diseases like human atherosclerosis [1]. Numerous mouse strains are available today with phenotypes relevant to human cardiovascular diseases [1,2]. These mouse strains have prompted the development of techniques for assessing the cardiovascular function and morphology of living mice. Recently, several imaging techniques have been emerged as promising non-invasive imaging modalities, such as electron-beam computed tomography, magnetic resonance imaging, positron emission tomography, optical coherent tomography, and ultrasound biomicroscopy (UBM) [3,4]. Although these systems are capable of detecting anatomic and functional information, they may not be suitable to image mouse heart vasculatures. The small size and rapid movement of mouse hearts require systems acquiring images using temporal resolution of less than 10 ms with spatial resolution of 100 μm or less [4]. However, in mice, which have extremely small coronary arteries and high heart rates, the coronary circulation constitutes a great challenge for these available imaging techniques.
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Fedorova, O. A. "TO THE FAUNA OF MIDGES (DIPTERA: SIMULIIDAE) AND BITING MIDGES (DIPTERA: CERATOPOGONIDAE) YAMALO-NENETS AUTONOMOUS DISTRICT." In V International Scientific Conference CONCEPTUAL AND APPLIED ASPECTS OF INVERTEBRATE SCIENTIFIC RESEARCH AND BIOLOGICAL EDUCATION. Tomsk State University Press, 2020. http://dx.doi.org/10.17223/978-5-94621-931-0-2020-40.
Abstract:
On the territory of the Yamal-Nenets Autonomous District, the study of midges and biting midges was carried out during the exploration of new oil and gas deposits in the second half of the 20th century. Currently, the study of the spread of midges and biting midges is relevant, since they are carriers of a number of infectious and invasive diseases of animals and humans. The fauna of blood-sucking diptera insects of the Yamal-Nenets Autonomous Okrug is represented by 116 species. The faunal list of blood-sucking midges of the region is represented by 24 species, including 1 – Simulium paramorsitans, biting midges by 33 species, including 1 species –Culicoides punctatus. This species was first indicated both for the tundra zone and for the region. Today the topic is relevant and requires further research.
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Sharma, Sonika, and Banshi D. Gupta. "Fiber Optic SPR based Dopamine Sensor utilizing GNP/SnO2 Nanocomposite Sup-ported Molecular Imprinting." In JSAP-OSA Joint Symposia. Washington, D.C.: Optica Publishing Group, 2017. http://dx.doi.org/10.1364/jsap.2017.6a_a410_6.
Abstract:
Dopamine (DA) belongs to the catecholamine family of neurotransmitters and is very important for humans. It is produced in adrenal glands and several areas of the brain. Dopamine is formed by decarboxylation of DOPA and is a precursor of two other neurotransmitters adrenaline and noradrenalin. Dopamine is the most abundant of the catecholamine, hence affects many aspects of brain functionality such as movement, emotional response and ability to experience pain and pleasure. Dopamine also affects the cardiovascular and renal systems. Excessive secretion of DA (e.g., due to Huntington’s disease) is associated with failure in energy metabolism and causes untimely death. Differently low levels of dopamine in the central nervous system causes several neurological diseases, for example schizophrenia, Parkinson’s disease. Therefore, it is important to detect dopamine level efficiently in human body [1].
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Lyulchenko, A. S. "ANALYSIS OF THE FREQUENCY OF OCCURRENCE OF MOLECULAR GENETIC MARKERS OF PREDISPOSITION TO CARDIOVASCULAR PATHOLOGY IN ATHLETES." In SAKHAROV READINGS 2021: ENVIRONMENTAL PROBLEMS OF THE XXI CENTURY. International Sakharov Environmental Institute of Belarusian State University, 2021. http://dx.doi.org/10.46646/sakh-2021-2-58-62.
Abstract:
For decades, cardiovascular diseases have been the leading cause of disability and death worldwide. Among athletes, the risk of cardiovascular disease increases significantly due to extreme physical exertion. Genotyping of the DNA samples of athletes and the control group based on the selected candidate genes for the pathology of the cardiovascular system was carried out. Carriers of unfavorable genotypes that significantly increase the risk of thrombosis were identified in the formed groups: dangerous mutations of blood clotting factors II and V were detected in 3.2 % of gymnasts and 17.1% of representatives of fire and rescue sports.
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Киреева, Виктория, Viktoriya Kireeva, Г. Лифшиц, G. Lifshic, Н. Кох, N. Koh, Ю. Усольцев, Yu Usolcev, Константин Апарцин, and Konstantin Apartsin. "Advantages of a personalized approach to the prevention and treatment of cardiovascular diseases in the staff of the INC Of the SBRAS." In Topical issues of translational medicine: a collection of articles dedicated to the 5th anniversary of the day The creation of a department for biomedical research and technology of the Irkutsk Scientific Center Siberian Branch of RAS. Москва: INFRA-M Academic Publishing LLC., 2017. http://dx.doi.org/10.12737/conferencearticle_58be81ec9ed47.
Abstract:
Purpose of the study. To test the functional associations of polymorphic variants of genes in the regulation of blood pressure and vascular tone in employees of the ISC SB RAS. Materials and methods. The study involved patients, employees of the ISC SB RAS, being under care of the outpatient clinic of the Hospital of the ISC SB RAS. During routine laboratory testing the patients were taken 2 ml of blood for genetic analysis and further molecular genetic study on “Hypertension”, “Endothelial dysfunction”, “Pharmacogenetics”, “Inflammatory response” panels. Results. In the analysis of 12 genes coding for key proteins of hormonal enzyme blood pressure regulation systems, polymorphism of CYP11B2 showed statistically significant correlation with the presence of arterial hypertension, which makes its further study promising. The presence of allele C showed protective significance in relation to the development of hypertension with OR = 0,247. When checking associations of functional polymorphic variants of genes, the products of which are involved in the regulation of vascular tone, with hypertension in patients younger than 50 years old we found association of T/T rs5443GNB3 genotype with the debut of hypertensive disease under the age of 50. The data obtained allow the doctor to choose the most personalized and effective safe drug from certain groups, as well as its dose for employees having passed molecular genetic testing. These data can reveal predisposition to the most widespread and socially significant diseases in the surveyed subjects and provide specific personalized recommendations for the prevention of these diseases.
Reports on the topic "Blood Diseases Molecular aspects":
1
Shpigel, Nahum, Raul Barletta, Ilan Rosenshine, and Marcelo Chaffer. Identification and characterization of Mycobacterium paratuberculosis virulence genes expressed in vivo by negative selection. United States Department of Agriculture, January 2004. http://dx.doi.org/10.32747/2004.7696510.bard.
Abstract:
Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of a severe inflammatory bowel disease (IBD) in ruminants, known as Johne’s disease or paratuberculosis. Johne’s disease is considered to be one of the most serious diseases affecting dairy cattle both in Israel and worldwide. Heavy economic losses are incurred by dairy farmers due to the severe effect of subclinical infection on milk production, fertility, lower disease resistance and early culling. Its influence in the United States alone is staggering, causing an estimated loss of $1.5 billion to the agriculture industry every year. Isolation of MAP from intestinal tissue and blood of Crohn's patients has lead to concern that it plays a potential pathogenic role in promoting human IDB including Crohn’s disease. There is great concern following the identification of the organism in animal products and shedding of the organism to the environment by subclinically infected animals. Little is known about the molecular basis for MAP virulence. The goal of the original proposed research was to identify MAP genes that are required for the critical stage of initial infection and colonization of ruminants’ intestine by MAP. We proposed to develop and use signature tag mutagenesis (STM) screen to find MAP genes that are specifically required for survival in ruminants upon experimental infection. This research projected was approved as one-year feasibility study to prove the ability of the research team to establish the animal model for mutant screening and alternative in-vitro cell systems. In Israel, neonatal goat kids were repeatedly inoculated with either one of the following organisms; MAP K-10 strain and three transposon mutants of K-10 which were produced and screened by the US PI. Six months after the commencement of inoculation we have necropsied the goats and taken multiple tissue samples from the jejunum, ileum and mesenteric lymph nodes. Both PCR and histopathology analysis indicated on efficient MAP colonization of all the inoculated animals. We have established several systems in the Israeli PI’s laboratory; these include using IS900 PCR for the identification of MAP and using HSP65-based PCR for the differentiation between MAV and MAP. We used Southern blot analysis for the differentiation among transposon mutants of K-10. In addition the Israeli PI has set up a panel of in-vitro screening systems for MAP mutants. These include assays to test adhesion, phagocytosis and survival of MAP to/within macrophages, assays that determine the rate of MAPinduced apoptosis of macrophages and MAP-induced NO production by macrophages, and assays testing the interference with T cell ã Interferon production and T cell proliferation by MAP infected macrophages (macrophage studies were done in BoMac and RAW cell lines, mouse peritoneal macrophages and bovine peripheral blood monocytes derived macrophages, respectively). All partners involved in this project feel that we are currently on track with this novel, highly challenging and ambitious research project. We have managed to establish the above described research systems that will clearly enable us to achieve the original proposed scientific objectives. We have proven ourselves as excellent collaborative groups with very high levels of complementary expertise. The Israeli groups were very fortunate to work with the US group and in a very short time period to master numerous techniques in the field of Mycobacterium research. The Israeli group has proven its ability to run this complicated animal model. This research, if continued, may elucidate new and basic aspects related to the pathogenesis MAP. In addition the work may identify new targets for vaccine and drug development. Considering the possibility that MAP might be a cause of human Crohn’s disease, better understanding of virulence mechanisms of this organism might also be of public health interest as well.
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Eldar, Avigdor, and Donald L. Evans. Streptococcus iniae Infections in Trout and Tilapia: Host-Pathogen Interactions, the Immune Response Toward the Pathogen and Vaccine Formulation. United States Department of Agriculture, December 2000. http://dx.doi.org/10.32747/2000.7575286.bard.
Abstract:
In Israel and in the U.S., Streptococcus iniae is responsible for considerable losses in various fish species. Poor understanding of its virulence factors and limited know-how-to of vaccine formulation and administration are the main reasons for the limited efficacy of vaccines. Our strategy was that in order to Improve control measures, both aspects should be equally addressed. Our proposal included the following objectives: (i) construction of host-pathogen interaction models; (ii) characterization of virulence factors and immunodominant antigens, with assessment of their relative importance in terms of protection and (iii) genetic identification of virulence factors and genes, with evaluation of the protective effect of recombinant proteins. We have shown that two different serotypes are involved. Their capsular polysaccharides (CPS) were characterized, and proved to play an important role in immune evasion and in other consequences of the infection. This is an innovative finding in fish bacteriology and resembles what, in other fields, has become apparent in the recent years: S. iniae alters surface antigens. By so doing, the pathogen escapes immune destruction. Immunological assays (agar-gel immunodiffusion and antibody titers) confirmed that only limited cross recognition between the two types occurs and that capsular polysaccharides are immunodominant. Vaccination with purified CPS (as an acellular vaccine) results in protection. In vitro and ex-vivo models have allowed us to unravel additional insights of the host-pathogen interactions. S. iniae 173 (type II) produced DNA fragmentation of TMB-8 cells characteristic of cellular necrosis; the same isolate also prevented the development of apoptosis in NCC. This was determined by finding reduced expression of phosphotidylserine (PS) on the outer membrane leaflet of NCC. NCC treated with this isolate had very high levels of cellular necrosis compared to all other isolates. This cellular pathology was confirmed by observing reduced DNA laddering in these same treated cells. Transmission EM also showed characteristic necrotic cellular changes in treated cells. To determine if the (in vitro) PCD/apoptosis protective effects of #173 correlated with any in vivo activity, tilapia were injected IV with #173 and #164 (an Israeli type I strain). Following injection, purified NCC were tested (in vitro) for cytotoxicity against HL-60 target cells. Four significant observations were made : (i) fish injected with #173 had 100-400% increased cytotoxicity compared to #164 (ii) in vivo activation occurred within 5 minutes of injection; (iii) activation occurred only within the peripheral blood compartment; and (iv) the isolate that protected NCC from apoptosis in vitro caused in vivo activation of cytotoxicity. The levels of in vivo cytotoxicity responses are associated with certain pathogens (pathogen associated molecular patterns/PAMP) and with the tissue of origin of NCC. NCC from different tissue (i.e. PBL, anterior kidney, spleen) exist in different states of differentiation. Random amplified polymorphic DNA (RAPD) analysis revealed the "adaptation" of the bacterium to the vaccinated environment, suggesting a "Darwinian-like" evolution of any bacterium. Due to the selective pressure which has occurred in the vaccinated environment, type II strains, able to evade the protective response elicited by the vaccine, have evolved from type I strains. The increased virulence through the appropriation of a novel antigenic composition conforms with pathogenic mechanisms described for other streptococci. Vaccine efficacy was improved: water-in-oil formulations were found effective in inducing protection that lasted for a period of (at least) 6 months. Protection was evaluated by functional tests - the protective effect, and immunological parameters - elicitation of T- and B-cells proliferation. Vaccinated fish were found to be resistant to the disease for (at least) six months; protection was accompanied by activation of the cellular and the humoral branches.
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Chalutz, Edo, Charles Wilson, Samir Droby, Victor Gaba, Clauzell Stevens, Robert Fluhr, and Y. Lu. Induction of Resistance to Postharvest Diseases and Extension of Shelf-Life of Fruits and Vegetables by Ultra-Violet Light. United States Department of Agriculture, February 1994. http://dx.doi.org/10.32747/1994.7568093.bard.
Abstract:
Following preliminary observations by one of the collaborating scientists on this project and the completion of a 1-year, BARD-supported feasibility study (IS-1908-90F), this 3-year BARD project has been executed. The main objectives of the research were to elucidate biochemical and pathological aspects of UV-induced resistance in fruits and vegetables, to characterize physical and biological variables of induced resistance and delay of ripening, and to explore the application of the treatment as a control practice of postharvest diseases and shelf-life extension of fruits and vegetables. Our findings, which are detailed in numerous joint publications, have shown that the effect of UV-C light on induction of resistance and delay of ripening is a general one and of wide oddurrence. Apart from surface sterilization of the commodity, the reduction of decay of different fungi has been associated with and induced resistance phenomenon which gradually builds up within 24 to 48 hours after the UV treatment and can be reversed by visible light. In citrus, induced resistance has been associated with increased activity of the enzymes phenylalanine ammonia-lyase and peroxidase, and with the levels of endglucanase and chitinase. In tomato, resistance was correlated with the production of high levels of tomatine. Our study of some molecular aspects of the induced resistance in grapefruit has revealed the induction of a cDNA which represents a gene encoding for an isoflavone reductase-like protein that, in legumes, has been associated with phytoalexin biosynthesis. This gene was cloned and sequenced. Delay of ripening was associated in tomato with inhibition of ethylene production, carotenoid synthesis, and chlorophyll degradation and with the presence of high levels of polyamines. In peach fruit epiphytic populations of a yeast increased following the UV treatment. Pilot-size treatment and packing lines were constructed in the US and Israel to test the application of the UV treatment on a semi-commercial scale. Although effective in reduction of decay and delay of ripening, a number of problems will have to be addressed before practical application of this methodology can be realized. The main issues are associated with the temporal and variable response to the treatment, and its relationship to the maturity and date of harvest of the commodity.
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Sessa, Guido, and Gregory Martin. MAP kinase cascades activated by SlMAPKKKε and their involvement in tomato resistance to bacterial pathogens. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7699834.bard.
Abstract:
The research problem: Pseudomonas syringae pv. tomato (Pst) and Xanthomonas campestrispv. vesicatoria (Xcv) are the causal agents of tomato bacterial speck and spot diseases, respectively. These pathogens colonize the aerial parts of the plant and cause economically important losses to tomato yield worldwide. Control of speck and spot diseases by cultural practices or chemicals is not effective and genetic sources of resistance are very limited. In previous research supported by BARD, by gene expression profiling we identified signaling components involved in resistance to Xcvstrains. Follow up experiments revealed that a tomato gene encoding a MAP kinase kinase kinase (MAPKKKe) is required for resistance to Xcvand Pststrains. Goals: Central goal of this research was to investigate the molecular mechanisms by which MAPKKKεand associated MAP kinase cascades regulate host resistance. Specific objectives were to: 1. Determine whether MAPKKKεplays a broad role in defense signaling in plants; 2. Identify components of MAP kinase cascades acting downstream of MAPKKKε; 3. Determine the role of phosphorylation-related events in the function of MAPKKKε; 4. Isolate proteins directly activated by MAPKKKε-associatedMAPK modules. Our main achievements during this research program are in the following major areas: 1. Characterization of MAPKKKεas a positive regulator of cell death and dissection of downstream MAP kinase cascades (Melech-Bonfil et al., 2010; Melech-Bonfil and Sessa, 2011). The MAPKKKεgene was found to be required for tomato resistance to Xcvand Pstbacterial strains and for hypersensitive response cell death triggered by different R gene/effector gene pairs. In addition, overexpression analysis demonstrated that MAPKKKεis a positive regulator of cell death, whose activity depends on an intact kinase catalytic domain. Epistatic experiments delineated a signaling cascade downstream of MAPKKKεand identified SIPKK as a negative regulator of MAPKKKε-mediated cell death. Finally, genes encoding MAP kinase components downstream of MAPKKKεwere shown to contribute to tomato resistance to Xcv. 2. Identification of tomato proteins that interact with MAPKKKεand play a role in plant immunity (Oh et al., 2011). We identified proteins that interact with MAPKKKε. Among them, the 14-3-3 protein TFT7 was required for cell death mediated by several R proteins. In addition, TFT7 interacted with the MAPKK SlMKK2 and formed homodimersin vivo. Thus, TFT7 is proposed to recruit SlMKK2 and MAPKKK client proteins for efficient signal transfer. 3. Development of a chemical genetic approach to identify substrates of MAPKKKε-activated MAP kinase cascades (Salomon et al., 2009, 2011). This approach is based on engineering the kinase of interest to accept unnatural ATP analogs. For its implementation to identify substrates of MAPKKKε-activated MAP kinase modules, we sensitized the tomato MAP kinase SlMPK3 to ATP analogs and verified its ability to use them as phosphodonors. By using the sensitized SlMPK3 and radiolabeled N6(benzyl)ATP it should be possible to tag direct substrates of this kinase. 4. Development of methods to study immunity triggered by pathogen-associated molecular patterns (PAMPs) in tomato and N. benthamiana plants (Kim et al., 2009; Nguyen et al. 2010). We developed protocols for measuring various PTI-associatedphenotypes, including bacterial populations after pretreatment of leaves with PAMPs, induction of reporter genes, callose deposition at the cell wall, activation of MAP kinases, and a luciferase-based reporter system for use in protoplasts. Scientific and agricultural significance: Our research activities discovered and characterized a signal transduction pathway mediating plant immunity to bacterial pathogens. Increased understanding of molecular mechanisms of immunity will allow them to be manipulated by both molecular breeding and genetic engineering to produce plants with enhanced natural defense against disease. In addition, we successfully developed new biochemical and molecular methods that can be implemented in the study of plant immunity and other aspects of plant biology.
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Chejanovsky, Nor, and Bruce A. Webb. Potentiation of pest control by insect immunosuppression. United States Department of Agriculture, July 2004. http://dx.doi.org/10.32747/2004.7587236.bard.
Abstract:
Our original aims were to elucidate the mechanisms through which the immunosuppressive insect virus, the Campoletis sonorensis polydnavirus (CsV) promotes replication of a well-characterized pathogenic virus, the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) in hosts that are mildly or non-permissive to virus replication. According to the BARD panels criticism we modified our short-term goals (see below). Thus, in this feasibility study (one-year funding) we aimed to show that: 1. S. littoralis larvae mount an immune response against a baculovirus infection. 2. Immunosuppression of an insect pest improves the ability of a viral pathogen (a baculovirus) to infect the pest. 3. S. littoralis cells constitute an efficient tool to study some aspects of the anti- viral immune response. We achieved the above objectives by: 1. Finding melanized viral foci upon following the baculoviral infection in S . littoralis larvae infected with a polyhedra - positive AcMNPV recombinant that expressed the GFP gene under the control of the Drosophila heat shock promoter. 2. Studying the effect of AcMNPV-infection in S . littoralis immunosuppressed by parasitation with the Braconidae wasp Chelonus inanitus that bears the CiV polydna virus, that resulted in higher susceptibility of S. littoralis to AcMNPV- infection. 3. Proving that S. littoralis hemocytes resist AcMNPV -infection. 4. Defining SL2 as a granulocyte-like cell line and demonstrating that as littoralis hemocytic cell line undergoes apoptosis upon AcMNPV -infection. 5. Showing that some of the recombinant AcMNPV expressing the immuno-suppressive polydna virus CsV- vankyrin genes inhibit baculoviral-induced lysis of SL2 cells. This information paves the way to elucidate the mechanisms through which the immuno- suppressive polydna insect viruses promote replication of pathogenic baculoviruses in lepidopteran hosts that are mildly or non-permissive to virus- replication by: - Assessing the extent to which and the mechanisms whereby the immunosuppressive viruses, CiV and CsV or their genes enhance AcMNPV replication in polydnavirus- immunosuppressed H. zea and S. littoralis insects and S. littoralis cells. - Identifying CiV and CsV genes involved in the above immunosuppression (e.g. inhibiting cellular encapsulation and disrupting humoral immunity). This study will provide insight to the molecular mechanisms of viral pathogenesis and improve our understanding of insect immunity. This knowledge is of fundamental importance to controlling insect vectored diseases of humans, animals and plants and essential to developing novel means for pest control (including baculoviruses) that strategically weaken insect defenses to improve pathogen (i.e. biocontrol agent) infection and virulence.
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Gottlieb, Yuval, Bradley Mullens, and Richard Stouthamer. investigation of the role of bacterial symbionts in regulating the biology and vector competence of Culicoides vectors of animal viruses. United States Department of Agriculture, June 2015. http://dx.doi.org/10.32747/2015.7699865.bard.
Abstract:
Symbiotic bacteria have been shown to influence host reproduction and defense against biotic and abiotic stressors, and this relates to possible development of a symbiont-based control strategy. This project was based on the hypothesis that symbionts have a significant impact on Culicoides fitness and vector competence for animal viruses. The original objectives in our proposal were: 1. Molecular identification and localization of the newly-discovered symbiotic bacteria within C. imicola and C. schultzei in Israel and C. sonorensis in California. 2. Determination of the prevalence of symbiotic bacteria within different vector Culicoides populations. 3. Documentation of specific symbiont effects on vector reproduction and defense: 3a) test for cytoplasmic incompatibility in Cardinium-infected species; 3b) experimentally evaluate the role of the symbiont on infection or parasitism by key Culicoides natural enemies (iridescent virus and mermithid nematode). 4. Testing the role(s) of the symbionts in possible protection against infection of vector Culicoides by BTV. According to preliminary findings and difficulties in performing experimental procedures performed in other insect symbiosis systems where insect host cultures are easily maintained, we modified the last two objectives as follows: Obj. 3, we tested how symbionts affected general fitness of Israeli Culicoides species, and thoroughly described and evaluated the correlation between American Culicoides and their bacterial communities in the field. We also tried alternative methods to test symbiont-Culicoides interactions and launched studies to characterize low-temperature stress tolerances of the main US vector, which may be related to symbionts. Obj. 4, we tested the correlation between EHDV (instead of BTV) aquisition and Cardinium infection. Culicoides-bornearboviral diseases are emerging or re-emerging worldwide, causing direct and indirect economic losses as well as reduction in animal welfare. One novel strategy to reduce insects’ vectorial capacity is by manipulating specific symbionts to affect vector fitness or performance of the disease agent within. Little was known on the bacterial tenants occupying various Culicoides species, and thus, this project was initiated with the above aims. During this project, we were able to describe the symbiont Cardinium and whole bacterial communities in Israeli and American Culicoides species respectively. We showed that Cardinium infection prevalence is determined by land surface temperature, and this may be important to the larval stage. We also showed no patent significant effect of Cardinium on adult fitness parameters. We showed that the bacterial community in C. sonorensis varies significantly with the host’s developmental stage, but it varies little across multiple wastewater pond environments. This may indicate some specific biological interactions and allowed us to describe a “core microbiome” for C. sonorensis. The final set of analyses that include habitat sample is currently done, in order to separate the more intimately-associated bacteria from those inhabiting the gut contents or cuticle surface (which also could be important). We were also able to carefully study other biological aspects of Culicoides and were able to discriminate two species in C. schultzei group in Israel, and to investigate low temperature tolerances of C. sonorensis that may be related to symbionts. Scientific implications include the establishment of bacterial identification and interactions in Culicoides (our work is cited in other bacteria-Culicoides studies), the development molecular identification of C. schultzei group, and the detailed description of the microbiome of the immature and matched adult stages of C. sonorensis. Agricultural implications include understanding of intrinsic factors that govern Culicoides biology and population regulation, which may be relevant for vector control or reduction in pathogen transmission. Being able to precisely identify Culicoides species is central to understanding Culicoides borne disease epidemiology.