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1
Marcus Cornelis Maris van Dijk. Recognition and processing of apolipoprotein E-rich (neo)lipoproteins) by liver cells. [Netherlsnds: s.n.], 1992.
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2
Bach, Johann Sebastian. Cello suites nos. 1, 2, and 3, for guitar. New York: International Music Co., 1999.
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3
Ligeti, György. String quartets nos. 1 & 2 ; Ramifications ; Cello sonata ; Melodien. Hamburg: Deutsche Grammophon,c2003, 2003.
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4
Joëlle, Menrath, ed. Mobile attitude: Ce que les portables ont changé dans nos vies. Paris: Hachette, 2005.
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5
Girard, Serge. L'au-delà à l'écoute de nos prières: La prière des vivants et celle des morts. Chicoutimi, Québec: Éditions JCL, 1997.
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6
Settipani, Christian. Nos ancêtres de l'Antiquité: Études des possibilités de liens généalogiques entre les familles de l'Antiquité et celles du haut Moyen-Age européen. Paris: Éditions Christian, 1991.
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7
Settipani, Christian. Nos ancêtres de l'Antiquité: Études des possibilités de liens généalogiques entre les familles de l'Antiquité et celles du haut Moyen-Age européen. Paris: Editions Christian, 1991.
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8
Algoud, François Marie. Histoire de la volonté de perversion de l'intelligence et des mœurs: Du XVIe siècle à nos jours : les oppositions à celle-ci ; précédée de, Tout se tient, vers Dieu ou vers la bête? Chiré-en-Montreuil: Editions de Chiré, 1996.
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9
Miller, Ada. Nos separan los celos. Debolsillo, 2003.
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10
Miller, Ada. Nos Separan Los Celos. Plaza & Janes, 2005.
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11
Miller, Ada. Nos Separan Los Celos. Debolsillo, 2004.
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12
Pletnikov, Mikhail V., Guo-Li Ming, and Christopher A. Ross. Animal and Cellular Models of Psychotic Disorders. Edited by Dennis S. Charney, Eric J. Nestler, Pamela Sklar, and Joseph D. Buxbaum. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190681425.003.0015.
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Animal and cell models are experimental systems developed to study particular aspects of a disease, as no model can accurately reflect all features of the disease. In this critical review we mention some of the nongenetic models but focus on genetic mouse models, evaluate their advantages and limitations, and comment on potential new prospects for the field. The ability to reprogram somatic cells from patients and unaffected donors to induced pluripotent stem cells (iPSCs) has the potential to substantially enhance our knowledge of normal cellular development and disease pathogenesis. The use of cell and animal models will help elucidate basic cellular and molecular mechanisms of pathogenesis, which will enable the development of targeted therapeutic approaches.
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Birch, Jonathan. The Multicellular Organism as a Social Phenomenon. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780198733058.003.0007.
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As Hamilton observed, the stability of cooperation within clonal groups of cells is no mystery, since the cells’ inclusive fitness interests are aligned. However, the process of social group transformation, by means of which a social group of cells is transformed into a multicellular individual with a division of labour among multiple cell types, remains mysterious. In both multicellular organisms and eusocial insects, group size and the number of specialized types are closely linked. As Bourke has argued, positive feedback is likely to be crucial in explaining the relationship between size and complexity, and a social perspective on the organism helps us understand this feedback loop. This chapter proposes an expanded feedback loop in which the relationship between group size and specialization is mediated by the degree of redundancy (which may be either passive or active) in task structures.
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Peixoto, José Luís. Nadie nos mira. Ediciones Uniandes, 2018. http://dx.doi.org/10.51566/humalite2227.
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Nadie nos mira desarrolla la vida de dos generaciones en un pequeño poblado rural, acuciado por la soledad, los celos y la muerte. Los personajes son pastores, carpinteros, taberneros, sus mujeres e hijos, es decir, son personas comunes, últimos eslabones en el orden social humano. Para todos, hombres y mujeres, la vida parece un juego cuyo discurrir no puede ser cuestionado, apenas padecido, como no se cuestiona al destino. Un callejón sin salida cuyo ritmo es marcado por la aparición de un gigante o por las palabras del diablo. No hay rastro de religiosidad, de trascendencia: nadie pide por una vida diferente, más allá de lo evidente está solamente lo monstruoso.
15
Gutman, Anne. Los Celos de Gaspar (Peque~nos Desastres de Gaspar y Lola). Tandem Library, 2001.
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16
Joseph, Haydn. Trios for Violin, Cello and Piano, Nos. 1-6: Kalmus Edition. Alfred Publishing Company, 1985.
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17
Gutman, Anne. Los Celos De Gaspar (Peque~nos Desastres de Gaspar y Lola). Distribooks, 2002.
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18
Trios for Violin, Cello and Piano: Nos. 7-12, Kalmus Edition. Alfred Publishing Company, 1985.
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19
Joseph, Haydn. Trios for Violin, Cello and Piano: Nos. 13-17 (Kalmus Edition). Alfred Publishing Company, 1985.
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20
Anderson, Greg. The Cells of the Social Body. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780190886646.003.0013.
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Within their cosmic ecology, the Athenians took it for granted that their polis was a “communion” (koinonia) of households, so in their experience there could be no equivalents of our modern distinctions between state and society or political and social realms. Households (oikoi) functioned as the cells of the social body, such that the vitality of the parts was inseparable from the vitality of the whole. Thus, the human “government” of the polis began not with assembly meetings but with the management of its constituent oikoi, which were the primary means of life and livelihood for all Athenians. The Athenians also took it for granted that the gods had deliberately designed males and females to play different, but complementary roles in the reproduction of social being. Women were expected to serve as “partners” to their husbands in the business of household management, performing a wide range of functions that were essential to the lives of their oikoi and therefore to the life of their polis. While they may not look like “citizens” to us, they were considered full members of the polis (politides) at the time. Terms like “patriarchy” and “misogyny,” so common in the modern literature, are accordingly unhelpful when describing gender relations in classical Athens.
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Tyndall, Alan, and Jacob M. van Laar. Stem cell therapies. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0085.
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Since the start of the international project in 1997, over 1500 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, with overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many cases, e.g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of the three running large prospective randomized controlled trials will allow modification of the protocols to reduce the high transplant-related mortality which relates to regimen intensity, age of patient, and comorbidity. Multipotent mesenchymal stromal cells (MSC) have been recently tested in various autoimmune diseases, exploiting their immune modulating properties and apparent low acute toxicity. MSC display immune privilege in that the patient requires no immunosuppression prior to allogeneic MSC infusion. Despite encouraging small phase I/II studies, no positive data from randomized prospective studies are as yet available in the peer-reviewed literature.
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Peake, Sandra L., and Matthew J. Maiden. Management of septic shock in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0298.
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The management of septic shock is a medical emergency. Following prompt recognition, treatment priorities are haemodynamic resuscitation, empirical antimicrobials, urgent control of the source of infection and monitoring the response to therapy. Haemodynamic resuscitation is focused on maintaining an adequate macrocirculation, while also ensuring adequacy of microcirculatory blood flow to the cells. Intravenous fluids and catecholamines have been the mainstay of therapy. However, the amount and type of fluids, choice of vasoactive medications, and the appropriate resuscitation endpoints have been questioned. Greater awareness of the importance of resuscitating the microcirculation and cell function have led to endpoints such as venous O2 saturation and changes in lactate levels becoming resuscitation targets. Urgent definitive treatment of the infection is also crucial. This requires prompt broad-spectrum empirical antimicrobial therapy, draining infected collections and removing infected medical devices. Despite extensive research, no new therapies have improved survival from septic shock.
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Nash, Kermit B. Psychosocial Aspects of Sickle Cell Disease: Past, Present, and Future Directions of Research (Journal of Health & Social Policy, Vol 5., Nos 3/4). Haworth Pr Inc, 1994.
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24
Tyndall, Alan, and Jacob M. van Laar. Stem cell therapies. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199642489.003.0085_update_003.
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Since the start of the international project in 1997, over 2000 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, with overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many cases, e.g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of the three running large prospective randomized controlled trials will allow modification of the protocols to reduce the high transplant-related mortality which relates to regimen intensity, age of patient, and comorbidity. Multipotent mesenchymal stromal cells (MSC) have been recently tested in various autoimmune diseases, exploiting their immune modulating properties and apparent low acute toxicity. MSC display immune privilege in that the patient requires no immunosuppression prior to allogeneic MSC infusion. Despite encouraging many small phase I/II studies, only 2 prospective controlled trials which achieved their primary endpoints have been published.
25
Solomon, E. Human Gene Mapping 11 (Journal Cytogenetics & Cell Genetics, Vol. 58, Nos.1-4, 1991). S. Karger AG (Switzerland), 1991.
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26
Ehrlich, Benjamin. Cajal and Dream Research. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190619619.003.0003.
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Cajal published a total of about three hundred and fifty scientific articles. The majority of these are concerned with the structure of the nervous system, six of them are on the subject of psychology, and only a single one is on dreaming. Although he did not value the content of dreams, Cajal was fascinated by their neurobiological mechanisms. During sleep, the cells throughout the brain that are hyperactive during daytime operations—especially those responsible for “the critical faculty”—are exhausted and rest; meanwhile, the fresh cells that store unused impressions are free to perform their gymnastics, randomly synthesizing their impulses. Through analysis of thousands of dreams through visual dreaming in a technique he referred to as “the introspective method,” he concluded that there was no involvement from any cells in the retina. This avant-garde finding reflects our contemporary thinking about dreaming.
27
Dalton, Michelle. Managing Blood Loss in a Jehovah’s Witness Patient. Edited by Erin S. Williams, Olutoyin A. Olutoye, Catherine P. Seipel, and Titilopemi A. O. Aina. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190678333.003.0069.
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The Jehovah’s Witnesses are a unique group of patients that can pose a challenge to the anesthesiologist given their desire to avoid transfusion of blood products. This religious belief can include refusal of red cells, white cells, plasma, as well as platelets. The perioperative care of such patients can include the use of bloodless techniques in order to respect their beliefs. Given the desire to avoid blood products, it is imperative to utilize strategies that will prevent unnecessary transfusion. It is also important to understand the ethical and or legal ramifications of overriding parental/adolescent requests for no transfusion as well as acceptance of adolescent transfusion refusal.
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LEDESMA-ALBERT, Aida. Handbooks Engineering Science and Technology TIX. ECORFAN, 2021. http://dx.doi.org/10.35429/h.2021.9.1.1.128.
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Global warming and climate change coincide in their main causes, the massive emission of greenhouse gases, which retain heat in the atmosphere and on the earth's surface through the so-called greenhouse effect. The generation of electricity by means of fossil fuels is an important emitter of greenhouse gases (CO2, CH4, N2O), and halogenated compounds containing F, Cl, and Br. With the purpose of contributing to the construction of viable solutions to the current energy situation of the country and in the foundation of a sustainable future, the use of solar energy for the generation of electricity by means of solar panels represents an option. The purpose of this study is to describe and control the solar cell protection material Ethylene-Vinyl-Acetate (EVA), as a contribution to the Quality Assurance of solar panels, since the function of this material is essential for the protection of solar cells, which are a vital part of the solar panel. The tests performed were: Gel content, adhesion test, and durability tests. The results obtained were within specification according to IEC 61215. From this work it is concluded that it is important to continue testing the whole process and components of the solar panels in order to guarantee the useful life of the finished product, as well as to contribute to sustainable development.
29
Haymann, Jean-Philippe, and Francois Lionnet. The patient with sickle cell anaemia. Edited by Giuseppe Remuzzi. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0167.
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In sickle cell anaemia (SCA) a single mutation in the haemoglobin beta-globin gene is responsible for a pleomorphic phenotype leading to acute and chronic life-threatening complications. Healthcare management programmes, patient and family education, infection prophylaxis (especially in childhood), and long-term treatment for some patients (such as hydroxyurea) have significantly improved survival, giving rise to some new long-term issues.Sickle cell-associated nephropathy (SCAN) leads in some cases to chronic renal failure with a significant impact on survival. SCAN is characterized by an increased effective plasma renal flow and glomerular filtration rate, glomerular hypertrophy, and damaged vasa recta system leading to albuminuria and impaired urinary concentration.Early onset of hyperfiltration occurs in 60% of SCA patients often associated with microalbuminuria. SCAN risk factors are still under investigation, but may be related to chronic haemolysis at an early time point. Other lesions in patients with sickle cell anaemia include papillary necrosis, and recurrent acute kidney injury in association with crises or infections.ACEI are recommended if there is proteinuria. There is no current agreement on whether angiotensin-converting enzyme inhibitors (ACEI) should be introduced earlier, but systematic screening for microalbuminuria and hypertension, and avoidance of nephrotoxic agents are strongly advised.Patients with sickle cell trait (carriers for sickle cell anaemia) are prone to microscopic haematuria and abnormalities of the vasa recta have been described. A very rare tumour, renal medullary carcinoma, is largely restricted to this group (in whom it is still extremely rare). Increased risk of other renal problems is still largely hypothetical rather than proven.The prevalence of nephropathies in other sickle cell diseases (in particular haemoglobin SC disease) is much lower.
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Kahn, S. Lowell. Bland Lipiodol-Assisted Thermal Ablation of Renal Cell Carcinoma. Edited by S. Lowell Kahn, Bulent Arslan, and Abdulrahman Masrani. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199986071.003.0073.
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Surgical resection of renal cell carcinoma (RCC) remains the standard of care given the excellent reported outcomes for early stage disease, with 5-year cancer-specific survival (CSS) rates of 97% for pT1a and 87% for pT1b tumors after nephrectomy. Outcomes after partial nephrectomy are equally encouraging, with 5- and 10-year CSS rates of 92% and 80%, respectively, across all stages and 96% and 90%, respectively, for tumors less than 4 cm. Transarterial embolization prior to thermal ablation for RCC is far less frequent, but it is described in the literature. To date, there are no randomized controlled studies that demonstrate a benefit of combined therapy over radiofrequency ablation (RFA) or cryoablation alone. However, lipiodol is profoundly radiopaque, and utilization prior to RFA or cryoablation may aid in the visualization of the tumor.
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Keshav, Satish, and Alexandra Kent. Immunology and genetics in gastrointestinal and hepatic medicine. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0196.
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The gut has a pivotal role in immune homeostasis. It is constantly exposed to a wide array of antigens in food, and resident and consumed microorganisms. It is estimated that the number of bacterial cells in the gastrointestinal tract is tenfold greater than the number of cells in the human body. The gut needs to recognize harmful bacteria, and consequently contains the largest number of immune cells in the body. However, it must remain tolerant to commensal bacteria. Bacteria express antigens that stimulate an immunological response via the gut-associated lymphoid tissue (GALT). The GALT includes the appendix, tonsils, Peyer’s patches, and mesenteric lymph nodes. Therefore, the intestinal immune system is finely balanced between tolerance and reactivity. An example of an abnormal response that generally the individual should be tolerant to is gliadin peptides in coeliac disease. An example of excessive tolerance to an otherwise controllable infection is cryptosporidiosis, which causes diarrhoea in patients with HIV infection. The understanding of genetics in disease has progressed rapidly with the introduction of genome-wide association studies. The Welcome Trust Case Control Consortium has performed extensive research on the genetics of many illnesses, including Crohn’s disease, ulcerative colitis, Barrett’s oesophagus, oesophageal adenocarcinoma, and primary biliary cholangitis. Although these studies have increased our understanding of the molecular basis of disease, they have had little impact on clinical management. This may change as studies associate genotype and phenotype. Several gastrointestinal diseases have an etiology based on immunological or genetic aberrations, and these immunological mechanisms and genetic mutations can be utilized for diagnostic purposes. However, there is no genetic or immunological marker that is 100% specific to a disease and, consequently, the markers are used to support clinical, histological, and/or radiological findings.
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Phipps, Lisa M., Titi Chen, and David C. H. Harris. Radiation nephropathy. Edited by Adrian Covic. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0091_update_001.
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Radiation nephropathy usually arises after inadvertent exposure of kidneys to radiotherapy. It may manifest as acute nephropathy as early as 6 months after exposure, or later as chronic nephropathy, hypertension, or asymptomatic proteinuria. Glomerular and peritubular endothelium and renal tubular cells are especially radiosensitive. There are no pathognomonic histological features, but renal pathology may be similar to that of haemolytic uraemic syndrome. Radiation nephropathy may be prevented by renal shielding and mitigated by radiation dose fractionation. Control of hypertension is important and angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists appear to have protective effects beyond those of blood pressure control.
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Cummings, Jeffrey L., and Kate Zhong. Clinical Trials and Drug Development in Neurodegenerative Diseases. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190233563.003.0018.
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This chapter describes the common therapeutic targets, approaches to clinical trial design, biomarkers, and therapeutic interventions across neurodegenerative disorders (NDDs). Each unique NDD-Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), etc.-has a unique phenotype associated with the regional cell population most affected. Each disease, however, is associated with protein misfolding, oxidation, inflammation, apoptosis, and cell death. If vulnerable cell populations include transmitter source nuclei, transmitter deficits also emerge (e.g. cholinergic abnormalities in AD and dopaminergic deficits in PD). Biomarkers show regionally appropriate brain atrophy or process-related cerebrospinal deficits. Clinical trial designs share features for symptomatic interventions (e.g. cholinesterase inhibitors in AD and dopamine agents in PD) and disease-modifying therapies. Biomarkers play similar roles in trials for NDD, including demonstrating target engagement and supporting disease modification. No disease-modifying therapies have been approved for any NDDs; all programs face similar pharmacokinetic, pharmacodynamic, and regulatory challenges in therapeutic development.
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Patin, Stéphane, ed. Les enjeux du numérique en sciences sociales et humaines. Editions des archives contemporaines, 2020. http://dx.doi.org/10.17184/eac.9782813003867.
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Devenu « univers », « ère », « révolution » ou même « culture », le numérique est un phénomène technologique, social et culturel qui affecte les activités les plus ordinaires de notre vie quotidienne. Il modifie notre rapport à la temporalité −immédiateté, simultanéité, accélération− et à l’espace où nous sommes passés successivement d’une culture sédentaire, celle de la chaise et d’ un ordinateur du web 1.0 ; à une culture nomade, celle des dispositifs mobiles du web 2.0. Il change sinon bouleverse nos relations interpersonnelles, nos modes de penser, d’imaginer et de créer, de travailler, d’accéder au savoir ainsi que nos façons de produire et de diffuser les connaissances et les expériences du monde. En français et en espagnol, les onze contributions d’enseignants-chercheurs et de professionnels réunies dans cet ouvrage mettent en lumière comment, au XXIe siècle, le numérique touche aussi bien la _praxis_ que _l’épistémè_ des sciences humaines. Analyse discursive de SMS, de messages sur_ WhatsApp_, de _Tweets_, de commentaires en ligne, de textes juridiques et statutaires, didactisation des outils numériques en langues maternelles, traduction et adaptation de spots publicitaires, pratique numérique dans le tourisme culturel, numérisation de collections à la Bibliothèque nationale de France ou au Château de Versailles, diffusion de séries sur des plateformes numériques sont autant d’exemples qui témoignent d’ une humanité technologique façonnée par le numérique… Un numérique ouvrant la voie à un éventuel _homo numericus_ doté d’une multitude d’écrans et de claviers lui obéissant au doigt et à l’œil.
35
Tracy, Balzer. Thin Places: An Evangelical Journey into Celtic Christianity. Abilene Christian University Press, 2007.
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36
Tracy, Balzer. Thin Places: An Evangelical Journey into Celtic Christianity. Leafwood Publishers, 2007.
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37
Nestler, Eric J. The Biological Basis of Depression. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190603342.003.0001.
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Most major advances in biomedical research have relied on the use of animal and cell models of disease. This is a particularly difficult challenge in psychiatry, because many core symptoms of mental illnesses are inherently inaccessible in animals. Moreover, because still today there are no bona fide molecular-cellular abnormalities that are pathogenomic for these illnesses, cell models are even more far afield. This chapter reviews efforts to overcome these obstacles and use animal and cell studies to better understand the biological basis of depression and to develop improved treatments. An important distinction is made between acute vs. chronic stress models as well as differentiating the changes that stress induces in brain that mediate deleterious maladaptations as opposed to homeostatic adaptations that help the individual cope with the stress. Studies along these lines are making major strides in identifying candidate molecular pathways that should be mined for new antidepressant treatments. However, a major gap in the field is the great difficulty in testing novel mechanisms in humans; closing this gap is one of the highest priorities for the field.
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Thun, Michael J., and Neal D. Freedman. Tobacco. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190238667.003.0011.
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Tobacco is the leading preventable cause of cancer and other non-communicable diseases worldwide. IARC and the U.S. Surgeon General designate over twenty cancer sites or subsites as causally related to active cigarette smoking, including lung, oral cavity, nasal cavity and accessory sinuses, naso- oro- and hypopharynx, larynx, esophagus (squamous cell carcinoma and adenocarcinoma), stomach, pancreas, colorectum, liver, kidney (adeno- and transitional cell carcinoma), ureter, urinary bladder, uterine cervix, ovary (mucinous), and acute myeloid leukemia. Even this list may be incomplete, as it does not include sites for which the evidence is still considered limited, such as advanced prostate cancer and breast cancer. In addition to cigarettes, all other forms of smoked and conventional smokeless tobacco products, as well as involuntary exposure to tobacco smoke, cause cancer. The use of multiple tobacco products continues to complicate tobacco control, as does the recent introduction of novel products such as e-cigarettes.
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Walsh, Denis M., and Philippe Huneman. Introduction: Challenging the Modern Synthesis. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780199377176.003.0012.
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The modern evolutionary synthesis arose out of the conjunction of the Mendelian theory of inheritance and the neo-Darwinian theory of population change early in the 20th century.1 In the nearly 100 years since its inception, the modern evolutionary synthesis has grown to encompass practically all fields of comparative biology—ecology, ethology, paleontology, systematics, cell biology, physiology, genetics, development. Theodosius Dobzhansky’s dictum—“nothing in biology makes sense except in the light of evolution” (...
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Nageshwaran, Sathiji, Heather C. Wilson, Anthony Dickenson, and David Ledingham. Inflammatory disorders of the central nervous system. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199664368.003.0006.
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Primary neuroinflammatory disorders of the central nervous system (multiple sclerosis, neuromyelitis optica (NMO), transverse myelitis, optic neuritis, acute disseminated encephalomyelitis (ADEM), primary angiitis of the central nervous system, autoimmune limbic encephalitis, and Susac’s syndrome) and multisystem diseases with inflammatory involvement of the central nervous system (sarcoidosis, systemic lupus erythematosus (SLE), giant cell arteritis, Behçet’s disease, Sjögren’s, and other vasculitides) are discussed in depth, covering the aetiology, clinical features and evidence-based treatment.
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Cui, Zhao, Neil Turner, and Ming-hui Zhao. Antiglomerular basement membrane disease. Edited by Neil Turner. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0074_update_001.
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Individuals appear to be predisposed to antiglomerular basement membrane (anti-GBM) disease by carrying a predisposing human leucocyte antigen type, DRB1*1501 being identified as the highest risk factor, and there are likely to be other predisposing genes or influences on top of which a relatively rare ‘second hit’ leads to the development of autoimmunity. In anti-GBM disease this appears to have a self-perpetuating, accelerating component, that may be to do with antibodies and altered antigen presentation. Lymphocyte depletion may also predispose to the disease. A number of second hits have been identified and they seem to share a theme of damage to the glomerulus. There may be a prolonged (months to years) and usually subclinical phase in anti-GBM disease in which usually relatively low level antibody titres are associated with variable haematuria, sometimes minor pulmonary haemorrhage, but often no symptoms. Damage to the lung seems to determine whether there is a pulmonary component to the disease. Without pulmonary damage caused typically by smoking, inhalation of other fumes, and potentially infection or oxygen toxicity, the disease remains an isolated kidney disease. Antibodies appear to be an important component of the disease, but cell-mediated immunity is also critical to the clinical picture. In animal models, cell-mediated immunity triggered by the GBM antigen can cause severe renal damage in the absence of pathogenic antibody. The development of specific antibody also requires T-cell sensitization and help, and suppressing the response is likely to require suppressing both antibody and cell-mediated immunity. Antibodies recognize one major and some other epitopes, which are now well described. T-cell epitopes are becoming better understood. Evidence from animal models also suggests that the damage in anti-GBM disease is dependent on complement, macrophages, and neutrophils.
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Cui, Zhao, Neil Turner, and Ming-hui Zhao. Antiglomerular basement membrane disease. Edited by Neil Turner. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0073_update_001.
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Cyclophosphamide and plasma exchange are the standard of care in rapidly progressive glomerulonephritis or lung haemorrhage caused by antiglomerular basement membrane (anti-GBM) disease, and it is unusual to encounter patients at earlier stages. Steroids are universally used in addition. There is some evidence that plasma exchange may not be a critical part of treatment at an earlier stage. There is no more than anecdotal evidence for other therapies. Slower-onset therapies such as antibodies to B cells are rarely appropriate. If untreated, patients with severe anti-GBM disease will not recover renal function and are at risk of pulmonary haemorrhage. Evidence for the pathogenicity of circulating anti-GBM antibodies provides rationale for removal of circulating antibodies as rapidly as possible, whilst simultaneously inhibiting their synthesis. This was behind the introduction of the combination of plasma exchange with immunosuppressive therapy in mid 1970s, which revolutionized outcomes. Plasmapheresis aims to remove circulating pathogenic antibodies against GBM and possibly other mediators; cyclophosphamide prevents further synthesis of autoantibodies; and steroids act as anti-inflammatory agents to attenuate the glomerular inflammatory response initiated by anti-GBM antibodies. It is clear from experimental models and occasional observations in man that the anti-cell mediated effects of current therapies are important too. Outcomes vary, but in general patient survival is now good, while renal survival remains poor, in many series less than 50% at 1 year. Treatment is toxic and after an early peak in deaths due to pulmonary haemorrhage, secondary infections are the next threat. It may therefore be best not to immunosuppress patients with a very poor renal prognosis who appear to be at low risk of pulmonary haemorrhage. Treatment can usually be curtailed after 3 months without recurrence. ANCA and anti-GBM antibodies occur together in some patients. This is typically an older group which often has features of vasculitis, and the anti-GBM response may often be secondary. Longer treatment as for small vessel vasculitis is usually indicated.
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Magalhaes, Eric, Angelo Polito, Andréa Polito, and Tarek Sharshar. Sepsis-Associated Encephalopathy. Oxford University Press, 2014. http://dx.doi.org/10.1093/med/9780199653461.003.0032.
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Brain dysfunction is a major complication of sepsis and is characterized by alteration of consciousness, ranging from delirium to coma and marked electroencephalographic changes. It reflects a constellation of dynamic biological mechanisms, including neurotransmitter imbalance, macro- and microcirculatory dysfunction resulting in ischaemia, endothelial activation, alteration of the blood-brain barrier impairment with passage of neurotoxic mediators, activation of microglial cells within the central nervous system, cumulatively resulting in a neuroinflammatory state. Sepsis-associated brain dysfunction is associated with increased mortality and long-term cognitive decline, whose mechanisms might include microglial activation, axonopathy, or cerebral microinfarction. There is no specific treatment, other than the management of the underlying septic source, correction of physiological and metabolic abnormalities, and limiting the use of medications with neurotoxic effects.
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Vaziri, Nosratola D. Oxidative stress and its implications in chronic kidney disease. Edited by David J. Goldsmith. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0112.
Full textAbstract:
Reactive oxygen species (ROS) are produced at low levels physiologically and their production conveys signals and has specific functions. Control mechanisms ensure that this does not cause damage. ROS are highly reactive and cytotoxic and are also deliberately produced by inflammatory cells (granulocytes, macrophages) to kill pathogens. If these chemicals are released inappropriately or excessively, or if control mechanisms are under-functioning, bystander or unintended tissue damage may be caused. The concept of oxidative stress is based on the idea that in certain states, commonly inflammatory states, release of oxygen radicals may be excessive, or control mechanisms weakened, so that tissue damage occurs. In CKD, both overproduction and diminished control may apply. No effective therapies acting via these pathways have been established so far though there remain some candidates.
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Devlin, Hugh, and Rebecca Craven. Diabetes. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198759782.003.0007.
Full textAbstract:
Diabetes in relation to dentistry is the topic of this chapter. The incidence of diabetes is increasingly rapidly, hand-in-hand with the increase in obesity. Obesity predisposes patients to an increased insulin resistance, i.e. reduces their ability to increase the glucose transport into adipocytes, muscle, and liver cells. The pancreas responds by producing more insulin but when it can no longer produce enough to overcome the insulin resistance, the blood glucose rises. Diabetes is characterized by raised blood glucose. We describe the devastating long-term effects of diabetes, in particular the microvascular and macrovascular medical complications. The dental complications include an increased severity of periodontal disease, oral candidiasis, and dry mouth but in those who are poorly controlled the impaired defence mechanisms can lead to severe head and neck infections and osteomyelitis. A final summary lists the important clinical recommendations for treatment of diabetic patients.
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Newman, Stuart A. Toward a Nonidealist Evolutionary Synthesis. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780199377176.003.0006.
Full textAbstract:
The received model of evolution sees all inherited features resulting from deterministic networks of interacting genes, implying that living systems are reducible to information in genetic programs. The model requires these programs and their associated phenotypes to have evolved by an isotropic search process occurring in gradual steps with no preferred morphological outcomes. The alternative is to recognize that clusters and aggregates of cells, the raw material of evolution, constitute middle-scale material systems. This implies the necessity of bringing the modern physics of mesoscale matter into the explanatory framework for the evolution of development. The relevant, often nonlinear, physical processes were mobilized at the inception of the phyla when their signature morphological outcomes first appeared and remain as efficient causes, albeit transformed, in present-day embryos. This physicogenetic perspective reengages with concepts of saltation, orthogenesis, and environment-induced plasticity long excluded from evolutionary theory.
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Alexander, D. J., N. Phin, and M. Zuckerman. Influenza. Edited by I. H. Brown. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198570028.003.0037.
Full textAbstract:
Influenza is a highly infectious, acute illness which has affected humans and animals since ancient times. Influenza viruses form the Orthomyxoviridae family and are grouped into types A, B, and C on the basis of the antigenic nature of the internal nucleocapsid or the matrix protein. Infl uenza A viruses infect a large variety of animal species, including humans, pigs, horses, sea mammals, and birds, occasionally producing devastating pandemics in humans, such as in 1918 when it has been estimated that between 50–100 million deaths occurred worldwide.There are two important viral surface glycoproteins, the haemagglutinin (HA) and neuraminidase (NA). The HA binds to sialic acid receptors on the membrane of host cells and is the primary antigen against which a host’s antibody response is targeted. The NA cleaves the sialic acid bond attaching new viral particles to the cell membrane of host cells allowing their release. The NA is also the target of the neuraminidase inhibitor class of antiviral agents that include oseltamivir and zanamivir and newer agents such as peramivir. Both these glycoproteins are important antigens for inducing protective immunity in the host and therefore show the greatest variation.Influenza A viruses are classified into 16 antigenically distinct HA (H1–16) and 9 NA subtypes (N1–9). Although viruses of relatively few subtype combinations have been isolated from mammalian species, all subtypes, in most combinations, have been isolated from birds. Each virus possesses one HA and one NA subtype.Last century, the sudden emergence of antigenically different strains in humans, termed antigenic shift, occurred on three occasions, 1918 (H1N1), 1957 (H2N2) and 1968 (H3N2), resulting in pandemics. The frequent epidemics that occur between the pandemics are as a result of gradual antigenic change in the prevalent virus, termed antigenic drift. Epidemics throughout the world occur in the human population due to infection with influenza A viruses, such as H1N1 and H3N2 subtypes, or with influenza B virus. Phylogenetic studies have led to the suggestion that aquatic birds that show no signs of disease could be the source of many influenza A viruses in other species. The 1918 H1N1 pandemic strain is thought to have arisen as a result of spontaneous mutations within an avian H1N1 virus. However, most pandemic strains, such as the 1957 H2N2, 1968 H3N2 and 2009 pandemic H1N1, are considered to have emerged by genetic re-assortment of the segmented RNA genome of the virus, with the avian and human influenza A viruses infecting the same host.Influenza viruses do not pass readily between humans and birds but transmission between humans and other animals has been demonstrated. This has led to the suggestion that the proposed reassortment of human and avian influenza viruses takes place in an intermediate animal with subsequent infection of the human population. Pigs have been considered the leading contender for the role of intermediary because they may serve as hosts for productive infections of both avian and human viruses, and there is good evidence that they have been involved in interspecies transmission of influenza viruses; particularly the spread of H1N1 viruses to humans. Apart from public health measures related to the rapid identification of cases and isolation. The main control measures for influenza virus infections in human populations involves immunization and antiviral prophylaxis or treatment.
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Rees, David. Haemoglobinopathies. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0172.
Full textAbstract:
Inherited abnormalities of the globin genes are the commonest single-gene disorders in the world and fall into two main groups: thalassaemias and sickle cell disease. Thalassaemias are due to quantitative defects in globin chain synthesis which cause variable anaemia and ineffective erythropoiesis. Thalassaemia was initially thought to be a disease of the bones due to uncontrolled bone marrow expansion causing bony distortion, although this is now unusual with appropriate blood transfusions. Osteopenia, often severe, is a feature of most patients with thalassaemia major and intermedia, caused by bone marrow expansion, iron overload, endocrinopathy, and iron chelation. Treatment with bisphosphonates is generally recommended. Other rheumatological manifestations include arthropathy associated with the use of the iron chelator deferiprone. Sickle cell disease involves a group of conditions caused by polymerization of the abnormal -globin chain, resulting in abnormal erythrocytes which cause vaso-occlusion, vasculopathy, and ischaemic tissue damage. The characteristic symptom is acute bone pain caused by vaso-occlusion; typical episodes require treatment with opiate analgesia and resolve spontaneously by 5 days with no lasting bone damage. The frequency of acute episodes varies widely between patients. The incidence of osteomyelitis is increased, particularly with salmonella, although it is much rarer than acute vaso-occlusion. Avascular necrosis can affect the hips, and less commonly the shoulders and knees. Coincidental rheumatological disease sometimes complicates the condition, particularly systemic lupus erythematosus (SLE) which is more prevalent in populations at increased risk of sickle cell disease.
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Rees, David. Haemoglobinopathies. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199642489.003.0172_update_001.
Full textAbstract:
Inherited abnormalities of the globin genes are the commonest single-gene disorders in the world and fall into two main groups: thalassaemias and sickle cell disease. Thalassaemias are due to quantitative defects in globin chain synthesis which cause variable anaemia and ineffective erythropoiesis. Thalassaemia was initially thought to be a disease of the bones due to uncontrolled bone marrow expansion causing bony distortion, although this is now unusual with appropriate blood transfusions. Osteopenia, often severe, is a feature of most patients with thalassaemia major and intermedia, caused by bone marrow expansion, iron overload, endocrinopathy, and iron chelation. Treatment with bisphosphonates is generally recommended. Other rheumatological manifestations include arthropathy associated with the use of the iron chelator deferiprone. Sickle cell disease involves a group of conditions caused by polymerization of the abnormal -globin chain, resulting in abnormal erythrocytes which cause vaso-occlusion, vasculopathy, and ischaemic tissue damage. The characteristic symptom is acute bone pain caused by vaso-occlusion; typical episodes require treatment with opiate analgesia and resolve spontaneously by 5 days with no lasting bone damage. The frequency of acute episodes varies widely between patients. The incidence of osteomyelitis is increased, particularly with salmonella, although it is much rarer than acute vaso-occlusion. Avascular necrosis can affect the hips, and less commonly the shoulders and knees. Coincidental rheumatological disease sometimes complicates the condition, particularly systemic lupus erythematosus (SLE) which is more prevalent in populations at increased risk of sickle cell disease.
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Lima, Estela de Oliveira, Larissa Silva Zambrana Moraes, and Rafael Guilen de Oliveira. CÉLULAS-TRONCO MESENQUIMAIS E EXOSSOMOS - ORIGEM, APLICAÇÃO & DESAFIOS. Seven Editora, 2022. http://dx.doi.org/10.56238/celulastronco2022.
Full textAbstract:
As ciências biomédicas têm se desenvolvido consideravelmente nos últimos anos, o que implica em avanços significativos na área da saúde. Nesse contexto, a medicina regenerativa vem apresentando alternativas cada vez mais próximas de soluções personalizadas, que atendam às demandas particulares de cada paciente e de cada situação. Isso se deve principalmente por incorporar às propostas terapêuticas tratamentos à base de células e/ou de componentes biológicos, buscando a regeneração do tecido afetado, bem como da sua função. Nesse cenário, as células-tronco mesenquimais (MSCs) e seus produtos têm se tornado alvo de diversos estudos para aplicação médica por suas características de multipotência, autorrenovação e diferenciação. Além disso, seu potencial para aplicação clínica também é evidenciado devido às atividades imunomodulatória e regenerativa, características tanto da própria célula quanto de sua ação parácrina, exercida principalmente por meio da liberação de exossomos. As próprias células tronco mesenquimais e seus exossomos representam alternativas terapêuticas, sejam como produtos para terapia celular (MSCs), ou terapias cell-free (exossomos isolados). Diante dessas possibilidades e do potencial médico que ambas propostas apresentam, este livro teve como objetivo principal tornar este conhecimento mais acessível à comunidade acadêmica brasileira, bem como a países de língua portuguesa. Para isso, o livro aborda desde a origem das células, passando por análises comparativas das terapias 8 celulares e cell-free, até os novos desafios para otimização da expansão celular e produção de vesículas exossomais, visando escalonamento de produção para aplicação médica. Acreditando no potencial que as células tronco mesenquimais e seus produtos apresentam para a medicina regenerativa, surgiu este livro, que acreditamos possa contribuir para a divulgação do conhecimento e para o surgimento de inovações na área, tornando estratégias terapêuticas dessa natureza mais acessíveis e aplicáveis.