tbuckley/cabot-search huggingface dataset:
Analysis of the HLA-restricted influenza-specific cytotoxic T lymphocyte response in transgenic mice carrying a chimeric human-mouse class I major histocompatibility complex.
Authors: A Vitiello, D Marchesini, J Furze, L A Sherman, R W Chesnut
Journal: The Journal of Experimental Medicine (1991)

Transgenic murine lines have been constructed that express a chimeric class I molecule composed of the alpha 1 and alpha 2 domains of HLA-A2.1 and the alpha 3, transmembrane, and cytoplasmic domains of H-2Kb. Upon immunization with influenza virus, transgenic mice developed a strong A2.1Kb-restricted cytotoxic T lymphocyte (CTL) response specific for the same matrix protein epitope that serves as the dominant A2.1-restricted determinant in the equivalent human response. Fine specificity analysis of CTL clones using truncated peptides revealed strong similarity between the response repertoire of transgenic mice and that previously reported using influenza-specific A2.1-restricted CTL clones from humans. This suggests that even when considering T cell responses by different species, the alpha 1 and alpha 2 domains of the restriction element play a dominant role in determining the CTL specific repertoire. Thus, substituting the alpha 3 domain of A2.1 with a murine counterpart has permitted development of a transgenic strain that should serve as an excellent model system in studies of HLA-restricted responses.
Muscle dysfunction versus wear and tear as a cause of exercise related osteoarthritis: an epidemiological update
Authors: Ian Shrier
Journal: British Journal of Sports Medicine (2004)

There are two main hypotheses for the cause of exercise related osteoarthritis: wear and tear of the articular cartilage and muscle dysfunction. This is a review of the clinical literature to see which hypothesis has the greatest support. Clinical studies support the muscle dysfunction hypothesis over the wear and tear hypothesis.
Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study
Authors: Elizabeth V. Asztalos
Journal: JAMA Pediatrics (2013)

A single course of antenatal corticosteroid therapy is recommended for pregnant women at risk of preterm birth between 24 and 33 weeks' gestational age. However, 50% of women remain pregnant 7 to 14 days later, leading to the question of whether additional courses should be given to women remaining at risk for preterm birth. The Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) was an international randomized clinical trial that compared multiple courses of antenatal corticosteroids with a single course in women at risk of preterm birth.To determine the effects of single vs multiple courses of antenatal corticosteroid therapy on death or neurodevelopmental disability (neuromotor, neurosensory, or neurocognitive/neurobehavioral function) at 5 years of age in children whose mothers participated in MACS. Our secondary aims were to determine the effect on height, weight, head circumference, blood pressure, intelligence, and specific cognitive (visual, spatial, and language) skills.Cohort follow-up study of children seen between June 2006 and May 2012 at 55 centers. In total, 1724 women (2141 children) were eligible for the study, of whom 1728 children (80.7% of the 2141 eligible children) participated and 1719 children contributed to the primary outcome.Single and multiple courses of antenatal corticosteroid therapy.The primary outcome was death or survival with a neurodevelopmental disability in 1 of the following domains: neuromotor (nonambulatory cerebral palsy), neurosensory (blindness, deafness, or need for visual/hearing aids), or neurocognitive/neurobehavioral function (abnormal attention, memory, or behavior).There was no significant difference between the groups in the risk of death or neurodevelopmental disability: 217 of 871 children (24.9%) in the multiple-courses group vs 210 of 848 children (24.8%) in the single-course group (odds ratio, 1.02 [95% CI, 0.81 to 1.29]; P = .84).Multiple courses, compared with a single course, of antenatal corticosteroid therapy did not increase or decrease the risk of death or disability at 5 years of age. Because of a lack of strong conclusive evidence of short-term or long-term benefits, it remains our opinion that multiple courses not be recommended in women with ongoing risk of preterm birth.clinicaltrials.gov Identifier: NCT00187382.
Impaired absorption of cholesterol and bile acids in patients with an ileoanal anastomosis
Authors: K Hakala, M Vuoristo, P Luukkonen, H J Järvinen, T A Miettinen
Journal: Gut (1997)

Background —No data exist on cholesterol absorption in patients with an ileoanal anastomosis (IAA). Aims —To study cholesterol absorption and its effects on cholesterol and bile acid metabolism in patients with an IAA. Patients and methods —Cholesterol absorption, and serum, biliary, and faecal lipids were studied in 24 patients with an IAA and 20 controls. Results —Fractional cholesterol absorption was significantly lower in the patients (36% versus 47% in controls). Surprisingly, the calculated intestinal influx of endogenous cholesterol was reduced so that the absolute absorption of cholesterol was decreased; elimination of cholesterol as faecal neutral steroids remained normal. Thus, the slightly increased cholesterol synthesis was mainly due to increased faecal bile acid excretion, which, in turn, was associated with reduced absorption and biliary secretion of bile acids. Serum total and low density lipoprotein (LDL) cholesterol and LDL triglycerides were lower in the patients. Molar percentage and saturation index of biliary cholesterol were slightly higher in patients with an IAA. Proportions of secondary bile acids in bile and faeces were diminished, and faecal unidentified bile acids were higher in patients. Conclusions —Cholesterol absorption is significantly impaired in patients with an IAA, and is closely related to changes in serum and biliary lipids observed in these patients.
Expression of inducible stress protein 70 in rat heart myogenic cells confers protection against simulated ischemia-induced injury.
Authors: R Mestril, S H Chi, M R Sayen, K O'Reilly, W H Dillmann
Journal: Journal of Clinical Investigation (1994)

Myocardial ischemia markedly increases the expression of several members of the stress/heat shock protein (HSP) family, especially the inducible HSP70 isoforms. Increased expression of HSP70 has been shown to exert a protective effect against a lethal heat shock. We have examined the possibility of using this resistance to a lethal heat shock as a protective effect against an ischemic-like stress in vitro using a rat embryonic heart-derived cell line H9c2 (2-1). Myogenic cells in which the heat shock proteins have been induced by a previous heat shock are found to become resistant to a subsequent simulated ischemic stress. In addition, to address the question of how much does the presence of the HSP70 contribute to this protective effect, we have generated stably transfected cell lines overexpressing the human-inducible HSP70. Embryonal rat heart-derived H9c2(2-1) cells were used for this purpose. This stably transfected cell line was found to be significantly more resistant to an ischemic-like stress than control myogenic cells only expressing the selectable marker (neomycin) or the parental cell line H9c2(2-1). This finding implicates the inducible HSP70 protein as playing a major role in protecting cardiac cells against ischemic injury.
Increased Apoptosis in Cystinotic Fibroblasts and Renal Proximal Tubule Epithelial Cells Results from Cysteinylation of Protein Kinase Cδ
Authors: Margaret A Park, Vojislav Pejovic, Kathryn G Kerisit, Sacha Junius, Jess G Thoene
Journal: Journal of the American Society of Nephrology (2006)

Cystinosis is a rare genetic disease characterized by defective lysosomal cystine transport and increased lysosomal cystine. How lysosomal cystine causes the lethal nephropathic phenotype is unknown. It was shown recently that cultured fibroblasts and renal proximal tubule epithelial cells whose lysosomes are cystine-loaded display a two-fold or greater increase in apoptosis after both intrinsic and extrinsic stimuli. The mechanism for the increased apoptosis is unknown. Protein kinase Cdelta (PKCdelta) is a proapoptotic protein kinase that has been shown in vitro to be activated via cysteinylation. This report now shows that PKCdelta forms disulfide bonds specifically with cystine that is released from lysosomes in cultured fibroblasts and renal proximal tubule epithelial cells during apoptosis. PKCdelta in cystinotic fibroblasts and renal proximal tubule epithelial cells have a four- to six-fold greater association with its substrate, lamin B, and a 2.5-fold increase in specific activity after TNF-alpha exposure. Both RNA inhibition and chemical inhibition of PKCdelta resulted in a significant decrease in apoptosis in cystinotic cells but not in normal cells. It is proposed that abnormally increased apoptosis plays a role in evolution of the cystinotic phenotype.
Antibodies to PCSK9
Authors: Kara N. Maxwell, Jan L. Breslow
Journal: Circulation Research (2012)

L owering of LDL cholesterol, predominantly accom- plished clinically by statins, is one of the key components of both the prevention and medical management of coronary atherosclerosis; however, additional or alternative cholesterol lowering agents are needed for patients who fail to achieve goals or have adverse effects on statins.Owing to relatively rapid translation of basic science research on a novel regulatory pathway of the LDL receptor by PCSK9, a new class of such drugs with a different mode of action, and potentially better tolerance and less off-target effects may be just over the horizon.
Insights into insulin resistance and type 2 diabetes from knockout mouse models
Authors: T Kadowaki
Journal: Journal of Clinical Investigation (2000)

The pathogenesis of type 2 diabetes is characterized by two major features: peripheral insulin resistance and impaired insulin secretion from pancreatic β cells (1, 2). The application of transgenic mouse technology to the study of diabetes has been extensively reviewed (3). Here, I review the application of a complementary approach, gene knockout technology, to the problem of understanding insulin resistance and its sequelae. After reviewing the phenotypes of animals with individual targeted mutations in homozygous or heterozygous form, I turn to the effects of double mutations and show that interactions between mediators of insulin signaling can account for the development of overt diabetes.

Gene knockout technology allows the investigator to generate homozygous null mutant mice and to examine the effects of a total lack of a particular gene product. Resultant phenotypes are expected to reflect physiological functions of the specific gene in vivo. The effects of gene dosage can be studied by focusing on heterozygous null mutants. Moreover, crossing of various heterozygous and/or homozygous knockout animals can be used to reconstitute alterations in multiple genes. Conditional (i.e., tissue-specific or inducible) knockouts can also be created using the Cre/loxP system (4). This tool expands the application of the knockout approach to allow the study of mutations that would be lethal if expressed systemically, and it allows the study of specific effects of mutations in a particular tissue without influences from the other tissues.
Histiocytic necrotising lymphadenitis in systemic lupus erythematosus.
Authors: M D Litwin, B Kirkham, D R Henderson, S C Milazzo
Journal: Annals of the Rheumatic Diseases (1992)

Histiocytic necrotising lymphadenitis is the pathognomonic histological appearance of lymph nodes in Kikuchi9s disease, a condition characterised by a brief systemic illness and lymphadenopathy. The case is described of a young man, originally diagnosed as having Kikuchi9s disease by lymph node histology, who subsequently developed systemic lupus erythematosus with symmetrical polyarthritis, Coombs9 positive haemolytic anaemia and haemorrhagic pneumonitis. The case emphasises that a range of diseases is associated with histiocytic necrotising lymphadenitis, belying the unitary impression given by the term Kikuchi9s disease.
Indices of granulocyte activity in inflammatory bowel disease
Authors: S. P. Kane, A. V. Hoffbrand, G. Neale
Journal: Gut (1974)

In conditions with increased neutrophil production, the serum total vitamin B<sub>12</sub>-binding capacity (TBBC) is considered to correlate with the blood pool size of neutrophil granulocytes. The serum lysozyme, on the other hand, is a measure of neutrophil (and monocyte) turnover. The mean serum TBBC was significantly raised in patients with ulcerative colitis (range 1.23-5.51 ng/ml; mean 2.64 ng/ml) and patients with Crohn9s disease (range 1.58-9.29 ng/ml; mean 2.93 ng/ml). The elevated values were shown to be due to rises in the granulocyte-secreted binding proteins, transcobalamins I and III. The TBBC was shown to rise with increasing activity of disease and to correlate roughly with the blood neutrophil granulocyte count. Patients with inflammatory bowel disease also had a significantly raised mean level of serum lysozyme (range 3.1 to 10.4 μg/ml; mean 6.8 μg/ml), but there was no correlation in individual patients between serum lysozyme and total B<sub>12</sub>-binding capacity. These results are taken to indicate an enlarged granulocyte pool and increased granulocyte turnover in inflammatory bowel disease.
BETTER PLANNING REDUCES INJURY RISK IN SPORT STUDENTS
Authors: M Brink, M Pots, K Lemmink
Journal: British Journal of Sports Medicine (2014)

Background First year sport students have a considerable risk of injuries. Self-regulatory skills may lower this risk by enabling students to better cope with a sudden increase in physical load (sport participation) and psychosocial stressors (i.e. exams, new social networks). Objective The aim of this study was to identify if better self-regulatory skills reduce the risk for athletic injuries in sport students. Design Prospective cohort study with seven months injury follow-up. Setting Educational setting for students in Physical Education and Sport, Health and Management. Participants 341 freshmen sports students participated in the study. Assessment of risk factors Anthropometric characteristics, sports participation, injury history, and self-regulatory skills (planning, self-monitoring, evaluation, reflection, effort and self-efficacy) were assessed at the start of the academic year by digitalized questionnaires. Main outcome measurements The dependent variables were coded as injured (acute or overuse) or non-injured over a seven months period after baseline measures. Data were analyzed using multinomial logistic regression. Results A total of 139 athletic injuries were reported. The injury incidence rate per 1000 hours of sports participation was 1.62. Sixty-four percent of the injuries were acute and 36% of the injuries a result of overuse. Increasing hours of sports participation led to a higher risk of overuse injuries (OR: 1.17 95% CI 1.04–1.32), whereas higher scores on planning led to a lower injury risk of overuse injuries (OR: 0.20 95% CI 0.07–0.58). For acute injuries, no significant predictors were found. Conclusions Self-regulation seems an important skill in reducing injury risk in sport students, because better planning is associated with a lower injury risk. Future research is needed to study the effects of prevention programs that focus on improving self-regulatory skills.
Methylnaltrexone for Opioid-Induced Constipation in Advanced Illness
Authors: Jay Thomas, Sloan Karver, Gail Austin Cooney, Bruce H. Chamberlain, Charles Kevin Watt, Neal E. Slatkin, Nancy Stambler, Alton B. Kremer, Robert J. Israel
Journal: New England Journal of Medicine (2008)

Constipation is a distressing side effect of opioid treatment. As a quaternary amine, methylnaltrexone, a μ-opioid–receptor antagonist, has restricted ability to cross the blood–brain barrier. We investigated the safety and efficacy of subcutaneous methylnaltrexone for treating opioid-induced constipation in patients with advanced illness.
Electrophysiological Responses to Sensory Stimulation Under Hypnosis
Authors: E. A. SERAFETINIDES
Journal: American Journal of Psychiatry (1968)

EEG, EKG, respiratory rate, and galvanic skin response were recorded from a normal 23-year-old male subject under photic and auditory stimulation during a hypnotic session and a control nonhypnotic period. No appreciable differences in responses between the two conditions were found. However, the results of the experiment raise the possibility that a certain type of cerebral activation may characterize the hypnotic state.
Expression of the immunoregulatory molecule FcRH4 defines a distinctive tissue-based population of memory B cells
Authors: Götz R.A. Ehrhardt, Joyce T. Hsu, Lanier Gartland, Chuen-Miin Leu, Shuangyin Zhang, Randall S. Davis, Max D. Cooper
Journal: The Journal of Experimental Medicine (2005)

The FcRH4 transmembrane molecule, a member of the Fc receptor homologue family, can potently inhibit B cell receptor (BCR) signaling. We show that cell surface expression of this immunoregulatory molecule is restricted to a subpopulation of memory B cells, most of which lack the classical CD27 marker for memory B cells in humans. The FcRH4+ and FcRH4- memory B cells have undergone comparable levels of immunoglobulin isotype switching and somatic hypermutation, while neither subpopulation expresses the transcription factors involved in plasma cell differentiation. The FcRH4+ memory cells are morphologically distinctive large lymphocytes that express the CD69, CD80, and CD86 cell activation markers. They are also shown to be poised to secrete high levels of immunoglobulins in response to stimulation with T cell cytokines, but they fail to proliferate in response either to BCR ligation or Staphylococcus aureus stimulation. A heightened expression of the CCR1 and CCR5 chemokine receptors may facilitate their preferential localization in lymphoid tissues near epithelial surfaces. Cell surface FcRH4 expression thus marks a unique population of memory B cells with distinctive morphology, functional capabilities, and tissue localization.
Obesity in Children and Future Cardiometabolic Risk
Authors: Jennifer Logue, Naveed Sattar
Journal: Diabetes Care (2010)

Rates of pediatric obesity have increased substantially in recent years (1) and now pose a major risk for increased morbidity and premature mortality in adulthood for those affected, with cardiovascular disease (CVD) being a major contributor. In the current issue, Libman et al. (2) examine the relationship between glucose and insulin in overweight children and adolescents and a range of biomarkers for cardiovascular disease. They report that increased fasting and postprandial insulin are related to CVD risk factors, including systolic blood pressure and triglycerides, whereas glucose is not.

These results are perhaps not surprising given what we already know about glucose homeostasis in obese children and adolescents (3) and recent evidence supporting a relatively weak relationship between elevations in fasting glucose within the normal range and incident CVD events in adults (4). Hyperinsulinemia is the hallmark of metabolic dysfunction in children and adolescents, with hyperglycemia not manifesting until a very late stage of β-cell failure (3), making the process far lengthier than in adults and reflecting the ability of the young pancreas to better compensate.

Given the epidemic of childhood …
Lasers for the dermatologist
Authors: K.M. Acland, R.J. Barlow
Journal: British Journal of Dermatology (2000)

Journal Article Lasers for the dermatologist Get access K.M. Acland, K.M. Acland Dermatological Surgery and Laser Unit, St John's Institute of Dermatology, Lambeth Palace Road, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.J. Barlow R.J. Barlow Dermatological Surgery and Laser Unit, St John's Institute of Dermatology, Lambeth Palace Road, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 2, 1 August 2000, Pages 244–255, https://doi.org/10.1046/j.1365-2133.2000.03648.x Published: 01 August 2000
Negative Selection during the Peripheral Immune Response to Antigen
Authors: Stephen M. Anderton, Caius G. Radu, Pauline A. Lowrey, E. Sally Ward, David C. Wraith
Journal: The Journal of Experimental Medicine (2000)

Thymic selection depends on positive and negative selective mechanisms based on the avidity of T cell interaction with antigen–major histocompatibility complex complexes. However, peripheral mechanisms for the recruitment and clonal expansion of the responding T cell repertoire remain obscure. Here we provide evidence for an avidity-based model of peripheral T cell clonal expansion in response to antigenic challenge. We have used the encephalitogenic, H-2 Au-restricted, acetylated NH2-terminal nonameric peptide (Ac1-9) epitope from myelin basic protein as our model antigen. Peptide analogues were generated that varied in antigenic strength (as assessed by in vitro assay) based on differences in their binding affinity for Au. In vivo, these analogues elicited distinct repertoires of T cells that displayed marked differences in antigen sensitivity. Immunization with the weakest (wild-type) antigen expanded the high affinity T cells required to induce encephalomyelitis. In contrast, immunization with strongly antigenic analogues led to the elimination of T cells bearing high affinity T cell receptors by apoptosis, thereby preventing disease development. Moreover, the T cell repertoire was consistently tuned to respond to the immunizing antigen with the same activation threshold. This tuning mechanism provides a peripheral control against the expansion of autoreactive T cells and has implications for immunotherapy and vaccine design.
Road to language: Longer, more believable, more relevant
Authors: R. Allen Gardner
Journal: Behavioral and Brain Sciences (2006)

A realistic developmental view of language acquisition recognizes vocabulary and pragmatics as well as grammar with a lengthy period of growth in a favorable environment. Cross-fostering is a tool of behavioral biology for studying the interaction between genetic endowment and developmental environment. Sign language studies of cross-fostered chimpanzees measure development in a nearly human environment.