tbuckley/cabot-search huggingface dataset:
Mature B cells class switched to IgD are autoreactive in healthy individuals
Authors: Kristi Koelsch, Nai-Ying Zheng, Qingzhao Zhang, Andrew Duty, Christina Helms, Melissa D. Mathias, Mathew Jared, Kenneth Smith, J. Donald Capra, Patrick C. Wilson
Journal: Journal of Clinical Investigation (2007)

Determination of the origin and fate of autoreactive B cells is critical to understanding and treating autoimmune diseases. We report that, despite being derived from healthy people, antibodies from B cells that have class switched to IgD via genetic recombination (and thus become class switched to Cδ [Cδ-CS] cells) are highly reactive to self antigens. Over half of the antibodies from Cδ-CS B cells bind autoantigens on human epithelioma cell line 2 (HEp-2) cells or antinuclear antigens, and a quarter bind double-stranded DNA; both groups of antibodies are frequently polyreactive. Intriguingly, some Cδ-CS B cells have accumulated basic residues in the antibody variable regions that mediate anti-DNA reactivity via somatic hypermutation and selection, while other Cδ-CS B cells are naturally autoreactive. Though the total percentage was appreciably less than for Cδ-CS cells, a surprising 31% of IgG memory cell antibodies were somewhat autoreactive, and as expected, about 24% of naive cell antibodies were autoreactive. We interpret these findings to indicate either that autoreactive B cells can be induced to class switch to IgD or that autoreactive B cells that use IgD as the B cell receptor are not effectively deleted. Determination of the mechanism by which the majority of Cδ-CS B cells are autoreactive may be important in understanding peripheral tolerance mechanisms and may provide insight into the enigmatic function of the IgD antibody.
Airway Inflammation Driven by Antigen-specific Resident Lung CD4<sup>+</sup>T Cells in αβ -T Cell Receptor Transgenic Mice
Authors: PATRICK G. KNOTT, PAUL R. GATER, CLAUDE P. BERTRAND
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

CD4(+) T cells are thought to play a major role in the initiation and perpetuation of T helper cell, type 2 (Th2)-like allergic airway inflammation. However, it is not clear whether activation of resident antigen-specific CD4(+) T cells is in itself sufficient to induce such a phenotype. Using ovalbumin (OVA)-specific alphabeta-T cell receptor transgenic Balb/c DO11.10 mice, we were able to test this hypothesis. Nonsensitized DO11.10 mice but not wild-type mice responded to a primary OVA aerosol with a rapid and impressive bronchoalveolar lavage (BAL) neutrophilia followed by a smaller but significant eosinophilia. Responses in DO11.10 mice were mediated by OVA-specific activation of CD4(+) T cells because in vivo depletion of CD4(+) but not CD8(+) T cells abrogated inflammatory cell influx. Cytokines measured in BAL fluid (BALF) after OVA aerosol exposure of DO11.10 mice were indicative of a T helper cell, type 1 (Th1)-like immune response. Further, neutralization of interferon gamma (IFN-gamma) with antibody enhanced eosinophil influx, suggesting that IFN-gamma production was limiting the development of a Th2 response. Despite this, an increased prevalence of cells staining for mucus was seen in the bronchial epithelium, a feature more commonly associated with a Th2-immune response. Unlike what was seen in OVA-sensitized wild-type mice, multiple OVA aerosol exposures of DO11.10 mice failed to induce airway hyperresponsiveness (AHR) to inhaled methacholine. In conclusion, in vivo stimulation of resident lung CD4(+) T cells with antigen caused lung inflammation with characteristics of both a Th1- and Th2-immune response but was insufficient to directly induce AHR.
Transacetabular Herniation of Small Bowel and Right Adnexa
Authors: Richard M. Gore
Journal: JAMA (1983)

DURING the past 30 years, hip arthroplasty and total hip replacement have become increasingly popular in the treatment of severe degenerative and rheumatoid arthritis, intertrochanteric femoral neck fractures, and aseptic necrosis of the femoral head.<sup>1</sup>This procedure, which has helped rehabilitate thousands of patients, is associated with many complications that result from either mechanical or technical failures, infection, or the general complications of major surgery.<sup>2,3</sup>We present an unusual and previously unreported iatrogenic complication of hip surgery: herniation of the small bowel and right adnexa into the right hip joint through a bony defect in the acetabulum after a Girdlestone procedure. A brief review of the complications of total hip arthroplasty is also presented. <h3>Report of a Case</h3> A 31-year-old woman who had undergone a right total hip arthroplasty for degenerative joint disease secondary to Legg-Calvé-Perthes disease presented with an infected right hip. Since its implantation one year
Studies of Fat Lipolysis by Post-Heparin Human Plasma Lipoprotein Lipase and by Human Pancreatic Lipase
Authors: H. ENGELBERG
Journal: Circulation (1959)

Many studies indicate that unsaturated fats may lower serum cholesterol whereas saturated fats of animal origin usually increase it. The mechanism of these differing actions is unexplained, however. It has also been demonstrated that alimentary lipemia is cleared largely by an enzymatic lipolytic mechanism in which heparin is involved (heparin lipoprotein lipase). In this paper differences in hydrolysis of saturated and unsaturated fats by the heparin lipolytic factor are studied.
Difficulties in diagnosing and managing congenital dislocation of the hip.
Authors: T C Noble, C R Pullan, A W Craft, M A Leonard
Journal: BMJ (1978)

In a 10-year retrospective study of 25 921 consecutive deliveries in a neonatal unit in Newcastle upon Tyne 271 cases of congenital dislocation of the hips were identified. Of these, the outcome was unsatisfactory in 12: four diagnoses were missed at birth and eight children required further surgical treatment. Radiological abnormalities were detected in a further five children at long-term follow-up examination. From the results of this study and other published series it was concluded that lack of attention to detail was the main cause of inadequate diagnosis and management of congenital dislocation of the hips. More detailed instruction of junior staff, confirmation of the diagnosis by senior staff, the use of a non-removable splint early in treatment, and thorough follow-up by senior staff are all important.
GPs accept contract, but consultants ask for ballot on industrial action
Authors: Z. Kmietowicz
Journal: BMJ (2003)

GPs voted by four to one last week to accept a new contract that will bring to an end the current “red book” system of payment and 24 hour responsibility for patients—elements that have determined GPs' working practices for the past 50 years.

Negotiators hope that the new deal, which will see GPs' annual income rise by 26% over the next three years from an average of £65 000 ($108 000; €94 000) to £82 000, will lift morale in general practice and drive up recruitment.

Dr John Chisholm, chairman of the General Practitioners Committee, said on announcing the result of the …
A New Method for the Radiological Opacification of the Pancreas
Authors: S. Yoshimoto, S. Doi, M. Arao, K. Kawai
Journal: Endoscopy (1976)

Using an Olympus JF-B type fiberduodenoscope, endoscopic retrograde cholangiopancreatography (ERCP) has been carried out with the use of a newly deviced contrast medium which has been composed by putting non-ionic surfactant (poly-oxyethylene hydrogenated caster oil), in water-soluble iodided contrast medium. By this method a good opacification of the pancreas was obtained. In experimental studies in adult dogs the pancreas was always visualized when no less than 5% of non-ionic surfactant was added to the contrast medium. In clinical cases in humans a contrast medium containing only 1.6% of non-ionic surfactant was used, and a radiological opacification of the pancreas has not been obtained constantly, but no definite side effects have been found.
Testosterone Concentrations in Women and Men With NIDDM
Authors: Björn Andersson, Per Märin, Lauren Lissner, Alex Vermeulen, Per Björntorp
Journal: Diabetes Care (1994)

OBJECTIVE To evaluate androgen concentrations in relation to insulin resistance in men and women with and without NIDDM. Recent studies have indicated the potential importance of the regulation of insulin sensitivity by androgens in both women and men. Low sex hormone binding globulin (SHBG) concentration is an independent risk factor for the development of non-insulin-dependent diabetes mellitus (NIDDM) in women and is strongly associated statistically with signs of insulin resistance. RESEARCH DESIGN AND METHODS We compared measurements of anthropometric variables and SHBG, steroid hormone, and insulin concentrations of women and men who have NIDDM with those of control subjects. RESULTS Women with NIDDM had somewhat higher plasma insulin concentrations, lower SHBG, and higher free testosterone values than did control subjects with similar body mass index (BMI). Women with NIDDM had marginally higher waist-to-hip ratios (WHR). Plasma insulin concentrations correlated positively with BMI, WHR, and free testosterone and negatively with SHBG. In multivariate analyses, insulin concentrations remained positively associated with BMI and free testosterone. Men with NIDDM had higher fasting plasma insulin concentrations than did the nondiabetic control subjects. Testosterone and SHBG were lower in the diabetic men than in both control groups. The derived value of free testosterone was not different between groups. Univariate correlation analyses revealed tight statistical couplings between plasma insulin on the one hand and SHBG and testosterone concentrations (negative) on the other. In multivariate analyses, only the insulin-testosterone association remained. CONCLUSIONS Women with NIDDM have high levels of free testosterone and low levels of SHBG. Insulin resistance is closely correlated with these signs of hyperandrogenicity as well as with obesity. Men with NIDDM also have low levels of SHBG and, in contrast to women, low testosterone values. Insulin values correlate negatively with these hormonal factors. Based on the results of experimental work and intervention studies, we suggest that these androgen abnormalities might be causally related to insulin resistance in NIDDM.
Short-Term Particulate Threat: Pollution Standard May Not Protect Health
Authors: Bob Weinhold
Journal: Environmental Health Perspectives (2007)

Arsenic Upsets HeartbeatPossible Early Warning for Cardiovascular Risk Acute arsenic exposure can cause severe heartbeat abnormalities, and chronic exposure has been linked to coronary disease and cancer.Now researchers from Inner Mongolia, China, and the United States have begun to analyze the effects of chronic exposure on the electrical signals that regulate heartbeat [EHP 115:690-694; Mumford et al.].They found a correlation between exposure via drinking well water and signal changes associated with arrhythmia and death.Tens of millions of people worldwide drink groundwater contaminated with naturally occurring arsenic.Through metabolism, the inorganic arsenic found in drinking water is converted to more toxic methylated compounds.The research team focused on the QTc interval, a specific portion of the cardiac signal that corresponds to the active pumping (systole) phase of the heartbeat.QTc intervals of 0.45 second or longer are associated with cardiac risk.The team used electrocardiography to measure the QTc interval of 168 men and 145 women from four villages in Ba Men, an area of Inner Mongolia where the drilling of artesian wells in 1980 exposed residents to arsenic.Arsenic exposure was determined through analysis of toenail samples from participants and water samples from their wells.Arsenic exposure was categorized as low (21 µg/L or less), medium (100-300 µg/L), or high (430-609 µg/L).As exposure to arsenic increased, so did the occurrence of prolonged QTc interval, which was seen in 3.9% of the low exposure group, 11.1% of the medium exposure group, and 20.6% of the high exposure group.Women-who typically have a longer QTc interval than men-were more susceptible to this effect than men.Age, smoking, and pesticide exposure did not affect the association.The authors suggest that arsenic may affect QTc interval by altering the flow of potassium ions that are involved in cardiac signaling.They write that measurement of QTc interval may be useful in the early detection of cardiovascular risk among individuals exposed to arsenic, as well as in the identification of populations where such risk is high.The team is currently conducting a large follow-up study in the same population.Meanwhile, the Chinese government is helping to install water systems in the Ba Men area that will decrease arsenic exposure.-Kris Freeman
PDGF-A, PDGF-B, TGF?, and bFGF mRNA levels in patients with essential thrombocythemia treated with anagrelide
Authors: Paola R. Lev, Juan P. Salim, Laura I. Kornblihtt, Carlos J. Pirola, Rosana F. Marta, Paula G. Heller, Felisa C. Molinas
Journal: American Journal of Hematology (2005)

Plasmatic levels of PDGF-AB, TGFβ1, and bFGF are increased in patients with essential thrombocythemia (ET) while intraplatelet levels are low for PDGF, normal for TGFβ, and elevated for bFGF. To evaluate the contribution of gene expression to the dysregulated cytokine levels, we studied platelet PDGF-A, PDGF-B, TGFβ1, and bFGF mRNA in ET patients before and during anagrelide treatment. We found decreased PDGF-A and PDGF-B, increased TGFβ1, and normal bFGF mRNA levels. During treatment, mRNA levels remained decreased for PDGF-A, were increased for PDGF-B and normal for TGFβ1. In untreated patients, protein expression of PDGF paralleled its mRNA levels while different patterns of RNA and protein were found for TGFβ1 and bFGF. Am. J. Hematol. 78:155–157, 2005. © 2005 Wiley-Liss, Inc.
CONTAGIOUSNESS OF ACUTE ANTERIOR POLIOMYELITIS
Authors: J. C. Geiger
Journal: JAMA (1942)

Contagiousness through direct personal contact in epidemic and nonepidemic periods of acute anterior poliomyelitis is regarded by many departments of public health as a settled fact. The quarantine laws, however, as to the length of isolation applicable to contacts of this disease vary in states, counties and cities. The student of epidemiology is frankly at a loss in interpreting quarantine laws except from a legal point of view, and perhaps all such laws should be remodeled in order to meet modern epidemiologic methods and knowledge. The degree of contagiousness or, better termed, the infectivity rate, as determined by secondary cases, which can be attributed to contact, varies in epidemic and nonepidemic periods of acute anterior poliomyelitis. Moreover, the epidemiologic and clinical evidence appears definite and almost conclusive that the infectivity rate due to contact is far less in acute anterior poliomyelitis than in any other communicable disease. Perhaps the fact
DNA hypermethylation of the forkhead box protein 3 (<i>FOXP3</i>) promoter in CD4+ T cells of patients with systemic sclerosis
Authors: Y.Y. Wang, Q. Wang, X.H. Sun, R.Z. Liu, Y. Shu, T. Kanekura, J.H. Huang, Y.P. Li, J.C. Wang, M. Zhao, Q.J. Lu, R. Xiao
Journal: British Journal of Dermatology (2014)

Systemic sclerosis (SSc) is a complex autoimmune disease that involves dysregulation of immune homeostasis. The failure of impaired regulatory T cells (Tregs) to maintain immune homeostasis plays a major role in the development of SSc. Transcriptional silencing of the forkhead box protein 3 gene (FOXP3) via hypermethylation of regulatory regions has been identified as a hallmark of committed Tregs and several autoimmune disorders. To investigate whether aberrant expression and methylation of FOXP3 occurs in CD4+ T cells of patients with SSc and their roles in the pathogenesis of SSc. FOXP3 expression in CD4+ T cells was measured by real‐time quantitative reverse‐itranscriptase polymerase chain reaction and western blot. Bisulfite sequencing was performed to determine the methylation status of the FOXP3 proximal promoter sequence. The percentage of Treg cells was estimated by flow cytometry. Decreased FOXP3 expression was observed in CD4+ T cells from patients with SSc. The methylation levels of the FOXP3 regulatory sequences were elevated and inversely correlated with FOXP3 mRNA expression in patients with SSc. The number of Tregs was significantly reduced in patients with SSc. Treatment of SSc CD4+ T cells with a DNA methylation inhibitor, 5‐azacytidine, reduced the mean methylation levels, and enhanced FOXP3 expression and Treg generation. The promoter methylation status and expression level of FOXP3 are significantly associated with disease activity. The contribution of the hypermethylation of the FOXP3 promoter to decreased FOXP3 expression and the subsequent quantitative defects of Tregs may mediate the immune dysfunction in SSc.
TCT-137 Is Urinary Neutrophil Gelatinase-Associated Lipocalin the “Renal Troponin” in Invasive Cardiology?
Authors: Tilman Perrin, Eric Descombes, Stéphanie Gobet, Jean-Luc Magnin, Magali Gachet, Ould Hemett, Daniel Hayoz, Valérie Stolt, Gérard Baeriswyl, Jean-Christophe Stauffer, Jean-Jacques Goy, Mario Togni, Stéphane Cook
Journal: Journal of the American College of Cardiology (2012)
SALT-POOR DIET AND JEWISH DIETARY LAWS
Authors: Bruno Kisch
Journal: JAMA (1953)

<h3>To the Editor:—</h3> A salt-poor diet prescribed in cases of hypertension or congestive heart failure causes difficulties when prescribed to a person strictly adherent to Jewish dietary laws. These laws demand, for the purpose of removing any traces of blood from the surface of the meat, that it be abundantly salted before use. To eat meat without this preparation creates a religious problem and a conflict for the observing Jewish patient. Such meat has indeed a much higher sodium content than similar unprocessed material. Some Jewish hospitals tried to avoid the problem by using ammonium chloride instead of salt. According to Jewish law, this or the substitution of sugar for salt is not permissible. For a long time, I have used the following method to solve the difficulty. The patient was told that, after salting the meat in the religiously prescribed way, he should put it in water for one
Transforming Growth Factor β–Activated Kinase 1 Signaling Pathway Critically Regulates Myocardial Survival and Remodeling
Authors: Lei Li, Yi Chen, Jessica Doan, Jason Murray, Jeffery D. Molkentin, Qinghang Liu
Journal: Circulation (2014)

Programmed necrosis (necroptosis) plays an important role in development, tissue homeostasis, and disease pathogenesis. The molecular mechanisms that regulate necroptosis in the heart and its physiological relevance in myocardial remodeling and heart failure remain largely unknown.Here, we identified an obligate function for TAK1 (transforming growth factor β-activated kinase 1, gene name Map3k7) in regulating necroptotic myocyte death, myocardial remodeling, and heart failure propensity. Cardiac-specific ablation of Map3k7 in mice induced spontaneous apoptosis and necroptosis that led to adverse remodeling and heart failure, and these effects were abolished by ablation of tumor necrosis factor receptor-1. Mechanistically, TAK1 functions as a molecular switch in tumor necrosis factor receptor-1 signaling by regulating the formation of 2 cell death complexes, RIP 1 (receptor-interacting protein 1)-FADD (Fas-associated protein with death domain)-caspase 8 and RIP1-RIP3, a process that is dependent on FADD and caspase 8 as scaffolding molecules. Importantly, inhibition of RIP1 or RIP3 largely blocked necroptotic cell death, adverse remodeling, and heart failure in TAK1-deficient mice.These results indicate that TAK1 functions as a key survival factor in the heart by directly antagonizing necroptosis, which is critical for the maintenance of myocardial homeostasis and the prevention of adverse myocardial remodeling.
Live Longer…for Peanuts
Authors: Mitchell H. Katz
Journal: JAMA Internal Medicine (2015)

Hung N. Luu, MD, PhD; William J. Blot, PhD; Yong-Bing Xiang, MD, MPH; Hui Cai, MD, PhD; Margaret K. Hargreaves, PhD; Honglan Li, MD, MPH; Gong Yang, MD, MPH; Lisa Signorello, ScD; Yu-Tang Gao, MD; Wei Zheng, MD, PhD; Xiao-Ou Shu, MD, PhD
Erythrocytosis due to bisphosphoglycerate mutase deficiency with concurrent glucose‐6‐phosphate dehydrogenase (G‐6‐PD) deficiency
Authors: James D. Hoyer, Steven L. Allen, Ernest Beutler, Kathleen Kubik, Carol West, Virgil F. Fairbanks
Journal: American Journal of Hematology (2004)

Abstract A 28‐year‐old asymptomatic male of Iranian Jewish (Meshadi) heritage was found on routine exam to have an erythrocytosis (RBC = 6.22 × 10 12 /l, Hgb = 19.2 g/dl, Hct = 58.9%). Splenomegaly was absent on physical exam. There was no family history of erythrocytosis. His oxygen dissociation curve was left‐shifted with a p 50 of 19 mmHg (normal = 25–32 mmHg). Hemoglobin electrophoresis showed no abnormalities. DNA sequencing of the hemoglobin β globin gene and both α globin genes did not reveal a mutation. A 2,3‐bisphosphoglycerate (BPG) level was markedly decreased at 0.3 μmol/g Hb (normal = 11.4–19.4 μmol/g Hb). The patient's bisphosphoglycerate mutase (BPGM) enzyme activity was also markedly decreased at 0.16 IU/g Hb (normal = 4.13–5.43 IU/g Hb). A red cell enzyme panel revealed a markedly decreased G‐6‐PD level (0.3 U/g Hb, normal = 8.6–18.6 U/g Hb). His parents and a brother were also available for evaluation. Both parents showed normal 2,3‐BPG levels but BPGM activity approximately 50% of normal. Paradoxically, the brother showed normal BPGM activity but a slightly decreased 2,3‐BPG level. All family members had markedly decreased G‐6‐PD activity. DNA sequencing of the BPGM gene showed the propositus to be homozygous for 185 G→A, Arg 62 Gln in exon 2. Thus, the erythrocytosis in this patient is secondary to low 2,3‐BPG levels, due to a deficiency in BPG mutase. This appears due to consanguinity within this family. Am. J. Hematol. 75:205–208, 2004. © 2004 Wiley‐Liss, Inc.
Mystic The Statistic
Authors: Stanley Schor
Journal: JAMA (1969)

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The use of tissue-type plasminogen activator for acute myocardial infarction in the elderly: Results from thrombolysis in myocardial infarction phase I, open label studies and the thrombolysis in myocardial infarction phase II pilot study
Authors: Bernard R. Chaitman, Bruce Thompson, Mark D. Wittry, David Stump, William P. Hamilton, L. David Hillis, James G. Dwyer, Rachel E. Solomon, Genell L. Knatterud
Journal: Journal of the American College of Cardiology (1989)