tbuckley/cabot-search huggingface dataset:
HIV-1 Variation Diminishes CD4 T Lymphocyte Recognition
Authors: Gillian C. Harcourt, Sarah Garrard, Miles P. Davenport, Anne Edwards, Rodney E. Phillips
Journal: The Journal of Experimental Medicine (1998)

Effective long-term antiviral immunity requires specific cytotoxic T lymphocytes and CD4+ T lymphocyte help. Failure of these helper responses can be a principle cause of viral persistence. We sought evidence that variation in HIV-1 CD4+ T helper epitopes might contribute to this phenomenon. To determine this, we assayed fresh peripheral blood mononuclear cells from 43 asymptomatic HIV-1+ patients for proliferative responses to HIV-1 antigens. 12 (28%) showed a positive response, and we went on to map dominant epitopes in two individuals, to p24 Gag restricted by human histocompatibility leukocyte antigen (HLA)-DR1 and to p17 Gag restricted by HLA-DRB52c. Nine naturally occurring variants of the p24 Gag epitope were found in the proviral DNA of the individual in whom this response was detected. All variants bound to HLA-DR1, but three of these peptides failed to stimulate a CD4+ T lymphocyte line which recognized the index sequence. Antigenic variation was also detected in the p17 Gag epitope; a dominant viral variant present in the patient was well recognized by a specific CD4+ T lymphocyte line, whereas several natural mutants were not. Importantly, variants detected at both epitopes also failed to stimulate fresh uncultured cells while index peptide stimulated successfully. These results demonstrate that variant antigens arise in HIV-1+ patients which fail to stimulate the T cell antigen receptor of HLA class II–restricted lymphocytes, although the peptide epitopes are capable of being presented on the cell surface. In HIV-1 infection, naturally occurring HLA class II–restricted altered peptide ligands that fail to stimulate the circulating T lymphocyte repertoire may curtail helper responses at sites where variant viruses predominate.
Polymorphisms at<i>PRSS1–PRSS2</i>and<i>CLDN2–MORC4</i>loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study
Authors: Monique H Derikx, Peter Kovacs, Markus Scholz, Emmanuelle Masson, Jian-Min Chen, Claudia Ruffert, Peter Lichtner, Rene H M te Morsche, Giulia Martina Cavestro, Claude Férec, Joost P H Drenth, Heiko Witt, Jonas Rosendahl
Journal: Gut (2014)

<h3>Objective</h3> Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in <i>PRSS1</i>–<i>PRSS2</i> (<i>rs10273639</i>; near the gene encoding cationic trypsinogen) and <i>CLDN2</i>–<i>MORC4</i> loci (<i>rs7057398</i> in <i>RIPPLY1</i> and <i>rs12688220</i> in <i>MORC4</i>). We aimed to refine these findings in a large European cohort. <h3>Design</h3> We studied 3062 patients with alcohol-related CP (ACP) or NACP and 5107 controls. Also, 1559 German patients with alcohol-associated cirrhosis or alcohol dependence were included for comparison. We performed several meta-analyses to examine genotype–phenotype relationships. <h3>Results</h3> Association with ACP was found for <i>rs10273639</i> (OR, 0.63; 95% CI 0.55 to 0.72). ACP was also associated with variants <i>rs7057398</i> and <i>rs12688220</i> in men (OR, 2.26; 95% CI 1.94 to 2.63 and OR, 2.66; 95% CI 2.21 to 3.21, respectively) and in women (OR, 1.57; 95% CI 1.14 to 2.18 and OR 1.71; 95% CI 1.41 to 2.07, respectively). Similar results were obtained when German patients with ACP were compared with those with alcohol-associated cirrhosis or alcohol dependence. In the overall population of patients with NACP, association with <i>rs10273639</i> was absent (OR, 0.93; 95% CI 0.79 to 1.01), whereas <i>rs7057398</i> of the X chromosomal single nucleotide polymorphisms was associated with NACP in women only (OR, 1.32; 95% CI 1.15 to 1.51). <h3>Conclusions</h3> The single-nucleotide polymorphisms <i>rs10273639</i> at the <i>PRSS1–PRSS2</i> locus and <i>rs7057398</i> and <i>rs12688220</i> at the <i>CLDN2</i>–<i>MORC4</i> locus are associated with CP and strongly associate with ACP, but only <i>rs7057398</i> with NACP in female patients.
Protein synthesis by cultured jejunal mucosa from control subjects and patients with coeliac disease.
Authors: P E Jones, C L L'Hirondel, T J Peters
Journal: Gut (1981)

Jejunal biopsies from patients with coeliac disease and from controls were cultured in vitro for 24 hours with 14C-labelled leucine. The net rate of protein synthesis was found to be linear over 24 hours for mucosa from control subjects and patients with coeliac disease. Protein synthesis by mucosa from untreated coeliac patients was significantly greater than by control mucosa. Protein synthesis by treated gluten-sensitive coeliac mucosa was significantly less than that by untreated coeliac mucosa and did not differ from control mucosa. Protein synthesis by treated non-responsive coeliac mucosa was significantly less than untreated coeliac mucosa but greater than control mucosa. The differences in protein synthesis could not be accounted for by differences in the size of the enterocyte leucine pool. Analytical subcellular fractionation of cultured jejunal mucosa showed that most of the protein synthesised in vitro was found in the cytosol and endoplasmic reticulum-brush border fractions of the enterocyte.
A Major Role of p95/611-CTF, a Carboxy-Terminal Fragment of HER2, in the Down-modulation of the Estrogen Receptor in HER2-Positive Breast Cancers
Authors: Josep Lluís Parra-Palau, Kim Pedersen, Vicente Peg, Maurizio Scaltriti, Pier Davide Angelini, Marta Escorihuela, Sandra Mancilla, Alexandre Sánchez Pla, Santiago Ramón y Cajal, José Baselga, Joaquín Arribas
Journal: Cancer Research (2010)

Current classification of breast cancers depends in great part on the expression of human epidermal growth factor receptor 2 (HER2), a cell surface tyrosine kinase receptor, and estrogen receptor (ER), the nuclear receptor for estrogen. In addition to reliable biomarkers, these receptors are targets of effective and widely used antitumor drugs. During malignant progression, HER2 and ER can establish an intricate cross-talk. In some cases, HER2 overexpression leads to the downregulation of ER and undermining of anti-ER therapies. A subgroup of HER2-positive breast cancer patients with poor prognosis expresses a heterogeneous collection of HER2 carboxy-terminal fragments (CTF) collectively known as p95HER2. One of these fragments, 611-CTF, is oncogenic in a variety of preclinical models. However, because of the lack of an appropriate tool to specifically analyze its levels in the clinical setting, the value of 611-CTF as a biomarker has not been established yet. Here, we show that 611-CTF induces resistance to antiestrogen therapy and a more pronounced down-modulation of ER than that induced by full-length HER2. To validate this effect in breast cancer samples, we developed specific anti-611-CTF antibodies. With these antibodies, we showed that, whereas the frequency of ER positivity in HER2-positive/611-CTF-negative tumors (72.6%) is similar to that reported for HER2-negative tumors (70-80%), the number of ER-positive tumors in the 611-CTF-positive subgroup is very low (31.2%). These results reveal a mechanism of ER regulation mediated by HER2, which suggests a new strategy to improve responses to endocrine therapy in breast cancer.
Idiotypic self binding of a dominant germline idiotype (T15). Autobody activity is affected by antibody valency.
Authors: C Y Kang, H L Cheng, S Rudikoff, H Kohler
Journal: The Journal of Experimental Medicine (1987)

We have previously described (1-3) an IgM antibody that binds to PC, expresses the T15 idiotype, and binds also to itself or T15 if insolubilized. Because of the simultaneous presence of complementary idiotopes and paratopes this type of antibody has been termed autobody. The self binding involves the antigen-binding site because the F(ab')2 fragment of T15, PC, and no other haptens inhibit the self binding. DNA sequence analysis of 11E7-1 using primer extension cDNA sequencing showed that the variable sequences of H and L chains of 11E7-1 are identical to the germline sequence of the prototype T15 idiotype. Furthermore, monomeric and dimeric T15 IgA were shown to bind to insolubilized T15 and other T15+ antibodies including 11E7-1. Thus, the self-binding activity is an inherent property of the T15 germline sequence. The self binding is highly dependent on the polymeric state of the binding antibody since the IgM pentamer of 11E7-1 is about three fold more effective than the T15 dimer and 50 times more than the T15 monomer. These data suggest that the self-binding activity of a germline-encoded idiotype may play an important role in the biology of its expression, and more specifically, may be responsible for the establishment of its dominant expression.
998 ENTECAVIR (ETV) RESULTS IN HIGHER HBV DNA REDUCTION VERSUS ADEFOVIR (ADV) IN ANTIVIRAL-NAIVE HBEAG(+) ADULTS WITH HIGH HBVDNA: WEEK 96 RESULTS (E.A.R.L.Y. STUDY)
Authors: N. Leung, C.Y. Peng, J. Sollano, L. Lesmana, M.F. Yuen, L. Jeffers, H.W. Hann, M. Sherman, U. Diva, K. Mencarini, A. Cross, R. Wilber, J.C. Lopez-Talavera
Journal: Journal of Hepatology (2008)
Urticaria and hyperthyroidism
Authors: J.L. PACE, MAURICE GARRETTS
Journal: British Journal of Dermatology (1975)

A thyrotoxic patient presented with urticaria and this appeared to respond to beta‐blockade with practolol. Symptoms did not recur when radioactive iodine treatment took effect in spite of stopping the beta‐blocker. Possible mechanisms are discussed and it is stressed that more emphasis should be placed on this association.
THE INFLUENCE OF HIGH PROTEIN DIET ON THE KIDNEYS
Authors: A. James Miller
Journal: The Journal of Experimental Medicine (1925)

Seven groups of rats were fed on diets containing protein varying in amount from 1.36 to 40.13 per cent derived mainly from grain, casein, meat, and milk with carbohydrate, fat, and vitamines. From a number of animals one kidney was removed to double the load on the remaining one. The time of feeding was from 9 weeks to 6 months. Blood uric acid, blood urea nitrogen determinations, and microscopic examinations of the kidneys revealed no evidence of kidney damage. There was evidence of kidney hypertrophy consisting of increased weight of the kidney, large diameters of the capillary tufts, convoluted tubules, and kidneys in the animals receiving high protein diet. The nephrectomized animals that ate high protein had no kidney changes save hypertrophy and this amounted to an increase in weight of an average of 0.54 gm. or 85 per cent of the average weight of the right kidneys of the controls.
The Clara cell: a "Third Reich eponym"?
Authors: A. Winkelmann, T. Noack
Journal: European Respiratory Journal (2010)

German anatomist Max Clara (1899–1966) described the “Clara cell” of the bronchiolar epithelium in 1937. The present article investigates Clara's relationship with National Socialism, as well as his use of tissue from executed prisoners for research purposes, details about both of which are largely unknown to date. Our methodology for the present study focussed on analysis of material from historical archives and the publications of Clara and his co-workers. Clara was appointed as Chair of Anatomy at Leipzig University (Leipzig, Germany) in 1935. He owed his career, at least in part, to Nazi support. He was an active member of the Nazi party (Nationalsozialistische Deutsche Arbeiterpartei (NSDAP)) and engaged in university politics; this included making anti-Semitic statements about other academics in appointment procedures. Nevertheless, he also supported prosecuted colleagues. Much of Clara's histological research in Leipzig, including his original description of the bronchial epithelium, was based on tissue taken from prisoners executed in nearby Dresden (Germany). Max Clara was an active and outspoken Nazi and his histological research exploited the rising number of executions during the Nazi period. Clara's discovery is thus linked to the Nazi system. The facts given in the present paper invite discussion about the eponym's neglected history and its continued and problematic use in medical terminology.
The Tularemia Skin Test
Authors: THOMAS M. BUCHANAN
Journal: Annals of Internal Medicine (1971)

The tularemia skin test is a valuable diagnostic tool for the clinician and the epidemiologist. It is sensitive and specific for tularemia; it becomes positive earlier in the course of illness and is positive longer after infection than the agglutination test. Half of all patients with clinical tularemia are skin-test positive the day they present to the physician. It is a delayed hypersensitivity reaction read after 48 hr and can easily be administered and read at the bedside. It rarely causes a rise in the antibody titer and, once positive, may remain positive for as long as 40 years.
Endogenous Surfactant Turnover in Preterm Infants with Respiratory Distress Syndrome Studied with Stable Isotope Lipids
Authors: PAOLA CAVICCHIOLI, LUC J. I. ZIMMERMANN, PAOLA E. COGO, TAMARA BADON, GIUSEPPE GIORDANO, MIRKA TORRESIN, FRANCO ZACCHELLO, VIRGILIO P. CARNIELLI
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We studied surfactant kinetics on Day 1 of life in 11 preterm infants on mechanical ventilation by infusing stable isotope labeled palmitic (PA) and linoleic acid (LLA). Six infants received exogenous surfactant for the treatment of respiratory distress syndrome (RDS) and five did not meet treatment criteria because of minimal or no disease. The isotopic enrichment of plasma free PA and LLA and of surfactant phosphatidylcholine PA (PC-PA) and LLA (PC-LLA) from tracheal aspirates was measured by mass spectrometry. Significant isotopic enrichment could be measured in PC-PA and PC-LLA from all patients. The fractional synthesis rate (FSR) of PC-LLA was higher than that of PC-PA (22.7 ± 15.9 versus 12.1 ± 7.7% per day, p = 0.018). Half-life (HL) of PC-PA was longer than that of PC-LLA (94.7 ± 18.8 versus 46.6 ± 32.6 h, p = 0.028). Patients who received exogenous surfactant had longer secretion times (ST) and delayed peak times (PK) but FSR and HL were unaffected. We concluded that: (1) surfactant kinetics can be measured in preterm infants with stable isotope labeled lipids; (2) surfactant FSR and HL calculated with PA and LLA gave different results; (3) patients treated with exogenous surfactant had similar FSRs compared with the nontreated subjects but had longer ST and delayed PK; (4) FSR from plasma free fatty acids (present study) was higher than that from plasma glucose in our previous work (Bunt JEH, Zimmermann LJI, Wattimena D, van Beek R, Sauer PJJ, Carnielli VP. Am J Respir Crit Care Med 1998;157:810–814) in a comparable population of preterm infants with RDS.
Should Randomized Clinical Trials Be Required for Proton Radiotherapy?
Authors: Michael Goitein, James D. Cox
Journal: Journal of Clinical Oncology (2008)

Clinical Oncology 1 and other 2-4 journals reviewing and commenting on the record of proton beam therapy, as well as an analysis including some critical commentary by Brada et al. 5 All of these articles make the uncontested point that there are almost no randomized clinical trials (RCTs) comparing proton beam therapy with conventional x-ray therapy.We wish to address the issues of why this is, whether RCTs would be appropriate, and whether they are necessary before proton beam therapy is widely promulgated and reimbursed.In brief, the arguments for the use of protons in radiation therapy are as follows.( 1) Owing primarily to their depth dose characteristics (for each proton beam, virtually no dose is administered distal to the target volume and substantially less dose is administered than x-rays proximal to the target volume), the dose distributions that can be achieved with protons are in almost all cases superior to those possible with x-rays (with or without intensity modulation, which can be achieved with both modalities).
Indomethacin and naproxen suppositories in the treatment of rheumatoid arthritis.
Authors: H Berry, D Swinson, J Jones, E B Hamilton
Journal: Annals of the Rheumatic Diseases (1978)

A double-blind cross-over study of 35 out-patients with rheumatoid arthritis showed that Naproxen and Indomethacin suppositories were both effective forms of treatment in rheumatoid arthritis, both being significantly superior to placebo in terms of relief of morning stiffness.
Depression as a Predictor of Weight Regain Among Successful Weight Losers in the Diabetes Prevention Program
Authors: David W. Price, Yong Ma, Richard R. Rubin, Leigh Perreault, George A. Bray, David Marrero, William C. Knowler, Elizabeth Barrett-Connor, D. Yvette LaCoursiere
Journal: Diabetes Care (2012)

To determine whether depression symptoms or antidepressant medication use predicts weight regain in overweight individuals with impaired glucose tolerance (IGT) who are successful with initial weight loss.A total of 1,442 participants who successfully lost at least 3% of their baseline body weight after 12 months of participation in the randomized controlled Diabetes Prevention Program (DPP) continued in their assigned treatment group (metformin, intensive lifestyle, or placebo) and were followed into the Diabetes Prevention Program Outcome Study (DPPOS). Weight regain was defined as a return to baseline DPP body weight. Participant weight and antidepressant medication use were assessed every 6 months. Depression symptoms (Beck Depression Inventory [BDI] score ≥11) were assessed every 12 months.Only 2.7% of the overall cohort had moderate to severe depression symptoms at baseline; most of the participants with BDI score ≥11 had only mild symptoms during the period of observation. In unadjusted analyses, both depression symptoms (hazard ratio 1.31 [95% CI 1.03-1.67], P = 0.03) and antidepressant medication use at either the previous visit (1.72 [1.37-2.15], P < 0.0001) or cumulatively as percent of visits (1.005 [1.002-1.008], P = 0.0003) were predictors of subsequent weight regain. After adjustment for multiple covariates, antidepressant use remained a significant predictor of weight regain (P < 0.0001 for the previous study visit; P = 0.0005 for the cumulative measure), while depression symptoms did not.In individuals with IGT who do not have severe depression and who initially lose weight, antidepressant use may increase the risk of weight regain.
An unusual elevated lesion of the oesophagus
Authors: K. Sawada, K. Ikuta, K. Itabashi, Y. Suzuki, Y. Mizukami, M. Fujiya, K. Kubo, Y. Tamura, Y. Torimoto, Y. Kohgo
Journal: Gut (2010)

A 44-year-old man with a history of gastric cancer that was treated with distal gastrectomy 4 years ago underwent upper endoscopic examination in a follow-up study. The endoscopic examination revealed an elevated lesion 8 mm in size in the lower oesophagus (figure 1A) and narrow band imaging (NBI) endoscopy showed vascular augmentation as brownish spots on the surface of the elevated lesion (figure 1B). There was no abnormality in the stomach and oesophagus–squamous junction. Physical examination and a routine blood test, including …
IL-18 neutralization ameliorates obstruction-induced epithelial–mesenchymal transition and renal fibrosis
Authors: Ahmad H. Bani-Hani, Jeffery A. Leslie, Hiroshi Asanuma, Charles A. Dinarello, Matthew T. Campbell, Daniel R. Meldrum, Honji Zhang, Karen Hile, Kirstan K. Meldrum
Journal: Kidney International (2009)
Endogenous Cytosine Damage Products Alter the Site Selectivity of Human DNA Maintenance Methyltransferase DNMT1
Authors: Victoria Valinluck, Lawrence C. Sowers
Journal: Cancer Research (2007)

Abstract Alterations in cytosine methylation patterns are usually observed in human tumors. The consequences of altered cytosine methylation patterns include both inappropriate activation of transforming genes and silencing of tumor suppressor genes. Despite the biological effect of methylation changes, little is known about how such changes are caused. The heritability of cytosine methylation patterns from parent to progeny cells is attributed to the fidelity of the methylation-sensitive human maintenance methyltransferase DNMT1, which methylates with high specificity the unmethylated strand of a hemimethylated CpG sequence following DNA replication. We have been studying DNA damage that might alter the specificity of DNMT1, either inhibiting the methylation of hemimethylated sites or triggering the inappropriate methylation of previously unmethylated sites. Here, we show that known forms of endogenous DNA damage can cause either hypermethylation or hypomethylation. Inflammation-induced 5-halogenated cytosine damage products, including 5-chlorocytosine, mimic 5-methylcytosine and induce inappropriate DNMT1 methylation within a CpG sequence. In contrast, oxidation damage of the methyl group of 5-methylcytosine, with the formation of 5-hydroxymethylcytosine, prevents DNMT1 methylation of the target cytosine. We propose that reduced DNMT1 selectivity resulting from DNA damage could cause heritable changes in cytosine methylation patterns, resulting in human tumor formation. These data may provide a mechanistic link for the associations documented between inflammation and cancer. [Cancer Res 2007;67(3):946–50]
Acute Peritoneal Dialysis in Rats Results in a Marked Reduction of Interstitial Colloid Osmotic Pressure
Authors: Bert-Inge Rosengren, Bengt Rippe, Olav Tenstad, Helge Wiig
Journal: Journal of the American Society of Nephrology (2004)

The aim of this study was to investigate whether the interstitial colloid osmotic pressure (COPi) of peritoneum is of importance for peritoneal fluid reabsorption during peritoneal dialysis (PD). For testing this hypothesis, a method to isolate interstitial fluid from the peritoneal membrane and to measure the interstitial COPi in the normal peritoneum and directly after the initiation of PD needed to be developed and validated. Eighteen female rats were anesthetized subcutaneously in the neck region with fentanyl-midazolam (1:1). Nylon wicks were implanted postmortem by means of a plastic catheter in the tissue just underneath the peritoneal surface. The characteristics of this fluid were compared with that isolated from wicks that were implanted in intermuscular spaces in hindlimb muscle and back subcutis. All wicks were removed after 20 min and centrifuged. The wick fluid was collected and analyzed in a colloid osmometer constructed for submicroliter samples, and interstitial fluid COP was compared with that of plasma. PD was initiated by injecting 20 ml of 3.86% glucose-containing PD fluid (Dianeal) into the peritoneal cavity, over a dwell time of 4 h. Control rats received no PD. The ratio of COPi to that of plasma (COPp) during control was 0.65 ± 0.05 in peritoneum, 0.53 ± 0.04 in muscle, and 0.59 ± 0.05 in skin. After a PD dwell, the ratio was 0.29 ± 0.03 in peritoneum, 0.54 ± 0.08 in muscle, and 0.41 ± 0.06 in skin. Thus, the COP ratio in peritoneum fell by 55% (P = 0.014) and in skin by 30% (P = 0.03), whereas the COP ratio in muscle was unchanged. The results suggest that acute PD results in a marked fall of the COPi in the peritoneal membrane, shifting the Starling equilibrium toward an absorptive state. The effect was restricted to the peritoneal membrane and, to some extent, the skin. It is speculated that the increase in peritoneal hydrostatic pressure after PD causes an increase in interstitial tissue volume, with primarily a dilution of interstitial colloids.