tbuckley/cabot-search huggingface dataset:
Normal Human Kidney HLA-DR–Expressing Renal Microvascular Endothelial Cells
Authors: Kimberly A. Muczynski, David M. Ekle, David M. Coder, Susan K. Anderson
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Human, but not murine, renal peritubular and glomerular capillaries constitutively express class II major histocompatibility (MHC) proteins at high levels in normal human kidney. Expression of class II proteins on renal microvascular endothelial cells (RMEC) makes it available to circulating lymphocytes and imparts a surveillance capacity to RMEC for controlling inflammatory responses. In this report, the co-expression of HLA-DR and the endothelial marker CD31 are used to identify RMEC as a distinct population of cells within a standard renal biopsy using flow cytometry. A three-laser, multicolor flow cytometry analysis using Alexa dyes, developed for characterizing the expression of cell surface antigens, identifies RMEC as a population separate from HLA-DR-expressing leukocytes. HLA-DR RMEC co-express HLA-DP and HLA-DQ. RMEC also express the T cell costimulatory factor CD58 but not CD80, CD86, or CD40. On the basis of high HLA-DR expression, RMEC are isolated for culture using fluorescence-activated cell sorting and magnetic beads. Cultured RMEC require normal basal physiologic concentrations of gamma interferon (γIFN) to maintain HLA protein expression. This expression is regulated by CIITA, the MHC class II-specific transcription factor. Four tissue-specific promoters have been described for CIITA. In freshly isolated RMEC, RT-PCR and hybridization using specific oligonucleotide probes to CIITA promoter sequences identify only the statin-sensitive γIFN-induced promoter IV of CIITA. Therefore, the constitutive expression of HLA-DR on RMEC in normal human kidney is located in a position for immune surveillance, depends on basal physiologic concentrations of γIFN, and may be amenable to regulation with statins. E-mail: kzynski@u.washington.edu
Neratinib, an Irreversible Pan-ErbB Receptor Tyrosine Kinase Inhibitor: Results of a Phase II Trial in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Lecia V. Sequist, Benjamin Besse, Thomas J. Lynch, Vincent A. Miller, Kwok K. Wong, Barbara Gitlitz, Keith Eaton, Charles Zacharchuk, Amy Freyman, Christine Powell, Revathi Ananthakrishnan, Susan Quinn, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2010)

Purpose Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have had a significant impact on non–small-cell lung cancer (NSCLC) outcomes, particularly for patients with EGFR mutations. Resistance emerges after 9 to 12 months, primarily mediated by the T790M resistance mutation. We studied neratinib, an irreversible pan-ErbB TKI that may overcome T790M. Patients and Methods Patients with advanced NSCLC underwent EGFR sequencing of available tumor tissue at enrollment. Those with ≥ 12 weeks of prior TKI therapy were placed in arm A if they were EGFR mutation positive or arm B if they were wild-type. Arm C included TKI-naïve patients with adenocarcinoma and light smoking histories (≤ 20 pack-years). All patients received daily oral neratinib, initially at 320 mg but subsequently reduced to 240 mg because of excessive diarrhea. The primary end point was objective response rate (RR). Results One-hundred sixty-seven patients were treated: 91 in arm A, 48 in arm B, and 28 in arm C. Diarrhea was the most common toxicity; grade 3 incidence was 50% at 320 mg but improved to 25% after dose reduction. The RR was 3% in arm A and zero in arms B and C. No patients with known T790M responded. Notably, three of four patients with an exon 18 G719X EGFR mutation had a partial response and the fourth had stable disease lasting 40 weeks. Conclusion Neratinib had low activity in patients with prior benefit from TKIs and in TKI-naïve patients, potentially because of insufficient bioavailability from diarrhea-imposed dose limitation. Responses were seen in patients with the rare G719X EGFR mutation, highlighting the importance of obtaining comprehensive genetic information on trials of targeted agents.
Natural resistance against lymphoma grafts conveyed by H-2Dd transgene to C57BL mice.
Authors: P Höglund, H G Ljunggren, C Ohlén, L Ahrlund-Richter, G Scangos, C Bieberich, G Jay, G Klein, K Kärre
Journal: The Journal of Experimental Medicine (1988)

The H-2Dd transgenic strain D8 on C57BL background was more resistant to subcutaneous challenge of RBL-5 lymphoma cells than B6 controls. The direct role of the H-2Dd antigen was investigated by the use of (D8 x B6)F1 crosses and (D8 B6) x B6 backcrosses. The latter showed cosegregation with regard to Dd antigen expression and lymphoma resistance, both of which were inherited in a pattern consistent with control by a single dominant gene. The rejection potential in (D8 x B6)F1 mice appeared as strong as that seen in crosses between B6 and MHC congenic mice (on B10 background) carrying H-2Dd. The lymphoma resistance could be abrogated by treatment with anti-asialo GM1 antiserum or anti-NK 1.1 mAb, indicating a role for NK cells.
The lichen planus-like eruption after bone marrow transplantation
Authors: J.H. SAURAT, ELIANE GLUCKMAN, ANETTE BUSSEL, LILIANE DIDIERJEAN, A. PUISSANT
Journal: British Journal of Dermatology (1975)

Journal Article The lichen planus‐like eruption after bone marrow transplantation Get access J.H. SAURAT, J.H. SAURAT Hopital Saint‐Louis 2, Place du Docteur Fournier, 75475 Paris, Cedex 10 Search for other works by this author on: Oxford Academic Google Scholar ELIANE GLUCKMAN, ELIANE GLUCKMAN Hopital Saint‐Louis 2, Place du Docteur Fournier, 75475 Paris, Cedex 10 Search for other works by this author on: Oxford Academic Google Scholar ANETTE BUSSEL, ANETTE BUSSEL Hopital Saint‐Louis 2, Place du Docteur Fournier, 75475 Paris, Cedex 10 Search for other works by this author on: Oxford Academic Google Scholar LILIANE DIDIERJEAN, LILIANE DIDIERJEAN Search for other works by this author on: Oxford Academic Google Scholar A. PUISSANT A. PUISSANT Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 93, Issue 6, 1 December 1975, Pages 675–681, https://doi.org/10.1111/j.1365-2133.1975.tb05118.x Published: 01 December 1975
Idiopathic hypercalciuria
Authors: F L Coe, J H Parks
Journal: Journal of the American Society of Nephrology (1994)

The original contributions of Jacob Lemann to mineral metabolism, especially calcium metabolism and idopathic hypercalciuria, are reviewed. One group of studies concern acid base balance and calcium loss, showing that acid loads increase calcium loss in the urine. Another group of studies concern the calciuria of glucose or carbohydrate ingestion, with the observation that stone patients, who as a population are enriched with hypercalciuria, respond with more exaggerated calciuria to glucose loads than do normal people. Yet another body of work shows that normal men, when given noncalcemic loads of calcitriol, exhibit two essential features of idiopathic hypercalciuria--hyperabsorptive hypercalciuria and bone mineral loss on a low-calcium diet. The final group of studies presented worked on the problem of thiazide hypocalciuric action, and where the calcium goes that does not appear in the urine, as well as the effects of potassium bicarbonate and sodium loads on mineral balance and acid base status.
Prognostic Factors in Seminomas with Special Respect to HCG: Results of a Prospective Multicenter Study
Authors: L. Weissbach, R. Bussar-Maatz, U. L&ouml;hrs, G.E. Schubert, K. Mann, M. Hartmann, K.P. Dieckmann, J. Fassbinder
Journal: European Urology (1999)
Hepatic stellate cells express synemin, a protein bridging intermediate filaments to focal adhesions
Authors: N Uyama
Journal: Gut (2006)

<b>Background and aims:</b> In the liver, stellate cells play several important (patho)physiological roles. They express a broad but variable spectrum of intermediate filament (IF) proteins. The aim of this study was to investigate the expression and functions of the intermediate filament protein synemin in hepatic stellate cells (HSCs). <b>Methods:</b> In isolated and cultured rat HSCs, synemin expression was examined by quantitative reverse transcriptase polymerase chain reaction, western blotting, and immunocytochemistry. Protein–protein interaction between synemin and possible binding partners was investigated by co-immunoprecipitation and confocal microscopy. <b>Results:</b> Expression of synemin was significantly downregulated with increased culture time. In 1-day cultured HSCs, synemin associated with other IF proteins (GFAP, desmin, and vimentin), and with the focal adhesion proteins vinculin and talin, but not with α-actinin or paxillin. Synemin IF and focal adhesion proteins co-localised in long slender processes, but not in the lamellipodia. In human and rat liver tissue, the presence of synemin was investigated by immunohistochemistry. In normal rat and human livers, synemin immunoreactivity was found in HSCs, smooth muscle cells of hepatic arterioles, and nerve bundles in portal tracts, but not in portal fibroblasts. In CCl<sub>4</sub>-intoxicated rat livers and in human cirrhotic livers, immunoreactivity for synemin in the parenchymal tissue was decreased. Thus synemin was expressed in quiescent HSCs but not in portal fibroblasts; and synemin expression decreased with HSC activation in vivo during chronic liver damage and with HSC activation in culture. <b>Conclusions:</b> Synemin forms heteropolymeric filaments with type-III IF proteins and acts as a bridging protein between IFs and a specific type of focal adhesions.
Disparate Effects of Atorvastatin Compared With Simvastatin on C-Reactive Protein Concentrations in Patients With Type 2 Diabetes
Authors: Thozhukat Sathyapalan, Stephen L. Atkin, Eric S. Kilpatrick
Journal: Diabetes Care (2010)

Reduction in LDL and high sensitivity (hs) C-reactive protein (CRP) are independent indicators of successful cardiovascular risk reduction with statins. This study compared the effect of equivalent LDL-lowering doses of simvastatin and atorvastatin on hsCRP in type 2 diabetic patients.A crossover study of 26 patients with type 2 diabetes taking either 40 mg simvastatin or 10 mg atorvastatin was undertaken. After 3 months on one statin, lipids and hsCRP were measured on 10 occasions over a 5-week period. The same procedure was then followed taking the other statin.LDL was comparable on either treatment: atorvastatin 2.2 +/- 0.2 vs. 2.1 +/- 0.3 mmol/l (mean +/- SD; P = 0.19). CRP of individuals taking atorvastatin was significantly lower than when they were taking simvastatin (median 1.08 vs. 1.47 mg/l, P = 0.0002) and was less variable (median SD of logCRP 0.0036 vs. 0.178, P = 0.0001).Compared with simvastatin, atorvastatin reduced hsCRP and its variability in type 2 diabetic patients. This enhanced anti-inflammatory effect may prove beneficial if lower CRP is associated with improved cardiovascular risk.
Does RAGE protect smokers from COPD?
Authors: J.W. Upham, D.J. Smith, S.T. Yerkovich
Journal: European Respiratory Journal (2011)

From the authors:

We thank R.P. Young and co-workers for their comments on our recent article [1]. As we highlighted in our article, there are two recent reports indicating that single-nucleotide polymorphisms in the advanced glycosylation end product-specific receptor ( AGER ) gene, which encodes the …
Evaluation of liver disease progression in the German hepatitis C virus (1b)-contaminated anti-D cohort at 35 years after infection
Authors: Manfred Wiese, Janett Fischer, Micha Löbermann, Uwe Göbel, Kurt Grüngreiff, Wolfgang Güthoff, Ulrike Kullig, Franziska Richter, Ingolf Schiefke, Hannelore Tenckhoff, Alexander Zipprich, Thomas Berg, Tobias Müller
Journal: Hepatology (2013)

The natural course of HCV infection remains controversial. The German HCV (1b)-contaminated anti-D cohort provides an ideal population to investigate the natural course of HCV infection in a large, homogenous cohort of young women from the date of HCV inoculation. Our previous follow-up studies at 20 and 25 years after infection suggested slow fibrosis progression rates in this unique cohort. The aim of our prospective, community-based, multicenter study was to reevaluate the liver disease progression in 718 patients of the original anti-D cohort at 35 years after infection. Patients with self-limited HCV infection (n = 189) were compared to those who failed to eliminate the virus spontaneously (n = 529), comprising patients who were treatment naïve (n = 197) or achieved a sustained virological response (SVR; n = 149), respectively, failed to clear the virus (non-SVR; n = 183) after antiviral therapy. In the overall cohort, 9.3% of patients showed clinical signs of liver cirrhosis at 35 years after infection. Liver disease progression largely depended on HCV infection status. The highest proportion of patients with clinical signs of end-stage liver disease was observed in the non-SVR group (15.3%), whereas decreased cirrhosis rates were detected in the SVR group (6%) and in patients with self-limited HCV infection (1.1%; P = 6.2 × 10(-6)). Overall survival was significantly enhanced after SVR, compared to treatment-naïve patients or non-SVR (P = 0.027).The present study provides further evidence for a mild, but significant, disease progression at 35 years after infection in the German HCV (1b)-contaminated anti-D cohort. Patients with self-limited HCV infection or SVR after antiviral treatment were protected from progressive liver disease and showed the best clinical long-term outcome.
Descriptive epidemiology of central nervous system germ cell tumors: nonpineal analysis
Authors: J. L. Villano, I. Y. Virk, V. Ramirez, J. M. Propp, H. H. Engelhard, B. J. McCarthy
Journal: Neuro-Oncology (2009)

Central nervous system (CNS) germ cell tumors (GCT) have not been epidemiologically well described. Our study describes 2 population-based series of nonpineal CNS GCT. Data on all primary (malignant and nonmalignant) CNS (ICD-O-3 sites: C70.0–C72.9, C75.1–C75.3) GCT diagnosed between 2000 and 2004 from the Central Brain Tumor Registry of the United States (CBTRUS) and on all malignant GCT diagnosed between 1992 and 2005 from the Surveillance, Epidemiology, and End Results (SEER) were analyzed. Of 234 nonpineal GCT in CBTRUS, the most common site was brain, NOS (31.6%). Males had a greater frequency (59.7%) than females (40.3%). However, by age group, the male-to-female incidence rate ratio (IRR) differed: children (0–14 years) had an IRR of 1.1, young adults (15–29 years) an IRR of 2.3, and adults (aged 30+) an IRR of 1.0. For children and young adults, most tumors were malignant (86.8% and 89.0%, respectively), whereas for adults, more than half were nonmalignant (56.8%). Germinoma was the most frequent diagnosis (61.5%). In SEER, the frequency of malignant GCT in the CNS (2.5%) was greater than that in the mediastinum (2.1%). Of 408 malignant CNS GCT, 216 (52.9%) were nonpineal. The male-to-female IRR was 1.5. Overall relative survival for nonpineal CNS malignant GCT was 85.3% at 2 years, 77.3% at 5 years, and 67.6% at 10 years. Previous studies of GCT that have not stratified by site have suggested greater gender disparity. Nonpineal CNS GCT show no significant gender preference, yet have outcomes similar to pineal GCT.
Short-chain fatty acids induce γ-globin gene expression by displacement of a HDAC3-NCoR repressor complex
Authors: Rishikesh Mankidy, Douglas V. Faller, Rodwell Mabaera, Christopher H. Lowrey, Michael S. Boosalis, Gary L. White, Serguei A. Castaneda, Susan P. Perrine
Journal: Blood (2006)
Assessing the Validity of Surrogate Outcomes for ESRD
Authors: Min Jun, Tanvir Chowdhury Turin, Mark Woodward, Vlado Perkovic, Hiddo J Lambers Heerspink, Braden J Manns, Marcello Tonelli, Brenda R Hemmelgarn
Journal: Journal of the American Society of Nephrology (2015)

Validation of current and promising surrogate outcomes for ESRD in randomized controlled trials (RCTs) has been limited. We conducted a systematic review and meta-analysis of RCTs to further inform the ability of surrogate outcomes for ESRD to predict the efficacy of various interventions on ESRD. MEDLINE, EMBASE, and CENTRAL (from inception through September 2013) were searched. All RCTs in adults with proteinuria, diabetes, or CKD stages 1-4 or renal transplant recipients reporting ≥10 ESRD events and a surrogate outcome (change in proteinuria or doubling of serum creatinine [DSCR]) for ESRD during a ≥1-year follow-up were included. Two reviewers abstracted trial characteristics and outcome data independently. To assess the correlation between the surrogate outcomes and ESRD, we determined the treatment effect ratio (TER), defined as the ratio of the treatment effects on ESRD and the effects on the change in surrogate outcomes. TERs close to 1 indicate greater agreement between ESRD and the surrogate, and these ratios were pooled across interventions. We identified 27 trials (97,458 participants; 4187 participants with ESRD). Seven trials reported the effects on change in proteinuria and showed consistent effects for proteinuria and ESRD (TER, 0.82; 95% confidence interval, 0.59 to 1.16), with minimal heterogeneity. Twenty trials reported on DSCR. Treatment effects on DSCR were consistent with the effects on ESRD (TER, 0.98; 95% confidence interval, 0.85 to 1.14), with moderate heterogeneity. In conclusion, DSCR is generally a good surrogate for ESRD, whereas data on proteinuria were limited. Further assessment of the surrogacy of proteinuria using prospective RCTs is warranted.
Direct immunoassay of triiodothyronine in human serum
Authors: P. R. Larsen
Journal: Journal of Clinical Investigation (1972)

A sensitive and precise radioimmunoassay for the direct measurement of triiodothyronine (T(3)) in human serum has been designed using sodium salicylate to block T(3)-TBG binding. This assay is sufficiently sensitive to quantitate T(3) accurately in 50-100 mul of normal serum and to measure quantities as small as 12.5 pg in 0.2 ml of hypothyroid serum. The T(3) values observed in euthyroid subjects and in patients with various thyroid diseases are as follows: euthyroid (38) 1.10+/-0.25 (SD) ng/ml, hypothyroid (25) 0.39+/-0.21 (SD) ng/ml, and hyperthyroid (24) 5.46+/-4.42 (SD) ng/ml. The levels of T(3) parallel the thyroxine (T(4)) concentration in the sera of these subjects. In eight pregnant women at the time of delivery, T(3) concentrations were in the upper normal range (mean 1.33 ng/ml). The levels of T(3) in cord serum obtained at the time of delivery of these patients (mean 0.53 ng/ml) are distinctly lower and close to the hypothyroid mean. Administration of 10 U of bovine thyroid-stimulating hormone (TSH) to euthyroid subjects causes a two-fold increase in serum T(3) levels within 8 hr. At this time, the increase in serum T(4) concentration is only 41%. In two subjects in whom thyroid secretion was acutely inhibited, one after pituitary surgery and another after thyroidectomy, the serum T(3) fell into the hypothyroid range within 1-2 days. Thus, serum T(3) concentrations appear to be a sensitive index of acute changes in thyroid hormone secretion and should prove to be a useful adjunct to both the clinical and physiological evaluation of thyroid function.
Platelet kinetics in asthmatic patients with and without aspirin intolerance.
Authors: V Plaza, F Casals, A Alonso, C Picado
Journal: Thorax (1992)

BACKGROUND: A reduced platelet survival time has been described in asthmatic patients. There is also good evidence that platelets are involved in aspirin induced asthma. Since aspirin intolerant patients usually suffer from an active disease and often require anti-inflammatory treatment, it has been suggested that platelet survival time may be shorter in aspirin intolerant asthmatic subjects than in aspirin tolerant subjects. The objective of this study was to investigate this hypothesis. METHODS: Thirteen asthmatic subjects (six aspirin tolerant and seven aspirin intolerant) in a stable clinical condition and ten healthy subjects were studied. Platelet kinetics and survival time were measured with indium-111 labelled autologous platelets. RESULTS: Mean (SD) platelet sequestration ratios in the spleen and liver were lower in asthmatic (2.3 (0.9) and 0.6 (0.2) respectively) than in healthy subjects (3.2 (0.7) and 1.1 (0.4) respectively). However, mean (SD) platelet survival time in asthmatic subjects (8 (2.7) days) did not differ from that in healthy subjects (7.6 (1.1) days). No differences were observed in platelet kinetics between aspirin tolerant and aspirin intolerant patients. CONCLUSIONS: These results suggest the existence of an active non-splenic pool of platelets in patients with asthma. However, they failed to show platelet kinetic differences among asthmatic subjects with and without aspirin intolerance and do not support previous studies suggesting an altered platelet survival in stable asthma.
Why Selection Might Be Stronger When Populations Are Small: Intron Size and Density Predict within and between-Species Usage of Exonic Splice Associated<i>cis-</i>Motifs
Authors: XianMing Wu, Laurence D. Hurst
Journal: Molecular Biology and Evolution (2015)

The nearly neutral theory predicts that small effective population size provides the conditions for weakened selection. This is postulated to explain why our genome is more "bloated" than that of, for example, yeast, ours having large introns and large intergene spacer. If a bloated genome is also an error prone genome might it, however, be the case that selection for error-mitigating properties is stronger in our genome? We examine this notion using splicing as an exemplar, not least because large introns can predispose to noisy splicing. We thus ask whether, owing to genomic decay, selection for splice error-control mechanisms is stronger, not weaker, in species with large introns and small populations. In humans much information defining splice sites is in cis-exonic motifs, most notably exonic splice enhancers (ESEs). These act as splice-error control elements. Here then we ask whether within and between-species intron size is a predictor of the commonality of exonic cis-splicing motifs. We show that, as predicted, the proportion of synonymous sites that are ESE-associated and under selection in humans is weakly positively correlated with the size of the flanking intron. In a phylogenetically controlled framework, we observe, also as expected, that mean intron size is both predicted by Ne.μ and is a good predictor of cis-motif usage across species, this usage coevolving with splice site definition. Unexpectedly, however, across taxa intron density is a better predictor of cis-motif usage than intron size. We propose that selection for splice-related motifs is driven by a need to avoid decoy splice sites that will be more common in genes with many and large introns. That intron number and density predict ESE usage within human genes is consistent with this, as is the finding of intragenic heterogeneity in ESE density. As intronic content and splice site usage across species is also well predicted by Ne.μ, the result also suggests an unusual circumstance in which selection (for cis-modifiers of splicing) might be stronger when population sizes are smaller, as here splicing is noisier, resulting in a greater need to control error-prone splicing.