tbuckley/cabot-search huggingface dataset:
Cell-Associated and Extracellular Phospholipid Transfer Protein in Human Coronary Atherosclerosis
Authors: Kevin D. O’Brien, Simona Vuletic, Thomas O. McDonald, Gertrud Wolfbauer, Katherine Lewis, An-Yue Tu, Santica Marcovina, Thomas N. Wight, Alan Chait, John J. Albers
Journal: Circulation (2003)

Phospholipid transfer protein (PLTP) plays an important role in HDL particle metabolism and may modulate hepatic secretion of apolipoprotein B-containing lipoproteins. However, whether PLTP might participate directly in human atherosclerotic lesion formation is unknown.The cellular and extracellular distributions of PLTP were determined in normal and atherosclerotic human coronary lesions with a monoclonal antibody to human PLTP. Cell types (smooth muscle cells [SMCs] or macrophages), apolipoproteins (apoA-I, apoB, and apoE), and extracellular matrix proteoglycans (biglycan and versican) were identified on adjacent sections with monospecific antibodies. Minimal extracellular PLTP was detected in nonatherosclerotic coronary arteries, but extracellular and cellular PLTP immunostaining was widespread in atherosclerotic lesions. PLTP was detected in foam cell SMCs and in foam cell macrophages, which suggests that cellular cholesterol accumulation might increase PLTP expression in both cell types. This was confirmed by in vitro studies demonstrating that cholesterol loading of macrophages leads to 2- to 3-fold increases in PLTP steady-state mRNA levels, protein expression, and activity. PLTP also was detected in an extracellular distribution, colocalizing with apoA-I, apoB, apoE, and the vascular proteoglycan biglycan. In gel mobility shift assays, both active and inactive recombinant PLTP markedly increased HDL binding to biglycan, which suggests that PLTP may mediate lipoprotein binding to proteoglycans independent of its phospholipid transfer activity.PLTP is present in human atherosclerotic lesions, and its distribution suggests roles for PLTP in both cellular cholesterol metabolism and lipoprotein retention on extracellular matrix.
Gender-specific association of androgenetic alopecia with metabolic syndrome in a middle-aged Korean population
Authors: S.M. Yi, S.W. Son, K.G. Lee, S.H. Kim, S.K. Lee, E.R. Cho, I.-H. Kim, C. Shin
Journal: British Journal of Dermatology (2012)

Although several previous studies have investigated the association between metabolic syndrome (MetS) and androgenetic alopecia (AGA), the study results have been inconsistent.The aim of this study was to investigate the relationship between the presence of MetS and AGA according to gender in a middle-aged Korean population.A population-based cross-sectional study was conducted on a sample from the Korean Genome Epidemiology Study. In total, 3408 subjects (1707 men and 1701 women) were enrolled between January 2008 and February 2010. The Norwood classification for men and Ludwig classification for women were used for assessment of the degree of hair loss. Information on components of MetS together with other possible risk factors was collected.In men, the risk of having Norwood type IV or greater was not increased for subjects with MetS compared with those without MetS. In women, the risk of having Ludwig type I or greater was significantly increased for subjects with MetS compared with those without MetS after controlling for age and smoking status (OR 1.68, 95% CI 1.14-2.48; P=0.01). Similar results were also observed for the number of fulfilled components of MetS [odds ratio (OR) 1.38, 95% confidence interval (CI) 1.00-1.91; P<0.05]. When each component of MetS was considered individually, associations between AGA and all five components of MetS (waist circumference, triglycerides, high-density lipoprotein-C, blood glucose, and blood pressure) were not statistically significant. When multiple regression was used to adjust for age, family history and smoking, there was no significant association between the prevalence of MetS and moderate to severe AGA in the male group. On the contrary, a statistically significant positive association was noted between the prevalence of MetS and AGA in the female group.Our analysis of AGA and the prevalence of MetS in a large population-based cohort demonstrated quite different findings compared with previous reports. The different results according to gender suggest that there may be different mechanisms that are yet to be defined between male and female AGA.
Rituximab and Statins
Authors: Joseph R. Carver, Tyler Johnson, Stephen J. Schuster
Journal: Journal of Clinical Oncology (2010)

TO THE EDITOR: We read with interest the article by Nowakowski et al concerning statin use and prognosis in patients with lymphoma treated in the rituximab era. As a result of the work of Winiarska et al and correspondence with Rabinowitz, we reviewed our recent experience at the Abramson Cancer Center of the University of Pennsylvania (Philadelphia, PA) in a similar cohort of patients. After approval by the institutional review board, we examined the medical records of 108 patients with non-Hodgkin’s lymphoma who were treated with rituximab. The primary end point was clinical response 1 year after therapy completion. Response was defined according to standard definitions. We used 2 analysis to compare the proportions of complete responders, partial responders, and nonresponders in the statin group with those in the nonstatin group. We found no significant difference in these proportions between the two groups. According to our analysis, the proportion of complete responders in the statin group was 0.7 versus 0.662 in the nonstatin group (P .75; 95% CI, 0.760 to 1.470). Additional analysis revealed no relationship between type of statin, dose used, or duration of therapy before start of chemotherapy. Our findings are consistent with those of Nowakowski et al and represent additional evidence that the concurrent use of statins in the clinical setting during treatment of patients with lymphoma does not adversely affect outcome.
Peptide-induced conformational changes in class I heavy chains alter major histocompatibility complex recognition.
Authors: J A Bluestone, S Jameson, S Miller, R Dick
Journal: The Journal of Experimental Medicine (1992)

Small peptides, derived from endogenous proteins bind within the antigen binding groove created by the beta-pleated sheets and alpha helices of the alpha 1 and alpha 2 domains of the class I molecule of the major histocompatibility complex (MHC). However, the precise role of peptide in class I MHC conformation remains unclear. Here, we have shown that, in at least some instances, changes induced in the MHC molecule by the binding of distinct peptides can be identified as specific alterations in serological epitopes expressed on the class I protein. The nature of specific peptides expressed by class I-bearing cells may, therefore, have a dramatic influence on T cell development, self-tolerance, and alloreactivity.
The N-terminal portion of parathyroid hormone-related protein mediates the inhibition of apical Na+/H+ exchange in opossum kidney cells.
Authors: S Maeda, S Wu, J Green, H Kim, R Bosch, I Lee, J Adams, T L Clemens, I Kurtz
Journal: Journal of the American Society of Nephrology (1998)

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) can activate a common receptor in several different cell types. Both PTH and N-terminal PTHrP peptides have been shown to acutely inhibit the apical Na+/H+ exchanger in the renal proximal tubule. In this study, the ability of various PTHrP fragments to inhibit apical Na+/H+ exchange was investigated. In addition, the signal transduction events associated with PTHrP inhibition of apical Na+/H+ exchange in polarized OK-P cells were characterized. Both PTHrP-(1-34)NH2 and recombinant full-length PTHrP-(1-141) inhibited apical Na+/H+ exchange activity by approximately 50%. These changes occurred in close temporal association with significant (threefold) increases in cellular cAMP accumulation. PTHrP-(1-34)NH2 had no effect on intracellular Ca2+, inositol phosphate production, or protein kinase C activity. PTHrP peptides, including PTHrP-(38-64)NH2, PTHrP-(67-86)NH2, PTHrP-(102-107)NH2, and PTHrP-(107-139)NH2, which lack the PTH-like N terminus, had no effect on the antiporter activity or cAMP accumulation. The results demonstrate that the N-terminal portion of the PTHrP molecule is responsible for inhibition of the apical Na+/H+ antiporter in OK-P cells.
Phospholipase D Prevents Etoposide-Induced Apoptosis by Inhibiting the Expression of Early Growth Response-1 and Phosphatase and Tensin Homologue Deleted on Chromosome 10
Authors: Joommo Kim, Young Han Lee, Taeg Kyu Kwon, Jong-Soo Chang, Kwang Chul Chung, Do Sik Min
Journal: Cancer Research (2006)

Abstract Phospholipase D (PLD) has emerged as a critical regulator of cell proliferation and survival signaling. We show for the first time that elevated expression of PLD isozymes attenuates expression of the tumor suppressors early growth response-1 (Egr-1) and the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor and apoptosis during etoposide treatment. When formation of phosphatidic acid was inhibited by overexpression of catalytically inactive PLD during etoposide treatment, expression of Egr-1 and PTEN and the apoptotic effect of etoposide were not inhibited. This suggests that PLD inhibits expression of these tumor suppressors and inhibits apoptosis. Deletion of a specific Egr-1-binding site present in the PTEN promoter blocked etoposide-induced PTEN activity and elevated expression of PLD decreased the sensitivity to apoptosis induced by ectopic expression of Egr-1. Etoposide-induced activation of Akt was potentiated by overexpression of PLD and PLD-stimulated suppression of Egr-1 was blocked by inhibition of phosphatidylinositol 3-kinase/Akt survival pathway at the both transcriptional and posttranscriptional levels. These results show that survival signals generated by PLD attenuate expression of Egr-1 by activation of phosphatidylinositol 3-kinase signaling pathway and induction of PTEN by Egr-1, which confers resistance to apoptosis. (Cancer Res 2006; 66(2): 784-93)
The Biological Variation of Sex Hormone-Binding Globulin in Type 2 Diabetes
Authors: Vijay Jayagopal, Eric S. Kilpatrick, Paul E. Jennings, Steve Holding, David A. Hepburn, Stephen L. Atkin
Journal: Diabetes Care (2004)

Quantitative determination of insulin resistance is technically demanding and expensive. We have recently shown (1) that insulin resistance determined using the homeostasis model assessment of insulin resistance (HOMA-IR) has a significantly greater biological variability in individuals with type 2 diabetes than in healthy ones. A surrogate marker of insulin resistance that was reproducible, stable, and easily measured would be invaluable for both research and clinical practice, particularly for following insulin-sensitizing therapy, such as metformin and the thiazolidinediones. A low sex hormone-binding globulin (SHBG) concentration reflects hyperinsulinemic insulin resistance and has been proposed as such a surrogate measure (2–4). This study aimed to compare the biological variation of SHBG and insulin resistance in type 2 diabetes to determine the potential for SHBG as a surrogate marker of insulin resistance in type 2 diabetes.

Subjects were initially recruited for a study to assess the biological variation of insulin resistance in individuals with type 2 diabetes (1). Postmenopausal Caucasian subjects ( n = 12) with type 2 diabetes (median age 62 years, range 50–73, and median BMI 31.6 kg/m2, range 25.1–35.7) and 11 age- and weight-matched, healthy, postmenopausal Caucasian control subjects …
Acid-base status and intracellular pH regulation in lymphocytes from rats with genetic hypertension.
Authors: D Batlle, J Redon, C Gutterman, M LaPointe, A Saleh, A Sharma, G Rombola, M Ye, W Alsheikha, L Gomez
Journal: Journal of the American Society of Nephrology (1994)

This article reviews work from this laboratory dealing with acid-base status and intracellular pH (pHi) regulation in rat genetic models of hypertension. With freshly isolated thymic lymphocytes, pHi and its regulation were examined in the spontaneously hypertensive rat (SHR). In this rat model, pHi was found to be reduced as compared with that of lymphocytes from normotensive Wistar-Kyoto (WKY) rats. The activity of the Na+/H+ antiporter assessed after stimulation by acute cell acidification was similar in lymphocytes from SHR and WKY rats both in the nominal absence of HCO3- and in media containing HCO3- (22 mM). The kinetic properties of the Na+/H+ antiporter, examined as a function of pHi with the Hill kinetic model, revealed no significant differences between lymphocytes from SHR and WKY rats. The kinetic properties of the Na(+)-dependent and Na(+)-independent Cl(-)-HCO3- exchangers, examined as a function of external Cl-, were also virtually identical in lymphocytes from SHR and WKY rats. Unlike the Na(+)-H+ exchanger and the Na(+)-independent Cl(-)-HCO3- exchanger, which had their highest activities at extremes of pHi (low pHi, Na(+)-H+ exchanger; high pHi, Na(+)-independent Cl(-)-HCO3- exchanger), the Na(+)-dependent Cl(-)-HCO3- exchanger had its maximal activity near steady-state pHi. In Dahl/Rapp salt-sensitive rats with hypertension, the pHi of thymic lymphocytes was also reduced as compared with that of normotensive salt-resistant animals. In this model, renal net acid excretion in salt-sensitive rats was augmented as compared with that of salt-resistant rats. The increase in renal acid excretion was due to an increase in both ammonium and titratable acid excretion and was observed while animals were placed on high, normal and low salt diets. The findings of intracellular acidosis and enhanced renal acid excretion suggest that cellular acid overproduction is augmented in salt-sensitive hypertension.
Influence of rate-dependent cellular uncoupling on conduction change during simulated ischemia in guinea pig papillary muscles: effect of verapamil.
Authors: Y Hiramatsu, J W Buchanan, S B Knisley, G G Koch, S Kropp, L S Gettes
Journal: Circulation Research (1989)

This study was performed to determine if the changes in cellular coupling induced by simulated ischemia were rate-dependent and if they contributed to the rate-dependent conduction slowing that occurs in this setting. We also sought to determine if the known ability of verapamil to prevent ischemia-induced conduction changes might be related to the preservation of cellular coupling. We studied the effects of increasing stimulation frequency from 0.5 to 2.0 Hz on the simultaneous changes in the maximum rate of rise (Vmax) of the action potential upstroke, conduction velocity, and internal longitudinal resistance (ri) determined by the voltage ratio method in superfused guinea pig papillary muscles under conditions of simulated ischemia (SI). When stimulation frequency was 0.5 Hz, 30 minutes of SI caused a 16.5% decrease in Vmax, a 16% increase in ri, and a 12.9% decrease in conduction velocity. When stimulation frequency was increased to 2.0 Hz, 30 minutes of SI caused a 30% decrease in Vmax, a 72.9% increase in ri, and a 21.4% decrease in conduction velocity. Thus, the changes were rate-dependent. Verapamil (1 X 10(-6) M) did not influence the changes in these parameters during SI at 0.5 Hz nor the decrease in Vmax during SI at 2.0 Hz, but it did prevent the rate-dependent increase in ri. Verapamil also prevented the rate-dependent decrease in conduction velocity induced by SI. Our results suggest that during simulated ischemia the rate-dependent component of the increase in Ri contributes to the rate-dependence of the conduction slowing.(ABSTRACT TRUNCATED AT 250 WORDS)
Amyloid Precursor Protein Processing and Alzheimer's Disease
Authors: Richard J. O'Brien, Philip C. Wong
Journal: Annual Review of Neuroscience (2011)

Alzheimer's disease (AD), the leading cause of dementia worldwide, is characterized by the accumulation of the β-amyloid peptide (Aβ) within the brain along with hyperphosphorylated and cleaved forms of the microtubule-associated protein tau. Genetic, biochemical, and behavioral research suggest that physiologic generation of the neurotoxic Aβ peptide from sequential amyloid precursor protein (APP) proteolysis is the crucial step in the development of AD. APP is a single-pass transmembrane protein expressed at high levels in the brain and metabolized in a rapid and highly complex fashion by a series of sequential proteases, including the intramembranous γ-secretase complex, which also process other key regulatory molecules. Why Aβ accumulates in the brains of elderly individuals is unclear but could relate to changes in APP metabolism or Aβ elimination. Lessons learned from biochemical and genetic studies of APP processing will be crucial to the development of therapeutic targets to treat AD.
Surgery in the treatment of malignant pleural mesothelioma: recruitment into trials should be the default position
Authors: Avijit Datta, Rhiannon Smith, Francesca Fiorentino, Tom Treasure
Journal: Thorax (2013)

<h3>Background</h3> Europe is at the peak of an epidemic of malignant pleural mesothelioma and the burden of disease is likely to continue rising in the large areas of the world where asbestos remains unregulated. Patients with mesothelioma present with thoracic symptoms and radiological changes so respiratory physicians take a leading role in diagnosis and management. Belief that the modest survival times reported after radical surgery, whether alone or as part of multimodal therapy, are longer than they it would have been without surgery relies on data from highly selected, uncontrolled, retrospectively analysed case series. The only randomised study, the Mesothelioma and Radical Surgery (MARS) trial showed no benefit. A simple modelling study of registry patients, described here, shows that an impression of longer survival is eroded when patients who were never candidates for operation on grounds of histology, performance status and age are sequentially excluded from the model. <h3>Conclusion</h3> Whenever the question arises `Might an operation help me?9 there are two responses that can and should be given. The first is that there is doubt about whether there is any survival or symptomatic benefit from surgery but we know that there is harm. The second is that there are on-going studies, including two randomised trials, which patients should be informed about. The authors suggest that the default position for clinicians should be to encourage recruitment into these trials.
Altered cytokine expression of peripheral blood lymphocytes in polymyositis and dermatomyositis
Authors: M Aleksza
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To investigate the intracellular and soluble cytokine levels and T cell subsets in peripheral blood of patients with active and inactive polymyositis and dermatomyositis. <b>Methods:</b> The frequencies of T and B lymphocytes, T helper (Th), and T cytotoxic (Tc) cells and of interferon γ (IFNγ), interleukin (IL)4, and IL10 expression of CD4+ or CD8+ cells were determined by flow cytometry. The concentrations of soluble cytokines were measured with commercial enzyme linked immunosorbent assays. <b>Results:</b> In active dermatomyositis there was a decreased percentage of T (CD3+) lymphocytes and Tc (CD8+) lymphocytes, decreased IFNγ expression of CD4+ and CD8+ cells, but an increase in B and IL4 producing CD4+ lymphocyte frequencies. These prominent changes disappeared in the inactive stage of the disease. In polymyositis no significant change in these lymphocyte subsets or in intracellular cytokine expression could be detected in either the active or the inactive form. The frequency of IL4+/IFNγ+ Th cells was calculated and a significantly increased Th2/Th1 frequency was found in active dermatomyositis, and a decreased frequency in inactive dermatomyositis, compared with the control population. <b>Conclusions:</b> There appears to be a difference between polymyositis and dermatomyositis in the level of peripheral blood lymphocytes and their intracellular cytokine content. These findings provide further evidence for a difference in the pathogenesis of polymyositis and dermatomyositis.
New genes in the evolution of the neural crest differentiation program
Authors: Juan-Ramon Martinez-Morales, Thorsten Henrich, Mirana Ramialison, Joachim Wittbrodt, Juan-Ramon Martinez-Morales
Journal: Genome biology (2007)

Development of the vertebrate head depends on the multipotency and migratory behavior of neural crest derivatives. This cell population is considered a vertebrate innovation and, accordingly, chordate ancestors lacked neural crest counterparts. The identification of neural crest specification genes expressed in the neural plate of basal chordates, in addition to the discovery of pigmented migratory cells in ascidians, has challenged this hypothesis. These new findings revive the debate on what is new and what is ancient in the genetic program that controls neural crest formation.To determine the origin of neural crest genes, we analyzed Phenotype Ontology annotations to select genes that control the development of this tissue. Using a sequential blast pipeline, we phylogenetically classified these genes, as well as those associated with other tissues, in order to define tissue-specific profiles of gene emergence. Of neural crest genes, 9% are vertebrate innovations. Our comparative analyses show that, among different tissues, the neural crest exhibits a particularly high rate of gene emergence during vertebrate evolution. A remarkable proportion of the new neural crest genes encode soluble ligands that control neural crest precursor specification into each cell lineage, including pigmented, neural, glial, and skeletal derivatives.We propose that the evolution of the neural crest is linked not only to the recruitment of ancestral regulatory genes but also to the emergence of signaling peptides that control the increasingly complex lineage diversification of this plastic cell population.