tbuckley/cabot-search huggingface dataset:
High-density lipoprotein loses its anti-inflammatory capacity by accumulation of pro-inflammatory-serum amyloid A
Authors: Markus Tölle, Tao Huang, Mirjam Schuchardt, Vera Jankowski, Nicole Prüfer, Joachim Jankowski, Uwe J.F. Tietge, Walter Zidek, Markus van der Giet
Journal: Cardiovascular Research (2012)

AimsHigh-density lipoprotein (HDL) is known to have potent anti-inflammatory properties. Monocyte chemoattractant protein-1 is an important pro-inflammatory cytokine in early atherogenesis. There is evidence that HDL can lose its protective function during inflammatory disease. In patients with end-stage renal disease (ESRD), epidemiological studies have documented that the inverse correlation between HDL-cholesterol and cardiovascular risk is lost. Many structural modifications leading to reduced HDL function have been characterized, but the functional consequences are not fully understood.
Molecular Biology and Pathology of Lymphangiogenesis
Authors: Terhi Karpanen, Kari Alitalo
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

The lymphatic vasculature is essential for the maintenance of tissue fluid balance, immune surveillance, and adsorption fatty acids in the gut. The lymphatic vessels are also crucially involved in the pathogenesis of diseases such as tumor metastasis, lymphedema, and various inflammatory conditions. Attempts to control or treat these diseases have drawn a lot of interest to lymphatic vascular research during the past few years. Recently, several markers specific for lymphatic endothelium and models for lymphatic vascular research have been characterized, enabling great technical progress in lymphatic vascular biology, and many critical regulators of lymphatic vessel growth have been identified. Despite these significant achievements, our understanding of the lymphatic vessel development and pathogenesis is still rather limited. Several key questions remain to be resolved, including the relative contributions of different pathways targeting lymphatic vasculature, the molecular and cellular processes of lymphatic maturation, and the detailed mechanisms of tumor metastasis via the lymphatic system.
Altered protamine expression and diminished spermatogenesis: what is the link?
Authors: Douglas T. Carrell, Benjamin R. Emery, Sue Hammoud
Journal: Human Reproduction Update (2007)

During the elongating spermatid stage of spermiogenesis, human sperm chromatin undergoes a complex transition in which histones are extensively replaced by protamines in a carefully regulated transition including histone modifications and intermediate and temporary replacement of the histones by sperm-specific transition proteins. The replacement of most histones by protamines 1 and 2 facilitates a high order of chromatin packaging necessary for normal sperm function and may also be necessary for DNA silencing and imprinting changes within the sperm cell. Protamines 1 and 2 are usually expressed in nearly equal quantities, but elevated or diminished protamine 1/protamine 2 ratios are observed in some infertile men and is often associated with severe spermatogenesis defects. Human and animal studies demonstrate that expression of the protamine proteins is uniquely regulated by transcription/translation factors, including storage of the mRNA in ribonucleoprotein (RNP) particles composed of the mRNA, transcription factors and a kinesin molecule necessary for transport of the RNP to the cytoplasm and removal of transcriptional activators from the nucleus. Recent studies indicate that most patients with abnormal protamine protein levels have elevated levels of protamine transcript in the mature sperm cell, indicating a possible defect in transcription or translation. The regulation of protamine expression is unique and includes several possible mechanisms which may be responsible for dysregulation of protamine expression and concurrent broad spectrum defects in spermatogenesis. We suggest two hypotheses: (i) that abnormal protamine expression is indicative of a generalized defect in mRNA storage and/or translation which affects other mRNA transcripts or (ii) that protamines may act as a checkpoint of spermatogenesis.
Effect of amino acid-based formula on gastroesophageal reflux in infants with persistent distress
Authors: R.G. Heine, D.J.S. Cameron, D.E.M. Francis, C.W. Chow, J. Brown, M. Heddle, D.J. Moore, G.P. Davidson, D.J. Hill
Journal: Journal of Allergy and Clinical Immunology (2003)
Functional Tissue Engineering of Autologous Tunica Albuginea: A Possible Graft for Peyronie’s Disease Surgery
Authors: Dirk Schultheiss, Ralf R Lorenz, Roland Meister, Mareike Westphal, Alexander I Gabouev, Heike Mertsching, Christian Biancosino, Norbert Schlote, Jörg Wefer, Michael Winkler, Christian G Stief, Udo Jonas
Journal: European Urology (2004)
Autoimmune Folate Deficiency and the Rise and Fall of “Horror Autotoxicus”
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (2005)

In 1904, a little more than a century ago, Julius Donath, a senior physician working in the Vienna Merchants' Hospital, and Karl Landsteiner, the chair of the pathology department at the University of Vienna and one of the founders of immunochemistry, reported the first known autoimmune disease in humans, paroxysmal cold hemoglobinuria. They showed that an antibody in this disease reacted in the cold with the patient's own erythrocytes. By definition, the Donath–Landsteiner antibody was an autoantibody. This revolutionary discovery flew in the face of "horror autotoxicus," a principle that Paul Ehrlich had expounded after failing to find autoantibodies in . . .
Intragastric nitrites, nitrosamines, and bacterial overgrowth during cimetidine treatment.
Authors: R W Stockbrugger, P B Cotton, N Eugenides, B A Bartholomew, M J Hill, C L Walters
Journal: Gut (1982)

A six week course of cimetidine (1 g/day) healed peptic ulcers in 20 of 23 patients (14 with duodenal ulcer, nine with gastric ulcer). Reduction of basal acid output by 73% and peak acid output by 36% led to a rise in concentrations of intragastric aerobic bacteria and nitrate-reducing bacteria. While the mean intragastric concentration of nitrate was unchanged by treatment, there were statistically significant rises in nitrite and N-nitrosamine concentrations. The conversion from nitrates to nitrites was closely related to the occurrence of nitrate-reducing bacteria. In three patients the intragastric milieu had returned to normal two months after cimetidine treatment had been discontinued. Mean nitrite and N-nitrosamine concentrations did not return to pre-treatment levels in the group of eight patients who remained on maintenance cimetidine (0.4 g at night-time) for three months after the full dose treatment. This study shows that cimetidine treatment can create an intragastric milieu resembling that of atrophic gastritis. Large scale and long-term studies are necessary to establish whether these findings have any clinical significance.
Second primary malignancies following diagnosis of small-cell lung cancer.
Authors: U Sagman, M Lishner, E Maki, F A Shepherd, R Haddad, W K Evans, G DeBoer, D Payne, J F Pringle, J L Yeoh
Journal: Journal of Clinical Oncology (1992)

The records of 800 patients with small-cell carcinoma of the lung (SCLC) treated between 1971 and 1985 at University of Toronto-affiliated hospitals were reviewed for the occurrence and relative risk of second primary malignancies (SPMs). Almost all patients who developed a SPM were treated previously with chemotherapy and radiation therapy.Nineteen metachronous SPMs (MSPMs) and 11 synchronous SPMs (SSPMs) were identified. SSPMs were detected between 1 and 12 months after the diagnosis of SCLC. The MSPMs were identified between 1 and 10 years after the diagnosis of SCLC. MSPMs included non-small-cell lung cancer (NSCLC) (four patients), hematologic malignancies (HM) (three patients), and 12 with other solid tumors (OST). The median survival times after the diagnosis of MSPM was 33 months, 10 months, and 1 month, respectively, for those with NSCLC, OST, and HM. Expected cancer incidence rates were used to compute a relative risk rate for developing a MSPM in a subset of 392 patients on whom accurate follow-up information was available. The calculated relative risk for all tumors was 3.73. The relative risk for the development of secondary NSCLC was 6.83.We suggest that increased predisposition to SPM may relate to secondary effects of multimodality treatment and biologic considerations.
Glucokinase activity in the arcuate nucleus regulates glucose intake
Authors: Syed Hussain, Errol Richardson, Yue Ma, Christopher Holton, Ivan De Backer, Niki Buckley, Waljit Dhillo, Gavin Bewick, Shuai Zhang, David Carling, Steve Bloom, James Gardiner
Journal: Journal of Clinical Investigation (2014)

The brain relies on a constant supply of glucose, its primary fuel, for optimal function. A taste-independent mechanism within the CNS that promotes glucose delivery to the brain has been postulated to maintain glucose homeostasis; however, evidence for such a mechanism is lacking. Here, we determined that glucokinase activity within the hypothalamic arcuate nucleus is involved in regulation of dietary glucose intake. In fasted rats, glucokinase activity was specifically increased in the arcuate nucleus but not other regions of the hypothalamus. Moreover, pharmacologic and genetic activation of glucokinase in the arcuate nucleus of rodent models increased glucose ingestion, while decreased arcuate nucleus glucokinase activity reduced glucose intake. Pharmacologic targeting of potential downstream glucokinase effectors revealed that ATP-sensitive potassium channel and P/Q calcium channel activity are required for glucokinase-mediated glucose intake. Additionally, altered glucokinase activity affected release of the orexigenic neurotransmitter neuropeptide Y in response to glucose. Together, our results suggest that glucokinase activity in the arcuate nucleus specifically regulates glucose intake and that appetite for glucose is an important driver of overall food intake. Arcuate nucleus glucokinase activation may represent a CNS mechanism that underlies the oft-described phenomena of the "sweet tooth" and carbohydrate craving.
High-dose circumferential chemodenervation of the internal anal sphincter: A new treatment modality for uncomplicated chronic anal fissure: A retrospective cohort study (with video)
Authors: Porter H. Glover, Shou-jiang Tang, James Z. Whatley, Eric D. Davis, Kellen T. Jex, Ruonan Wu, Christopher J. Lahr
Journal: International Journal of Surgery (2015)
P185 An evaluative study of breath sounds teaching
Authors: C. F. Ramsay
Journal: Thorax (2011)

<h3>Introduction</h3> Recorded breath sounds on CD and electronic stethoscopes that can record and playback sounds open up new possibilities for teaching and analysing factors contributing to breath sounds variability. <h3>Aims</h3> Assessment of the intra and inter tutor variability in describing recorded breath sounds and of medical students learning preferences for breath sounds teaching. <h3>Methods</h3> Seven tutors (four consultants and three specialist registrars in respiratory medicine) were played twenty-two recorded breath sounds. Tutors were asked to “write down exactly how you would teach a student to describe the breath sounds”. Within the twenty-two recordings five identical breath sounds were played twice, one sound was played at two different volumes and two patients were each played at two differing expiratory efforts. A feedback session with the tutors was subsequently held. A separate student evaluation comprised an anonymous questionnaire at the end of their clinical attachment. Twenty-one students were asked to choose their two preferred methods of learning chest auscultation. <h3>Results</h3> All tutors gave a précis of the most important feature(s) rather than structured responses. There was a very large degree of inter-observer variability, which was difficult to quantify partly due to the lack of structured descriptions. Recordings at different expiratory efforts resulted in different descriptions from all tutors. When listening to identical pairs of recorded breath sounds 29% of the tutors9 descriptions were concordant, 42% partly concordant and 29% different. Abstract P185 figure 1 shows the intra-tutor variability and students9 preferred learning methods. For the vast majority of students, experience examining a patient with a tutor or with a tutor using a recording stethoscope was the preferred learning method. Twelve of the twenty-one students had experience of being taught with a recording stethoscope and ten of these students put it down as one of their two preferences. <h3>Conclusions</h3> There was significant intra-tutor variability in describing breath sounds comparable with previous studies in this area. A structured methodology would assist in assessing inter tutor concordance. Both students and tutors preferred teaching with patients to recordings. A recording stethoscope was perceived to be a useful adjunct to teaching by students.
Characterization of <i>SEMA3A</i> -Encoded Semaphorin as a Naturally Occurring K <sub>v</sub> 4.3 Protein Inhibitor and its Contribution to Brugada Syndrome
Authors: Nicole J. Boczek, Dan Ye, Eric K. Johnson, Wei Wang, Lia Crotti, David J. Tester, Federica Dagradi, Yuka Mizusawa, Margherita Torchio, Marielle Alders, John R. Giudicessi, Arthur A.M. Wilde, Peter J. Schwartz, Jeanne M. Nerbonne, Michael J. Ackerman
Journal: Circulation Research (2014)

Semaphorin 3A (SEMA3A)-encoded semaphorin is a chemorepellent that disrupts neural patterning in the nervous and cardiac systems. In addition, SEMA3A has an amino acid motif that is analogous to hanatoxin, an inhibitor of voltage-gated K(+) channels. SEMA3A-knockout mice exhibit an abnormal ECG pattern and are prone to ventricular arrhythmias and sudden cardiac death.Our aim was to determine whether SEMA3A is a naturally occurring protein inhibitor of Kv4.3 (Ito) channels and its potential contribution to Brugada syndrome.Kv4.3, Nav1.5, Cav1.2, or Kv4.2 were coexpressed or perfused with SEMA3A in HEK293 cells, and electrophysiological properties were examined via whole-cell patch clamp technique. SEMA3A selectively altered Kv4.3 by significantly reducing peak current density without perturbing Kv4.3 cell surface protein expression. SEMA3A also reduced Ito current density in cardiomyocytes derived from human-induced pluripotent stem cells. Disruption of a putative toxin binding domain on Kv4.3 was used to assess physical interactions between SEMA3A and Kv4.3. These findings in combination with coimmunoprecipitations of SEMA3A and Kv4.3 revealed a potential direct binding interaction between these proteins. Comprehensive mutational analysis of SEMA3A was performed on 198 unrelated SCN5A genotype-negative patients with Brugada syndrome, and 2 rare SEMA3A missense mutations were identified. The SEMA3A mutations disrupted SEMA3A's ability to inhibit Kv4.3 channels, resulting in a significant gain of Kv4.3 current compared with wild-type SEMA3A.This study is the first to demonstrate SEMA3A as a naturally occurring protein that selectively inhibits Kv4.3 and SEMA3A as a possible Brugada syndrome susceptibility gene through a Kv4.3 gain-of-function mechanism.
ΔNp63α Promotes Breast Cancer Cell Motility through the Selective Activation of Components of the Epithelial-to-Mesenchymal Transition Program
Authors: Tuyen T. Dang, Matthew A. Esparza, Erin A. Maine, Jill M. Westcott, Gray W. Pearson
Journal: Cancer Research (2015)

Abstract Cell identity signals influence the invasive capability of tumor cells, as demonstrated by the selection for programs of epithelial-to-mesenchymal transition (EMT) during malignant progression. Breast cancer cells retain canonical epithelial traits and invade collectively as cohesive groups of cells, but the signaling pathways critical to their invasive capabilities are still incompletely understood. Here we report that the transcription factor ΔNp63α drives the migration of basal-like breast cancer (BLBC) cells by inducing a hybrid mesenchymal/epithelial state. Through a combination of expression analysis and functional testing across multiple BLBC cell populations, we determined that ΔNp63α induces migration by elevating the expression of the EMT program components Slug and Axl. Interestingly, ΔNp63α also increased the expression of miR-205, which can silence ZEB1/2 to prevent the loss of epithelial character caused by EMT induction. In clinical specimens, co-expression of various elements of the ΔNp63α pathway confirmed its implication in motility signaling in BLBC. We observed that activation of the ΔNp63α pathway occurred during the transition from noninvasive ductal carcinoma in situ to invasive breast cancer. Notably, in an orthotopic tumor model, Slug expression was sufficient to induce collective invasion of E-cadherin–expressing BLBC cells. Together, our results illustrate how ΔNp63α can drive breast cancer cell invasion by selectively engaging promigratory components of the EMT program while, in parallel, still promoting the retention of epithelial character. Cancer Res; 75(18); 3925–35. ©2015 AACR.
Zinc supplementation in children with cholera in Bangladesh: randomised controlled trial
Authors: S K Roy, M Jahangir Hossain, Wajiha Khatun, Barnali Chakraborty, S Chowdhury, Afroza Begum, Syeda Mah-e-Muneer, Sohana Shafique, Mansura Khanam, R Chowdhury
Journal: BMJ (2008)

<b>Objective</b> To investigate the impact of zinc supplementation in children with cholera. <b>Design</b> Double blind, randomised, placebo controlled trial. <b>Setting</b> Dhaka Hospital, Bangladesh. <b>Participants</b> 179 children aged 3-14 years with watery diarrhoea and stool dark field examination positive for <i>Vibrio cholerae</i> and confirmed by stool culture. <b>Intervention</b> Children were randomised to receive 30 mg elemental zinc per day (n=90) or placebo (n=89) until recovery. All children received erythromycin suspension orally in a dose of 12.5 mg/kg every six hours for three days. <b>Main outcome measures</b> Duration of diarrhoea and stool output. Results 82 children in each group completed the study. More patients in the zinc group than in the control group recovered by two days (49% v 32%, P=0.032) and by three days (81% v 68%, P=0.03). Zinc supplemented patients had 12% shorter duration of diarrhoea than control patients (64.1 v 72.8 h, P=0.028) and 11% less stool output (1.6 v 1.8 kg/day, P=0.039). <b>Conclusion</b> Zinc supplementation significantly reduced the duration of diarrhoea and stool output in children with cholera. Children with cholera should be supplemented with zinc to reduce its duration and severity. <b>Trial registration</b> Clinical trials NCT00226616.
HES-1 preserves purified hematopoietic stem cells ex vivo and accumulates side population cells in vivo
Authors: Atsushi Kunisato, Shigeru Chiba, Etsuko Nakagami-Yamaguchi, Keiki Kumano, Toshiki Saito, Shigeo Masuda, Tomoyuki Yamaguchi, Masatake Osawa, Ryoichiro Kageyama, Hiromitsu Nakauchi, Mitsuo Nishikawa, Hisamaru Hirai
Journal: Blood (2003)
Effects of two modes of resistance training on speed leg explosive power and anaerobic power of college men students
Authors: Umesh Muktamath, D Maniazhagu, Vinuta Muktamatha, Basavaraj Ganiger
Journal: British Journal of Sports Medicine (2010)

The purpose of the present investigation is to find out the effects of two modes of resistance training on speed leg explosive power and anaerobic power of male college students. To achieve this purpose, 45 male students were selected from Alagappa Arts College, Karaikudi, Tamil Nadu as subjects. Their age ranged from 18 to 25 years. They were divided into three equal groups of 15 subjects each and assigned to experimental group I, experimental group II and control group. In a week, the experimental group I underwent plyometric training, experimental group II underwent circuit training and control group was not given any specific training. All the subjects underwent the test of speed, leg explosive power and anaerobic power. They were assessed before and after the training period of 8 weeks. The analysis of covariance was used to analyse the data. The study revealed that the speed, leg explosive power and anaerobic power were significantly improved due to the influence of two modes of resistance training.
Cholera toxin inhibits IL-12 production and CD8α+ dendritic cell differentiation by cAMP-mediated inhibition of IRF8 function
Authors: Andrea la Sala, Jianping He, Leopoldo Laricchia-Robbio, Stefania Gorini, Akiko Iwasaki, Michael Braun, George S. Yap, Alan Sher, Keiko Ozato, Brian Kelsall
Journal: The Journal of Experimental Medicine (2009)

Prior studies have demonstrated that cholera toxin (CT) and other cAMP-inducing factors inhibit interleukin (IL)-12 production from monocytes and dendritic cells (DCs). We show that CT inhibits Th1 responses in vivo in mice infected with Toxoplasma gondii. This correlated with low serum IL-12 levels and a selective reduction in the numbers of CD8α+ conventional DCs (cDCs) in lymphoid organs. CT inhibited the function of interferon (IFN) regulatory factor (IRF) 8, a transcription factor known to positively regulate IL-12p35 and p40 gene expression, and the differentiation of CD8α+ and plasmacytoid DCs (pDCs). Fluorescence recovery after photobleaching analysis showed that exposure to CT, forskolin, or dibutyryl (db) cAMP blocked LPS and IFN-γ–induced IRF8 binding to chromatin. Moreover, CT and dbcAMP inhibited the binding of IRF8 to the IFN-stimulated response element (ISRE)–like element in the mouse IL-12p40 promoter, likely by blocking the formation of ISRE-binding IRF1–IRF8 heterocomplexes. Furthermore, CT inhibited the differentiation of pDCs from fms-like tyrosine kinase 3 ligand–treated bone marrow cells in vitro. Therefore, because IRF8 is essential for IL-12 production and the differentiation of CD8α+ cDCs and pDCs, these data suggest that CT and other Gs-protein agonists can affect IL-12 production and DC differentiation via a common mechanism involving IRF8.
Insulin sensitivity differs among ethnic groups with a compensatory response in beta-cell function.
Authors: K C Chiu, P Cohan, N P Lee, L M Chuang
Journal: Diabetes Care (2000)

OBJECTIVE: A drastic difference is evident in the prevalence of type 2 diabetes among ethnic groups. We examined the role of beta-cell function and insulin sensitivity in this disparity among 4 ethnic groups. RESEARCH DESIGN AND METHODS: beta-Cell function and insulin sensitivity were assessed in 77 healthy glucose-tolerant subjects using a hyperglycemic clamp (18 Asian-Americans, 9 African-Americans, 34 Caucasians, and 16 Mexican-Americans). RESULTS: A wide range of variation was evident in clinical features of the studied subjects. Insulin sensitivity index and the second-phase insulin response differed among the 4 groups (P = 0.0023 and P = 0.0082, respectively), whereas the first-phase insulin response was marginally different (P = 0.1090). Stepwise regression analysis revealed that ethnicity was an independent determinant for the insulin sensitivity index (P = 0.0014) after adjusting for sex, age, diastolic blood pressure, waist-to-hip ratio, and BMI. Also, a compensatory response of beta-cell function was observed among the ethnic groups. CONCLUSIONS: In this study, we observed a drastic difference in insulin sensitivity among the different ethnic groups and observed that their beta-cell function compensates for the prevailing insulin sensitivity. The difference in the prevalence of abnormal glucose tolerance in different ethnic groups could be a result of differences in insulin sensitivity