tbuckley/cabot-search huggingface dataset:
The Thrombopoietin Receptor Can Mediate Proliferation without Activation of the Jak-STAT Pathway
Authors: Marion Dorsch, Pang-Dian Fan, Nika N. Danial, Paul B. Rothman, Stephen P. Goff
Journal: The Journal of Experimental Medicine (1997)

Cytokine receptors of the hematopoietic receptor superfamily lack intrinsic tyrosine kinase domains for the intracellular transmission of their signals. Instead all members of this family associate with Jak family nonreceptor tyrosine kinases. Upon ligand stimulation of the receptors, Jaks are activated to phosphorylate target substrates. These include STAT (signal transducers and activators of transcription) proteins, which after phosphorylation translocate to the nucleus and modulate gene expression. The exact role of the Jak-STAT pathway in conveying growth and differentiation signals remains unclear. Here we describe a deletion mutant of the thrombopoietin receptor (c-mpl) that has completely lost the capacity to activate Jaks and STATs but retains its ability to induce proliferation. This mutant still mediates TPO-induced phosphorylation of Shc, Vav, mitogen-activated protein kinase (MAPK) and Raf-1 as well as induction of c-fos and c-myc, although at somewhat reduced levels. Furthermore, we show that both wild-type and mutant receptors activate phosphatidylinositol (PI) 3-kinase upon thrombopoietin stimulation and that thrombopoietin-induced proliferation is inhibited in the presence of the PI 3-kinase inhibitor wortmannin. These results demonstrate that the Jak-STAT pathway is dispensable for the generation of mitogenic signals by a cytokine receptor.
Transient solitary pulmonary nodule caused by Dirofilaria immitis
Authors: M Cordero, MR Munoz, A Muro, F Simon
Journal: European Respiratory Journal (1990)

The second described case of solitary transient lung nodule caused by Dirofilaria immitis is reported. Diagnostic thoracotomy can be avoided with the use of enzyme-linked immunosorbent assay (ELISA), and hence a conservative serological follow-up is warranted in endemic areas.
T cell-mediated inhibition of the transfer of autoimmune diabetes in NOD mice.
Authors: C Boitard, R Yasunami, M Dardenne, J F Bach
Journal: The Journal of Experimental Medicine (1989)

The nonobese diabetic (NOD) mouse has recently been introduced as a model for insulin-dependent diabetes mellitus. The role of regulatory T cells in the development of antipancreatic autoimmunity in this model remains unclear. To evaluate the presence of suppressive phenomena, we used disease transfer by spleen cells from diabetic NOD mice into preirradiated adult recipients as a model for accelerated disease. Suppressor phenomena were detected by testing the protection afforded by lymphoid cells from nondiabetic NOD mice against diabetes transfer in irradiated recipients. Transfer of diabetes was delayed by reconstituting recipients with spleen cells from nondiabetic NOD donors. The greatest protection against diabetes transfer was conferred by spleen cells from 8-wk-old nondiabetic female NOD mice. Depletion experiments showed that the protection was dependent on CD4+ cells. Protection was also detected within thymic cells from nondiabetic NOD mice and protection conferred by spleen cells was abrogated by thymectomy of nondiabetic female, but not male, NOD donors at 3 wk of age. These findings indicate that suppressive CD4+ T cells that are dependent on the presence of the thymus may delay the onset of diabetes in female diabetes-prone NOD mice.
Relationship of Awareness of Dyskinesia in Schizophrenia to Insight Into Mental Illness
Authors: Celso Arango, Helene Adami, Jay D. Sherr, Gunvant K. Thaker, William T. Carpenter
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The purpose of this study was to determine whether lack of awareness of motor dysfunction and lack of insight into mental dysfunction are related and to evaluate the longitudinal stability of lack of awareness of abnormal movements in schizophrenia. METHOD: Forty-three patients with schizophrenia and tardive dyskinesia participated in the study. The Scale of Unawareness of Mental Disorder was used to assess insight. All patients still meeting inclusion criteria after 2 years (N=16) were reevaluated at follow-up. RESULTS: Twenty (46.5%) of the 43 patients had at least moderate unawareness of their tardive dyskinesia. Awareness of tardive dyskinesia was only modestly related to two of the five dimensions of insight into mental disorder assessed. Patients with the deficit syndrome showed significantly less awareness of their tardive dyskinesia than patients without the deficit syndrome. Lack of awareness of tardive dyskinesia was stable over time. CONCLUSIONS: Lack of awareness of tardive dyskinesia is a common feature in schizophrenia and is stable over time. Since patients are often unaware of dyskinesia, direct clinical examination is required to identify early tardive dyskinesia.
Vinorelbine (Navelbine) as a salvage treatment for advanced breast cancer
Authors: M. Degardin, J. Bonneterre, B. Hecquet, J.-M. Pion, A. Adeins, D. Horner, A. Demaille
Journal: Annals of Oncology (1994)

Vinorelbine (Navelbine), a new vinca alkaloid, is an effective drug in breast cancer. Our study was undertaken to assess the efficacy and tolerance of Navelbine in refractory advanced and/or metastatic breast cancer (AMBC).One hundred heavily pretreated patients with AMBC entered the study and were scheduled to receive 30 mg/m2 of Navelbine weekly by a 20 min i.v. infusion with dose adjustments according to tolerance. All patients had previously received at least one chemotherapy regimen including an anthracycline for advanced disease.Sixteen of the 100 assessable patients responded (1 complete response and 15 partial responses), for an overall response rate of 16% (IC 95: 8%-23%). The median duration of response was 5 months (3-18). Responses were seen in lymph nodes (13/27), breast (11/34), soft tissue and skin (13/36), lung (3/14) and liver (2/25), but not in bone metastases. The main toxicities (WHO grade > or = 3) were granulocytopenia and anemia in, respectively, 51% and 9% of all 100 eligible patients. Thrombocytopenia and other non-haematological toxicities consisting of peripheral neuropathy, constipation, nausea/vomiting, alopecia and phlebitis were rare and mild.Vinorelbine is an active drug in AMBC, particularly in breast, lymph nodes and skin/soft tissue sites, with an excellent tolerance. Since the mean dose intensity was 19.7 mg/m2/week, a dose of 20 mg/m2/week is recommended for heavily pretreated patients (radiotherapy and chemotherapy).
Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy
Authors: Lubna Choudhury, Heiko Mahrholdt, Anja Wagner, Kelly M. Choi, Michael D. Elliott, Francis J. Klocke, Robert O. Bonow, Robert M. Judd, Raymond J. Kim
Journal: Journal of the American College of Cardiology (2002)
Therapy for chronic graft-versus-host disease: a randomized trial comparing cyclosporine plus prednisone versus prednisone alone
Authors: Sibel Koc, Wendy Leisenring, Mary E. D. Flowers, Claudio Anasetti, H. Joachim Deeg, Richard A. Nash, Jean E. Sanders, Robert P. Witherspoon, Rainer Storb, Frederick R. Appelbaum, Paul J. Martin
Journal: Blood (2002)
Longitudinal analysis of sleep in relation to BMI and body fat in children: the FLAME study
Authors: P. J. Carter, B. J. Taylor, S. M. Williams, R. W. Taylor
Journal: BMJ (2011)

To determine whether reduced sleep is associated with differences in body composition and the risk of becoming overweight in young children.Longitudinal study with repeated annual measurements.Dunedin, New Zealand.244 children recruited from a birth cohort and followed from age 3 to 7.Body mass index (BMI), fat mass (kg), and fat free mass (kg) measured with bioelectrical impedance; dual energy x ray absorptiometry; physical activity and sleep duration measured with accelerometry; dietary intake (fruit and vegetables, non-core foods), television viewing, and family factors (maternal BMI and education, birth weight, smoking during pregnancy) measured with questionnaire.After adjustment for multiple confounders, each additional hour of sleep at ages 3-5 was associated with a reduction in BMI of 0.48 (95% confidence interval 0.01 to 0.96) and a reduced risk of being overweight (BMI ≥ 85th centile) of 0.39 (0.24 to 0.63) at age 7. Further adjustment for BMI at age 3 strengthened these relations. These differences in BMI were explained by differences in fat mass index (-0.43, -0.82 to -0.03) more than by differences in fat free mass index (-0.21, -0.41 to -0.00).Young children who do not get enough sleep are at increased risk of becoming overweight, even after adjustment for initial weight status and multiple confounding factors. This weight gain is a result of increased fat deposition in both sexes rather than additional accumulation of fat free mass.
Selected Methodological Issues in Evaluating Community-Based Health Promotion and Disease Prevention Programs
Authors: T. D. Koepsell, E. H. Wagner, A. C. Cheadle, D. L. Patrick, D. C. Martin, P. H. Diehr, E. B. Perrin, A. R. Kristal, C. H. Allan-Andrilla, L. J. Dey
Journal: Annual Review of Public Health (1992)

In recent decades, there has been remarkable growth in scientific research examining the multiple ways in which racism can adversely affect health. This interest has been driven in part by the striking persistence of racial/ethnic inequities in health and ...Read More
Respiratory epithelial ion transport in patients with disseminated bronchiectasis
Authors: I Danner, P Boisseau, E Chailleux, D Escande
Journal: European Respiratory Journal (1999)

The nosological limits between disseminated bronchiectasis and cystic fibrosis (CF) remain unclear. In patients with isolated congenital bilateral absence of the vas deferens, a forme fruste of the CF disease, a normal baseline nasal transepithelial potential difference (PD) but an impaired response to pharmacological interventions have been reported. The purpose of the present study was to explore ion transport in respiratory epithelium from patients with disseminated bronchiectasis. The PD under both baseline and pharmacological interventions was investigated in 13 healthy subjects, six patients with genetically proven CF and 15 patients with disseminated bronchiectasis as confirmed by computed tomography scan. Baseline PD was similar in the control and bronchiectasis groups but, as expected, was significantly more negative in the CF group. Patients with bronchiectasis responded to pharmacological tests (sequential perfusion with amiloride, chloride-free solution, isoprenaline and uridine triphosphate (UTP) similarly to healthy subjects. In contrast, CF patients exhibited an increased response to amiloride and an impaired response to chloride-free solution and isoprenaline. The data show that patients with disseminated bronchiectasis exhibit normal electrophysiological properties in their nasal epithelium. Nasal transepithelial potential difference including pharmacological tests may appear a valuable diagnostic procedure for cystic fibrosis with disseminated bronchiectasis.
Predicting response to RAD001 treatment in post-menopausal women with ER-positive breast cancer using the breast cancer DSA™ research tool (Almac).
Authors: VS Sabine, A McCulla, CL Wilson, AH Sims, F McDyer, C McCluskey, I Halfpenny, GR Oliver, EJ Macaskill, L Renshaw, JS Thomas, JM Dixon, JM Bartlett
Journal: Cancer Research (2009)

Abstract Abstract #2032 Background: RAD001 (everolimus) is a rapamycin derivative that inhibits mTOR and its downstream substrates and has shown promising results in Phase I trials. The aim of this study was to assess the feasibility of predicting patient response to RAD001 treatment from pre-treatment biopsies.&amp;#x2028; Materials &amp; Methods: 32 post-menopausal, ER-positive early breast cancer patients received 5mg RAD001 pre-operative treatment daily for 14 days prior to primary surgery. 25 patients completed the regimen, 6 patients withdrew and 1 did not start treatment. Biopsies were taken at diagnosis and at surgery from the RAD001 treated patients. Pre-treatment samples were flash frozen prior to RNA isolation. Patient response status was classified based on the % of Ki-67 positive cells determined by immunohistochemistry in the post-treatment biopsy (Macaskill et al., 2006: Breast Cancer Research &amp; Treatment: 100: S1: S286). RNA from the pre-treatment group was analysed using the Almac Diagnostics Breast Cancer DSATM Research Tool, which represents ∼60,000 normal breast and breast cancer transcripts and Illumina Human Ref.8 chip v2 containing ∼24,500 transcripts representing well-categorised and most commonly known genes, irrespective of disease or tissue. For each array platform, modulated genes were identified using statistically robust gene selection methods. In addition, the sequence content of the two platforms was compared by probe-level analysis using BLAST.&amp;#x2028; Results &amp; Discussion: Preliminary assessment of the expression differences between the non-responder and responder groups using the DSA™ Research Tool demonstrated 169 up-regulated and 93 down-regulated genes. This list is comprised of genes involved in chemokine activity, cell adhesion and transport. Cross-platform content comparison demonstrated that the Illumina bead arrays represented 41% of transcripts on the DSA™ Research Tool whilst 82% of the Illumina beadarray transcripts were represented on the DSA™ Research Tool. Genes of interest identified will be validated by quantitative real time PCR and the key pathways reported.&amp;#x2028; These datasets have enabled us to begin the identification of tumours most suited to RAD001 treatment and may be used as a guide for the generation of a gene expression classifier for predicting patient response to RAD001.&amp;#x2028; Acknowledgements: This work was supported by a grant from Breast Cancer Research Treatment, UK. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2032.
Efficacy of Divalproex vs Lithium and Placebo in the Treatment of Mania
Authors: Charles L. Bowden
Journal: JAMA (1994)

<h3>Objective.</h3> —To compare the effectiveness of divalproex sodium with that of lithium and placebo in patients with acute mania. <h3>Design.</h3> —Randomized, double-blind, parallel-group study of treatment outcomes in patients with manic-depressive illness. <h3>Patients.</h3> —A total of 179 hospitalized, acutely manic patients meeting the Research Diagnostic Criteria for manic disorder, approximately half of whom had been nonresponsive to lithium previously, were studied at nine university-affiliated hospitals. <h3>Interventions.</h3> —After a minimum 3-day washout period, random assignment for 21 days to divalproex, lithium, or placebo in a 2:1:2 ratio. Dosage of divalproex and lithium was increased if tolerated to a target concentration of 1041 μmol/L (150 μg/ mL) or 1.5 mmol/L (conventionally expressed as milliequivalents per liter), respectively. <h3>Main Outcome Measures.</h3> —Primary outcome measures were changes in the Mania Rating scale derived from the Schedule for Affective Disorders and Schizophrenia. <h3>Results.</h3> —Intent-to-treat analysis for efficacy was based on data from 68, 35, and 73 patients in the divalproex, lithium, and placebo groups, respectively. Groups were initially comparable except that all eight patients with four or more manic episodes in the previous year were in the divalproex group. In 30%, 33%, and 51% of the above groups, treatment was prematurely terminated due to lack of efficacy, with fewer premature terminations from divalproex than placebo (<i>P</i>=.017). The proportions of patients improving at least 50% were higher for divalproex and lithium groups than for the placebo group: 48% for divalproex (<i>P</i>=.004) and 49% for lithium (<i>P</i>=.025) vs 25% for placebo. Divalproex was as effective in rapid-cycling manic patients as in other patients. <h3>Conclusions.</h3> —Both divalproex and lithium were significantly more effective than placebo in reducing the symptoms of acute mania. The efficacy of divalproex appears to be independent of prior responsiveness to lithium. (<i>JAMA</i>. 1994;271:918-924)
Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in MYST3-linked cases
Authors: A Murati, C Gervais, N Carbuccia, P Finetti, N Cervera, J Adélaïde, S Struski, E Lippert, F Mugneret, I Tigaud, D Penther, C Bastard, B Poppe, F Speleman, L Baranger, I Luquet, P Cornillet-Lefebvre, N Nadal, F Nguyen-Khac, C Pérot, S Olschwang, F Bertucci, M Chaffanet, M Lessard, M-J Mozziconacci, D Birnbaum
Journal: Leukemia (2008)
Autonomic Nervous System Pharmacogenomics: A Progress Report
Authors: Shelli L. Kirstein, Paul A. Insel
Journal: Pharmacological Reviews (2004)

Pharmacogenetics, the inherited basis for interindividual differences in drug response, has rapidly expanded with the advent of new molecular tools and the sequencing of the human genome, yielding pharmacogenomics. We review here recent ideas and findings regarding pharmacogenomics of components of the autonomic nervous system, in particular, neuronal nicotinic acetylcholine receptors, postsynaptic receptors with which the parasympathetic and sympathetic neurotransmitters, acetylcholine (ACh) and norepinephrine, respectively, interact. The receptor subtypes that mediate these responses, M<sub>1-3</sub> muscarinic cholinergic receptors (mAChRs), and α<sub>1A,B,D</sub>-, α<sub>2A,B,C</sub>-, and β<sub>1,2,3</sub>-adrenergic receptors (AR), show highly variable expression of genetic variants; variants of mAChRs and α<sub>1</sub>-ARs are relatively rare, whereas α<sub>2</sub>-AR and β-AR subtype variants are quite common. The largest amount of data is available regarding variants of the latter ARs and represents efforts to associate certain receptor genotypes, most commonly, single nucleotide polymorphisms, with particular phenotypes (e.g., cardiovascular and metabolic responses). In vitro and in vivo studies have yielded inconsistent results; definitive conclusions are limited. We identify several conceptual and methodological problems with available data: sample size, ethnicity, tissue differences, coding versus noncoding variants, limited studies of haplotypes, and interaction among variants. Thus, although progress has been made in identifying genetic variation that influences drug response for autonomic nervous system components, we are still at the early stages of defining the most critical genetic determinants and their role in human physiology and pharmacology.
Health-Related Quality of Life in Patients With Newly Diagnosed Type 1 Diabetes
Authors: Huberta E. Hart, William K. Redekop, Jan H. Assink, Betty Meyboom - de Jong, Henk J.G. Bilo
Journal: Diabetes Care (2003)

Having type 1 diabetes will permanently change a patient’s life. From the moment of diagnosis, patients will have to consider their diet, insulin therapy, exercise, and self-monitoring of blood glucose every day. This will influence a patient’s health-related quality of life (1).

The aim of this study was to investigate the health-related quality of life of patients with newly diagnosed type 1 diabetes in the first year after diagnosis and to compare their health-related quality of life, 1 year after diagnosis, with people of comparable age from the …
Visceral hypersensitivity in non-erosive reflux disease
Authors: C. H. Knowles, Q. Aziz
Journal: Gut (2007)

Non-erosive reflux disease (NERD) is defined as the presence of classic symptoms of gastro-oesophageal reflux disease (GORD) in the absence of oesophageal mucosal injury (or Barrett’s oesophagus) as determined by inspection at upper gastrointestinal endoscopy.1 As such it is regarded as being one of the two main phenotypes of GORD, the other being erosive oesophagitis (EO) where ulceration or erosions are evident. GORD is common, with estimates of 20–44% of Western populations having symptoms of GORD at least once a month and 20% weekly.2 The proportion of such patients with NERD is estimated to be between 503 and 70%.4 It is acknowledged that responses to standard acid suppressive treatments are 20–30% lower in patients with NERD than those with EO.5 Considering this, and the high prevalence of NERD, which is likely to increase in parallel with societal body mass index,6 the pathophysiological understanding of this condition remains a priority.

The concept of visceral hypersensitivity (VH) is now well established in a variety of overtly inflammatory as well as functional gastrointestinal conditions.7 ,8 This review introduces the molecular and physiological basis of VH, particularly in respect of acid-sensing receptors, and presents the evidence that VH plays an important role in the pathophysiology of NERD.

Within the spectrum of GORD, the pathophysiological relationship of EO and NERD remains the subject of debate.9 The classical and perhaps intuitive view that NERD is a mild form of GORD that might progress with time to EO is supported by some physiological, anatomical and histopathological findings. For instance, whilst demonstration of acid exposure is not a requirement for the definition of EO or NERD, there are studies that demonstrate that acid exposure as determined by 24 h pH studies is abnormal in only 45% of NERD patients …
Functional Transverse Interconnections within the His Bundle and the Bundle Branches
Authors: RALPH LAZZARA, BILLY K. YEH, PHILIP SAMET
Journal: Circulation Research (1973)

The existence of transverse interconnections within the His bundle and the bundle branches was investigated in excised preparations from dogs and rabbits. The preparations included the His bundle or one of the bundle branches along with portions of the peripheral conduction system. They were superfused with Tyrode's solution, and conventional electrophysiological techniques for extra- and intracellular recordings were employed. The effects of incisions and of intracellular stimulation within the proximal conduction system on distal activation were observed. Transection of 90% of a right bundle branch or intracellular stimulation within that bundle branch did not alter the distal activation pattern observed during surface stimulation of fully recovered fibers. Transection of 90% of the left bundle branch or intracellular stimulation produced a temporal shift of no more than 4 msec in the activation of widely scattered distal sites. Intracellular stimulation in the left bundle branch never produced dispersion of more than 3 msec in distal activation compared with the effects of surface stimulation. Intracellular stimulation at various points within the His bundle always activated the right bundle branch in a manner identical with activation during physiological atrioventricular conduction. Transverse velocity in the conduction system was less than longitudinal velocity. It is concluded that functional transverse interconnections are relatively numerous in the His bundle and the bundle branches.
Providing the Providers — Remedying Africa's Shortage of Health Care Workers
Authors: Pooja Kumar
Journal: New England Journal of Medicine (2007)

Dr. Cyril Nkabinde, an intern at Prince Mshiyeni Memorial Hospital in Durban, South Africa, grew up dreaming of becoming a doctor — an ambition he inherited from his mother, whose own dream had been thwarted by apartheid. Nkabinde's goal of working as a family physician in rural KwaZulu-Natal has kept him on track, even as he's watched medical school classmates depart for business careers and superiors quit medicine because of a chronic lack of health care resources. Now, as he prepares to marry a fellow physician, Nkabinde realizes that his dream may not be achievable. "The hope is to go . . .