tbuckley/cabot-search huggingface dataset:
Sleep apnoea and visceral adiposity in middle-aged male and female subjects
Authors: Ilia Kritikou, Maria Basta, Rafel Tappouni, Slobodanha Pejovic, Julio Fernandez-Mendoza, Racha Nazir, Michelle L. Shaffer, Duanping Liao, Edward O. Bixler, George P. Chrousos, Alexandros N. Vgontzas
Journal: European Respiratory Journal (2012)

In obese male subjects, visceral adiposity has been associated with obstructive sleep apnoea (OSA), while studies in overweight males and females are limited. Our goal was to examine the association between OSA and visceral fat in a relatively nonobese population and assess the effects of 2 months placebo-controlled continuous positive airway pressure (CPAP) use on abdominal fat. 81 subjects, 22 middle-aged males and 20 post-menopausal females with OSA, and 19 male and 20 female controls were studied in the sleep laboratory for four nights. Abdominal (visceral (VAT) and subcutaneous (SAT) adipose tissue) and liver fat were assessed with computed tomography. OSA patients were re-assessed post-CPAP and post sham-CPAP. Apnoeic males had significantly higher VAT than controls, while apnoeic females had higher SAT than controls. In both sexes, OSA was associated with increased liver fat. In males, apnoea was associated with VAT whereas in females it was associated with subcutaneous, visceral and total fat. CPAP did not affect abdominal and liver fat. In overweight males, visceral adiposity is associated with OSA whereas in females it is associated with global adiposity. In overweight males, our therapeutic goal should be the reduction of visceral adiposity and its metabolic correlates, whereas, in females, weight loss may be sufficient. Short-term CPAP treatment does not affect general, abdominal or intra-hepatic adiposity.
Pathogenetic Mechanisms of Diabetic Nephropathy
Authors: Francesco P Schena, Loreto Gesualdo
Journal: Journal of the American Society of Nephrology (2005)

Diabetes is the leading cause of ESRD because diabetic nephropathy develops in 30 to 40% of patients. Diabetic nephropathy does not develop in the absence of hyperglycemia, even in the presence of a genetic predisposition. Multigenetic predisposition contributes in the development of diabetic nephropathy, thus supporting that many factors are involved in the pathogenesis of the disease. Hyperglycemia induces renal damage directly or through hemodynamic modifications. It induces activation of protein kinase C, increased production of advanced glycosylation end products, and diacylglycerol synthesis. In addition, it is responsible for hemodynamic alterations such as glomerular hyperfiltration, shear stress, and microalbuminuria. These alterations contribute to an abnormal stimulation of resident renal cells that produce more TGF-β1. This growth factor upregulates GLUT-1, which induces an increased intracellular glucose transport and d-glucose uptake. TGF-β1 causes augmented extracellular matrix protein deposition (collagen types I, IV, V, and VI; fibronectin, and laminin) at the glomerular level, thus inducing mesangial expansion and glomerular basement membrane thickening. However, low enzymatic degradation of extracellular matrix contributes to an excessive accumulation. Because hyperglycemia is the principal factor responsible for structural alterations at the renal level, glycemic control remains the main target of the therapy, whereas pancreas transplantation is the best approach for reducing the renal lesions.
Oncolytic Viral Therapy for Cervical and Ovarian Cancer Cells by Sindbis Virus AR339 Strain
Authors: Youichi Unno, Yuji Shino, Fukuo Kondo, Natsuhiko Igarashi, Gang Wang, Ryuhi Shimura, Taketo Yamaguchi, Takehide Asano, Hiromitsu Saisho, Souei Sekiya, Hiroshi Shirasawa
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Recently, the application of replication-competent viruses has been studied as anticancer agents. Sindbis virus (SIN) is an RNA virus that belongs to the Alphavirus genus in the Togaviridae virus family. The AR339 strain of SIN has not been reported to induce any serious disease to humans. Experimental Design: In this study, we evaluated the feasibility of the replication-competent SIN AR339 strain as an agent for cervical and ovarian cancer therapy. Results: SIN infection was able to induce cytopathic effects and apoptosis in two cervical cancer cells (HeLaS3 and C33A) and three ovarian cancer cells (HOC-1, HAC-2, and OMC-3) but not in normal human keratinocytes in vitro. The analysis of cell viability, virus protein synthesis, and viral growth showed the cancer-specific cytotoxicity and virus growth of SIN. In nude mice, i.t. and i.v. inoculation of SIN resulted in significant regression of established cervical tumors implanted at their backs. Histologic studies revealed that systemic treatment with the single injection of SIN induces necrosis within tumors at a remote site. In the metastasis model of ovarian cancer, suppression of ascites formation was observed in nude mice with i.p. SIN treatment. By using an in vivo green fluorescent protein imaging system, we also showed that systemic treatment with SIN targeted tumors specifically. Conclusions: Our study suggested that SIN AR339 strain has a possibility as a novel agent for human cervical and ovarian cancer therapy.
Kinetics of IL-10 production after segmental antigen challenge of atopic asthmatic subjects
Authors: Annette M. Colavita, Annette T. Hastie, Ali I. Musani, Rodolfo M. Pascual, Alan J. Reinach, H.Todd Lustine, Steve A. Galati, James G. Zangrilli, James E. Fish, Stephen P. Peters
Journal: Journal of Allergy and Clinical Immunology (2000)
Chronic lymphocytic leukemia: an updated review.
Authors: G B Faguet
Journal: Journal of Clinical Oncology (1994)

PURPOSE To review recent advances in the pathogenesis, biology, diagnosis, and management of chronic lymphocytic leukemia (CLL). DESIGN A literature search restricted to English-language articles, abstracts, book chapters, and reports published between 1975 and 1993 was conducted both electronically using MEDLINE and CANCERLIT and manually using the bibliographies of the electronically retrieved data base. Of approximately 1,000 publications identified for analysis, 233 were selected as representative of important advances in CLL. RESULTS The last 10 years have witnessed renewed interest in the biology and treatment of CLL, a disease long viewed by clinicians as following an indolent course and perceived by investigators as uninspiring. This interest, based on advances in understanding the lineage and biology of CLL and on the advent of new and more efficacious chemotherapeutic agents, has led to improvements in patient survival and, for the first time, to complete remissions (CRs) in large subsets of patients. As we learn to use these agents better, especially in combination chemotherapy, alternative therapeutic modalities, are being vigorously pursued, including high-dose ablative chemotherapy with allogeneic or autologous bone marrow transplantation (BMT) rescue and the use of powerful tumor-cell target-specific immunoreagents. These therapeutic advances, coupled with the recent availability of molecular probes to ascertain objectively minimal remnant disease posttreatment, provide a basis for developing and assessing ever more efficacious and potentially curative treatment strategies for the management of this disease. CONCLUSION For the first time since the original 1924 monograph by Minot and Isaacs, the cure of subsets of patients with CLL appears not to be an unreasonable goal.
Inhibition of A. fumigatus growth by human respiratory cells
Authors: Viviane Balloy, Jean-Paul Latgé, Michel Chignard
Journal: European Respiratory Journal (2012)

The innate immune response to fungi mainly involves macrophages and neutrophils. By contrast, the possible participation of respiratory epithelial cells (REC) has been poorly studied. In the present study we observed that REC display the property of inhibiting mycelium development of Aspergillus fumigatus (A.f) and that this activity is linked to PI3 kinase activation.  Bronchial cells (BEAS-2B cell line) were incubated with A.f and the growth of the fungus was estimated by optical microscopy observation and measurement of galactomannan concentrations in the extracellular media. The role of PI3 kinase was evidenced by the use of the specific inhibitor LY294002 (30 µM). Spore internalization in REC was followed by epifluorescence. FITC-labeled spores (green) when outside of cells were further labelled with an anti-FITC antibody labeled with a red fluorochrome (Alexafluor 568).  In the presence of REC, most of the spores do not germinate as opposed to spores incubated in the absence of cells. The growth quantification by galactomamann concentration measurements display a 4.5 lower concentration in the presence of cells. The anti-aspergillus activity is inhibited when cells are incubated with LY294002, indicating the involvement of the PI3 kinase pathway. Of note, inhibitors of p38 MAP kinase and ERK1/2 are inactive. We evidenced that the activity is directed against the spores and not again the hyphae but is not linked to the spore internalization.  In conclusion, as macrophages and neutrophils, REC play a role in the anti-aspergillus activity. They are able to prevent the mycelium development and as such potentially prevent its dissemination.  Funding: Work supported in part by a grant from Vaincre la Mucoviscidose.
Phase II Trial of Trastuzumab in Combination With Cytotoxic Chemotherapy for Treatment of Metastatic Osteosarcoma With Human Epidermal Growth Factor Receptor 2 Overexpression: A Report From the Children's Oncology Group
Authors: David Ebb, Paul Meyers, Holcombe Grier, Mark Bernstein, Richard Gorlick, Steven E. Lipshultz, Mark Krailo, Meenakshi Devidas, Donald A. Barkauskas, Gene P. Siegal, William Shay Ferguson, George Douglas Letson, Karen Marcus, Allen Goorin, Peter Beardsley, Neyssa Marina
Journal: Journal of Clinical Oncology (2012)

Despite efforts to intensify chemotherapy, survival for patients with metastatic osteosarcoma remains poor. Overexpression of human epidermal growth factor receptor 2 (HER2) in osteosarcoma has been shown to predict poor therapeutic response and decreased survival. This study tests the safety and feasibility of delivering biologically targeted therapy by combining trastuzumab with standard chemotherapy in patients with metastatic osteosarcoma and HER2 overexpression.Among 96 evaluable patients with newly diagnosed metastatic osteosarcoma, 41 had tumors that were HER2-positive by immunohistochemistry. All patients received chemotherapy with cisplatin, doxorubicin, methotrexate, ifosfamide, and etoposide. Dexrazoxane was administered with doxorubicin to minimize the risk of cardiotoxicity from treatment with trastuzumab and anthracycline. Only patients with HER2 overexpression received concurrent therapy with trastuzumab given for 34 consecutive weeks.The 30-month event-free and overall survival rates for patients with HER2 overexpression treated with chemotherapy and trastuzumab were 32% and 59%, respectively. For patients without HER2 overexpression, treated with chemotherapy alone, the 30-month event-free and overall survival rates were 32% and 50%, respectively. There was no clinically significant short-term cardiotoxicity in patients treated with trastuzumab and doxorubicin.Despite intensive chemotherapy plus trastuzumab for patients with HER2-positive disease, the outcome for all patients was poor, with no significant difference between the HER2-positive and HER2-negative groups. Although our findings suggest that trastuzumab can be safely delivered in combination with anthracycline-based chemotherapy and dexrazoxane, its therapeutic benefit remains uncertain. Definitive assessment of trastuzumab's potential role in treating osteosarcoma would require a randomized study of patients with HER2-positive disease.
Fibrinolysis or Primary PCI in ST-Segment Elevation Myocardial Infarction
Authors: Paul W. Armstrong, Anthony H. Gershlick, Patrick Goldstein, Robert Wilcox, Thierry Danays, Yves Lambert, Vitaly Sulimov, Fernando Rosell Ortiz, Miodrag Ostojic, Robert C. Welsh, Antonio C. Carvalho, John Nanas, Hans-Richard Arntz, Sigrun Halvorsen, Kurt Huber, Stefan Grajek, Claudio Fresco, Erich Bluhmki, Anne Regelin, Katleen Vandenberghe, Kris Bogaerts, Frans Van de Werf
Journal: New England Journal of Medicine (2013)

It is not known whether prehospital fibrinolysis, coupled with timely coronary angiography, provides a clinical outcome similar to that with primary percutaneous coronary intervention (PCI) early after acute ST-segment elevation myocardial infarction (STEMI).Among 1892 patients with STEMI who presented within 3 hours after symptom onset and who were unable to undergo primary PCI within 1 hour, patients were randomly assigned to undergo either primary PCI or fibrinolytic therapy with bolus tenecteplase (amended to half dose in patients ≥75 years of age), clopidogrel, and enoxaparin before transport to a PCI-capable hospital. Emergency coronary angiography was performed if fibrinolysis failed; otherwise, angiography was performed 6 to 24 hours after randomization. The primary end point was a composite of death, shock, congestive heart failure, or reinfarction up to 30 days.The primary end point occurred in 116 of 939 patients (12.4%) in the fibrinolysis group and in 135 of 943 patients (14.3%) in the primary PCI group (relative risk in the fibrinolysis group, 0.86; 95% confidence interval, 0.68 to 1.09; P=0.21). Emergency angiography was required in 36.3% of patients in the fibrinolysis group, whereas the remainder of patients underwent angiography at a median of 17 hours after randomization. More intracranial hemorrhages occurred in the fibrinolysis group than in the primary PCI group (1.0% vs. 0.2%, P=0.04; after protocol amendment, 0.5% vs. 0.3%, P=0.45). The rates of nonintracranial bleeding were similar in the two groups.Prehospital fibrinolysis with timely coronary angiography resulted in effective reperfusion in patients with early STEMI who could not undergo primary PCI within 1 hour after the first medical contact. However, fibrinolysis was associated with a slightly increased risk of intracranial bleeding. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT00623623.).
The role of intra-ovarian interactions in the regulation of follicle dominance
Authors: S J Baker, N Spears
Journal: Human Reproduction Update (1999)

The processes that precisely control the selection of ovulatory follicles from a growing cohort are poorly understood. This reduction in follicle number occurs through several phases of selection, consequently we limit the use of the term 'selection' to the first major reduction of growing follicles, at the pre- to early antral stage. The final process of selection, achieving the appropriate ovulatory number, is referred to as 'dominance'. We discuss possible mechanisms that could bring about these reductions and highlight intra-ovarian involvement, particularly via follicle-follicle interactions. Analogies are drawn between local ovarian events and processes commonly reported in the determination of cell fate in developmental biology. Two facets of intra-follicular interactions are proposed: initially that follicle-follicle interactions mediate early selection processes at the preantral stage, and later that during antral development dominant follicles directly affect the fate of the subordinate cohort members.
Pigment-lightening effect of N,N'-dilinoleylcystamine on human melanoma cells
Authors: J.S. Hwang, H. Choi, H.S. Rho, H.J. Shin, D.H. Kim, J. Lee, B.G. Lee, I. Chang
Journal: British Journal of Dermatology (2004)

Cystamine and linoleic acid have been reported to reduce melanin synthesis in vitro and in vivo. N,N'-dilinoleylcystamine (DLC) is a compound of cystamine and linoleic acid connected by an ester bond.To investigate the effects of DLC on melanin synthesis using cultured human melanoma cells.Levels of total melanin, eumelanin and phaeomelanin, tyrosinase protein and tyrosinase activity in situ were measured in HM3KO melanoma cells. Changes in degree of pigmentation were quantified by image analysis and compared with absorbance values. Tyrosinase from HM3KO cells was used to measure the direct effect of DLC on DOPA and DOPAchrome production.At concentrations of 1.4-14 micromol L-1, DLC reduced the pigmentation of HM3KO melanoma cells but did not affect cell growth. The visual decrease in pigmentation produced by DLC was more dramatic than the decrease in total melanin content as measured by absorbance at 500 nm. DLC treatment decreased eumelanin synthesis and increased phaeomelanin synthesis in HM3KO melanoma cells. An in situ tyrosinase assay showed that DLC inhibited tyrosinase activity, as well as the level of tyrosinase protein.These results suggest that DLC has pigment-lightening effects on HM3KO melanoma cells, produced by reducing the level of eumelanin while increasing the level of phaeomelanin.
Influence of Acute Renal Failure on Coronary Vasoregulation in Dogs
Authors: John G. Kingma, Chantal Vincent, Jacques R. Rouleau, Iris Kingma
Journal: Journal of the American Society of Nephrology (2006)

Impaired renal function is associated with an increased risk for cardiovascular events and death, but the pathophysiology is poorly defined. The hypothesis that coronary blood flow regulation and distribution of ventricular blood flow could be compromised during acute renal failure (ARF) was tested. In two separate groups (n = 14 each) of dogs with ARF, (1) coronary autoregulation (pressure-flow relations), vascular reserve (reactive hyperemia), and myocardial blood flow distribution (microspheres) and (2) coronary vessel responses to intracoronary infusion of select endothelium-dependent and -independent vasodilators were evaluated. In addition, coronary pressure-flow relations and vascular reserve after inhibition of nitric oxide and prostaglandin release were evaluated. Under resting conditions, myocardial oxygen consumption increased in dogs with ARF compared with no renal failure (NRF; 11.8 ± 9.2 versus 5.0 ± 1.5 ml O2/min per 100 g; P = 0.01), and the autoregulatory break point of the coronary pressure-flow relation was shifted to higher diastolic coronary pressures (60 ± 17 versus 52 ± 8 mmHg in NRF; P = 0.003); the latter was shifted further rightward after inhibition of both nitric oxide and prostaglandin release. The endocardial/epicardial blood flow ratio was comparable for both groups, suggesting preserved ventricular distribution of blood flow. In dogs with ARF, coronary vascular conductance also was reduced (P = 0.001 versus NRF), but coronary zero-flow pressure was unchanged. Vessel reactivity to each endothelium-dependent/independent compound also was blunted significantly. In conclusion, under resting conditions, coronary vascular tone, reserve, and vessel reactivity are markedly diminished with ARF, suggesting impaired vascular function. Consequently, during ARF, small increases in myocardial oxygen demand would induce subendocardial ischemia as a result of a limited capacity to increase oxygen supply and thereby contribute to higher risk for adverse coronary events and mortality.
Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution computed tomography, chest radiography, and pulmonary function tests
Authors: J K Dawson
Journal: Thorax (2001)

Background-Fibrosing alveolitis (FA) is a common and serious complication of rheumatoid arthritis (RA).Before the availability of high resolution computed tomographic (HRCT) scanning, it was diYcult to diagnose accurately without recourse to biopsy.Prospective studies have reported a prevalence of interstitial lung disease (ILD) of 19-44%.The term ILD used by these authors encompasses a variety of appearances on HRCT scans.This prospective study used HRCT scanning to determine the true prevalence of FA in hospital outpatients with RA, and to study associated clinical characteristics.Methods-One hundred and fifty consecutive patients with RA were selected from a hospital outpatient department, irrespective of the presence or absence of chest disease.All underwent a detailed clinical assessment, chest HRCT scanning, and conventional chest radiography within 4 weeks of full pulmonary function tests.Results-Seventy percent of patients were current or reformed cigarette smokers.Twenty eight (19%) had FA, most frequently of reticular pattern, and 12 of this group (43%) also had emphysematous bullae.None of the previously suggested risk factors for developing FA were confirmed.Fifty four percent of patients with HRCT evidence of FA had bilateral basal chest crackles, 82% had a reduced carbon monoxide transfer factor (TLCO), 14% had restrictive pulmonary function tests, and 14% had bilateral chest radiographic signs of FA.Conclusions-HRCT evidence of FA was present in 19% of hospital outpatients with RA.Abnormalities on chest examination or on full pulmonary function tests, even without restrictive changes or chest radiographic abnormalities, should prompt physicians to request a chest HRCT scan when investigating dyspnoea in patients with RA.
Phenotypic Characterization of Disseminated Cells with <i>TSC2</i> Loss of Heterozygosity in Patients with Lymphangioleiomyomatosis
Authors: Xiong Cai, Gustavo Pacheco-Rodriguez, Qing-Yuan Fan, Mary Haughey, Leigh Samsel, Souheil El-Chemaly, Hai-Ping Wu, J. Philip McCoy, Wendy K. Steagall, Jing-Ping Lin, Thomas N. Darling, Joel Moss
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Lymphangioleiomyomatosis (LAM), occurring sporadically (S-LAM) or in patients with tuberous sclerosis complex (TSC), results from abnormal proliferation of LAM cells exhibiting mutations or loss of heterozygosity (LOH) of the TSC genes, TSC1 or TSC2.Objectives: To identify molecular markers useful for isolating LAM cells from body fluids and determine the frequency of TSC1 or TSC2 LOH.Methods: Candidate cell surface markers were identified using gene microarray analysis of human TSC2−/− cells. Cells from bronchoalveolar lavage fluid (BALF), urine, chylous effusions, and blood were sorted based on reactivity with antibodies against these proteins (e.g., CD9, CD44v6) and analyzed for LOH using TSC1- and TSC2-related microsatellite markers and single nucleotide polymorphisms in the TSC2 gene.Measurements and Main Results: CD44v6+CD9+ cells from BALF, urine, and chyle showed TSC2 LOH in 80%, 69%, and 50% of patient samples, respectively. LAM cells with TSC2 LOH were detected in more than 90% of blood samples. LAM cells from different body fluids of the same patients showed, in most cases, identical LOH patterns, that is, loss of alleles at the same microsatellite loci. In a few patients with S-LAM, LAM cells from different body fluids differed in LOH patterns. No patients with S-LAM with TSC1 LOH were identified, suggesting that TSC2 abnormalities are responsible for the vast majority of S-LAM cases and that TSC1-disease may be subclinical.Conclusions: Our data support a common genetic origin of LAM cells in most patients with S-LAM, consistent with a metastatic model. In some cases, however, there was evidence for genetic heterogeneity between LAM cells in different sites or within a site.