tbuckley/cabot-search huggingface dataset:
Impact of nasal continuous positive airway pressure treatment on quality of life in patients with obstructive sleep apnoea
Authors: J Bolitschek, A Schmeiser-Rieder, R Schobersberger, A Rosenberger, M Kunze, K Aigner
Journal: European Respiratory Journal (1998)

Quality-of-life (QoL) issues have become increasingly important in health care practice and research. Obstructive sleep apnoea syndrome (OSAS) results in an especially serious reduction in QoL. The purpose of this study was to measure the QoL (life satisfaction) of OSAS patients treated with nasal continuous positive airway pressure (nCPAP). We aimed to determine whether and to what extent the QoL of OSAS patients using nCPAP differs from that of randomly selected subjects without this disorder. The QoL of 67 patients treated for at least 3 months with nCPAP, 21 OSAS patients at the time of OSAS diagnosis, and 113 randomly selected persons visiting the hospital (controls) was investigated with the help of the Munich life-quality dimension list (MLDL), an instrument for cognitive assessment of elementary components (physical condition, psyche, social life, everyday life) of QoL. It was found that QoL of OSAS patients treated with nCPAP did not significantly differ from that of control subjects with regard to elementary components. The 21 untreated OSAS patients showed significantly lower scores in all four subcategories: physical condition (p<0.0005), psyche (p<0.01), social life (p<0.0005) and everyday life (p<0.007). Thus, it may be concluded that nasal continuous positive airway pressure therapy has an important impact on the quality of life of obstructive sleep apnoea syndrome patients, and signifies a further advantage in addition to clinical aspects. Treated patients are as satisfied or dissatisfied with their life as persons without this illness.
Linear Scleroderma
Authors: VINCENT FALANGA
Journal: Annals of Internal Medicine (1986)

The clinical features and natural history of linear scleroderma in 53 patients and the laboratory tests helpful in the management of this disease are described. No patient had Raynaud's phenomenon or signs of systemic connective tissue disease in a mean follow-up of 10 years. Blood eosinophilia (greater than 300 cells/mm3) was present in half the patients, usually those with clinically active disease rather than inactive disease (p less than 0.02). An elevated serum IgG level correlated with the presence of joint contractures (p less than 0.02). Antinuclear antibodies, commoner in patients with extensive and prolonged disease, were present in 31% and 46% of patients whose sera were tested on mouse kidney and HEp-2 cells, respectively. Antibodies to single-stranded DNA, present in 50% of patients, were associated with extensive disease, joint contractures (p less than 0.001), and active disease of greater than 2 years' duration (p less than 0.001). Discordance in immune reactivity indicates that at least three serum autoantibodies exist in these patients: antibodies to single-stranded DNA and antinuclear antibodies with homogeneous and nucleolar immunofluorescence patterns.
TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations
Authors: A Pardanani, J Hood, T Lasho, R L Levine, M B Martin, G Noronha, C Finke, C C Mak, R Mesa, H Zhu, R Soll, D G Gilliland, A Tefferi
Journal: Leukemia (2007)
Exercise therapy in polycystic ovary syndrome: a systematic review
Authors: C. L. Harrison, C. B. Lombard, L. J. Moran, H. J. Teede
Journal: Human Reproduction Update (2010)

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting 8-12% of women. Lifestyle modification, including increased physical activity, is the first-line approach in managing PCOS. A systematic review was performed to identify and describe the effect of exercise as an independent intervention on clinical outcomes in PCOS.Five databases were searched with no time limit. A pre-specified definition of PCOS was not used. Studies were included if exercise therapy (aerobic and/or resistance) could be evaluated as an independent treatment against a comparison group. Outcomes measured included cardiovascular risk factors [insulin resistance (IR), lipid profiles, blood pressure and weight] and reproductive measures (ovulation, menstrual regularity and fertility outcomes). Quality analysis was performed based on the Cochrane Handbook of Systematic Reviews and the Quality of Reporting of Meta-Analyses checklist.Eight manuscripts were identified (five randomized controlled trials and three cohort studies). All studies involved moderate intensity physical activity and most were of either 12 or 24 weeks duration with frequency and duration of exercise sessions ranging between studies. The most consistent improvements included improved ovulation, reduced IR (9-30%) and weight loss (4.5-10%). Improvements were not dependant on the type of exercise, frequency or length of exercise sessions.Exercise-specific interventions in PCOS are limited. Studies vary considerably in design, intensity and outcome measures; therefore conclusive results remain elusive. Larger, optimally designed studies are needed to both gain insights into the mechanisms of exercise action and to evaluate the public health impact of exercise of PCOS.
Low CSF Concentration of a Dopamine Metabolite in Tobacco Smokers
Authors: Thomas D. Geracioti, Scott A. West, Dewleen G. Baker, Kelly K. Hill, Nosa N. Ekhator, Matthew D. Wortman, Paul E. Keck, Andrew B. Norman
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: To screen for dopaminergic abnormalities in tobacco smokers and patients with posttraumatic stress disorder (PTSD), the authors determined serial CSF and plasma concentrations of the dopamine metabolite homovanillic acid (HVA). METHOD: Continuous subarachnoid sampling was used to obtain 37 serial CSF samples over 6 hours in 13 normal volunteers and 11 patients with combat-related PTSD; 10 smoked and 14 had never smoked. The smokers were abstinent from tobacco for 11 to 17 hours. RESULTS: The smokers had markedly lower CSF, but not plasma, HVA levels. Their CSF HVA concentrations averaged only 54% of the concentrations of the nonsmokers, independent of diagnosis. CONCLUSIONS: Smokers' low CSF concentrations of HVA may be associated either with chronic inhalation of nicotine or other constituents of tobacco smoke or with acute abstinence. Any possible basal dopaminergic abnormalities in patients with PTSD are small relative to the abnormalities associated with smoking.
Peripheral airway/alveolar nitric oxide concentration in asthma
Authors: B. Mahut, C. Delclaux
Journal: Thorax (2010)

We read with great interest the paper by Gelb and colleagues1 who suggest that peripheral airway/alveolar nitric oxide (NO) concentration after correction for axial NO back-diffusion (CalvNOcorrected) is normal during asthma exacerbation (with a hypothesis of an incidence of >30% of its increase). If one admits that an exacerbation constitutes the ultimate expression of loss of asthma control, their results are in line with ours demonstrating that CalvNOcorrected is not a marker of asthma control.2 Nevertheless, some of their patients with an exacerbation had an increase in CalvNOcorrected …
Synergistic Function of Smad4 and PTEN in Suppressing Forestomach Squamous Cell Carcinoma in the Mouse
Authors: Yan Teng, An-Na Sun, Xiao-Chen Pan, Guan Yang, Lei-Lei Yang, Ming-Rong Wang, Xiao Yang
Journal: Cancer Research (2006)

The genetic bases underlying esophageal tumorigenesis are poorly understood. Our previous studies have shown that coordinated deletion of the Smad4 and PTEN genes results in accelerated hair loss and skin tumor formation in mice. Herein, we exemplify that the concomitant inactivation of Smad4 and PTEN accelerates spontaneous forestomach carcinogenesis at complete penetrance during the first 2 months of age. All of the forestomach tumors were invasive squamous cell carcinomas (SCCs), which recapitulated the natural history and pathologic features of human esophageal SCCs. A small population of the SCC lesions was accompanied by adenocarcinomas at the adjacent submucosa region in the double mutant mice. The rapid progression of forestomach tumor formation in the Smad4 and PTEN double knockout mice corresponded to a dramatic increase in esophageal and forestomach epithelial proliferation. The decreased expression of p27, p21, and p16 together with the overexpression of cyclin D1 contributed cooperatively to the accelerated forestomach tumorigenesis in the double mutant mice. Our results point strongly to the crucial relevance of synergy between Smad4 and PTEN to suppress forestomach tumorigenesis through the cooperative induction of cell cycle inhibitors.
Essential Immunoregulatory Role for BCAP in B Cell Development and Function
Authors: Tetsuo Yamazaki, Kiyoshi Takeda, Kumiko Gotoh, Hiroshi Takeshima, Shizuo Akira, Tomohiro Kurosaki
Journal: The Journal of Experimental Medicine (2002)

BCAP was recently cloned as a binding molecule to phosphoinositide 3-kinase (PI3K). To investigate the role of BCAP, mutant mice deficient in BCAP were generated. While BCAP-deficient mice are viable, they have decreased numbers of mature B cells and B1 B cell deficiency. The mice produce lower titers of serum immunoglobulin (Ig)M and IgG3, and mount attenuated responses to T cell–independent type II antigen. Upon B cell receptor cross-linking, BCAP-deficient B cells exhibit reduced Ca2+ mobilization and poor proliferative responses. These findings demonstrate that BCAP plays a pivotal immunoregulatory role in B cell development and humoral immune responses.
Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD
Authors: D. A. Lomas, E. K. Silverman, L. D. Edwards, N. W. Locantore, B. E. Miller, D. H. Horstman, R. Tal-Singer
Journal: European Respiratory Journal (2009)

Surfactant protein (SP)-D is a lung-derived protein that has been proposed as a biomarker for inflammatory lung disease. Serum SP-D was evaluated as a biomarker for components of chronic obstructive pulmonary disease (COPD) in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort and its response assessed to the administration of the anti-inflammatory agent prednisolone. The median level of serum SP-D was significantly elevated in 1,888 individuals with COPD compared to 296 current and former smokers without airflow obstruction (121.1 and 114.3 ng x mL(-1), respectively; p = 0.021) and 201 nonsmokers (82.2 ng x ml(-1); p<0.001). There was no correlation with the severity of COPD. Individuals with COPD who had a serum SP-D concentration that was greater than the 95th percentile of nonsmokers (175.4 ng x mL(-1)) showed an increased risk of exacerbations over the following 12 months (adjusted OR 1.30; 95% CI 1.03-1.63). Treatment with 20 mg x day(-1) prednisolone for 4 weeks resulted in a fall in serum SP-D levels (126.0 to 82.1 ng x mL(-1); p<0.001) but no significant change in post-bronchodilator forced expiratory volume in 1 s. Serum SP-D concentration is raised in smokers and may be useful in identifying individuals who are at increased risk of exacerbations of COPD. It may represent an intermediate measure for the development of novel anti-inflammatory agents.
Effect of Alendronate on Bone Mineral Density and Biochemical Markers of Bone Turnover in Type 2 Diabetic Women
Authors: Theresa H.M. Keegan, Ann V. Schwartz, Douglas C. Bauer, Deborah E. Sellmeyer, Jennifer L. Kelsey
Journal: Diabetes Care (2004)

OBJECTIVE—Alendronate sodium (ALN) increases bone mineral density (BMD) in heterogeneous populations of postmenopausal women, but its effect is unknown in women with type 2 diabetes. The objective of this project was to compare changes in BMD during 3 years of ALN treatment versus placebo in diabetic women. RESEARCH DESIGN AND METHODS—We used data from the Fracture Intervention Trial, a randomized blinded placebo-controlled trial conducted at 11 centers in which 6,458 women aged 54–81 years with a femoral neck BMD of ≤0.68 g/cm2 were randomly assigned to either placebo or 5 mg/day ALN for 2 years, followed by 10 mg/day for the remainder of the trial. BMD was measured by dual-energy X-ray absorptiometry. Type 2 diabetes (n = 297) was defined by self-report, use of insulin or other hypoglycemic agents, or a random nonfasting glucose value ≥200 mg/dl. RESULTS—In diabetic women, 3 years of ALN treatment was associated with increased BMD at all sites studied, including 6.6% at the lumbar spine and 2.4% at the hip, whereas women in the placebo group experienced a decrease in BMD at all sites except the lumbar spine. The safety/tolerability of ALN was similar to placebo, except for abdominal pain, which was more likely in the ALN group. CONCLUSIONS—ALN increased BMD relative to placebo in older women with type 2 diabetes and was generally well tolerated as a treatment for osteoporosis. Increases in BMD with ALN therapy compared with placebo were similar between women with and without diabetes.
Obesity, increased linear growth, and risk of type 1 diabetes in children.
Authors: E Hyppönen, S M Virtanen, M G Kenward, M Knip, H K Akerblom
Journal: Diabetes Care (2000)

OBJECTIVE: The purpose of the present study was to evaluate the effect of obesity and linear growth on the risk of developing type 1 diabetes in children. RESEARCH DESIGN AND METHODS: The study population consists of all diabetic children &amp;lt;15 years of age diagnosed from September 1986 to April 1989 in Finland and their birth date- and sex-matched population-based control subjects. Growth data were obtained from well-baby clinics and school health care units for 586 diabetic and 571 control subjects, resulting in a total of 18,823 paired weight-height observations. RESULTS: Both boys and girls who developed type 1 diabetes were heavier and taller throughout childhood than control children. A 10% unit increment in relative weight was associated with a 50-60% increase in the risk of type 1 diabetes before 3 years of age and a 20-40% increase from 3 to 10 years of age. The increase in risk of type 1 diabetes for 1 SD score increment in relative height was 20-30%. Obesity (relative weight &amp;gt; 120%) after 3 years of age was associated with a more than twofold risk of developing type 1 diabetes. CONCLUSIONS: The present observation that obesity and rapid linear growth are risk factors for type 1 diabetes in children indicates that the increase in the prevalence of obesity and secular growth that has occurred in most industrialized countries over the last decades may be involved in the increase in type 1 diabetes incidence simultaneously observed in many countries.
The major histocompatibility complex-restricted antigen receptor on T cells. IV. An antiidiotypic antibody predicts both antigen and I-specificity.
Authors: P Marrack, R Shimonkevitz, C Hannum, K Haskins, J Kappler
Journal: The Journal of Experimental Medicine (1983)

In order to prove that a monoclonal antibody, KJ1-26.1, reacted with the idiotypic portion of the receptor for antigen plus major histocompatibility complex product (Ag/MHC) on the T cell hybridoma D0-11.10, 397 independent T cell hybridomas prepared from BALB/c T cells primed with ovalbumin were screened by ELISA for reactivity with the antibody. Of these T cell hybridomas one, 7D0-286, and a subclone of this hybridoma, 7D0-286.2, reacted strongly and consistently with KJ1-26.1. Further analysis revealed that KJ1-26.1 blocked the reaction of 7D0-286 with Ag/MHC, and that 7D0-286 had the same fine specificity both for Ag and MHC as D0-11.10. None of 207 other BALB/c T cell hybridomas specific for ovalbumin shared these fine specificity patterns. Thus, reaction with KJ1-26.1 defined the specificity of a T cell hybridoma both for Ag and MHC, suggesting that KJ1-26.1 reacted with the receptors for Ag/MHC on the T cells in question. KJ1-26.1 precipitated an 85-kdalton molecule from 7D0-286.2 that on reduction ran as a diffuse spot of approximately 43 kdaltons. A similar molecule was precipitated from D0-11.10.
Vaccination with SPf66, a chemically synthesised vaccine, against Plasmodium falciparum malaria in Colombia
Authors: M.V. Valero, L.R. Amador, C. Galindo, J. Figueroa, M.S. Bello, L.A. Murillo, A.L. Mora, G. Patarroyo, C.L. Rocha, M. Rojas, J.J. Aponte, L.E. Sarmiento, D.M. Lozada, C.G. Coronell, N.M. Ortega, J.E. Rosas, M.E. Patarroyo, P.L. Alonso
Journal: The Lancet (1993)
Expression of Hypoxia-Inducible Factor-1α and -2α in Hypoxic and Ischemic Rat Kidneys
Authors: Christian Rosenberger, Stefano Mandriota, Jan Steffen Ju[Combining Diaeresis]rgensen, Michael S. Wiesener, Jan H. Ho[Combining Diaeresis]rstrup, Ulrich Frei, Peter J. Ratcliffe, Patrick H. Maxwell, Sebastian Bachmann, Kai-Uwe Eckardt
Journal: Journal of the American Society of Nephrology (2002)

Oxygen tensions in the kidney are heterogeneous, and their changes presumably play an important role in renal physiologic and pathophysiologic processes. A family of hypoxia-inducible transcription factors (HIF) have been identified as mediators of transcriptional responses to hypoxia, which include the regulation of erythropoietin, metabolic adaptation, vascular tone, and neoangiogenesis. In vitro , the oxygen-regulated subunits HIF-1α and -2α are expressed in inverse relationship to oxygen tensions in every cell line investigated to date. The characteristics and functional significance of the HIF response in vivo are largely unknown. High-amplification immunohistochemical analyses were used to study the expression of HIF-1α and -2α in kidneys of rats exposed to systemic hypoxia bleeding anemia, functional anemia (0.1% carbon monoxide), renal ischemia, or cobaltous chloride (which is known to mimic hypoxia). These treatments led to marked nuclear accumulation of HIF-1α and -2α in different renal cell populations. HIF-1α was mainly induced in tubular cells, including proximal segments with exposure to anemia/carbon monoxide, in distal segments with cobaltous chloride treatment, and in connecting tubules and collecting ducts with all stimuli. Staining for HIF-1α colocalized with inducible expression of the target genes heme oxygenase-1 and glucose transporter-1. HIF-2α was not expressed in tubular cells but was expressed in endothelial cells of a small subset of glomeruli and in peritubular endothelial cells and fibroblasts. The kidney demonstrates a marked potential for upregulation of HIF, but accumulation of HIF-1α and HIF-2α is selective with respect to cell type, kidney zone, and experimental conditions, with the expression patterns partly matching known oxygen profiles. The expression of HIF-2α in peritubular fibroblasts suggests a role in erythropoietin regulation.
A Hypomorphic Mutation in the Mouse Laminin α5 Gene Causes Polycystic Kidney Disease
Authors: M. Brendan Shannon, Bruce L. Patton, Scott J. Harvey, Jeffrey H. Miner
Journal: Journal of the American Society of Nephrology (2006)

Extracellular matrix abnormalities have been found in both human and animal models of polycystic kidney disease (PKD). A new mouse PKD model has been produced through insertion of a PGKneo cassette in an intron of the gene that encodes laminin α5 (Lama5), a major tubular and glomerular basement membrane component that is important for glomerulogenesis and ureteric bud branching. Lama5neo represents a hypomorphic allele as a result of aberrant splicing. Lama5neo/neo mice exhibit PKD, proteinuria, and death from renal failure by 4 wk of age. This contrasts with mice that totally lack Lama5, which die in utero with multiple developmental defects. At 2 d of age, Lama5neo/neo mice exhibited mild proteinuria and microscopic cystic transformation. By 2 wk, cysts were grossly apparent in cortex and medulla, involving both nephron and collecting duct segments. Tubular basement membranes seemed to form normally, and early cyst basement membranes showed normal ultrastructure but developed marked thickening as cysts enlarged. Overall, Lama5 protein levels were severely reduced as a result of mRNA frameshift caused by exon skipping. This was accompanied by aberrant accumulation of laminin-332 (α3β3γ2; formerly called laminin-5) in some cysts, as also observed in human PKD. This constitutes the first evidence that a primary defect in an extracellular matrix component can cause PKD.
Successful treatment of chronic refractory pure red cell aplasia with antithymocyte globulin: Correlation with in vitro erythroid culture studies
Authors: Kenneth F. Mangan, Richard K. Shadduck
Journal: American Journal of Hematology (1984)

Abstract Two contrasting cases of chronic refractory pure red cell aplasia (PRCA) responsive to a commercial preparation of horse antihuman thymocyte globulin (ATG) are reported. Both cases were refractory to trials of cyclophosphamide, corticosteroids, and plasmapheresis. One patient developed a reticulocytosis after a single intravenous infusion of ATG; the other patient responded after administration of 14.7 g of ATG over a 28‐day course. At presentation, erythroid progenitors (CFU‐E and BFU‐E) in one patient were normal; in the second patient, the number of erythroid progenitors was severely reduced. Neither patient had a serum IgG inhibitor to progenitor cells as judged by in vitro erythroid colony studies. Both patients had increased numbers of marrow T‐cells and co‐culture studies in one case were consistent with T‐cell‐mediated suppression of erythropoiesis. These studies confirm that ATG is a useful agent in the treatment of refractory PRCA. However, ATG may not act by removal of T suppressor cells in all cases.