tbuckley/cabot-search huggingface dataset:
Sustained Effects of Interleukin-1 Receptor Antagonist Treatment in Type 2 Diabetes
Authors: Claus M. Larsen, Mirjam Faulenbach, Allan Vaag, Jan A. Ehses, Marc Y. Donath, Thomas Mandrup-Poulsen
Journal: Diabetes Care (2009)

OBJECTIVE Interleukin (IL)-1 impairs insulin secretion and induces β-cell apoptosis. Pancreatic β-cell IL-1 expression is increased and interleukin-1 receptor antagonist (IL-1Ra) expression reduced in patients with type 2 diabetes. Treatment with recombinant IL-1Ra improves glycemia and β-cell function and reduces inflammatory markers in patients with type 2 diabetes. Here we investigated the durability of these responses. RESEARCH DESIGN AND METHODS Among 70 ambulatory patients who had type 2 diabetes, A1C &amp;gt;7.5%, and BMI &amp;gt;27 kg/m2 and were randomly assigned to receive 13 weeks of anakinra, a recombinant human IL-1Ra, or placebo, 67 completed treatment and were included in this double-blind 39-week follow-up study. Primary outcome was change in β-cell function after anakinra withdrawal. Analysis was done by intention to treat. RESULTS Thirty-nine weeks after anakinra withdrawal, the proinsulin-to-insulin (PI/I) ratio but not stimulated C-peptide remained improved (by −0.07 [95% CI −0.14 to −0.02], P = 0.011) compared with values in placebo-treated patients. Interestingly, a subgroup characterized by genetically determined low baseline IL-1Ra serum levels maintained the improved stimulated C-peptide obtained by 13 weeks of IL-1Ra treatment. Reductions in C-reactive protein (−3.2 mg/l [−6.2 to −1.1], P = 0.014) and in IL-6 (−1.4 ng/l [−2.6 to −0.3], P = 0.036) were maintained until the end of study. CONCLUSIONS IL-1 blockade with anakinra induces improvement of the PI/I ratio and markers of systemic inflammation lasting 39 weeks after treatment withdrawal.
Clinical outcome of pretreated B-cell chronic lymphocytic leukemia following alemtuzumab therapy: a retrospective study on various cytogenetic risk categories
Authors: M. Fiegl, M. Erdel, I. Tinhofer, Y. Brychtova, A. Panovska, M. Doubek, K. Eigenberger, C. Fonatsch, G. Hopfinger, H. Mühlberger, A. Zabernigg, F. Falkner, G. Gastl, J. Mayer, R. Greil
Journal: Annals of Oncology (2010)
Isoproterenol Activates Extracellular Signal–Regulated Protein Kinases in Cardiomyocytes Through Calcineurin
Authors: Yunzeng Zou, Atsushi Yao, Weidong Zhu, Sumiyo Kudoh, Yukio Hiroi, Masaki Shimoyama, Hiroki Uozumi, Osami Kohmoto, Toshiyuki Takahashi, Futoshi Shibasaki, Ryozo Nagai, Yoshio Yazaki, Issei Komuro
Journal: Circulation (2001)

Background —Extracellular signal–regulated kinases (ERKs) and calcineurin have been reported to play important roles in the development of cardiac hypertrophy. We examined here the relation between calcineurin and ERKs in cardiomyocytes. Methods and Results —Isoproterenol activated ERKs in cultured cardiomyocytes of neonatal rats, and the activation was abolished by chelation of extracellular Ca 2+ with EGTA, blockade of L-type Ca 2+ channels with nifedipine, or depletion of intracellular Ca 2+ stores with thapsigargin. Isoproterenol-induced activation of ERKs was also significantly suppressed by calcineurin inhibitors in cultured cardiomyocytes as well as in the hearts of mice. Isoproterenol failed to activate ERKs in either the cultured cardiomyocytes or the hearts of mice that overexpress the dominant negative mutant of calcineurin. Isoproterenol elevated intracellular Ca 2+ levels at both systolic and diastolic phases and dose-dependently activated calcineurin. Inhibition of calcineurin also attenuated isoproterenol-stimulated phosphorylation of Src, Shc, and Raf-1 kinase. The immunocytochemistry revealed that calcineurin was localized in the Z band, and isoproterenol induced translocation of calcineurin and ERKs into the nucleus. Conclusions —Calcineurin, which is activated by marked elevation of intracellular Ca 2+ levels by the Ca 2+ -induced Ca 2+ release mechanism, regulates isoproterenol-induced activation of ERKs in cardiomyocytes.
Relationship Among Alcohol, Body Weight, and Cardiovascular Risk Factors in 27,030 Korean Men
Authors: Ki-Chul Sung, Sun H. Kim, Gerald M. Reaven
Journal: Diabetes Care (2007)

Recent studies suggest a lower risk for overweight/obesity in moderate alcohol drinkers. However, the validity of this relationship and its impact on the putative benefits of alcohol consumption on cardiovascular disease (CVD) risk has not been well evaluated.We assessed the impact of BMI on the relationship between alcohol consumption and CVD risk factors (blood pressure, lipid panel, and glucose and insulin concentrations) in 27,030 healthy Korean men with no major comorbidities or medication intake seen in a large urban Korean hospital.BMI and overweight prevalence increased linearly with alcohol intake (P < 0.001). Alcohol intake was also positively associated with blood pressure and triglyceride, HDL, and fasting glucose concentrations (P < 0.001) and negatively associated with LDL and insulin concentrations (P < 0.001). With nondrinkers as the reference group, the odds ratio for having insulin in the top quartile also declined linearly when adjusted for age, BMI, smoking, and exercise, with the heaviest drinkers (>40 g/day) having an odds ratio of 0.71 (95% CI 0.62-0.82) (P < 0.001). The relationship between alcohol and CVD risk factors was similar in normal-weight and overweight individuals.Alcohol intake is associated with increasing BMI and several metabolic abnormalities, including higher fasting glucose. Paradoxically, it is also associated with lower insulin concentrations. The clinical significance of these findings needs further investigation.
High oesophageal stricture with hiatal hernia and a lower oesophagus lined by columnar epithelium
Authors: B. Corrin, G. K. Harrison, H. R. M. Johnson
Journal: Thorax (1970)

A 23-year-old man with a six months9 history of dysphagia was found to have hiatus hernia with reflux and a stricture of the mid-oesophagus. Death from unrelated causes permitted detailed histological examination. This showed a high squamo-columnar junction with ulceration confined to the squamous epithelium immediately above the junction. The columnar epithelium of the lower oesophagus was largely of cardiac type, but a few gastric body type glands were present at the lowermost end. This mixed pattern and the complete lack of inflammation or fibrosis beneath the columnar epithelium favours a congenital rather than metaplastic origin. A high squamo-columnar junction is of clinical significance only in the presence of reflux when oesophagitis and stricture develop at an unusually high level.
Reactive arthritis after an outbreak of Yersinia pseudotuberculosis serotype O:3 infection
Authors: T Hannu
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To determine the occurrence and clinical characteristics of reactive arthritis (ReA) after an outbreak of <i>Yersinia pseudotuberculosis</i> serotype O:3 infection. <b>Methods:</b> From 15 October to 6 November 1998, a widespread outbreak of <i>Y pseudotuberculosis</i> serotype O:3 occurred in Finland. A questionnaire on musculoskeletal symptoms was mailed to 38 patients with infection confirmed by culture. All patients who reported joint symptoms were interviewed by phone and their medical records of outpatient visits or hospital admission because of recent joint symptoms were reviewed. <b>Results:</b> Thirty three of 38 (87%) patients returned the questionnaire. Reactive musculoskeletal symptoms were reported by 5/33 (15%): four patients (12%) fulfilled the criteria for ReA and one additional patient had reactive enthesopathy. The patients with ReA were adults (age range 40–47 years), whereas the patient with reactive enthesopathy was a 14 year old boy. In all patients with ReA, the arthritis was polyarticular. In addition to peripheral arthritis, other musculoskeletal symptoms included sacroiliitis (one patient), pain in Achilles tendon (one patient), and heel pain (two patients). HLA-B27 was positive in all the three patients tested. In three of four patients with ReA, the duration of acute arthritis was over six months. <b>Conclusion:</b><i>Y pseudotuberculosis</i> serotype O:3 infection is frequently associated with ReA and the clinical picture is severe.
Nicotinic Acetylcholine Receptor Polymorphism, Smoking Behavior, and Tobacco-Related Cancer and Lung and Cardiovascular Diseases: A Cohort Study
Authors: Diljit Kaur-Knudsen, Stig E. Bojesen, Anne Tybjærg-Hansen, Børge G. Nordestgaard
Journal: Journal of Clinical Oncology (2011)

We examined the associations between the nicotinic acetylcholine receptor polymorphism (rs1051730) on chromosome 15q25 marking the gene cluster CHRNA3-CHRNB4-CHRNA5, smoking behavior, and tobacco-related cancer and lung and cardiovascular diseases in the general population.Ten thousand three hundred thirty participants from the Copenhagen City Heart Study were genotyped and observed prospectively with up to 18 years of 100% complete follow-up. Smoking behavior was measured at baseline. End points were lung cancer, bladder cancer, chronic obstructive pulmonary disease, ischemic heart disease, and ischemic stroke.Multifactorially adjusted and genotype-adjusted subhazard ratios for a cumulative tobacco consumption above 40 pack-years versus 0 pack-years were 32.5 (95% CI, 12.0 to 87.7) for lung cancer, 2.2 (95% CI, 1.1 to 4.5) for bladder cancer, 9.4 (95% CI, 6.9 to 12.7) for chronic obstructive pulmonary disease, 1.5 (95% CI, 1.3 to 1.8) for ischemic heart disease, and 1.1 (95% CI, 0.8 to 1.4) for ischemic stroke. Among smoking noncarriers and homozygotes, daily tobacco consumption was 16 and 18 g/d (P < .001), cumulative tobacco consumption was 28 and 31 pack-years (P = .003), and smoking inhalation was 71.9% and 78.1% (P < .001), respectively. Multifactorially adjusted and smoking behavior-adjusted subhazard ratios for homozygotes versus noncarriers were 1.6 (95% CI, 1.1 to 2.2) for lung cancer, 1.7 (95% CI, 1.0 to 3.0) for bladder cancer, 1.3 (95% CI, 1.1 to 1.6) for chronic obstructive pulmonary disease, 0.9 (95% CI, 0.7 to 1.0) for ischemic heart disease, and 1.1 (95% CI, 0.8 to 1.4) for ischemic stroke.Although smoking is associated with major tobacco-related diseases in the general population, the nicotinic acetylcholine receptor polymorphism is associated with additional increased risk of lung cancer, bladder cancer, and chronic obstructive pulmonary disease after adjustment for smoking.
Correlates of Treatment Patterns Among Youth With Type 2 Diabetes
Authors: Angela Badaru, Georgeanna J. Klingensmith, Dana Dabelea, Elizabeth J. Mayer-Davis, Lawrence Dolan, Jean M. Lawrence, Santica Marcovina, Daniel Beavers, Beatriz L. Rodriguez, Giuseppina Imperatore, Catherine Pihoker
Journal: Diabetes Care (2013)

OBJECTIVE To describe treatment regimens in youth with type 2 diabetes and examine associations between regimens, demographic and clinical characteristics, and glycemic control. RESEARCH DESIGN AND METHODS This report includes 474 youth with a clinical diagnosis of type 2 diabetes who completed a SEARCH for Diabetes in Youth study visit. Diabetes treatment regimen was categorized as lifestyle alone, metformin monotherapy, any oral hypoglycemic agent (OHA) other than metformin or two or more OHAs, insulin monotherapy, and insulin plus any OHA(s). Association of treatment with demographic and clinical characteristics (fasting C-peptide [FCP], diabetes duration, and self-monitoring of blood glucose [SMBG]), and A1C was assessed by χ2 and ANOVA. Multiple linear regression models were used to evaluate independent associations of treatment regimens and A1C, adjusting for demographics, diabetes duration, FCP, and SMBG. RESULTS Over 50% of participants reported treatment with metformin alone or lifestyle. Of the autoantibody-negative youth, 40% were on metformin alone, while 33% were on insulin-containing regimens. Participants on metformin alone had a lower A1C (7.0 ± 2.0%, 53 ± 22 mmol/mol) than those on insulin alone (9.2 ± 2.7%, 77 ± 30 mmol/mol) or insulin plus OHA (8.6 ± 2.6%, 70 ± 28 mmol/mol) (P &amp;lt; 0.001). These differences remained significant after adjustment (7.5 ± 0.3%, 58 ± 3 mmol/mol; 9.1 ± 0.4%, 76 ± 4 mmol/mol; and 8.6 ± 0.4%, 70 ± 4 mmol/mol) (P &amp;lt; 0.001) and were more striking in those with diabetes for ≥2 years (7.9 ± 2.8, 9.9 ± 2.8, and 9.8 ± 2.6%). Over one-half of those on insulin-containing therapies still experience treatment failure (A1C ≥8%, 64 mmol/mol). CONCLUSIONS Approximately half of youth with type 2 diabetes were managed with lifestyle or metformin alone and had better glycemic control than individuals using other therapies. Those with longer diabetes duration in particular commonly experienced treatment failures, and more effective management strategies are needed.
A neutrophil elastase inhibitor prevents bleomycin-induced pulmonary fibrosis in mice
Authors: Akihiro Takemasa, Yoshiki Ishii, Takeshi Fukuda
Journal: European Respiratory Journal (2012)

Neutrophil elastase plays pivotal roles in the pathogenesis of pulmonary fibrosis. The neutrophil elastase inhibitor, sivelestat, could alleviate pulmonary fibrosis; however, the antifibrotic mechanisms have not yet been clarified. We examined the antifibrotic mechanisms, mainly focusing on a key fibrotic cytokine, transforming growth factor (TGF)-β1, in this study. To elucidate the antifibrotic mechanisms of sivelestat, we examined a murine model of bleomycin-induced early-stage pulmonary fibrosis. After intratracheal instillation of bleomycin, sivelestat was administered intraperitoneally once a day for 7 or 14 days. Bronchoalveolar lavage fluid and lung samples were examined on day 7 or day 14 after bleomycin instillation. In the bleomycin-induced early-stage pulmonary fibrosis model, the neutrophil elastase level was increased in the lungs. Sivelestat significantly inhibited the increase in lung collagen content, fibrotic changes, the numbers of total cells (including macrophages, neutrophils and lymphocytes), the levels of the active form of TGF-β1 and phospho-Smad2 in bleomycin-induced early-stage pulmonary fibrosis. The total TGF-β1 levels and relative changes of TGF-β1 mRNA expression, however, were not decreased significantly by sivelestat. These results suggest that sivelestat alleviated bleomycin-induced pulmonary fibrosis via inhibition of both TGF-β activation and inflammatory cell recruitment in the lung.
Assessment of pulmonary macrophage and neutrophil function in sequential bronchoalveolar lavage aspirates in sarcoidosis.
Authors: C A Kelly, C Ward, S C Stenton, D J Hendrick, E H Walters
Journal: Thorax (1988)

Bronchoalveolar lavage was performed in eight patients with biopsy proved sarcoidosis and eight control subjects matched for age and smoking habit, three sequential 60 ml aliquots of sterile saline being used. Each aliquot was aspirated and analysed separately to determine total and differential cell counts. Cellular metabolic activity was stimulated with latex and measured by means of luminol enhanced chemiluminescence to assess neutrophil activity and lucigenin enhanced chemiluminescence to assess macrophage activity. In control subjects mean total cell counts were significantly greater in the second aspirate than in the first, but fell slightly in the third. Similarly, in the patients with sarcoidosis mean total cell counts increased from aspirate 1 to a maximum in aspirate 2, before falling again marginally in aspirate 3. The only significant difference in cell counts between patients with sarcoidosis and controls was an approximately threefold increase in total lymphocyte counts in the former in each of the three aspirates. Luminol chemiluminescence was similar in patients with sarcoidosis to that in controls in the first aspirate, but was significantly greater in the second and third aspirates. Lucigenin chemiluminescence was also significantly greater in the second and third aspirates only. Thus in patients with sarcoidosis lymphocyte numbers are increased in all three aspirates whereas cellular metabolic activity is increased to a greater extent in later aspirates, which may reflect events occurring in the periphery of the lung segment.
Release of heparan sulfate from endothelial cells. Implications for pathogenesis of hyperacute rejection.
Authors: J L Platt, G M Vercellotti, B J Lindman, T R Oegema, F H Bach, A P Dalmasso
Journal: The Journal of Experimental Medicine (1990)

Heparan sulfate proteoglycan associated with endothelial cells in normal blood vessels inhibits intravascular coagulation and egress of blood cells and plasma proteins, key features of hyperacute rejection. It was shown herein that exposure of cultured porcine endothelium to human serum as a source of natural antibodies and complement caused cleavage and release of 5% of endothelial cell proteoglycans within 4 min and greater than 50% within 1 h. Proteoglycan release depended on activation of the classical complement pathway and preceded irreversible cell injury. These findings suggest that loss of endothelial cell proteoglycan may be a critical step in the pathogenesis of hyperacute rejection and in diseases involving humoral injury to endothelial cells.
Use of Heart Rate Reserve and Rating of Perceived Exertion to Prescribe Exercise Intensity in Diabetic Autonomic Neuropathy
Authors: Sheri R. Colberg, David P. Swain, Aaron I. Vinik
Journal: Diabetes Care (2003)

OBJECTIVE—Individuals with diabetic autonomic neuropathy (DAN) exhibit an increased resting heart rate but depressed maximal heart rate. Thus, the purpose of this study was to examine the validity of using either percent of heart rate reserve (HRR) or a rating of perceived exertion (RPE) scale to prescribe exercise intensity in diabetic individuals both with and without DAN. RESEARCH DESIGN AND METHODS—The subjects consisted of 23 individuals with type 2 diabetes, ages 45–75 years, with (DAN; n = 13) or without (No DAN; n = 10) clinical signs of DAN, as assessed by heart rate variability using the expiration-to-inspiration ratio of the R-R interval. Peak aerobic capacity was determined using a graded protocol on a cycle ergometer, with RPE, heart rate, and Vo2 values recorded at each stage. RESULTS—The subjects were similar with the exception of depressed autonomic function in DAN subjects. Peak respiratory exchange ratio values were significantly higher (P &amp;lt; 0.05) in the DAN group (1.08 ± 0.02 vs. 1.02 ± 0.01 in No DAN subjects), although DAN subjects exhibited a significantly lower (P &amp;lt; 0.05) peak exercise heart rate. A similarly highly linear relationship between %HRR and percent Vo2 reserve (Vo2R) existed for both groups (r = 0.98). A similar slightly weaker relationship (r = 0.94) was found between RPE and %Vo2R. CONCLUSIONS—In conclusion, in diabetic individuals, %HRR provides an accurate prediction of %Vo2R and can be used to prescribe and monitor exercise intensity, regardless of the presence of DAN. The RPE scale is also a valid, albeit slightly less accurate, method to monitor exercise intensity in diabetic individuals.
Breast Cancer After Chest Radiation Therapy for Childhood Cancer
Authors: Chaya S. Moskowitz, Joanne F. Chou, Suzanne L. Wolden, Jonine L. Bernstein, Jyoti Malhotra, Danielle Novetsky Friedman, Nidha Z. Mubdi, Wendy M. Leisenring, Marilyn Stovall, Sue Hammond, Susan A. Smith, Tara O. Henderson, John D. Boice, Melissa M. Hudson, Lisa R. Diller, Smita Bhatia, Lisa B. Kenney, Joseph P. Neglia, Colin B. Begg, Leslie L. Robison, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2014)

The risk of breast cancer is high in women treated for a childhood cancer with chest irradiation. We sought to examine variations in risk resulting from irradiation field and radiation dose.
IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4+ Th17 cells
Authors: Margherita Coccia, Oliver J. Harrison, Chris Schiering, Mark J. Asquith, Burkhard Becher, Fiona Powrie, Kevin J. Maloy
Journal: The Journal of Experimental Medicine (2012)

Although very high levels of interleukin (IL)-1β are present in the intestines of patients suffering from inflammatory bowel diseases (IBD), little is known about the contribution of IL-1β to intestinal pathology. Here, we used two complementary models of chronic intestinal inflammation to address the role of IL-1β in driving innate and adaptive pathology in the intestine. We show that IL-1β promotes innate immune pathology in Helicobacter hepaticus-triggered intestinal inflammation by augmenting the recruitment of granulocytes and the accumulation and activation of innate lymphoid cells (ILCs). Using a T cell transfer colitis model, we demonstrate a key role for T cell-specific IL-1 receptor (IL-1R) signals in the accumulation and survival of pathogenic CD4(+) T cells in the colon. Furthermore, we show that IL-1β promotes Th17 responses from CD4(+) T cells and ILCs in the intestine, and we describe synergistic interactions between IL-1β and IL-23 signals that sustain innate and adaptive inflammatory responses in the gut. These data identify multiple mechanisms through which IL-1β promotes intestinal pathology and suggest that targeting IL-1β may represent a useful therapeutic approach in IBD.
Follow-up Testing Among Children With Elevated Screening Blood Lead Levels
Authors: Alex R. Kemper
Journal: JAMA (2005)

Follow-up testing after an abnormal screening blood lead level is a key component of lead poisoning prevention.To measure the proportion of children with elevated screening lead levels who have follow-up testing and to determine factors associated with such care.Retrospective, observational cohort study of 3682 Michigan Medicaid-enrolled children aged 6 years or younger who had a screening blood lead level of at least 10 microg/dL (0.48 micromol/L) between January 1, 2002, and June 30, 2003.Testing within 180 days of an elevated screening lead level.Follow-up testing was received by 53.9% (95% confidence interval [CI], 52.2%-55.5%) of the children. In multivariate analysis adjusting for age, screening blood lead level results, and local health department catchment area, the relative risk of follow-up testing was lower for Hispanic or nonwhite children than for white children (0.91; 95% CI, 0.87-0.94), for children living in urban compared with rural areas (0.92; 95% CI, 0.89-0.96), and for children living in high- compared with low-risk lead areas (0.94; 95% CI, 0.92-0.96). Among children who did not have follow-up testing, 58.6% (95% CI, 56.3%-61.0%) had at least 1 medical encounter in the 6-month period after the elevated screening blood lead level, including encounters for evaluation and management (39.3%; 95% CI, 36.9%-41.6%) or preventive care (13.2%; 95% CI, 11.6%-14.8%).The rate of follow-up testing after an abnormal screening blood lead level was low, and children with increased likelihood of lead poisoning were less likely to receive follow-up testing. At least half of the children had a missed opportunity for follow-up testing. The observed disparities of care may increase the burden of cognitive impairment among at-risk children.
Near-Infrared Spectroscopy: A Novel, Noninvasive, Diagnostic Method for Detrusor Overactivity in Patients with Overactive Bladder Symptoms—A Preliminary and Experimental Study
Authors: Fawzy F. Farag, Frank M. Martens, Kathleen W. D'Hauwers, Wout F. Feitz, John P. Heesakkers
Journal: European Urology (2010)