tbuckley/cabot-search huggingface dataset:
Factors That Impact Symptomatic Diabetic Peripheral Neuropathy in Placebo-Administered Patients From Two 1-Year Clinical Trials
Authors: Solomon Tesfaye, Rup Tandan, Edward J. Bastyr, Keri A. Kles, Vladimir Skljarevski, Karen L. Price
Journal: Diabetes Care (2007)

The purpose of this study was to evaluate the change in neuropathy symptoms and disease progression in placebo-administered patients from two 1-year studies in which the impact of ruboxistaurin (RBX) in mild diabetic peripheral neuropathy (DPN) was tested.Data from 262 placebo-administered patients from two identical phase 3, randomized, double-blind trials were combined and analyzed.After 1 year, change in the neuropathy impairment score of lower limbs [NIS(LL)] (-0.63 points; P = 0.005), vibration detection threshold (VDT) (-0.42 just noticeable difference units; P = 0.003), and Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire (-3.73 points; P < 0.001) improved, whereas some electrophysiology measures and heart rate deep breathing (HRDB) (-0.78 beats; P = 0.003) worsened compared with baseline values. There was a small but significant worsening of A1C (0.28%; P < 0.001), and a greater percentage of patients were using analgesics at the end of the trials (33.6%; P = 0.003). At 1 year, the change in NTSS-6 directly correlated with changes in NIS(LL) and VDT and inversely correlated with the peroneal nerve conduction velocity. On logistic regression analyses, a > or = 50% reduction in NTSS-6 score was less likely in patients who used antihypertensive or chronic symptom medication at baseline.In placebo-administered patients with mild symptomatic DPN, there was a progressive improvement in symptoms over 12 months, whereas nerve conduction studies and HRDB declined, and clinically significant worsening of DPN would require > 1 year of observation.
Small splenic B cells that bind to antigen-specific T helper (Th) cells and face the site of cytokine production in the Th cells selectively proliferate: immunofluorescence microscopic studies of Th-B antigen-presenting cell interactions.
Authors: H Kupfer, C R Monks, A Kupfer
Journal: The Journal of Experimental Medicine (1994)

Antigen (Ag)-specific T helper (Th) cells regulate the proliferation and differentiation of Ag-specific B cells by secreting cytokines and by expressing activating receptors like gp39. In vitro, the cytokines and the activating receptors function in an Ag-nonspecific manner. It is unclear, therefore, how Ag specificity is imposed on B cell responses in physiological Th-B cell interactions. Here we studied, at the single cell level, the interactions between cloned Th cells and small splenic B cells, which served as Ag-specific antigen-presenting cells (APCs) to the Th cells. Digital confocal immunofluorescence microscopy of Th-B cell conjugates revealed significant variability in the molecular and cellular properties of these interactions, in spite of the fact that all the interactions in this system were expected to be Ag specific. After 30 h of incubation B cells began to divide, and this process was entirely dependent on the presence of both Th cells and Ag. Immunofluorescence microscopic studies showed that essentially all the mitotic B cells were bound to Th cells and faced the microtubule organizing center (MTOC) in the Th cells where interleukin 4 was highly concentrated. Other B cells that were bound to the same Th cells but were not close to the Th-MTOC remained in interphase. These results provide the first direct structural and functional evidence that the site of interaction of B cells with Th cells affects their immune response. We propose that, during Ag-induced Th-B cell interactions, B cells that are bound facing the Th-MTOC proliferate preferentially because they are the recipients of locally secreted cytokines. In addition, these B cells may interact with newly expressed receptors, which may also be locally inserted into the Th membrane. The polarized delivery of activating molecules towards the Th-bound APCs may impose functional specificity on effector molecules that otherwise are not Ag specific.
Hyperglycemia, Type 2 Diabetes, and Depressive Symptoms
Authors: Mika Kivimaki, Adam G. Tabak, G. David Batty, Archana Singh-Manoux, Markus Jokela, Tasnime N. Akbaraly, Daniel R. Witte, Eric J. Brunner, Michael G. Marmot, Debbie A. Lawlor
Journal: Diabetes Care (2009)

To examine the recent suggestion that impaired fasting glucose may protect against depression, whereas a diagnosis of diabetes might then result in depression.Cross-sectional analysis of 4,228 adults (mean age 60.7 years, 73.0% men) who underwent oral glucose tolerance testing and completed the Center for Epidemiologic Studies Depression scale (CES-D).After adjustment for demographic factors, health behaviors, and clinical measurements (BMI, waist circumference, lipid profile, and blood pressure), there was a U-shaped association between fasting glucose and depression (P(curve) = 0.001), with elevated CES-D at low and very high glucose levels. This finding was replicable with 2-h postload glucose (P = 0.11) and A1C (P = 0.007).The U-shaped association between blood glucose and CES-D, with the lowest depression risk seen among those in the normoglycemic range of A1C, did not support the hypothesized protective effect of hyperglycemia.
Differences in cardioprotective efficacy of adrenergic receptor antagonists and Ca2+ channel antagonists in an animal model of dilated cardiomyopathy. Effects on gross morphology, global cardiac function, and twitch force.
Authors: M G Glass, F Fuleihan, R Liao, A M Lincoff, R Chapados, R Hamlin, C S Apstein, P D Allen, J S Ingwall, R J Hajjar
Journal: Circulation Research (1993)

Turkey poults fed furazolidone (Fz) in high concentrations (700 ppm) develop dilated cardiomyopathy (Fz-DCM). We tested whether five cardioactive agents were cardioprotective in this model of heart failure, ie, whether they prevented dilatation and wall thinning and improved contractile performance. We compared the effects of chronic administration of a beta 1-selective and a nonselective beta-receptor antagonist, an alpha-receptor antagonist, and two Ca2+ channel antagonists in the presence of Fz administration. The greatest cardioprotection was found with treatment with either propranolol or nifedipine. At the gross morphological level, the effect of propranolol (a nonselective beta-adrenergic antagonist) was greater than the effect of atenolol (a selective beta 1-adrenergic antagonist), and the effect of nifedipine was greater than that of verapamil (Ca2+ channel antagonists), with all agents more cardioprotective than phenoxybenzamine (an alpha 1-adrenergic &gt; alpha 2-adrenergic antagonist). Differences in cardioprotective efficacy of each agent increased with increased concentration. These data indicate that the dose and choice of a specific type of Ca2+ channel antagonist or beta-receptor antagonist might be important in the treatment of dilated cardiomyopathy. All agents that were cardioprotective caused similar functional improvements at both the whole heart and isolated muscle levels. Compared with control animals, Fz-DCM animals showed a significant reduction in peak left ventricular (LV) developed pressure (92 +/- 17 versus 143 +/- 24 mm Hg, P &lt; .05), +dP/dt (1151 +/- 219 versus 2454 +/- 549 mm Hg/s), and -dP/dt (1128 +/- 291 versus 1875 +/- 396 mm Hg/s), with a significant increase in LV end-diastolic volumes (2.8 +/- 0.7 versus 0.16 +/- 0.1 mL for control animals, P &lt; .05). In contradistinction, LV + dP/dt and -dP/dt values for animals receiving Fz plus a cardioactive agent that demonstrated cardioprotection were not significantly different from control values. Peak LV developed pressures were also similar for Fz animals receiving an agent that demonstrated cardioprotection and control animals not receiving any pharmacologic agent. Isolated muscles from Fz-DCM animals as well as animals receiving Fz plus cardioprotective pharmacologic agents responded normally with regard to increasing extracellular Ca2+ concentrations. Peak twitch forces were greater for animals receiving cardioprotective agents plus Fz than control animals not receiving any pharmacologic agents or Fz alone. At higher stimulation rates, Fz-DCM muscles demonstrated a significantly reduced peak twitch force (4 +/- 0.5 versus 1.5 +/- 0.4 g/mm2 for control muscles versus Fz-DCM muscles, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)
Methylation of Human Papillomavirus Type 16 Genome and Risk of Cervical Precancer in a Costa Rican Population
Authors: Lisa Mirabello, Chang Sun, Arpita Ghosh, Ana C. Rodriguez, Mark Schiffman, Nicolas Wentzensen, Allan Hildesheim, Rolando Herrero, Sholom Wacholder, Attila Lorincz, Robert D. Burk
Journal: JNCI Journal of the National Cancer Institute (2012)

Previous studies have suggested an association between human papillomavirus type 16 (HPV16) genome methylation and cervical intraepithelial neoplasia grade 3 (CIN3) (ie, cervical precancer) and cancer, but the results have been inconsistent.We designed a case-control study within a large prospective cohort of women who underwent multiple screenings for cervical cancer in Guanacaste, Costa Rica. Diagnostic specimens were collected at the time of CIN3 diagnosis (n = 30 case subjects) and persistent HPV16 infection (persistence; n = 35 case subjects), prediagnostic specimens at the first HPV16-positive screening visit (n = 20 CIN3 case subjects; n = 35 persistence case subjects), and control specimens from women with infection clearance within 2 years (n = 34 control subjects). DNA extracted from specimens (cervical cells) was analyzed for methylation levels at 67 CpG sites throughout the HPV16 genome using pyrosequencing. Benjamini-Hochberg method was used to account for multiple testing. Associations between methylation levels and risk of CIN3 or persistence were assessed using logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs).Increased methylation in diagnostic vs control specimens at nine CpG sites, three in each L1, L2, and E2/E4 genomic regions, was associated with an increased risk of CIN3 (third tertile [high] vs first and second tertiles combined [low], OR = 3.29 [95% CI = 1.16 to 9.34] to 11.12 [95% CI = 2.29 to 76.80]) and persistence. High methylation at three of these CpG sites was associated with a much higher risk when combined compared with low methylation at these sites (OR = 52, 95% CI = 4.0 to 670). In prediagnostic vs control specimens, increased methylation at a CpG site (nucleotide position 4261) in L2 was associated with an increased risk of CIN3.In this HPV16-infected cohort, increased methylation of CpG sites within the HPV16 genome before diagnosis and at the time of diagnosis was associated with cervical precancer.
Overcoming resistance and restoring sensitivity to HER2-targeted therapies in breast cancer
Authors: M.S.N. Mohd Sharial, J. Crown, B.T. Hennessy
Journal: Annals of Oncology (2012)

Approximately 15%-23% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2), which leads to the activation of signaling pathways that stimulate cell proliferation and survival. HER2-targeted therapy has substantially improved outcomes in patients with HER2-positive breast cancer. However, both de novo and acquired resistance are observed.
Novel Mechanisms for Maintaining Endothelial Barrier Function in Sepsis
Authors: Marc S. Penn, Megan Kamath
Journal: Circulation (2012)

T he pathophysiology of multiple disease states, including sepsis, 1,2 hypertension, 1 atherosclerosis, [3][4][5] and ischemiareperfusion injury, 6 is characterized by loss of the endothelial barrier function leading to the accumulation of plasma-borne proteins, tissue edema, and cell death.Importantly therapeutic strategies that inhibit loss of endothelial barrier function have been associated with strategies that improve outcomes. 7There is growing understanding of the role of adherens in maintaining the integrity of the endothelial barrier function 8 and the molecular pathways that regulate adheren expression.
Osteopontin promotes host defense during Klebsiella pneumoniae-induced pneumonia
Authors: G.J.W. van der Windt, J.J. Hoogerwerf, A.F. de Vos, S. Florquin, T. van der Poll
Journal: European Respiratory Journal (2010)

Klebsiella pneumoniae is a common cause of nosocomial pneumonia. Osteopontin (OPN) is a phosphorylated glycoprotein involved in inflammatory processes, some of which is mediated by CD44. The aim of this study was to determine the role of OPN during K. pneumoniae-induced pneumonia. Wild-type (WT) and OPN knockout (KO) mice were intranasally infected with 10⁴ colony forming units of K. pneumoniae, or administered Klebsiella lipopolysaccharides (LPS). In addition, recombinant OPN (rOPN) was intranasally administered to WT and CD44 KO mice. During Klebsiella pneumonia, WT mice displayed elevated pulmonary and plasma OPN levels. OPN KO and WT mice showed similar pulmonary bacterial loads 6 h after infection; thereafter, Klebsiella loads were higher in lungs of OPN KO mice and the mortality rate in this group was higher than in WT mice. Early neutrophil recruitment into the bronchoalveolar space was impaired in the absence of OPN after intrapulmonary delivery of either Klebsiella bacteria or Klebsiella LPS. Moreover, rOPN induced neutrophil migration into the bronchoalveolar space, independent from CD44. In vitro, OPN did not affect K. pneumoniae growth or neutrophil function. In conclusion, OPN levels were rapidly increased in the bronchoalveolar space during K. pneumoniae pneumonia, where OPN serves a chemotactic function towards neutrophils, thereby facilitating an effective innate immune response.
Relationship Between Adiponectin and Glycemic Control, Blood Lipids, and Inflammatory Markers in Men With Type 2 Diabetes
Authors: Matthias B. Schulze, Eric B. Rimm, Iris Shai, Nader Rifai, Frank B. Hu
Journal: Diabetes Care (2004)

OBJECTIVE—Adiponectin, synthesized in the adipose tissue, appears to play an important role in hyperglycemia and dyslipidemia, as well as in inflammatory mechanisms, which lead to a markedly increased atherosclerotic risk in diabetic subjects. However, previous studies did not evaluate the complex relationships between adiponectin and the array of metabolic abnormalities commonly observed in diabetes. RESEARCH DESIGN AND METHODS—To examine the associations between plasma levels of adiponectin and HbA1c, blood lipids, and inflammatory markers, we obtained blood samples from 741 participants in the Health Professionals Follow-up Study with a diagnosis of type 2 diabetes. RESULTS—Plasma adiponectin levels were positively correlated with HDL cholesterol and negatively correlated with triglycerides, apolipoprotein B-100 (apoB100), C-reactive protein (CRP), and fibrinogen. These associations were not appreciably altered after controlling for lifestyle exposures, medical conditions, and obesity-associated variables. A 10-μg/ml higher level of plasma adiponectin was associated with lower HbA1c (−0.21% points, P = 0.001), triglycerides (−0.39 mmol/l, P &amp;lt; 0.001), apoB100 (−0.04 g/l, P &amp;lt; 0.001), CRP (−0.51 mg/l, P = 0.003), and fibrinogen (−0.53 μmol/l, P &amp;lt; 0.001) and higher HDL cholesterol (0.13 mmol/l, P &amp;lt; 0.001). Associations between adiponectin and inflammatory markers were furthermore independent of HbA1c and HDL cholesterol, suggesting that the anti-inflammatory properties of adiponectin are not mediated by potential effects on glycemic control and blood lipids. Our results were consistent among obese and nonobese men. CONCLUSIONS—Our study supports the hypothesis that increased adiponectin levels might be associated with better glycemic control, better lipid profile, and reduced inflammation in diabetic subjects. Measures that increase adiponectin levels might be valuable targets for decreasing the atherosclerotic risk present in diabetes.
Timing of Familial Breast Cancer in Sisters
Authors: Paola Rebora, Kamila Czene, Marie Reilly
Journal: JNCI Journal of the National Cancer Institute (2008)

BackgroundWomen who have had a first-degree relative diagnosed with breast cancer (ie, a positive family history) have a rate of breast cancer that is approximately twice that of all women their age, but it is unclear how they should perceive this risk at different ages or if they should be considered at higher risk for the remainder of their lifetime.
Extrahepatic portal vein thrombosis: aetiology and determinants of survival
Authors: H L A Janssen
Journal: Gut (2001)

<h3>BACKGROUND</h3> Malignancy, hypercoagulability, and conditions leading to decreased portal flow have been reported to contribute to the aetiology of extrahepatic portal vein thrombosis (EPVT). Mortality of patients with EPVT may be associated with these concurrent medical conditions or with manifestations of portal hypertension, such as variceal haemorrhage. <h3>PATIENTS AND METHODS</h3> To determine which variables have prognostic significance with respect to survival, we performed a retrospective study of 172 adult EPVT patients who were followed over the period 1984–1997 in eight university hospitals. <h3>RESULTS</h3> Mean follow up was 3.9 years (range 0.1–13.1). Overall survival was 70% (95% confidence interval (CI) 62–76%) at one year, 61% (95% CI, 52–67%) at five years, and 54% (95% CI, 45–62%) at 10 years. The one, five, and 10 year survival rates in the absence of cancer, cirrhosis, and mesenteric vein thrombosis were 95% (95% CI 87–98%), 89% (95% CI 78–94%), and 81% (95% CI 67–89%), respectively (n=83). Variables at diagnosis associated with reduced survival according to multivariate analysis were advanced age, malignancy, cirrhosis, mesenteric vein thrombosis, absence of abdominal inflammation, and serum levels of aminotransferase and albumin. The presence of variceal haemorrhage and myeloproliferative disorders did not influence survival. Only four patients died due to variceal haemorrhage and one due to complications of a portosystemic shunt procedure. <h3>CONCLUSION</h3> We conclude that mortality among patients with EPVT is related primarily to concurrent disorders leading to EPVT and not to complications of portal hypertension.
Carcinogenic Activity of Polycyclic Pseudoazulenes Containing Both Nitrogen and Sulfur Heterocycles&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: F. Zajdela, N. P. Buu-Hoï, P. Jacquignon, A. Croisy, F. Périn
Journal: JNCI Journal of the National Cancer Institute (1971)

Nine polycyclic pseudoazulenes derived from the nitrogen-and sulfur-containing heterocycles [1]benzothiopyrano[4,3-b]indole and thieno[3′,4′:5,6]thiopyrano[4,3-b]indole were tested for carcinogenicity in mice by subcutaneous injection. Three compounds, all belonging to the first group, were found to be sarcomagenic. The high activity of 6,13-dihydrobenzo[e][1]benzothiopyrano[4,3-b]indole is of particular interest because it surpasses that of the structurally related 7H-dibenzo[a,g]-carbazole.
A controlled therapeutic trial of long-term maintenance treatment of ulcerative colitis with sulphasalazine (Salazopyrin)
Authors: A. S. Dissanayake, S. C. Truelove
Journal: Gut (1973)

Sixty-four patients with proven ulcerative colitis who had been maintained on sulphasalazine as their sole form of treatment for a minimum period of one year were entered into a controlled trial of sulphasalazine versus dummy tablets for a period of six months. All the patients admitted were not only symptom-free but also showed no evidence of inflammation on sigmoidoscopy and rectal biopsy. A patient was judged to have relapsed when there was a recurrence of colitic symptoms accompanied by sigmoidoscopic and histological evidence of inflammation. The patients who received dummy tablets had more than four times the relapse rate of those receiving sulphasalazine. The results were similar in patients who had been on maintenance treatment with sulphasalazine for less than three years before entry into the trial and in those who had been on this treatment for more than three years. It is concluded that maintenance treatment of ulcerative colitis with sulphasalazine should be continued indefinitely unless contraindicated by side effects.
The best on infections: update from the 2010 ERS Congress
Authors: M. Miravitlles, G. Sotgiu, G. Dimopoulos, G. Rohde, R. Centis, G. Ferrara, S. Ewig, F. Blasi, G.B. Migliori
Journal: European Respiratory Journal (2011)

Respiratory tract infections and tuberculosis are among the leading reasons for seeking medical care. In this report the most recent advances in the field of clinical research and basic sciences of respiratory infections and tuberculosis are presented through the analysis of some of the best abstracts presented at the 20th European Respiratory Society Congress in Barcelona, Spain and their subsequent publications in major journals. The role of viruses in chronic obstructive pulmonary disease exacerbations, the importance of new biomarkers in the management and risk assessment of lower respiratory tract infections, new modalities of treatment of respiratory infections as well as new tools for the diagnosis of latent and active tuberculosis in special subgroups of patients (children and immunocompromised individuals), and the new epidemiological threat of multidrug-resistant and extensively drug-resistant tuberculosis cases are discussed.
CD34+CD7+ Leukemic Progenitor Cells May Be Involved in Maintenance and Clonal Evolution of Chronic Myeloid Leukemia
Authors: Nobuharu Kosugi, Yasuhiro Ebihara, Tatsutoshi Nakahata, Hiromitsu Saisho, Shigetaka Asano, Arinobu Tojo
Journal: Clinical Cancer Research (2005)

We analyzed CD34+ cells coexpressing CD7 in chronic myeloid leukemia (CML) in chronic phase (CP) or accelerated phase (AP) to clarify their role in progression or regression of the disease during treatment.Enumeration of CD34+CD7+ cells was done on bone marrow nucleated cells from normal donors and CML patients. Fluorescence in situ hybridization analysis was done on sorted CD34+CD7+and CD34+CD7- cells to examine the occupancy rate of each fraction by BCR-ABL+ cells with or without additional cytogenetic abnormalities.The proportion of CD34+CD7+cells was significantly affected by the treatment outcome and/or the disease status as follows: 20.5 +/- 10.4% in normal donors (n = 22), 18.1 +/- 10.2% in CP with major cytogenetic response (n = 14), 53.0 +/- 12.9% in CP at diagnosis (n = 18), 55.0 +/- 15.8% in CP with minor or no cytogenetic response (n = 28), and 70.2 +/- 18.1% in AP (n = 6). The proportion of CD34+CD7+cells decreased in parallel with cytogenetic improvement in individual patients. In six untreated CP patients, the ratio of BCR-ABL+ cells was comparable between each fraction. In three patients with major cytogenetic response, the ratio of BCR-ABL+ cells was remarkably lower in CD34+CD7- cells than in CD34+CD7+cells. In three AP patients with additional cytogenetic abnormalities, extra signals were detected at a much higher rate in CD34+CD7+ cells than in CD34+CD7- cells.Our results suggest that CD34+CD7+ cells may be involved in maintenance and clonal evolution of BCR-ABL+ cells in CML.
Clinical Note on the Treatment of Burns and Scalds
Authors: J. W. Browne
Journal: BMJ (1884)

u0"-°-HB MI 4AJRNL.fO3t. 11, 1884.to exist, and the various groups of ganglionic cells can therefore no longer be combined for synergic, orderly, or purposic action.There is no longer any harmony between the muscles which act, and their *antagonists which regulate the action ; wrong groups of muscles are called into play, which impair the action instead of facilitating it j and there is therefore useless expenditure of nerve-force, causing