tbuckley/cabot-search huggingface dataset:
Epalrestat, an aldose reductase ihibitor, reduces the levels of Nepsilon-(carboxymethyl)lysine protein adducts and their precursors in erythrocytes from diabetic patients.
Authors: Y Hamada, J Nakamura, K Naruse, T Komori, K Kato, Y Kasuya, R Nagai, S Horiuchi, N Hotta
Journal: Diabetes Care (2000)

OBJECTIVE: To clarify the role of the polyol pathway in the intracellular formation of advanced glycation end products in human tissues, we examined the effects of epalrestat, an aldose reductase inhibitor, on the level of Nepsilon-(carboxymethyl)lysine (CML) along with 3-deoxyglucosone (3-DG) and triosephosphates in erythrocytes from diabetic patients. Plasma thiobarbituric acid-reactive substances (TBARS) were also determined as indicators of oxidative stress. RESEARCH DESIGN AND METHODS: Blood samples were collected from 12 nondiabetic volunteers, 38 untreated type 2 diabetic patients, and 16 type 2 diabetic patients who had been treated with 150 mg epalrestat/day. Blood samples were also collected from 14 of the untreated type 2 diabetic patients before and after the administration of epalrestat for 2 months. The amount of erythrocyte CML was determined by a competitive enzyme-linked immunosorbent assay, and 3-DG was measured by high-performance liquid chromatography RESULTS: In diabetic patients not treated with epalrestat, the erythrocyte CML level was significantly elevated above levels seen in nondiabetic individuals (49.9 +/- 5.0 vs. 31.0 +/- 5.2 U/g protein, P &amp;lt; 0.05) and was significantly lower in patients receiving epalrestat (33.1 +/- 3.8 U/g protein, P &amp;lt; 0.05). Similar results were observed with 3-DG. The treatment of patients with epalrestat for 2 months significantly lowered the level of erythrocyte CML (46.2 +/- 5.6 at baseline vs. 34.4 +/- 5.0 U/g protein, P &amp;lt; 0.01) along with erythrocyte 3-DG (P &amp;lt; 0.05), triosephosphates (P &amp;lt; 0.05), fructose (P &amp;lt; 0.05), sorbitol (P &amp;lt; 0.05), and plasma TBARS (P &amp;lt; 0.05) without changes in plasma glucose and HbA(1c) levels. A positive correlation was evident between the erythrocyte CML and sorbitol (r = 0.49, P &amp;lt; 0.01) or fructose (r = 0.40, P &amp;lt; 0.05) levels in diabetic patients. CONCLUSIONS: The results indicate that epalrestat administration lowers CML and associated variables and that polyol metabolites are correlated with CML in the erythrocytes of diabetic patients. The observed results suggest that aldose reductase activity may play a substantial role in the intracellular formation of CML in the mediation of reactive intermediate metabolites and oxidative stress.
About saccade generation in reading
Authors: Françoise Vitu
Journal: Behavioral and Brain Sciences (1999)

In their model, Findlay &amp; Walker propose that where and when the eyes move is determined by two relatively independent processing streams. Whereas both saccade direction and amplitude result from a low-level visual analysis of the peripheral visual stimulation, saccade latency results mainly from higher-level processes related to processing of the central information. In the present commentary, reading eye movement data are put forward as evidence against a strict autonomy of “Where” and “When” processing streams. First, saccade direction and amplitude might be modified by high-level processes related to word identification. Second, the direction of a saccade directly affects its latency.
Poxviral-Based Prostate-Specific Antigen Vaccine in Prostate Cancer
Authors: Luis León, María C. Areses, Urbano Anido, Antonio Gómez, Ana M. Carballo
Journal: Journal of Clinical Oncology (2010)

ClinicalOncology, Kantoff et al 1 reported the results of a phase II randomized trial of a poxviral-based prostate-specific antigen vaccine (PROSTVAC) in metastatic castration-resistant prostate cancer.Eighty-two patients received PROSTVAC and 40 received control vectors.The primary end point was progression-free survival, which was similar in both groups (hazard ratio, 0.884; 95% CI, 0.568 to 1.375; P ϭ .6),but overall survival (OS) favored PROSTVAC arm (25.1 v 16.6 months).The authors conclude that PROSTVAC immunotherapy is associated with a 44% reduction in the death rate and an 8.5-month improvement in median OS.Although these data merit further exploration, we have concerns about whether both study arms are comparable.First, the difference in median age (71.6 v 79 years), percentage of lymph node involvement only (9.8% v 0%), and median survival estimated by Halabi nomogram may favor the PROSTVAC arm.Second, as Kantoff et al 1 point out, the lack of treatment data after initial progression limits the interpretation of the survival result.PROSTVAC plus subsequent treatment improved in 3 months the survival predicted by Halabi.In the control arm, OS is reduced by 4 months as estimated by the Halabi nomogram.Half of the patients in the control arm received PROSTVAC as second-line treatment.An interesting question is whether a higher percentage of patients in the PROSTVAC arm received second-line docetaxel, obtaining a benefit in survival.Third, Kantoff et al 1 mentioned that only docetaxel has been shown to affect survival in metastatic prostate cancer, by approximately 3 months.In the TAX 327 study, an OS of 19.2 months was reported in the every-3-weeks docetaxel arm. 2 Nevertheless, patients included in the TAX 327 had an disfavorable prognosis when compared with the PROSTVAC study.Patients in TAX 327 were more symptomatic with a higher median prostate-specific antigen, Eastern Cooperative Oncology Group performance status of 2 was permitted, and 30% of patients had a Gleason score of 8 to 10.In a retrospective subanalysis of 110 minimally symptomatic patients, Berthold et al 3 reported an OS of 28.4,25.9, and 22 months for docetaxel every 3 weeks, docetaxel every week, or mitoxantrone, respectively.These differences did not reach statistical significance as a result of the small number of patients, and the results should be interpreted with caution.These data suggest than docetaxel should offer similar results to PROSTVAC in this population and should be the control arm in a phase III study.We agree with Kantoff et al 1 that their findings are regarded as hypothesis generating, but OS data should be interpreted with caution in the absence of treatment information after progression to PROSTVAC or placebo.
Intravenous montelukast in acute asthma: expensive aminophylline?
Authors: O. J DEMPSEY
Journal: Thorax (2000)

We read with interest the recent paper by Dockhorn et al comparing the effects of single doses of intravenous and oral montelukast on forced expiratory volume in one second (FEV1) in patients with chronic persistent asthma.1 We agree with the accompanying editorial, that a study of montelukast in acute severe asthma is now warranted.2 Indeed, few published studies have examined the use of leukotriene receptor antagonists in patients with severe persistent asthma.3 

There are several …
The absolute and relative coronary flow velocity reserve after lumen enlargement by ultrasound-guided balloon angioplasty and stent implantation
Authors: R.A.M. van Liebergen, J.J. Piek, R.J.G. Peters, K.T. Koch, R.J. de Winter, C.E. Schotborgh
Journal: Journal of the American College of Cardiology (1998)
Low Hepatitis C Viral Load Predicts Better Long-Term Outcomes in Patients Undergoing Resection of Hepatocellular Carcinoma Irrespective of Serologic Eradication of Hepatitis C Virus
Authors: Junichi Shindoh, Kiyoshi Hasegawa, Yutaka Matsuyama, Yosuke Inoue, Takeaki Ishizawa, Taku Aoki, Yoshihiro Sakamoto, Yasuhiko Sugawara, Masatoshi Makuuchi, Norihiro Kokudo
Journal: Journal of Clinical Oncology (2012)

Hepatitis C virus (HCV) infection has been recognized as a potent risk factor for the postoperative recurrence of hepatocellular carcinoma (HCC). However, little is known about the impact of HCV viral load on surgical outcomes. The study objective was to investigate clinical significance of HCV viral load on long-term outcomes of HCC.Three hundred seventy patients who were classified as Child-Pugh class A and underwent curative liver resections for HCV-related HCC were divided into low and high viral load groups (≤ or > 5.3 log(10)IU/mL) based on the results of a minimum P value approach to predict moderate to severe activity of hepatitis; the clinical outcomes were then compared.The 5-year recurrence-free survival rate was 36.1% in the low viral load group and 12.4% in the high viral load group (P < .001). The 5-year overall survival rate was 76.6% in the low viral load group and 57.7% in the high viral load group (P < .001). Multivariate analysis confirmed significant correlation between high viral load and tumor recurrence with a hazard ratio of 1.87 (95% CI, 1.41 to 2.48; P < .001). Subanalysis revealed that the favorable results in the low viral load group were not attributed to whether or not serologic eradication of HCV was obtained both in primary and recurrent lesions.Low HCV viral load predicts better long-term surgical outcomes in patients with HCC regardless of the serologic eradication of HCV.
Membranous Nephropathy with Crescents
Authors: Amanda Walton Basford, Julia Lewis, Jamie P. Dwyer, Agnes B. Fogo
Journal: Journal of the American Society of Nephrology (2011)

Membranous nephropathy is a common cause of nephrotic syndrome in adults and can be primary or secondary to systemic lupus erythematosus, chronic infection, or drugs. Rapid decline in renal function in patients with membranous nephropathy may be due to renal vein thrombosis, malignant hypertension, or an additional superimposed destructive process involving the renal parenchyma. Crescents are rare in primary membranous nephropathy and thus suggest another underlying disease process, such as combined membranous and focal or diffuse lupus nephritis. However, in some patients with membranous nephropathy and crescents, the crescentic lesion may be due to a distinct, separate disease process, such as anti-glomerular basement membrane antibodies or anti-neutrophil cytoplasmic antibodies-related pauci-immune glomerulonephritis. Here we describe a case with such renal biopsy findings, review previous reported cases, and discuss possible implications for pathogenesis of the coexistence of these lesions.
Efficacy of fumaric acid ester monotherapy in psoriasis pustulosa palmoplantaris
Authors: H. Stander, A. Stadelmann, T. Luger, H. Traupe
Journal: British Journal of Dermatology (2003)

Sir, Psoriasis pustulosa palmoplantaris (PPP) considerably affects the quality of life because of its location, its chronic course and its poor response to treatment. Treatment modalities include photochemotherapy, systemic retinoids, methotrexate and immunosuppressive drugs such as ciclosporin and mycophenolate mofetil,1–3 which are frequently associated with serious side‐effects. Fumaric acid esters (FAE) have been shown to be safe and effective in severe plaque psoriasis.4–6 Further observations indicate FAE effectiveness even for those complicating forms of psoriasis such as psoriatic arthropathy, nail involvement, erythrodermic and generalized pustular psoriasis4, 5 which are still difficult to treat. However, the efficacy of FAE on isolated PPP has not been explored so far. This report describes the results of an open prospective clinical study with the aim of evaluating the efficacy of FAE monotherapy in patients who suffered from isolated PPP. Thirteen patients (eight female, five male) from 25 to 78 years of age (mean 52·5 years) suffering from isolated PPP were enrolled for treatment with FAE tablets [Fumaderm®, containing 120 mg dimethylfumarate (DMF) per tablet] for a period of 24 weeks. Patients were seen every 4 weeks for examination and laboratory investigations. The FAE dose was individually adjusted up to a maximum dose of 720 mg (six tablets) per day. Patients who had received active antipsoriatic treatment within the previous 3 weeks were excluded. During this study no accompanying antipsoriatic therapy was allowed except bland topical treatment with petrolatum either without or with 5% salicylic acid. A modified Psoriasis Area and Severity Index (PASI) called Psoriasis pustulosa palmoplantaris Area and Severity Index (PPPASI) was developed (Table 1). The score includes pustules and erosive lesions. A maximum score of 26 can be reached in the PPPASI. The PPPASI score was evaluated for each extremity separately (Table 1) and P‐values were calculated with a t‐test using the Microcal Origin program (OriginLab, Friedrichsdorf/Ts, Germany).
Nocturnal ventilatory support in patients with cystic fibrosis: comparison with supplemental oxygen
Authors: D Gozal
Journal: European Respiratory Journal (1997)

Progressive deterioration of lung function in cystic fibrosis (CF) patients may lead to significant hypoxaemia and hypercapnia, especially during sleep. The effects of bi-level noninvasive positive pressure nasal mask ventilation (NIPPV) on respiration and sleep were compared to those of low-flow oxygen therapy in six CF patients (mean +/- SD age 22.3 +/- 4.7 yrs, with severe lung disease (forced expiratory volume in one second (FEV1) 29.4 +/- 3.4% predicted). Compared to the control night, NIPPV and oxygen therapy significantly improved overall night-time oxygen saturation during both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep stages. However, significant increases in transcutaneous CO2 tension occurred during oxygen therapy, while NIPPV markedly improved alveolar ventilation during all sleep states. Sleep architecture and arousals remained unchanged during NIPPV and oxygen therapy treatment nights. We conclude that noninvasive positive pressure ventilation improves sleep-related hypoxaemia and hypercapnia in severe cystic fibrosis patients without affecting sleep. The long-term compliance and benefits of noninvasive positive pressure ventilation remain unclear.
Metabolic Effects of Chronic Cannabis Smoking
Authors: Ranganath Muniyappa, Sara Sable, Ronald Ouwerkerk, Andrea Mari, Ahmed M. Gharib, Mary Walter, Amber Courville, Gail Hall, Kong Y. Chen, Nora D. Volkow, George Kunos, Marilyn A. Huestis, Monica C. Skarulis
Journal: Diabetes Care (2013)

OBJECTIVE We examined if chronic cannabis smoking is associated with hepatic steatosis, insulin resistance, reduced β-cell function, or dyslipidemia in healthy individuals. RESEARCH DESIGN AND METHODS In a cross-sectional, case-control study, we studied cannabis smokers (n = 30; women, 12; men, 18; 27 ± 8 years) and control subjects (n = 30) matched for age, sex, ethnicity, and BMI (27 ± 6). Abdominal fat depots and intrahepatic fat content were quantified by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Insulin-sensitivity indices and various aspects of β-cell function were derived from oral glucose tolerance tests (OGTT). RESULTS Self-reported cannabis use was: 9.5 (2–38) years; joints/day: 6 (3–30) [median (range)]. Carbohydrate intake and percent calories from carbohydrates, but not total energy intake, were significantly higher in cannabis smokers. There were no group differences in percent total body fat, or hepatic fat, but cannabis smokers had a higher percent abdominal visceral fat (18 ± 9 vs. 12 ± 5%; P = 0.004). Cannabis smokers had lower plasma HDL cholesterol (49 ± 14 vs. 55 ± 13 mg/dL; P = 0.02), but fasting levels of glucose, insulin, total cholesterol, LDL cholesterol, triglycerides, or free fatty acids (FFA) were not different. Adipocyte insulin resistance index and percent FFA suppression during an OGTT was lower (P &amp;lt; 0.05) in cannabis smokers. However, oral glucose insulin sensitivity index, measures of β-cell function, or incretin concentrations did not differ between the groups. CONCLUSIONS Chronic cannabis smoking was associated with visceral adiposity and adipose tissue insulin resistance but not with hepatic steatosis, insulin insensitivity, impaired pancreatic β-cell function, or glucose intolerance.
Do the Health Benefits of Cycling Outweigh the Risks?
Authors: Jeroen Johan de Hartog, Hanna Boogaard, Hans Nijland, Gerard Hoek
Journal: Environmental Health Perspectives (2010)

Although from a societal point of view a modal shift from car to bicycle may have beneficial health effects due to decreased air pollution emissions, decreased greenhouse gas emissions, and increased levels of physical activity, shifts in individual adverse health effects such as higher exposure to air pollution and risk of a traffic accident may prevail.We describe whether the health benefits from the increased physical activity of a modal shift for urban commutes outweigh the health risks.We have summarized the literature for air pollution, traffic accidents, and physical activity using systematic reviews supplemented with recent key studies.We quantified the impact on all-cause mortality when 500,000 people would make a transition from car to bicycle for short trips on a daily basis in the Netherlands. We have expressed mortality impacts in life-years gained or lost, using life table calculations. For individuals who shift from car to bicycle, we estimated that beneficial effects of increased physical activity are substantially larger (3-14 months gained) than the potential mortality effect of increased inhaled air pollution doses (0.8-40 days lost) and the increase in traffic accidents (5-9 days lost). Societal benefits are even larger because of a modest reduction in air pollution and greenhouse gas emissions and traffic accidents.On average, the estimated health benefits of cycling were substantially larger than the risks relative to car driving for individuals shifting their mode of transport.
The association between Parkinson’s disease and melanoma: a systematic review and meta-analysis
Authors: Pei Huang, Xiao-Dong Yang, Sheng-Di Chen, Qin Xiao
Journal: Translational Neurodegeneration (2015)

To assess the association between Parkinson's disease (PD) and melanoma via systematic review and meta-analysis.Comprehensive search in PubMed, Web of Science, Embase and four China databases (SinoMed, WanFang data, CNKI and VIP database) of epidemiologic evidences on PD and melanoma published before April 30, 2015. Studies which reported risk estimates of melanoma among PD patients or risk estimates of PD in patients with melanoma were included. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated by random-effects models. Heterogeneity across studies was assessed using Cochran Q and I(2) statistics. Subgroup analyses and sensitivity analyses were conducted to evaluate sources of heterogeneity. Subgroup analyses were done according to temporal relationship, geographic region and gender respectively. We assessed publication bias using the Begg and Egger test. In addition, study appraisal was done using a scale for observational studies to ensure the quality of evidence.We identified 24 eligible studies on PD and melanoma with a total number of 292,275 PD patients: the pooled OR was 1.83 (95 % CI 1.46-2.30) overall, subgroup analyses by temporal relationship showed that risk of melanoma after PD diagnosis was significantly higher (OR 2.43, 95 % CI 1.77-3.32), but not before the diagnosis of PD (OR 1.09, 95 % CI 0.78-1.54). Subgroup analysis by geographic region showed that increased risk of melanoma in PD was found both in Europe (OR 1.44, 95 % CI 1.22-1.70) and in North America (OR 2.64, 95 % CI 1.63-4.28). Gender-specific subgroup analyses did not show difference between men (OR 1.64, 95 % CI 1.27-2.13) and women (OR 1.38, 95 % CI 1.04-1.82) in the risk of melanoma. In addition, we found the risk of non-melanoma skin cancers in PD was slightly higher (OR 1.20, 95 % CI 1.11-1.29) than general population. It was impossible to evaluate the association between PD and melanoma according to use of levodopa or gene polymorphism via meta-analysis since few observational or cohort studies have focused on it.An association between PD and melanoma was confirmed. Most of the evidences were of high quality, and the conclusion was robust. Further research is needed to explore the mechanisms underlying this relationship.
Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process.
Authors: X D Yang, R Tisch, S M Singer, Z A Cao, R S Liblau, R D Schreiber, H O McDevitt
Journal: The Journal of Experimental Medicine (1994)

Tumor necrosis factor (TNF) alpha is a cytokine that has potent immune regulatory functions. To assess the potential role of this cytokine in the early development of autoimmunity, we investigated the effect of TNF on the development of insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice, a spontaneous murine model for autoimmune, insulin-dependent type I diabetes. Treatment of newborn female NOD mice with TNF every other day for 3 wk, led to an earlier onset of disease (10 versus 15 wk of age in control mice) and 100% incidence before 20 wk of age (compared to 45% at 20 wk of age in control phosphate-buffered saline treated female mice). In contrast, administration of an anti-TNF monoclonal antibody, TN3.19.12, resulted in complete prevention of IDDM. In vitro proliferation assays demonstrated that mice treated with TNF developed an increased T cell response to a panel of beta cell autoantigens, whereas anti-TNF treatment resulted in unresponsiveness to the autoantigens. In addition, autoantibody responses to the panel of beta cell antigens paralleled the T cell responses. The effects mediated by TNF appear to be highly age dependent. Treatment of animals either from birth or from 2 wk of age had a similar effect. However, if treatment was initiated at 4 wk of age, TNF delayed disease onset. These data suggest that TNF has a critical role in the early development of autoimmunity towards beta-islet cells.
Rational Design of a Meningococcal Antigen Inducing Broad Protective Immunity
Authors: Maria Scarselli, Beatrice Aricò, Brunella Brunelli, Silvana Savino, Federica Di Marcello, Emmanuelle Palumbo, Daniele Veggi, Laura Ciucchi, Elena Cartocci, Matthew James Bottomley, Enrico Malito, Paola Lo Surdo, Maurizio Comanducci, Marzia Monica Giuliani, Francesca Cantini, Sara Dragonetti, Annalisa Colaprico, Francesco Doro, Patrizia Giannetti, Michele Pallaoro, Barbara Brogioni, Marta Tontini, Markus Hilleringmann, Vincenzo Nardi-Dei, Lucia Banci, Mariagrazia Pizza, Rino Rappuoli
Journal: Science Translational Medicine (2011)

A single chimeric protein induces protective immunity against all meningococcal B strains with implications for producing broadly protective vaccines.
Constraints in antigen presentation severely restrict T cell recognition of the allogeneic fetus
Authors: Adrian Erlebacher, Daniela Vencato, Kelly A. Price, Dorothy Zhang, Laurie H. Glimcher
Journal: Journal of Clinical Investigation (2007)

How the fetus escapes rejection by the maternal immune system remains one of the major unsolved questions in transplantation immunology. Using a system to visualize both CD4+ and CD8+ T cell responses during pregnancy in mice, we find that maternal T cells become aware of the fetal allograft exclusively through “indirect” antigen presentation, meaning that T cell engagement requires the uptake and processing of fetal/placental antigen by maternal APCs. This reliance on a relatively minor allorecognition pathway removes a major threat to fetal survival, since it avoids engaging the large number of T cells that typically drive acute transplant rejection through their ability to directly interact with foreign MHC molecules. Furthermore, CD8+ T cells that indirectly recognize fetal/placental antigen undergo clonal deletion without priming for cytotoxic effector function and cannot induce antigen-specific fetal demise even when artificially activated. Antigen presentation commenced only at mid-gestation, in association with the endovascular invasion of placental trophoblasts and the hematogenous release of placental debris. Our results suggest that limited pathways of antigen presentation, in conjunction with tandem mechanisms of immune evasion, contribute to the unique immunological status of the fetus. The pronounced degree of T cell ignorance of the fetus also has implications for the pathophysiology of immune-mediated early pregnancy loss.