tbuckley/cabot-search huggingface dataset:
Differential Gene Expression in Benign Prostate Epithelium of Men with and without Prostate Cancer: Evidence for a Prostate Cancer Field Effect
Authors: Michael C. Risk, Beatrice S. Knudsen, Ilsa Coleman, Ruth F. Dumpit, Alan R. Kristal, Nolwenn LeMeur, Robert C. Gentleman, Lawrence D. True, Peter S. Nelson, Daniel W. Lin
Journal: Clinical Cancer Research (2010)

Abstract Background: Several malignancies are known to exhibit a “field effect,” whereby regions beyond tumor boundaries harbor histologic or molecular changes that are associated with cancer. We sought to determine if histologically benign prostate epithelium collected from men with prostate cancer exhibits features indicative of premalignancy or field effect. Experimental Design: Prostate needle biopsies from 15 men with high-grade (Gleason 8-10) prostate cancer and 15 age- and body mass index–matched controls were identified from a biospecimen repository. Benign epithelia from each patient were isolated by laser capture microdissection. RNA was isolated, amplified, and used for microarray hybridization. Quantitative PCR was used to determine the expression of specific genes of interest. Alterations in protein expression were analyzed through immunohistochemistry. Results: Overall patterns of gene expression in microdissected benign prostate-associated benign epithelium (BABE) and cancer-associated benign epithelium (CABE) were similar. Two genes previously associated with prostate cancer, PSMA and SSTR1, were significantly upregulated in the CABE group (false discovery rate &amp;lt;1%). Expression of other prostate cancer–associated genes, including ERG, HOXC4, HOXC5, and MME, were also increased in CABE by quantitative reverse transcription-PCR, although other genes commonly altered in prostate cancer were not different between the BABE and CABE samples. The expression of MME and PSMA proteins on immunohistochemistry coincided with their mRNA alterations. Conclusion: Gene expression profiles between benign epithelia of patients with and without prostate cancer are very similar. However, these tissues exhibit differences in the expression levels of several genes previously associated with prostate cancer development or progression. These differences may comprise a field effect and represent early events in carcinogenesis. Clin Cancer Res; 16(22); 5414–23. ©2010 AACR.
Perinatal outcome and developmental studies on children born after IVF
Authors: F Olivennes, R Fanchin, N Lédée, C Righini, I J Kadoch, R Frydman
Journal: Human Reproduction Update (2002)

Since the first birth after IVF, many scientific papers have been published on the technical aspects of the IVF procedure, but few studies have addressed the issue of the perinatal outcome of IVF pregnancies and of the children’s development and well-being. A high rate of adverse outcome has been demonstrated in a large group of IVF pregnancies. Prematurity, low birth weight and perinatal mortality are higher than in the general population. The majority of these complications are related to multiple births, but they are also found in singleton pregnancies. An analysis of the multiple risk factors involved in these complications is needed. The infertile status of IVF patients clearly plays a role in the risk of adverse outcome. Age and parity may be important factors. The role of IVF itself has not been demonstrated convincingly. The effect of ovarian stimulation deserves further study. Most of the studies published on the follow-up of IVF children are reassuring, but it is clear that these studies are not sufficient to eliminate without doubt any adverse effects on the well-being of IVF children. All IVF pregnancies should be followed with great care, not because they are more precious than spontaneous pregnancies, but because they are exposed to an increased risk of complications. The main problem of IVF remains the high rate of multiple pregnancies, including twins.
The influence of preload and heart rate on Doppler echocardiographic indexes of left ventricular performance: comparison with invasive indexes in an experimental preparation.
Authors: K Wallmeyer, L S Wann, K B Sagar, J Kalbfleisch, H S Klopfenstein
Journal: Circulation (1986)

We evaluated the ability of Doppler echocardiography to assess left ventricular performance in six open-chest dogs studied under various conditions. Intravenous infusions of nitroglycerin were used to vary preload, atrial pacing was used to control heart rate, and changes in inotropic state were induced by two different doses of dobutamine (5 and 10 micrograms/kg/min iv) and by administration of propranolol (1 mg/kg iv). Left ventricular anterior wall myocardial segment length was used as an index of preload. Maximum aortic blood flow, peak acceleration of aortic blood flow, and dP/dt were measured with an electromagnetic flow probe around the ascending aorta and a high-fidelity pressure transducer in the left ventricle. A continuous-wave Doppler transducer applied to the aortic arch was used to measure peak aortic blood velocity, mean acceleration, time to peak velocity, and the systolic velocity integral. The differences between mean values obtained under different inotropic conditions were significant at the p less than .01 level for peak velocity and at the p less than .05 level for mean acceleration. Within a given animal, Doppler measurements of peak velocity correlated very closely with maximum aortic flow (r = .96), maximum acceleration of aortic flow (r = .95), and with maximum dP/dt (r = .92). Mean acceleration measured by Doppler echocardiography also correlated very closely with conventional indexes, but was subject to greater interobserver variability. Doppler measurements of time to peak and the systolic velocity integral correlated less well with conventional hemodynamic indexes.(ABSTRACT TRUNCATED AT 250 WORDS)
Studies with live attenuated influenza virus in chronic bronchitis.
Authors: I G Winson, J M Smit, C W Potter, P Howard
Journal: Thorax (1977)

The use of live, recombinant virus for immunisation against influenza produced a number of respiratory illnesses, some severe, in patients with chronic obstructive airways disease. These patients are probably more susceptible to the influenza virus than are normal subjects. Special care will be needed in testing these viruses on patients with respiratory disease.
High Levels of Education Are Associated With an Increased Risk of Latent Autoimmune Diabetes in Adults
Authors: Lisa Olsson, Anders Ahlbom, Valdemar Grill, Kristian Midthjell, Sofia Carlsson
Journal: Diabetes Care (2010)

OBJECTIVE To investigate whether the risk for autoimmune diabetes in adults differs between socioeconomic groups and to compare such risk with that for type 2 diabetes. RESEARCH DESIGN AND METHODS The inhabitants of the Norwegian county of Nord-Trøndelag were investigated by questionnaires and clinical examinations on three occasions during 1984–2008. We used information from a subset consisting of 56,296 subjects (participating in at least two surveys), including 122 incident cases of autoimmune diabetes in adults (aged ≥35 and anti-GAD positive) and 1,555 cases of type 2 diabetes (aged ≥35 and anti-GAD negative). Hazard ratios (HRs) of diabetes associated with self-reported education and occupation were estimated by Cox proportional hazards models. RESULTS High levels of education (university versus primary school) were associated with an increased risk of autoimmune diabetes (HR 1.98 [95% CI 1.21–3.26]), after adjustment for BMI, lifestyle factors, and family history of diabetes. Case subjects with high levels of education had lower levels of C-peptide, tended to have higher levels of anti-GAD, and were more often treated with insulin. Conversely, these subjects had a reduced risk of type 2 diabetes (HR 0.69 [95% CI 0.57–0.82]), a risk that was partly explained by lower BMI and more physical activity (adjusted HR 0.89 [95% CI 0.74–1.06]). CONCLUSIONS High levels of education are associated with an increased risk of autoimmune diabetes in adults, a finding that may be mediated by effects on autoimmune activity. Because the association is not explained by traditional risk factors, other, currently unidentified, environmental factors are likely to be involved.
Inhibins, activins and follistatin in reproduction
Authors: D. M. de Kretser
Journal: Human Reproduction Update (2002)

The regulation of reproductive processes involves a complex network of communication systems between the brain, endocrine organs, the gonads and other reproductive tissues. Classically, our understanding has focused on the role of endocrine hormones, but more recently interest has also dwelt on the paracrine and autocrine regulation of these cell systems. In this review, the structure and physiology of the inhibins, activins and follistatin are discussed in terms of the evidence supporting their role as endocrine hormones, and how they might function as paracrine factors within the pituitary, gonad and associated tissues. With the advent of more specific techniques and assays for their measurement, the potential of inhibins, activins and follistatin as clinical markers of reproductive function and in the screening of various pathologies is also evaluated.
Racial and Ethnic Differences in Outcome in Zidovudine-Treated Patients With Advanced HIV Disease
Authors: P J Easterbrook, J C Keruly, T Creagh-Kirk, D D Richman, R E Chaisson, R D Moore
Journal: JAMA (1991)

OBJECTIVES--To determine if racial-ethnic differences exist in survival, disease progression, and development of myelosuppression in zidovudine-treated patients with advanced human immunodeficiency virus (HIV) disease. DESIGN--Prospective observational study.-Hospital and private clinics in 12 metropolitan centers.-The study included 754 non-Hispanic white, 165 black, and 106 Hispanic patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex (ARC) who received up to 2 years of zidovudine therapy. OUTCOME MEASURES--Survival, development of Pneumocystis carinii pneumonia (PCP), other opportunistic infections, and myelosuppression. RESULTS--At initiation of zidovudine therapy, Hispanic and particularly black patients had more advanced HIV disease than white patients, as indicated by lower baseline CD4+ counts, hematocrits, and AIDS-defining diagnoses. Black patients with AIDS also had a worse prognosis compared with white and Hispanic patients with AIDS. The product-limit survival rates at 2 years for white, black, and Hispanic patients with AIDS were 40%, 27%, and 39%, respectively (black vs white, P = .01; Hispanic vs white, P = .32, by the log-rank test). The respective proportions of patients who developed PCP at 2 years were 46%, 66%, and 44% (black vs white, P = .0001; Hispanic vs white, P = .86) and for other opportunistic infections the proportions were 56%, 63%, and 63%, respectively (black vs white, P = .03; Hispanic vs white, P = .09). There were no significant racial-ethnic differences in survival or in the development of opportunistic infections for patients with ARC, and there were no differences in the incidence of myelosuppression or dose reduction or suspension for patients with either ARC or AIDS. After adjusting for more advanced HIV disease (mainly low CD4+ counts and hematocrits), black race was no longer a significant independent predictor of survival. Adjustment for racial differences in the use of PCP prophylaxis accounted for most of the excess risk for the development of PCP in black patients compared with white patients with AIDS. CONCLUSIONS--Racial differences in survival and the development of opportunistic infections are mainly due to the more advanced HIV disease in black patients when zidovudine therapy is started and to their less frequent use of PCP prophylaxis. Innovative approaches are needed to ensure more widespread use of and earlier access to zidovudine therapy and PCP prophylaxis.
Daclatasvir and asunaprevir plus peginterferon alfa and ribavirin in HCV genotype 1 or 4 non-responders
Authors: Donald Jensen, Kenneth E. Sherman, Christophe Hézode, Stanislas Pol, Stefan Zeuzem, Victor de Ledinghen, Albert Tran, Magdy Elkhashab, Ziad H. Younes, Marcelo Kugelmas, Stefan Mauss, Gregory Everson, Velimir Luketic, John Vierling, Lawrence Serfaty, Maurizia Brunetto, Jeong Heo, David Bernstein, Fiona McPhee, Delphine Hennicken, Patricia Mendez, Eric Hughes, Stephanie Noviello
Journal: Journal of Hepatology (2015)
Transmural Flow Modulates Cell and Fluid Transport Functions of Lymphatic Endothelium
Authors: Dimana O. Miteva, Joseph M. Rutkowski, J. Brandon Dixon, Witold Kilarski, Jacqueline D. Shields, Melody A. Swartz
Journal: Circulation Research (2010)

Rationale: Lymphatic transport of peripheral interstitial fluid and dendritic cells (DCs) is important for both adaptive immunity and maintenance of tolerance to self-antigens. Lymphatic drainage can change rapidly and dramatically on tissue injury or inflammation, and therefore increased fluid flow may serve as an important early cue for inflammation; however, the effects of transmural flow on lymphatic function are unknown. Objective: Here we tested the hypothesis that lymph drainage regulates the fluid and cell transport functions of lymphatic endothelium. Methods and Results: Using in vitro and in vivo models, we demonstrated that lymphatic endothelium is sensitive to low levels of transmural flow. Basal-to-luminal flow (0.1 and 1 μm/sec) increased lymphatic permeability, dextran transport, and aquaporin-2 expression, as well as DC transmigration into lymphatics. The latter was associated with increased lymphatic expression of the DC homing chemokine CCL21 and the adhesion molecules intercellular adhesion molecule-1 and E-selectin. In addition, transmural flow induced delocalization and downregulation of vascular endothelial cadherin and PECAM-1 (platelet/endothelial cell adhesion molecule-1). Flow-enhanced DC transmigration could be reversed by blocking CCR7, intercellular adhesion molecule-1, or E-selectin. In an experimental model of lymphedema, where lymphatic drainage is greatly reduced or absent, lymphatic endothelial expression of CCL21 was nearly absent. Conclusions: These findings introduce transmural flow as an important regulator of lymphatic endothelial function and suggest that flow might serve as an early inflammatory signal for lymphatics, causing them to regulate transport functions to facilitate the delivery of soluble antigens and DCs to lymph nodes.
Painful rib syndrome--a review of 76 cases.
Authors: E M Scott, B B Scott
Journal: Gut (1993)

The painful rib syndrome consists of three features: pain in the lower chest or upper abdomen, a tender spot on the costal margin, and reproduction of the pain on pressing the tender spot. This is a common cause for referral to a general medical/gastroenterology clinic, accounting for 3% of new referrals in Lincoln. Seventy six consecutive patients were studied. The mean age was 48 years and 70% were women. Forty three per cent had been investigated, often extensively, before referral, and eight had had a non-curative cholecystectomy. The case notes from all patients were reviewed and a follow up questionnaire was sent after a mean period of four years to those 72 still alive, of which 56 replied. Thirty nine (70%) still had the pain although all except three had learnt to live with it. Despite a firm diagnosis being given, 25 (33%) patients were referred again to hospital by their general practitioner. All further investigations were negative apart from the finding of gall stones in three patients. The four patients who died had died from unrelated causes. The painful rib syndrome is common but underdiagnosed. It is a safe, clinical diagnosis requiring no investigation. Systematic firm palpation of the costal margin in recommended in all patients presenting with pain in the lower chest or upper abdomen.
Statins and Reduced Risk of Hepatocellular Carcinoma in Patients With Hepatitis C Virus Infection: Further Evidence Is Warranted
Authors: Stefanos Bonovas, Georgios Nikolopoulos, Nikolaos M. Sitaras
Journal: Journal of Clinical Oncology (2013)

The population-based cohort study by Tsan et al 1 showed that statin use was associated with a significantly reduced risk of hepatocellular carcinoma (HCC) in patients with hepatitis C virus infection (adjusted hazard ratio, 0.53; 95% CI, 0.49 to 0.58).However, we would like to raise a significant issue.As the authors acknowledge, not all possible confounding factors were adjusted for, including body mass index, smoking, alcohol use, and other indicators of health and socioeconomic status.3][4][5][6] In particular, individuals of higher socioeconomic classes are more likely to be given a statin.A social gradient in statin use may reflect social inequalities in health care use or health care quality, as well as systematic differences in factors such as tobacco use, nutrition, physical activity, and obesity.Thus, socioeconomic inequalities in statin use may have confounded the observed association between statin use and the risk of HCC in patients with hepatitis C virus infection, especially given that meta-analyses of randomized clinical trials have constantly shown that statins do not affect cancer risk. 7,8Nevertheless, we agree that statins merit further study in high-risk populations to elucidate their potential role in HCC chemoprevention.
Phase II Trial of Temozolomide in Patients with Relapsed Sensitive or Refractory Small Cell Lung Cancer, with Assessment of Methylguanine-DNA Methyltransferase as a Potential Biomarker
Authors: M. Catherine Pietanza, Kyuichi Kadota, Kety Huberman, Camelia S. Sima, John J. Fiore, Dyana K. Sumner, William D. Travis, Adriana Heguy, Michelle S. Ginsberg, Andrei I. Holodny, Timothy A. Chan, Naiyer A. Rizvi, Christopher G. Azzoli, Gregory J. Riely, Mark G. Kris, Lee M. Krug
Journal: Clinical Cancer Research (2012)

This phase II study was conducted to assess the efficacy of temozolomide in patients with relapsed small cell lung cancer (SCLC).Patients with disease progression after one or two prior chemotherapy regimens received temozolomide at 75 mg/m(2)/d for 21 days of a 28-day cycle. The primary endpoint was the overall response rate [ORR; complete response (CR) plus partial response (PR)], which was evaluated separately in sensitive and refractory cohorts. In the available tissue, we assessed O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status by PCR and MGMT expression by immunohistochemistry.Sixty-four patients were accrued: 48 patients in the sensitive cohort and 16 in the refractory group. One CR and 10 PRs were noted in sensitive patients [ORR, 23%; 95% confidence interval (CI), 12%-37%]. Two PRs were seen in the refractory cohort (ORR, 13%; 95% CI, 2%-38%). As second- and third-line treatment, the ORR was 22% (95% CI, 9%-40%) and 19% (95% CI, 7%-36%), respectively. Among patients with target brain lesions, 38% had a CR or PR (95% CI, 14%-68%). Grade ≥3 thrombocytopenia and neutropenia were observed in nine patients (14%). A greater number of cases with methylated MGMT had a response compared to those with unmethylated MGMT (38% vs. 7%; P = 0.08).Temozolomide has activity in relapsed SCLC, particularly for brain metastases. Response to temozolomide may correlate with MGMT methylation in SCLC.
Hypertensive response to exercise: a marker of altered metabolism in endurance athletes?
Authors: J Turmel, V Bougault, L P Boulet, P Poirier
Journal: British Journal of Sports Medicine (2011)

Background Inappropriate high blood pressure response to exercise in non athletes is known to be a predictor for future resting systemic hypertension. However, the relevance of exercise hypertension in endurance athletes is not known. Objective Assess the differences in heart rate variability (HRV), 24-h ambulatory blood pressure monitoring (ABPM) and lipid profile in athletes with an hypertensive response to exercise, and athletes with normal response to exercise. Design This study was a prospective cross-sectional study. 47 provincial and national athletes without previous diagnosis of systemic hypertension or other cardiovascular disease, training at least 10 h/week were consecutively recruited. 38 athletes completed the study. Intervention: Athletes underwent an ABPM, a 24-h HRV assessment (Holter), a maximal exercise test and blood samples. Hypertensive response to exercise was defined as systolic blood pressure (SBP) ≥220 mm Hg or diastolic blood pressure (DBP) &gt; 100 mm Hg. Results Two athletes had systemic hypertension (SBP: 139 ± 3, DBP: 81 ± 8 mm Hg) on 24 h-ABPM and 14 athletes showed hypertensive response to exercise (SBP: 243 ± 20, DBP: 77 ± 13 mm Hg). Lower values of high density lipoprotein (HDL) (1.27 ± 0.19 vs 1.51 ± 0.23 g/L, p=0.04) and Apo-A1 (1.31 ± 0.14 vs 1.56 ± 0.15 g/L, p=0.003) were observed in athletes with hypertensive responses to exercise. The latter also had higher values of night time SBP on ABPM compared to athletes with a normal response to exercise (116 ± 6 vs 106 ± 8 mm Hg, p=0.02). No difference was found between both groups regarding HRV indices. Conclusion Higher values of night time SBP on ABPM and lower values of HDL and Apo-A1 were observed in athletes with hypertensive response to exercise. These observations may be the first sign of minor metabolic disturbance in endurance athletes, although parameters remain within de normal values.
Vibration-induced hyperresponsiveness of arterial smooth muscle to noradrenaline with special reference to Raynaud's phenomenon in vibration disease
Authors: T. AZUMA, T. OHHASHI, M. SAKAGUCHI
Journal: Cardiovascular Research (1978)

Effects of in vitro and in vivo vibratory stimulations were studied on dose-response relationships of noradrenaline in excised femoral arteries of dogs and rats. The responsiveness of these arteries were enhanced after the application of the stimulation. The degree of the hyperresponsiveness was dependent upon frequency, amplitude, and duration of the stimulation. Based on the experimental results, a possible explanation was offered for Raynaud's phenomenon in vibration disease.