tbuckley/cabot-search huggingface dataset:
STUDIES ON THE TRANSMISSION OF HUMAN VIRAL HEPATITIS TO MARMOSET MONKEYS
Authors: F. Deinhardt, A. W. Holmes, R. B. Capps, H. Popper
Journal: The Journal of Experimental Medicine (1967)

Inoculation of human serums or plasmas obtained during the early acute phase of viral hepatitis induced chemical and morphological hepatic disease in marmosets in two out of five experimental series. The disease was transmissible in series from marmoset to marmoset with an apparent increased virulence of the causative agent in later marmoset passages. The chemical evidence for the disease was elevation of the activity of SGOT and SICD and of serum bilirubin. In serial liver biopsy specimens interpreted under code, a hepatitis, exhibiting some of the characteristics of human viral hepatitis, was readily distinguishable from nonspecific changes. The morphological changes preceded the biochemical alterations and persisted after them. The data reported in these studies indicate that marmosets may be susceptible to human hepatitis. If these observations are confirmed, these animals may provide good experimental models for this disease. Final proof that the hepatitis observed in marmosets is caused by agents of human viral hepatitis is still lacking.
The Apoptosome Pathway to Caspase Activation in Primary Human Neutrophils Exhibits Dramatically Reduced Requirements for Cytochrome <i>c </i>
Authors: Brona M. Murphy, Amanda J. O'Neill, Colin Adrain, R. William G. Watson, Seamus J. Martin
Journal: The Journal of Experimental Medicine (2003)

Caspase activation is a central event in numerous forms of apoptosis and results in the proteolytic degradation of multiple substrate proteins that contribute to the apoptotic phenotype. An important route to caspase activation proceeds via assembly of the “apoptosome” as a result of the cell stress–associated release of mitochondrial cytochrome c. Previous studies have shown that primary neutrophils are largely incapable of mitochondrial respiration, suggesting that these cells either lack functional mitochondria or possess a defective respiratory chain. This prompted us to examine whether neutrophils retain an intact cytochrome c/apoptotic protease-activating factor 1 (Apaf-1) pathway to caspase activation and apoptosis. We show that primary human neutrophils contain barely detectable levels of cytochrome c as well as other mitochondrial proteins. Surprisingly, neutrophil cell–free extracts readily supported Apaf-1–dependent caspase activation, suggesting that these cells may assemble cytochrome c–independent apoptosomes. However, further analysis revealed that the trace amount of cytochrome c present in neutrophils is both necessary and sufficient for Apaf-1–dependent caspase activation in these cells. Thus, neutrophils have a lowered threshold requirement for cytochrome c in the Apaf-1–dependent cell death pathway. These observations suggest that neutrophils retain cytochrome c for the purpose of assembling functional apoptosomes rather than for oxidative phosphorylation.
Detection of early lung impairment with aerosol bolus dispersion
Authors: P Brand, T Tuch, O Manuwald, W Bischof, J Heinrich, HE Wichmann, T Beinert, J Heyder
Journal: European Respiratory Journal (1994)

The broadening of inhaled aerosol boluses (aerosol bolus dispersion) during respiration provides a noninvasive measure of convective gas mixing in the lungs. In this study, the sensitivity and specificity of this technique for the diagnosis of early lung impairment due to cigarette smoking was evaluated. Two hundred and sixteen randomly selected subjects (126 smokers and 90 nonsmokers) were investigated with aerosol dispersion in comparison to conventional lung function tests. The cumulative cigarette consumption of the subjects was quantified by "pack-years" (PY). Smokers were classified into the following groups: 0 < PY < or = 10; 10 < PY < or = 20; 20 < PY < or = 30; and PY > 30. Forced expiratory volume in one second (FEV1), maximal expiratory flow at 25, 50 and 75% vital capacity (MEF25, MEF50 and MEF75) decreased significantly with increasing cigarette consumption. In comparison to nonsmokers, FEV1 was significantly reduced in smokers of 10 < PY < or = 30, and MEF75 was significantly reduced in smokers of PY > 20. Aerosol bolus dispersion increased with increasing PY. For all groups of smokers, even those with PY < 10, bolus dispersion was significantly increased in comparison to lifelong nonsmokers, indicating alterations in convective gas mixing in the lungs. Calculation of receiver operating characteristics for the lung function parameters under consideration showed that bolus dispersion has a higher sensitivity and specificity than conventional lung function parameters. Hence, the aerosol bolus dispersion test could be a promising epidemiological tool to study early abnormalities in intrapulmonary gas mixing due to environmental factors.
Oestrogen receptor beta and melanoma: a comparative study
Authors: V. de Giorgi, A. Gori, S. Gandini, F. Papi, M. Grazzini, S. Rossari, A. Simoni, V. Maio, D. Massi
Journal: British Journal of Dermatology (2012)

Background Oncological research has focused on evaluating oestrogen receptors (ERs) in oestrogen‐related tumours, and understanding the potential role of ERs in the pathophysiology of cancer. Objectives To investigate the significance of oestrogen receptor beta (ERβ) in melanoma. Methods We prospectively evaluated ERβ expression in malignant melanoma (MM) tissue and adjacent healthy skin by quantitative immunohistochemistry at the Department of Dermatology of the University of Florence, from 1998 to 2010. Results ERβ was detected with varying staining intensity in the 66 malignant melanocytic lesions. After adjusting for age and sex, we found that ERβ expression was significantly lower in melanoma tissue compared with adjacent healthy skin (P <0·0001). We also found significantly lower ERβ levels in thick melanoma tissue compared with thin melanoma tissue. In addition, there was a positive association between Breslow thickness and the difference of ERβ expression between healthy tissue and melanoma tissue (P = 0·0004). Consistent with sex differences in melanoma survival, men showed significantly lower levels of ERβ than women in both melanoma (P = 0·05) and healthy tissues (P = 0·02). Conclusions ERβ expression is inversely associated with Breslow thickness and is significantly influenced by sex in MM.
Quantity and Quality of Sleep and Incidence of Type 2 Diabetes
Authors: Francesco P. Cappuccio, Lanfranco D'Elia, Pasquale Strazzullo, Michelle A. Miller
Journal: Diabetes Care (2009)

OBJECTIVE To assess the relationship between habitual sleep disturbances and the incidence of type 2 diabetes and to obtain an estimate of the risk. RESEARCH DESIGN AND METHODS We conducted a systematic search of publications using MEDLINE (1955–April 2009), EMBASE, and the Cochrane Library and manual searches without language restrictions. We included studies if they were prospective with follow-up &amp;gt;3 years and had an assessment of sleep disturbances at baseline and incidence of type 2 diabetes. We recorded several characteristics for each study. We extracted quantity and quality of sleep, how they were assessed, and incident cases defined with different validated methods. We extracted relative risks (RRs) and 95% CI and pooled them using random-effects models. We performed sensitivity analysis and assessed heterogeneity and publication bias. RESULTS We included 10 studies (13 independent cohort samples; 107,756 male and female participants, follow-up range 4.2–32 years, and 3,586 incident cases of type 2 diabetes). In pooled analyses, quantity and quality of sleep predicted the risk of development of type 2 diabetes. For short duration of sleep (≤5–6 h/night), the RR was 1.28 (95% CI 1.03–1.60, P = 0.024, heterogeneity P = 0.015); for long duration of sleep (&amp;gt;8–9 h/night), the RR was 1.48 (1.13–1.96, P = 0.005); for difficulty in initiating sleep, the RR was 1.57 (1.25–1.97, P &amp;lt; 0.0001); and for difficulty in maintaining sleep, the RR was 1.84 (1.39–2.43, P &amp;lt; 0.0001). CONCLUSIONS Quantity and quality of sleep consistently and significantly predict the risk of the development of type 2 diabetes. The mechanisms underlying this relation may differ between short and long sleepers.
Protease-Activated Receptor (PAR) 2, but not PAR1, Signaling Promotes the Development of Mammary Adenocarcinoma in Polyoma Middle T Mice
Authors: Henri H. Versteeg, Florence Schaffner, Marjolein Kerver, Lesley G. Ellies, Patricia Andrade-Gordon, Barbara M. Mueller, Wolfram Ruf
Journal: Cancer Research (2008)

Abstract The G protein–coupled protease-activated receptors (PAR) are key signaling components for proteases in vascular biology and tumor progression. To address the contributions of PAR1 and PAR2 to breast cancer development, we established cohorts of mouse mammary tumor virus–polyoma middle T (PyMT) PAR1−/− and PAR2−/− mice, considering that the PyMT model recapitulates aspects of human disease. Appearance of palpable tumors, tumor expansion, and metastasis was indistinguishable between wild-type and PAR1−/− mice. PAR1−/− breast cancer cells were no longer responsive to thrombin in vitro, excluding compensatory up-regulation of alternative thrombin receptors and indicating that thrombin-PAR1 signaling is dispensable in breast tumor microenvironments. In contrast, palpable tumors and multifocal disease developed slower in PAR2−/− mice, and as a consequence of delayed tumor onset, metastasis was reduced. Analysis of early tumors showed persistence of adenomas with delayed appearance of vascularized adenocarcinomas in PAR2−/− mice. Furthermore, CXCL1 production by early PAR2−/− tumors was reduced. These results are consistent with previous xenograft data that implicated breast cancer PAR2 signaling in the induction of proangiogenic growth factors and chemokines. This study establishes that protease signaling contributes to mammary tumor development and that PAR2, rather than the thrombin receptor PAR1, plays a crucial role in the angiogenic switch. [Cancer Res 2008;68(17):7219–27]
Chest CT screening of asbestos-exposed workers: lung lesions and incidental findings
Authors: T. Vierikko, R. Järvenpää, T. Autti, P. Oksa, M. Huuskonen, S. Kaleva, J. Laurikka, S. Kajander, K. Paakkola, S. Saarelainen, E-R. Salomaa, A. Tossavainen, P. Tukiainen, J. Uitti, T. Vehmas
Journal: European Respiratory Journal (2006)

The objective of the present study is to determine the feasibility of chest computed tomography (CT) in screening for lung cancer among asbestos-exposed workers. In total, 633 workers were included in the present study and were examined with chest radiography and high-resolution CT (HRCT). A total of 180 current and ex-smokers (cessation within the previous 10 yrs) were also screened with spiral CT. Noncalcified lung nodules were considered positive findings. The incidental CT findings not related to asbestos exposure were registered and further examined when needed. Noncalcified lung nodules were detected in 86 workers. Five histologically confirmed lung cancers were found. Only one of the five cancers was also detected by plain chest radiography and three were from the group of patients with a pre-estimated lower cancer probability. Two lung cancers were stage Ia and were radically operated. In total, 277 individuals presented 343 incidental findings of which 46 required further examination. Four of these were regarded as clinically important. In conclusion, computed tomography and high-resolution computed tomography proved to be superior to plain radiography in detecting lung cancer in asbestos-exposed workers with many confounding chest findings. The numerous incidental findings are a major concern for future screenings, which should be considered for asbestos-exposed ex-smokers and current smokers.
Opportunistic infections in patients with inflammatory bowel disease: prevention and diagnosis
Authors: N Viget, G Vernier-Massouille, D Salmon-Ceron, Y Yazdanpanah, J-F Colombel
Journal: Gut (2007)

Because of the increasing use of immunosuppressive and biological drugs, the occurrence of opportunistic infections has become a key safety issue for patients with inflammatory bowel disease (IBD). Consequently, improvement of healthcare workers' knowledge of this domain is urgent. In this review, the preventive measures that would help to reduce the rate of opportunistic infections in patients with IBD are listed, and the management of situations frequently confronting doctors is considered. In the absence of national and international recommendations, the information given here should help doctors to optimise patient outcomes.
Radiologic course of primary sclerosing cholangitis: Assessment by three-dimensional magnetic resonance cholangiography and predictive features of progression
Authors: Ana Ruiz, Sara Lemoinne, Fabrice Carrat, Christophe Corpechot, Olivier Chazouillères, Lionel Arrivé
Journal: Hepatology (2013)

Magnetic resonance imaging (MRI) with magnetic resonance cholangiography (MRC) has become the radiologic standard of reference for diagnosis of primary sclerosing cholangitis (PSC). However, natural history of radiologic features of PSC is poorly known. In the current study, we aimed at analyzing the course of PSC using three-dimensional (3D) MRC and liver MRI to find predictive radiologic features of progression. PSC patients, followed up in our center, with at least two 3D MRCs performed in at least a 1-year interval, were retrospectively reviewed. We built an interpretation standard model to score precisely bile ducts and liver parenchyma features. The primary endpoint was overall radiologic course, including worsening, improvement, or stabilization. Radiologic features were analyzed by logistic regression. We reviewed 289 MRIs from 64 patients upon a mean radiologic follow-up of 4 years (range, 1-9). Radiologic features worsened in 37 patients (58%) and stabilized in 27 (42%); no patient showed improvement. Multivariate analysis resulted in two MRI progression risk scores, based on the combination of predictive radiologic features (score without gadolinium administration = 1 × dilatation of intrahepatic bile ducts + 2 × dysmorphy + 1 × portal hypertension; score with gadolinium administration = 1 × dysmorphy + 1 × parenchymal enhancement heterogeneity). These scores were associated with radiologic progression, with an area under the curve of 80 and 83% ± 4%. Conclusion: A majority of PSC patients develop radiologic aggravation upon MRI over 4 years. Two simple scores can predict radiologic progression.(Hepatology 2014;58:242–250)
Is previous history a reliable predictor for acute mountain sickness susceptibility? A meta-analysis of diagnostic accuracy
Authors: Martin J MacInnis, Keith R Lohse, Jenny K Strong, Michael S Koehle
Journal: British Journal of Sports Medicine (2013)

Purpose The goal of this meta-analysis was to determine the clinical utility of acute mountain sickness (AMS) history to predict future incidents of AMS. Method 17 studies (n=7921 participants) were included following a systematic review of the literature. A bivariate random-effects model was used to calculate the summary sensitivity and specificity of the diagnostic test, and moderator variables were tested to explain the heterogeneity across studies. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) method was used to assess concerns for bias and applicability for the included studies. Results The history of AMS had a low diagnostic accuracy for the prediction of future AMS incidents: the summary sensitivity was 0.50 (95% CI (0.40 to 0.59)) and the summary specificity was 0.72 (95% CI (0.66 to 0.78)). There was significant heterogeneity in the sensitivity and specificity across studies, which we modelled using moderator analysis. Studies that restricted the use of acetazolamide and dexamethasone had not only a higher sensitivity (0.66) relative to those that did not (0.44; p=0.03) but also an increased false-positive rate (0.39 vs 0.23, p=0.03). The QUADAS-2 analysis showed that AMS histories were insufficiently detailed, and few studies controlled for prophylactic medication use or recent altitude exposure, leading to high risks of bias and concerns for applicability. Conclusions The use of AMS history to guide prophylactic strategies for high-altitude ascent is not supported by the literature; however, the low sensitivity and specificity of this diagnostic test could reflect the quality of the available studies. Ensuring that the characteristics of the history and future ascents are similar may improve the clinical utility of AMS history.
Diseases of the Reticulo-Endothelial System and Hematology (The Red Cell and Some of its Problems)
Authors: W H Crosby
Journal: Annual Review of Medicine (1957)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Inhibition of Tritiated Thymidine Incorporation in Cultured Cells by Rat Kidney Extract&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K. Klein, M. L. Coetzee, R. Madhav, P. Ove
Journal: JNCI Journal of the National Cancer Institute (1979)

KCl extract from rat kidney, rat liver, and Morris hepatomas inhibited [3H]thymidine incorporation into cultured cells. Tissues came from male inbred BUF rats. The most pronounced inhibition was achieved with the kidney extract. Protein synthesis was not inhibited during a 24-hour exposure of the cells to the inhibitor. Incorporation of [3H]deoxycytidine was inhibited, as was cell growth, when the kidney KCl extract was present for several days. [3H]thymidine incorporation was inhibited almost immediately after the addition of the extract. The inhibition was reversible. Regular [3H]thymidine incorporation was restored 24 hours after removal of the inhibitor, which was neither arginase nor a thymidine-degrading enzyme. The inhibitor was stable to heat (80 degrees C for 10 min) and resistant to trypsin, pronase, DNase, and RNase. Exposure of the extract to proteolytic enzymes, hyaluronidase, and neuraminidase resulted in a loss of inhibitory activity only after extensive dialysis of the treated extract. The inhibitor appeared to be a mucoprotein in which the carbohydrate moiety may be responsible for the inhibition. The KCl extract also inhibited RNA synthesis and DNA synthesis by the de novo pathway. The inhibition of phosphorylation of thymidine, however, appeared to be the primary action of the inhibitor.
Localization of heparin-binding EGF-like growth factor in the smooth muscle cells and macrophages of human atherosclerotic plaques.
Authors: J Miyagawa, S Higashiyama, S Kawata, Y Inui, S Tamura, K Yamamoto, M Nishida, T Nakamura, S Yamashita, Y Matsuzawa
Journal: Journal of Clinical Investigation (1995)

Heparin-binding EGF-like growth factor (HB-EGF) is a potent chemoattractant and mitogen for smooth muscle cells (SMC) in culture. To elucidate whether HB-EGF is implicated in the pathogenesis of human atherosclerosis, we examined immunohistochemical localization of HB-EGF in human aortic walls and atherosclerotic plaques. The medial SMC of the aorta in babies and children synthesized HB-EGF protein, while the number of SMC producing HB-EGF was dramatically decreased in young and middle-aged adults. In atherosclerotic plaques, however, marked production of HB-EGF protein was detected in SMC and macrophages of the plaques. Furthermore, EGF receptors, to which HB-EGF is known to bind, were detected in plaque SMC. These data suggest that HB-EGF may be implicated in the migration and proliferation of SMC that occurs in the normal development of arterial walls, and in the formation of atherosclerotic plaques.
Retention of corneodesmosomes and increased expression of protease inhibitors in dandruff
Authors: B. Singh, M. Haftek, C.R. Harding
Journal: British Journal of Dermatology (2014)

Dandruff is a common, relapsing and uncomfortable scalp condition affecting a large proportion of the global population. The appearance of flakes on the scalp and in the hair line, and associated itch are thought to be consequences of a damaged skin barrier, altered corneocyte cohesion and abnormal desquamation in dandruff. The balance between skin proteases and protease inhibitors is essential for driving the key events, including corneodesmosome degradation, in the desquamation process and to maintain stratum corneum (SC) barrier integrity.To investigate the distribution of corneodesmosomes, the key component of the SC cohesivity and barrier function, and the protease inhibitors lympho-epithelial Kazal-type-related inhibitor (LEKTI-1) and squamous cell carcinoma antigen (SCCA1) in the scalp of dandruff-affected participants.The methods utilized were immunohistochemistry, scanning immunoelectron microscopy, phase-contrast microscopy, Western blotting and serine protease activity assay on tape-stripped SC or scalp skin biopsies.In SC samples from healthy subjects, corneodesmosomes were peripherally located in the corneocytes. In samples of dandruff lesions, corneodesmosomes were located both peripherally and on the entire surface area of the corneocytes. LEKTI-1 and SCCA1 protein levels and parakeratosis were found to be highly elevated in the lesional samples.The persistence of nonperipheral corneodesmosomes is a characteristic feature of the perturbed desquamation seen in dandruff. The increased expression levels of LEKTI-1 and SCCA1 are consistent with the view that the dandruff condition is characterized by an imbalance in protease-protease inhibitor interaction in the SC.
EFFECT OF PHOTO-OXIDATION ON ISOHEMAGGLUTINATING ANTIBODIES
Authors: William C. Boyd
Journal: The Journal of Experimental Medicine (1946)

Photo-oxidation (in the presence of eosin Y as a sensitizer) of isohemagglutinating sera destroyed their agglutinating activity gradually, but did not seem to convert any of the agglutinins studied into inhibiting ("incomplete" or "blocking") antibody.