tbuckley/cabot-search huggingface dataset:
Assessment of Autoimmune Responses Associated with Asbestos Exposure in Libby, Montana, USA
Authors: Jean C. Pfau, Jami J. Sentissi, Greg Weller, Elizabeth A. Putnam
Journal: Environmental Health Perspectives (2004)

Systemic autoimmune responses are associated with certain environmental exposures, including crystalline particles such as silica. Positive antinuclear antibody (ANA) tests have been reported in small cohorts exposed to asbestos, but many questions remain regarding the prevalence, pattern, and significance of autoantibodies associated with asbestos exposures. The population in Libby, Montana, provides a unique opportunity for such a study because of both occupational and environmental exposures that have occurred as a result of the mining of asbestos-contaminated vermiculite near the community. As part of a multifaceted assessment of the impact of asbestos exposures on this population, this study explored the possibility of exacerbated autoimmune responses. Age- and sex-matched sets of 50 serum samples from Libby and Missoula, Montana (unexposed), were tested for ANA on HEp-2 cells using indirect immunofluorescence. Data included frequency of positive tests, ANA titers, staining patterns, and scored fluorescence intensity, all against known controls. Serum immunoglobulin A (IgA), rheumatoid factor, and antibodies to extractable nuclear antigen (ENA) were also tested. The Libby samples showed significantly higher frequency of positive ANA and ENA tests, increased mean fluorescence intensity and titers of the ANAs, and higher serum IgA, compared with Missoula samples. In the Libby samples, positive correlations were found between ANA titers and both lung disease severity and extent of exposure. The results support the hypothesis that asbestos exposure is associated with autoimmune responses and suggests that a relationship exists between those responses and asbestos-related disease processes.
Therapy of psoriasis: comparison of photochemotherapy and several variants of phototherapy
Authors: H. WEELDEN, E. YOUNG, J.C. LEUN
Journal: British Journal of Dermatology (1980)

Four treatments involving light were compared in two series of patients with severe psoriasis. The first series consisted of ten patients, who were treated by the method of paired comparisons. The treatments given were: (1) exposure to fluorescent sunlamps (B); (2) the same, supplemented by fluorescent UV-A lamps (A+B); (3) the same as (2) with the addition of the radiation from germicidal lamps (A+B+C); (4) photochemotherapy with oral 8-MOP followed by UV-A (PUVA); (5) one of the fields served as control, receiving no light at all. The second series consisted of thirty patients. They were treated either with PUVA or with a placebo capsule followed by A+B (pUVAB). The phototherapies examined differed from many previous attempts in that the increments in dose were made sufficiently large to overcome the increasing tolerance of the skin to light during the treatment. It is concluded (a) that phototherapy, if conducted in this way, is as effective as PUVA, and (b) that the effectiveness achieved with the phototherapies examined is due to the light from the fluorescent sunlamps (B).
An Atlas of Clinical Neurology
Authors: Donna Bergen
Journal: JAMA (1983)

This book is a personal overview of clinical neurological syndromes, with all the faults and virtues that implies. Photographs in the<i>Atlas</i>are from the personal collection of the senior author, and their number and variety suggest the staggering richness of clinical experience that the authors bring to this book. The text is a ramble through clinical neurology, with some chapters arranged according to body part ("The Head and Neck") and others by specific diagnosis ("Syringomyelia," and "Neurosyphilis"). The text is discursive and not always relevant to photographs, and the selection of some material seems capricious. For example, there is a long discussion of hypothryoidism but none of hyperthyroidism; pictures of the latter are, however, included. Some of the pictures selected are odd, for instance, pictures of normal-appearing people with neurological disease, apparently included simply for their outward normality. The book's virtues, however, far outweigh its faults. The quality of
Incidence of Cancer of the Cervix: Triumph or Tragedy?
Authors: Frank Matthews
Journal: JAMA (1989)

<h3>To the Editor.—</h3> Few people besides Dr Koss<sup>1</sup>could have covered the strong and weak points of the Papanicolaou (Pap) smear so well. However, I raise an objection to the subtitle of his article, "A Triumph and a Tragedy." For those of us from the pre-Pap years, the triumph should be trumpeted abroad; the tragedy deserves no more than extremely fine print. There is considerable danger in even suggesting that the two are equal. To me, a pathology resident at a large university hospital in the late 1950s, it seemed that we did an autopsy a week on some woman between 30 and 50 years of age who had died of invasive cervical carcinoma. Carcinoma in situ was a rarity, found almost exclusively adjacent to invasive tumors; I did not hear of cervical dysplasia until after my training. Today, solely because of 30 years of using the Pap smear,
Safety of Changing Intravenous Delivery Systems at Longer Than 24-Hour Intervals
Authors: JEFFREY D. BAND
Journal: Annals of Internal Medicine (1979)

Routinely changing the intravenous delivery system (fluid containers and administration set) every 24 h is widely practiced in American hospitals to reduce the risk of septicemia caused by contaminated infusate. We did a prospective clinical study to ascertain whether changing at longer intervals could be justified. At the conclusion of infusion therapy through one system, both the cannula and an aliquot of remaining fluid were cultured quantitatively. Of 790 infusions, contaminated infusate was detected in one (0.39%) of 258 discontinued and sampled after 1 to 24 h of continuous use, three (0.84%) of 359 after 25 to 48 h, and one (0.58%) of 173 after 49 to 71 h; none of these five contaminated systems produced septicemia. However, five cannula-related septicemias were identified during the study, none associated with concordant contamination of infusate. Routinely replacing the delivery system every 48 h seems to be justified and could result in considerable savings to hospitals. Infection of the cannula wound and contamination of infusate seem to be unrelated.
Aseptic Meningitis in Association with Herpes Progenitalis
Authors: Maurizio Terni, Piero Caccialanza, Enzo Cassai, Elliott Kieff
Journal: New England Journal of Medicine (1971)

MOST isolates of herpes-simplex virus (HSV) can be segregated into two groups, designated HSV-1 and HSV-2, on the basis of neutralization tests and plaque morphology. HSV-1 strains have usually bee...
HYDRONEPHROSIS DUE TO KINKING OF THE UPPER END OF THE URETER
Authors: R. P. Rowlands
Journal: BMJ (1930)

MTHicAL JoVRTTs ( 81----IM Br. abortu.s.A positive reaction is characterized by the appearance in six hours of a slightly raised oedematous plaque, 4 to 6 cm. in diameter, distingcuished in colour from that of the surrounding skin; the reactioni, which nmay be accompanied by paini, persists for abouit two days.According to Burnet, the iiitra(lermal test is often positive when the agglutination reaction is negative, and he con- siders, therefore, that it is of greater diagniostic value than the agglutination test.This may hold truio in melitenisis infections, bhut it is douibtful in abortts infec- tions; Huddlesoni and Johnsoni,3 for example, in a small series of cases, encountere(d one subject who failed to react to tlhe intradermal test, even thougl his seruim had an acgluitinin titre of 1 in 500.The test lhas the advantage of simplicity, and is well worthy of trial oln a large scale.
Improving health &amp; performance: nutritional supplements, science of pacing, and the concussion tool (SCAT2)
Authors: Karim M Khan
Journal: British Journal of Sports Medicine (2009)

Sickle cell nephropathy is a common complication in patients with sickle cell hemoglobinopathies. In these disorders, polymerization of mutated hemoglobin S results in deformation of red blood cells, which can cause endothelial cell injury in the kidney that may lead to thrombus formation when severe or manifest by multilayering of the basement membranes (glomerular and/or peritubular capillaries) in milder forms of injury. As the injury progresses, the subsequent ischemia, tubular dysfunction, and glomerular scarring can result in CKD or ESRD. Sickle cell nephropathy can occur in patients with homozygous hemoglobin SS or heterozygous hemoglobin S (hemoglobin SC, hemoglobin S/<i>β</i><sup>0</sup>-thalassemia, and hemoglobin S/<i>β</i><sup>+</sup>-thalassemia). Clinical manifestations resulting from hemoglobin S polymerization are often milder in patients with heterozygous hemoglobin S. These patients may not present with clinically apparent acute sickle cell crises, but these milder forms can provide a unique view of the kidney injury in sickle cell disease. Here, we report a patient with hemoglobin SC disease who showed peritubular capillary and vasa recta thrombi and capillary basement membrane alterations primarily involving the renal medulla. This patient highlights the vascular occlusion and endothelial cell injury in the medulla that contribute to sickle cell nephropathy.
Assessment and Prognostic Relevance of Right Ventricular Contractile Reserve in Patients With Severe Pulmonary Hypertension
Authors: Ekkehard Grünig, Henning Tiede, Esi Otuwa Enyimayew, Nicola Ehlken, Hans-Jürgen Seyfarth, Eduardo Bossone, Antonello D’Andrea, Robert Naeije, Horst Olschewski, Silvia Ulrich, Christian Nagel, Michael Halank, Christine Fischer
Journal: Circulation (2013)

Background— This study sought to analyze a new approach to assess exercise-induced pulmonary artery systolic pressure (PASP) increase by means of stress Doppler echocardiography as a possible measure of right ventricular contractile reserve in patients with severe pulmonary hypertension and right heart failure. Methods and Results— In this prospective study, patients with invasively diagnosed pulmonary arterial hypertension or inoperable chronic thromboembolic pulmonary hypertension and impaired right ventricular pump function despite a stable targeted pulmonary arterial hypertension medication underwent a broad panel of noninvasive assessments, including stress echocardiography and cardiopulmonary exercise testing. On the basis of the assumption that exercise-induced PASP is a measure of right ventricular contractile reserve, patients were classified into 2 groups according to an exercise-induced PASP increase above or below the median. Patients were followed up for 3.0±1.8 years. Univariate and multivariate analyses were used for factors predicting survival. Of 124 patients, 66 were below the median exercise-induced PASP increase of 30 mm Hg (low PASP), and 58 patients were above the median (high PASP). These groups were not significantly different in terms of medication and resting hemodynamics. Low PASP was associated with a significantly lower 6-minute walking distance, peak o 2 per kilogram, and 1-, 3-, and 4-year survival rates (92%, 69%, and 48%, respectively, versus 96%, 92%, and 89%). In the multivariate Cox model analysis adjusted for age and sex, PASP increase during exercise and peak o 2 per kilogram remained independent prognostic markers (hazard ratio, 2.56 for peak o 2 per kilogram and 2.84 for PASP increase). Conclusions— Exercise-induced PASP increase is of high clinical and prognostic relevance in pulmonary hypertension patients and may indicate right ventricular contractile reserve. Stress Doppler echocardiography may be a useful tool for prognostic assessment in pulmonary hypertension patients.
Abstract A2: A Study of the effects of MDV3100 in the tumor microenvironment of bone metastatic castrate resistant prostate cancer (bmCRPC)
Authors: Eleni Efstathiou, Patricia Troncoso, James Mohler, Christopher J. Logothetis, Mark Titus, Dimitra Tsavachidou, Sijin Wen, Anh Hoang, Robynne Ashe, Maria Karlou, Craig Berman
Journal: Cancer Research (2012)

Abstract Background: Androgen signaling remains a central driver in castrate-resistant prostate cancer. We performed a study to determine the effect of the antiandrogen MDV 3100 on bone marrow infiltrating CRPC. Methods: From February 2010 to June 2011, we performed an open-label, observational study of 60 bmCRPC patients (pts), who underwent transilial bone marrow biopsy (BMB) at baseline, 8 weeks and end of study. Pts received MDV3100 160mg orally once daily. The primary objective was to evaluate androgen signaling in bone marrow infiltrating cancer and testosterone in blood (BT) and bone marrow (BMT) and correlate findings with clinical observations. Androgen receptor (AR) c-terminus n-terminus, AR Variant 7 (ARV7), ERG, CYP17, phospho Src (pSrc), expression and mitotic index (Ki67 ) were assessed by immunohistochemistry, AR copy number by qPCR and BT and BMT by liquid chromatography mass spectrometry. Initial Findings: Maximal PSA decline of ≥50% occurred in 29 (48%) of 60 pts, and ≥90% in 13 (22%). Tumor involvement in BMB was detected in 28 (47%) pretreatment BMBs. Paired tumor infiltrated BMBs were found in 23 (38%) pts. Increased androgen receptor expression (n-terminal antibody used for IHC) was observed at pretreatment with heterogeneous CYP17 and pSrc extent of expression. Pretreatment intense nuclear AR expression combined with ≥10% CYP17 tumor expression or increased BMT correlate with ≥50% PSA decline (p value 0.02). AR subcellular localization shift from dominant nuclear to cytoplasmic and regression of bone marrow tumor infiltration correlate with ≥50% PSA decline (p value 0.05). Increased pretreatment p-Src expression is associated with lack of PSA decline (p value 0.002). Increase in BMT and BT is observed after 8 weeks of MDV3100 (mean pretreatment BMT 0.026 ng/ml, Wk8 BMT 0.04 in 33pts, p value 0.0001) (pretreatment BT 0.041, wk8 BT 0.066 in 37 pts, p value &amp;lt;0.0001). Interpretation: Pretreatment expression profile is consistent with persistent androgen signaling in bmCRPC. MDV3100 induces pharmacodynamic changes in androgen signaling. AR changes likely account for the reported therapeutic effect of MDV3100. These data prompt exploratory combinations of MDV3100 with androgen biosynthesis inhibitors and src inhibitors. Citation Format: Eleni Efstathiou, Patricia Troncoso, James Mohler, Christopher J. Logothetis, Mark Titus, Dimitra Tsavachidou, Sijin Wen, Anh Hoang, Robynne Ashe, Maria Karlou, Craig Berman. A study of the effects of MDV3100 in the tumor microenvironment of bone metastatic castrate-resistant prostate cancer (bmCRPC) [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A2.
Programme for specialization in family medicine
Authors: M. R. Polliack, J. H. Medalie
Journal: BMJ (1969)

A programme for specialized training in family medicine at Tel Aviv University Medical School provides four years of postgraduate study, two of which are in recognized hospital departments and two in clinics recognized for training in family medicine. At the end of this four-year period the graduate must submit a thesis of original work or an approved research project on an aspect of family medicine. Continuing contact of the trainee with both the family medicine clinic and the hospital departments is maintained throughout the period. While in hospital the trainee spends half a day a week in the family clinic with his personal tutor, and when in the clinic he spends half a day a week in the hospital.This programme has been provisionally accepted as meeting the formal requirements of the Israel Medical Association for specialization in family medicine, and the first physician has started training.
Endothelial nitric oxide synthase gene polymorphisms in Behcet's disease and rheumatic diseases with vasculitis
Authors: J U Kim
Journal: Annals of the Rheumatic Diseases (2003)

To assess potential associations between Korean Behçet's disease (BD) or other rheumatic diseases with vasculitis and two polymorphisms of the endothelial nitric oxide synthase (eNOS) gene, which include the Glu298Asp polymorphism in exon 7 and a variable number of tandem repeats (VNTR) polymorphism in intron 4.65 patients with BD, 27 with rheumatic diseases with vasculitis, and 80 controls were studied. Analyses of the Glu298Asp polymorphism in exon 7 and VNTR polymorphism in intron 4 of the eNOS gene were made by the polymerase chain reaction (PCR)-restriction fragment length polymorphism technique and PCR genotyping, respectively. Additionally, HLA-B51 typing was performed in the BD group and controls by a two step PCR sequence-specific primers method.Significant differences in Glu298Asp genotype frequencies were found between the BD or vasculitis groups and the controls (BD group v controls: p(corr)=0.006; vasculitis group v controls: p<0.001). The Asp298 frequency was much higher in the BD and vasculitis groups than in the controls. Even after stratification of the BD group based on the results of HLA-B51 testing, a significant association of the Glu298Asp polymorphism was still found (p=0.002, Mantel-Haenszel weighted odds ratio 4.3, 95% confidence interval 1.7 to 10.9). Distribution of the genotype frequencies in two eNOS gene polymorphisms was similar in connective tissue diseases-associated vasculitis and primary vasculitic syndromes. In contrast, distribution of alleles and genotypes of VNTR polymorphism did not differ between BD or vasculitis groups and the controls.The Glu298Asp polymorphism in exon 7 of the eNOS gene seems to be a susceptibility gene for Korean BD and other rheumatic diseases.
IMPROVEMENT OF ECHOCARDIOGRAPHIC PARAMETERS ASSOCIATED WITH NT-PROBNP GUIDED HEART FAILURE MANAGEMENT: MECHANISTIC INSIGHTS FROM THE PROBNP OUTPATIENT TAILORED CHRONIC HEART FAILURE (PROTECT) STUDY
Authors: Rory B. Weiner, Aaron L. Baggish, Annabel A. Chen-Tournoux, Jane E. Marshall, Han-Na Kim, Anju Bhardwaj, Asim A. Mohammed, Shafiq U. Rehman, Linda Barajas, Justine Barajas, Shawn A. Gregory, Stephanie A. Moore, Marc J. Semigran, James L. Januzzi
Journal: Journal of the American College of Cardiology (2011)
Abstract 2367: High expression of <i>GAPDH</i> is relevant to lung adenocarcinoma with low expression of the tumor suppressor gene Deleted in Liver Cancer-1 (<i>DLC1</i>)
Authors: Dunrui Wang, Guangxian Zhang
Journal: Cancer Research (2014)

Abstract Although glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is often considered to be a stable housekeeping marker gene, we recently determined that high levels of GAPDH mRNA expression in solid tumors was highly correlated with the expression of a group of genes, most of which are classified as cell cycle-dependent (Wang et al. PLoS One, 2013). In the current project, we have further evaluated the role of GAPDH in lung adenocarcinoma. Using data from an integrated microarray gene expression dataset and The Cancer Genome Atlas (TCGA) Project, we have now found a correlation between high mRNA expression of GAPDH and low expression of the tumor suppressor gene Deleted in Liver Cancer-1 (DLC1). DLC1 encodes a protein with strong RhoGAP (GTPase activating protein) activity and is inactivated in various human malignancies. In lung adenocarcinoma, low DLC1 expression occurred frequently together with up-regulation of GAPDH. The correlation coefficient of GAPDH and DLC1 expression in the integrated gene expression dataset was -0.6. In addition, high GAPDH and low DLC1 expression in lung cancer was associated with unfavorable prognosis. The combination of DLC1 expression level and GAPDH level improved the predictive prognostic power compared with that of the individual gene level alone. Pathway analysis indicated that low DLC1 in lung cancer was accompanied by increased expression of genes implicated in glycolysis and reduced expression of fructose-1,6-bisphosphatase (FBP1) in gluconeogenesis. Our findings suggest that GAPDH may contribute to the regulation of cell cycle genes and of tumor suppressor genes in cancer. Citation Format: Dunrui Wang, Guangxian Zhang. High expression of GAPDH is relevant to lung adenocarcinoma with low expression of the tumor suppressor gene Deleted in Liver Cancer-1 (DLC1). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2367. doi:10.1158/1538-7445.AM2014-2367
Cadmium Alters the Biotransformation of Carcinogenic Aromatic Amines by Arylamine <i>N</i> -Acetyltransferase Xenobiotic-Metabolizing Enzymes: Molecular, Cellular, and <i>in Vivo</i> Studies
Authors: Nilusha Ragunathan, Julien Dairou, Elodie Sanfins, Florent Busi, Christophe Noll, Nathalie Janel, Jean-Marie Dupret, Fernando Rodrigues-Lima
Journal: Environmental Health Perspectives (2010)

Cadmium (Cd) is a carcinogenic heavy metal of environmental concern. Exposure to both Cd and carcinogenic organic compounds, such as polycyclic aromatic hydrocarbons or aromatic amines (AAs), is a common environmental problem. Human arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that play a key role in the biotransformation of AA carcinogens. Changes in NAT activity have long been associated with variations in susceptibility to different cancers in relation with exposure to certain AAs.We explored the possible interactions between Cd and the NAT-dependent biotransformation of carcinogenic AAs.We exposed purified enzymes, lung epithelial cells, and mouse models to Cd and subsequently analyzed NAT-dependent metabolism of AAs.We found that Cd, at biologically relevant concentrations, impairs the NAT-dependent acetylation of carcinogenic AAs such as 2-aminofluorene (2-AF) in lung epithelial cells. NAT activity was strongly impaired in the tissues of mice exposed to Cd. Accordingly, mice exposed to Cd and 2-AF displayed altered in vivo toxicokinetics with a significant decrease (~ 50%) in acetylated 2-AF in plasma. We found that human NAT1 was rapidly and irreversibly inhibited by Cd [median inhibitory concentration (IC₅₀) ≈ 55 nM; rate inhibition constant (k(inact)) = 5 × 10⁴ M⁻¹ • sec⁻¹], with results of acetyl coenzyme A (acetyl-CoA) protection assays indicating that Cd-mediated inhibition was due to the reaction of metal with the active-site cysteine residue of the enzyme. We found similar results for human NAT2, although this isoform was less sensitive to inactivation (IC₅₀ ≈ 1 μM; k(inact) = 1 × 10⁴ M⁻¹ • sec⁻¹).Our data suggest that Cd can alter the metabolism of carcinogenic AAs through the impairment of the NAT-dependent pathway, which may have important toxicological consequences.