tbuckley/cabot-search huggingface dataset:
Hepatitis C virus infection in patients with leukemia
Authors: Yasuhiko Fujii, Kohei Kaku, Masahisa Tanaka, Miki Yosizaki, Toshio Kaneko, Noboru Matumoto
Journal: American Journal of Hematology (1994)

Abstract We have studied 30 patients with acute leukemia by the second‐generation assay for antibodies to hepatitis C virus (HCV) to determine the incidence of HCV infection and the impact of anti‐HCV positivity on liver disease. After a complete remission, 21/30 (70%) patients were anti‐HCV‐positive. During chemotherapy the anti‐HCV‐positive patients had more severe liver disease than the anti‐HCV‐negative patients, and they had a higher incidence of chronic hepatitis (13/21; 62% vs. 1/9; 11%, P &lt; 0.01). During subsequent follow‐up, 15/30 (50%) patients relapsed and 15/30 (50%) patients completed the chemotherapy protocols. After a relapse 12/15 (80%) patients were anti‐HCV‐positive and they had more severe liver disease than the anti‐HCV‐negative patients. Among the patients who completed chemotherapy (n = 15), biochemical evidence of chronic hepatitis was found in 9/9 (100%) anti‐HCV‐positive, and 2/6 (33%) anti‐HCV‐negative cases during off‐therapy follow‐up after therapy‐withdrawal ( P &lt; 0.05). These results indicate that HCV plays an important role in the etiology of chronic hepatitis which could worsen the final prognosis of successfully treated patients with leukemia. © 1994 Wiley‐Liss, Inc.
ACTIONS OF ADENOSINE AT ITS RECEPTORS IN THE CNS: Insights from Knockouts and Drugs
Authors: Bertil B. Fredholm, Jiang-Fan Chen, Susan A. Masino, Jean-Marie Vaugeois
Journal: The Annual Review of Pharmacology and Toxicology (2004)

Adenosine and its receptors have been the topic of many recent reviews. These reviews provide a good summary of much of the relevant literature--including the older literature. We have, therefore, chosen to focus the present review on the insights gained from recent studies on genetically modified mice, particularly with respect to the function of adenosine receptors and their potential as therapeutic targets. The information gained from studies of drug effects is discussed in this context, and discrepancies between genetic and pharmacological results are highlighted.
Alcohol and retinoid metabolism
Authors: H K SEITZ
Journal: Gut (2000)

See article on page 825 

The complex interactions between the metabolism of retinoids and ethanol have been reported for a long time. Clinically, chronic ethanol consumption leads to vitamin A deficiency but also to enhanced toxicity of vitamin A and beta-carotene when supplemented. Changes in retinol metabolism due to alcohol may have a pathophysiological impact in both alcoholic liver disease and alcohol associated cancer as retinoic acid, the most active form of vitamin A, is an important regulator of normal epithelial cell growth, function, and differentiation. Under normal conditions, ingested retinol is metabolised to retinaldehyde via cytosolic alcohol dehydrogenase (ADH), microsomal retinol dehydrogenase (three types), and several types of cytosolic retinol dehydrogenases, and retinaldehyde is further oxidised to retinoic acid via aldehyde dehydrogenase (ALDH). Retinoic acid binds to retinoic acid receptors (RAR), initiating intracellular signal transduction leading to a cascade of events and finally to a decrease in cell regeneration. The main molecular action of retinoic acid involves either transactivation through direct binding to retinoic acid response elements (RARE) in target gene promoters, thereby transcriptionally activating a series of genes with distinct antiproliferative activity, or transrepression of activator protein (AP-1) and regulation of apoptosis. It is not surprising that this complex interaction between ethanol and metabolism of retinoids occurs as both substrates share common pathways, namely (a) ADH, (b) ALDH, and (c) cytochrome P4502E1 (CYP2E1).

It has been shown that chronic ethanol consumption decreases hepatic retinol and retinoic acid concentrations due to various mechanisms including, increased mobilisation of retinyl esters to extrahepatic tissues and enhanced hepatic metabolism of retinol and retinoic acid to polar metabolites, predominantly via induced CYP2E1.1 2These metabolites …
Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a Multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer Trial.
Authors: A Horwich, D T Sleijfer, S D Fosså, S B Kaye, R T Oliver, M H Cullen, G M Mead, R de Wit, P H de Mulder, D P Dearnaley, P A Cook, R J Sylvester, S P Stenning
Journal: Journal of Clinical Oncology (1997)

PURPOSE This prospective randomized multicenter trial was designed to evaluate the efficacy of carboplatin plus etoposide and bleomycin (CEB) versus cisplatin plus etoposide and bleomycin (BEP) in first-line chemotherapy of patients with good-risk nonseminomatous germ cell tumors. PATIENTS AND METHODS Between September 1989 and May 1993, a total of 598 patients with good-risk nonseminomatous germ cell tumors were randomized to receive four cycles of either BEP or CEB. In each cycle, the etoposide dose was 120 mg/m2 on days 1, 2, and 3, and the bleomycin dose was 30 U on day 2. BEP patients received cisplatin at 20 mg/m2/d on days 1 to 5 or 50 mg/m2 on days 1 and 2. For CEB patients, the carboplatin dose was calculated from the glomerular filtration rate to achieve a serum concentration x time of 5 mg/mL x minutes. Chemotherapy was recycled at 21-day intervals to a total of four cycles. RESULTS Of patients assessable for response, 253 of 268 (94.4%) of those allocated to receive BEP achieved a complete response, compared with 227 of 260 (87.3%) allocated to receive CEB (P = .009). There were 30 treatment failures in the 300 patients allocated to BEP and 79 in the 298 allocated to CEB (log-rank chi 2 = 26.9; P &lt; .001), which led to failure-free rates at 1 year of 91% (95% confidence interval [CI], 88% to 94%) and 77% (95% CI, 72% to 82%), respectively. There were 10 deaths in patients allocated to BEP and 27 in patients allocated to CEB (log-rank chi 2 = 8.77; P = .003), which led to 3-year survival rates of 97% (95% CI, 95% to 99%) and 90% (95% CI, 86% to 94%), respectively. CONCLUSION With these drug doses and schedules, combination chemotherapy based on carboplatin was inferior to that based on cisplatin. This BEP regimen that contains moderate doses of etoposide and bleomycin is effective in the treatment of patients with good-prognosis metastatic nonseminoma.
The regulation of trophoblast differentiation by oxygen in the first trimester of pregnancy
Authors: J.L. James, P.R. Stone, L.W. Chamley
Journal: Human Reproduction Update (2005)

In the first trimester of human pregnancy villous cytotrophoblasts are able to differentiate to form either the overlying syncytiotrophoblast layer or, in anchoring villi, extravillous trophoblasts which grow out from the villi and invade into the maternal decidua, acting to both physically attach the placenta to the decidua, and modify the maternal spiral arteries to sustain pregnancy. During the first 10-12 weeks of gestation, extravillous trophoblast plugs block the spiral arteries and prevent maternal blood flow entering the intervillous space, thereby creating an environment of physiological hypoxia in which placental and fetal development occur. As extravillous trophoblasts migrate away from the villus they differentiate from a proliferative to an invasive phenotype. The hypoxic environment of the first trimester is believed to play an important role in the regulation of trophoblast differentiation. However, there is currently a large body of conflicting experimental evidence concerning this topic. This review examines the experimental evidence to date on the role of oxygen in trophoblast differentiation.
Associations between Intimate Partner Violence and Health among Men Who Have Sex with Men: A Systematic Review and Meta-Analysis
Authors: Ana Maria Buller, Karen M. Devries, Louise M. Howard, Loraine J. Bacchus
Journal: PLoS Medicine (2014)

Background Intimate partner violence (IPV) among men who have sex with men (MSM) is a significant problem. Little is known about the association between IPV and health for MSM. We aimed to estimate the association between experience and perpetration of IPV, and various health conditions and sexual risk behaviours among MSM. Methods and Findings We searched 13 electronic databases up to 23 October 2013 to identify research studies reporting the odds of health conditions or sexual risk behaviours for MSM experiencing or perpetrating IPV. Nineteen studies with 13,797 participants were included in the review. Random effects meta-analyses were performed to estimate pooled odds ratios (ORs). Exposure to IPV as a victim was associated with increased odds of substance use (OR = 1.88, 95% CIOR 1.59–2.22, I2 = 46.9%, 95% CII2 0%–78%), being HIV positive (OR = 1.46, 95% CIOR 1.26–1.69, I2 = 0.0%, 95% CII2 0%–62%), reporting depressive symptoms (OR = 1.52, 95% CIOR 1.24–1.86, I2 = 9.9%, 95% CII2 0%–91%), and engagement in unprotected anal sex (OR = 1.72, 95% CIOR 1.44–2.05, I2 = 0.0%, 95% CII2 0%–68%). Perpetration of IPV was associated with increased odds of substance use (OR = 1.99, 95% CIOR 1.33–2.99, I2 = 73.1%). These results should be interpreted with caution because of methodological weaknesses such as the lack of validated tools to measure IPV in this population and the diversity of recall periods and key outcomes in the identified studies. Conclusions MSM who are victims of IPV are more likely to engage in substance use, suffer from depressive symptoms, be HIV positive, and engage in unprotected anal sex. MSM who perpetrate IPV are more likely to engage in substance use. Our results highlight the need for research into effective interventions to prevent IPV in MSM, as well as the importance of providing health care professionals with training in how to address issues of IPV among MSM and the need to raise awareness of local and national support services. Please see later in the article for the Editors' Summary
M<scp>AMMALIAN</scp> S<scp>ELENIUM</scp>-C<scp>ONTAINING</scp> P<scp>ROTEINS</scp>
Authors: Dietrich Behne, Antonios Kyriakopoulos
Journal: Annual Review of Nutrition (2001)

▪ Abstract Mammalian selenium-containing proteins can be divided into three groups: proteins containing nonspecifically incorporated selenium, specific selenium-binding proteins, and specific selenocysteine-containing selenoproteins. Selenoproteins with known functions identified so far include five glutathione peroxidases, two deiodinases, several thioredoxin reductases, and selenophosphate synthetase 2. Alternative splicing leads to a greater variety of selenoproteins, as was shown in the cases of a specific sperm nuclei glutathione peroxidase and some thioredoxin reductases. Selenoprotein P, selenoprotein W, a 15-kDa selenoprotein, an 18-kDa selenoprotein, and several selenoproteins identified in silico from nucleotide sequence databases were found to contain selenocysteine but their functions are not known. Gel electrophoretic separation of tissue samples from rats labeled in vivo with 75 Se showed the existence of further selenium-containing proteins.
Frederick C. Goetz, MD: A Profile of the Intersection Among Science, the Fine Arts, and Education
Authors: Byron J. Hoogwerf, David M. Kendall, Elizabeth R. Seaquist
Journal: Diabetes Care (2014)

There is a link between Oliver Wendell Holmes' poem “The One-Hoss Shay” (1) and every patient with diabetes who has ever received a kidney or pancreas transplant. Yet, most of the 4,128 diabetes patients in the U.S. who received renal transplants in 2011 (2) and the 1,051 diabetes patients who received a pancreas transplant in 2011 (3) do not know how Dr. Frederick C. Goetz (1922–2012) used this delightful poem as parallel to how the medical profession viewed patients with diabetes. Dr. Goetz, who always preferred to be addressed as “Fred” by any who knew him, played a seminal role in assuring that both renal and pancreas transplantation were available to suitable patients with diabetes. While today this is considered a standard of clinical care, Fred maintained his equanimity in the face of much skepticism and criticism—often from friends and colleagues. This profile outlines Fred’s role in the history of renal and pancreas transplantation, but also strives to capture some of the “essence” of Frederick C. Goetz—as a caregiver, physician, scientist, and teacher. This profile is written from the perspective of three physicians, each of whom first met Fred while they were medical students at the University of Minnesota and whose collective observations and collaboration with Fred spanned more than three decades of his academic career.

Fred was born and raised in Fond du Lac, WI. He graduated from Harvard College (1943) and Harvard Medical School (1946). He served in the U.S. Army as a physician in Korea where he met his future wife, Mary Rose Riordan. After a residency, chief residency, and fellowship (with Dr. George Thorn) at Massachusetts General Hospital, he joined the University of Minnesota as the Director of Diabetes Research. His career was focused on diabetes and its complications. His personal life was filled with interests …
Peroxynitrite Inhibits Ca <sup>2+</sup> -Activated K <sup>+</sup> Channel Activity in Smooth Muscle of Human Coronary Arterioles
Authors: Yanping Liu, Ken Terata, Qiang Chai, Hongwei Li, Leonard H. Kleinman, David D. Gutterman
Journal: Circulation Research (2002)

We examined the hypothesis that ONOO − , a product of the interaction between superoxide (O 2 ·− ) and nitric oxide (NO), inhibits calcium-activated K + (K Ca ) channel activity in vascular smooth muscle cells (VSMCs) of human coronary arterioles (HCAs), thereby reducing hyperpolarization-mediated vasodilation. HCAs were dissected from right atrial appendages. The interaction of ONOO − with microvessels was determined by immunohistochemistry using a nitrotyrosine antibody. Strong staining was observed in arteries exposed to authentic ONOO − or to sodium nitroprusside (SNP)+xanthine (XA)+xanthine oxidase (XO). Dilation to 10 −8 mol/L bradykinin (BK) was abolished in vessels exposed to ONOO − (−2.5±8%; P &lt;0.05) but not DC-ONOO − (65±8%). Reduced dilation to BK was also observed after application of XO and SNP. Dilation to NS1619 (K Ca channel opener) was reduced in endothelial denuded arterioles treated with ONOO − . In isolated VSMCs, whole-cell peak K + current density was reduced by ONOO − (control 65±15 pA/pF; ONOO − 42±9 pA/pF; P &lt;0.05). Iberiotoxin had no further effect on whole-cell K + current. In inside-out patches, ONOO − but not DC-ONOO − decreased open state probability (NP o ) of K Ca channel by 50±12%. O 2 ·− generated by XA+XO had no effect on BK-induced dilation and NP o of K Ca channels. These results suggest that ONOO − , but not O 2 ·− , inhibits K Ca channel activity in VSMCs possibly by a direct effect. This mechanism may contribute to impaired EDHF-mediated dilation in conditions such as ischemia/reperfusion where increased activity of NO synthase occurs in the presence of excess of O 2 ·− .
IDIOTYPY OF RABBIT ANTIBODIES
Authors: Jacques Oudin, Mauricette Michel
Journal: The Journal of Experimental Medicine (1969)

The idiotypic patterns detected in the anti-Salmonella typhi serum of one given bleeding have been sought in other bleedings of the same rabbit. Idiotypic patterns carried by antibodies of the second bleeding are not always found in those of the first bleeding. Bifurcated precipitation zones in gels (double diffusion in cells) have been observed in the reaction of several anti-idiotypic sera with the sera of the first and second bleedings of three rabbits, and apparently indicate that idiotypic patterns which were carried by the same molecule in the first bleeding were carried by two separate molecules in the second bleeding. In a comparison of idiotypy of two anti-S. typhi serum samples of one rabbit, the collection of which had been separated by a very long interruption of the immunization, all the idiotypes detected in the early bleeding were also detected in the late bleeding; several idiotypes were detected in the serum of the late bleeding and not in that of the early bleeding. Idiotypy has been observed and compared in IgM and in IgG antibodies. There are, in each of these two classes, antibodies that are not distinguished from antibodies of the other class by anti-idiotypic sera, and consequently that carry the same idiotypic patterns. A comparison has been made between the idiotypy of the two kinds of antibodies which, in anti-S. typhi sera, are precipitated and not precipitated by the polysaccharide. Certain idiotypic patterns are carried only by the antibodies of the first kind. There are also idiotypic patterns which are carried by antibodies of these two kinds, among which certain anti-idiotypic antibodies do not discriminate. Possible cellular implications of observations made on idiotypy at different stages of the immunization of one individual have been discussed.
TGF-β/Smad3 Signaling Promotes Renal Fibrosis by Inhibiting miR-29
Authors: Wei Qin, Arthur C.K. Chung, Xiao R. Huang, Xiao-Ming Meng, David S.C. Hui, Cheuk-Man Yu, Joseph J.Y. Sung, Hui Y. Lan
Journal: Journal of the American Society of Nephrology (2011)

TGF-β/Smad3 signaling promotes fibrosis, but the development of therapeutic interventions involving this pathway will require the identification and ultimate targeting of downstream fibrosis-specific genes. In this study, using a microRNA microarray and real-time PCR, wild-type mice had reduced expression of miR-29 along with the development of progressive renal fibrosis in obstructive nephropathy. In contrast, Smad3 knockout mice had increased expression of miR-29 along with the absence of renal fibrosis in the same model of obstruction. In cultured fibroblasts and tubular epithelial cells, Smad3 mediated TGF-β(1)-induced downregulation of miR-29 by binding to the promoter of miR-29. Furthermore, miR-29 acted as a downstream inhibitor and therapeutic microRNA for TGF-β/Smad3-mediated fibrosis. In vitro, overexpression of miR-29b inhibited, but knockdown of miR-29 enhanced, TGF-β(1)-induced expression of collagens I and III by renal tubular cells. Ultrasound-mediated gene delivery of miR-29b either before or after established obstructive nephropathy blocked progressive renal fibrosis. In conclusion, miR-29 is a downstream inhibitor of TGF-β/Smad3-mediated fibrosis and may have therapeutic potential for diseases involving fibrosis.
Dye laser treatment of port-wine stains: Comparison of the continuous-wave dye laser with a robotized scanning device and the pulsed dye laser
Authors: Jeffrey S Dover, Roy Geronemus, Robert S Stern, Deirdre O'Hare, Kenneth A Arndt
Journal: Journal of the American Academy of Dermatology (1995)

Background: Despite good results in the treatment of most port-wine stains (PWS) with continuous-wave visible-light lasers, light PWS and those in certain locations respond less favorably and have a higher risk of scarring. Robotized scanning devices such as the Hexascan device have been developed for continuous-wave laser sources to produce greater target specificity, to increase reproducibility of results, and to decrease the incidence of adverse effects. Objective: The purpose of this study was to compare the effects of the same wavelength of light (585 nm) on test sites within PWS with the flashlamp-pumped pulsed dye laser and a continuous-wave tunable dye laser scanned through a Hexascan robotized scanning device. Methods: Two adjacent, noncontiguous sites within PWS were treated in 29 patients, one site with the flashlamp-pumped pulsed dye laser and the other with an argon-pumped continuous-wave tunable dye laser affixed to a Hexascan device. Results: Twenty-eight patients completed the study. The pulsed dye laser was found to be superior to the continuous-wave dye laser with the Hexascan device in 45% of patients, whereas the continuous-wave tunable dye laser with the Hexascan device was considered superior in 15%. There was no difference in the remaining 40%. Undesirable side effects were infrequent with both treatments. There was no significant difference in hypopigmentation or atrophic and hypertrophic scarring, but hyperpigmentation was more frequent with the continuous-wave dye laser with the Hexascan device. Conclusion: Both the pulsed dye laser and continuous tunable-wave dye laser with the Hexascan device produce slight lightening after one treatment. The pulsed dye laser produces slightly greater lightening than the continuous-wave tunable dye laser with the Hexascan device 6 weeks after treatment of test areas within PWS in 40% of those treated. It also produced slightly less hypopigmentation and hyperpigmentation.
Metabolic clearance rates and interconversions of estrone and 17β-estradiol in normal males and females
Authors: Christopher Longcope, Donald S. Layne, James F. Tait
Journal: Journal of Clinical Investigation (1968)

The continuous infusion of 3H-6,7-estrone and 3H-6,7-estradiol has been used to study the metabolic clearance rate (MCR), the interconversions, and the red cell uptake of these steroids in normal males and females. The whole blood MCR of estrone is 1,990 ± 120 liters per day/m2 (SE) in males and 1,910 ± 100 liters per day/m2 in females. The whole blood MCR of estradiol is 1,600 ± 80 liters per day/m2 in males and 1,360 ± 40 liters per day/m2 in females. The values in females do not vary significantly when studied in the follicular or luteal phase of the cycle. At least 35% of the total estrone metabolism in both sexes is extrasplanchnic and at least 25% of the total estradiol metabolism in males, and 15% in females is extrasplanchnic. The [ρ]BB2,1 [transfer constant of estradiol to estrone, which is equivalent to the fraction of the precursor (estradiol) converted to the product (estrone) when both the infusion of the precursor and the measurement of the product are in peripheral blood] is 15%; and the [ρ]BB1,2 [transfer constant of estrone to estradiol, which is equivalent to the fraction of the precursor (estrone) converted to product (estradiol) when both the infusion of the precusor and the measurement of the product are in peripheral blood] is 5% in both males and females. Our findings concerning the radioactivity in whole blood, as measured by our procedure, were the following: 15-20% of estrone in both sexes and 15% of estradiol in males is associated with red cells. Only 2% of the whole blood radioactivity of estradiol in females is associated with red cells. Changes in the distribution of radioactivity between plasma and red cells will influence the MCR as calculated from plasma, but not as calculated from whole blood.
DNA aptamers block L-selectin function in vivo. Inhibition of human lymphocyte trafficking in SCID mice.
Authors: B J Hicke, S R Watson, A Koenig, C K Lynott, R F Bargatze, Y F Chang, S Ringquist, L Moon-McDermott, S Jennings, T Fitzwater, H L Han, N Varki, I Albinana, M C Willis, A Varki, D Parma
Journal: Journal of Clinical Investigation (1996)

Selectins participate in the initial events leading to leukocyte extravasation from the blood into tissues. Thus the selectins have generated much interest as targets for antiinflammatory agents. Therapeutic molecules based on the monomeric carbohydrate ligand sialyl Lewis X (SLe(X)) have low affinities and are not specific for a given selectin. Using SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technology, we have generated aptamers specific for L-selectin that require divalent cations for binding and have low nanomolar affinity. In vitro, the deoxyoligonucleotides inhibit L-selectin binding to immobilized SLe(X) in static assays and inhibit L-selectin-mediated rolling of human lymphocytes and neutrophils on cytokine-activated endothelial cells in flow-based assays. These aptamers also block L-selectin-dependent lymphocyte trafficking in vivo, indicating their potential utility as therapeutics.