tbuckley/cabot-search huggingface dataset:
Effects of Monobutyl and Di( <i>n</i> -butyl) Phthalate <i>in Vitro</i> on Steroidogenesis and Leydig Cell Aggregation in Fetal Testis Explants from the Rat: Comparison with Effects <i>in Vivo</i> in the Fetal Rat and Neonatal Marmoset and <i>in Vitro</i> in the Human
Authors: Nina Hallmark, Marion Walker, Chris McKinnell, I. Kim Mahood, Hayley Scott, Rosemary Bayne, Shiona Coutts, Richard A. Anderson, Irene Greig, Keith Morris, Richard M. Sharpe
Journal: Environmental Health Perspectives (2006)

Certain phthalates can impair Leydig cell distribution and steroidogenesis in the fetal rat in utero, but it is unknown whether similar effects might occur in the human.Our aim in this study was to investigate the effects of di(n-butyl) phthalate (DBP), or its metabolite monobutyl phthalate (MBP), on testosterone production and Leydig cell aggregation (LCA) in fetal testis explants from the rat and human, and to compare the results with in vivo findings for DBP-exposed rats. We also wanted to determine if DBP/MBP affects testosterone production in vivo in the neonatal male marmoset.Fetal testis explants obtained from the rat [gestation day (GD)19.5] and from the human (15-19 weeks of gestation) were cultured for 24-48 hr with or without human chorionic gonadotropin (hCG) or 22R-hydroxycholesterol (22R-OH), and with or without DBP/MBP. Pregnant rats and neonatal male marmosets were dosed with 500 mg/kg/day DBP or MBP.Exposure of rats in utero to DBP (500 mg/kg/day) for 48 hr before GD21.5 induced major suppression of intratesticular testosterone levels and cytochrome P450 side chain cleavage enzyme (P450scc) expression; this short-term treatment induced LCA, but was less marked than longer term (GD13.5-20.5) DBP treatment. In vitro, MBP (10(-3) M) did not affect basal or 22R-OH-stimulated testosterone production by fetal rat testis explants but slightly attenuated hCG-stimulated steroidogenesis; MBP induced minor LCA in vitro. None of these parameters were affected in human fetal testis explants cultured with 10(-3) M MBP for up to 48 hr. Because the in vivo effects of DBP/MBP were not reproduced in vitro in the rat, the absence of MBP effects in vitro on fetal human testes is inconclusive. In newborn (Day 2-7) marmosets, administration of a single dose of 500 mg/kg MBP significantly (p = 0.019) suppressed blood testosterone levels 5 hr later. Similar treatment of newborn co-twin male marmosets for 14 days resulted in increased Leydig cell volume per testis (p = 0.011), compared with co-twin controls; this is consistent with MBP-induced inhibition of steroidogenesis followed by compensatory Leydig cell hyperplasia/hypertrophy.These findings suggest that MBP/DBP suppresses steroidogenesis by fetal-type Leydig cells in primates as in rodents, but this cannot be studied in vitro.
Doctor accused of killing patients "for enjoyment"
Authors: C. Dyer
Journal: BMJ (1999)

A British GP whose murder trial began this week killed 15 women patients for the enjoyment of exercising the power of life or death, the prosecution alleged at Preston crown court.

Dr Harold Shipman, aged 53, who practised in Hyde, Greater Manchester, denies murdering the women, mainly in their 60s or 70s, and forging the will of one of them, 81 year old Kathleen Grundy. …
Exposure-response relationship between passive smoking and adult pulmonary function.
Authors: X Xu, B Li
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The effects of exposure to environmental tobacco smoke (ETS) on pulmonary function were investigated in a random sample of 1,033 adults aged 40 to 69 yr from a residential area in Beijing. Compared with those not exposed, those exposed to ETS either at home or at work were associated with a 102-ml (SE = 40 ml) reduction in FEV1 and a 151-ml (SE = 44 ml) reduction in FVC after adjustment for confounding factors. Home and work ETS exposure was respectively associated with a 102-ml (SE = 33 ml) and 61-ml (SE = 34 ml) reduction in FEV1. When the subjects were grouped into three exposure categories (none, home only or work only, and both), the deficits in FEV1 and FVC in the third category were the greatest and statistically significant. The adverse effects of ETS were consistently observed in stratified analyses according to sex, occupational exposure, indoor use of coal stoves, and education. When ETS exposure was measured by the cigarettes smoked by other household members at home per day, an exposure-response association with FEV1 and FVC was again statistically significant. In conclusion, this study demonstrated that there is a significant association between exposure to ETS and reduced levels of FEV1 and FVC in adults, and such an association is dose-dependent.
NG-monomethyl L-arginine inhibits endothelium-derived relaxing factor-stimulated cyclic GMP accumulation in cocultures of endothelial and vascular smooth muscle cells by an action specific to the endothelial cell.
Authors: R A Johns, M J Peach, J Linden, A Tichotsky
Journal: Circulation Research (1990)

The effect of NG-monomethyl L-arginine (LNMMA), an analogue of L-arginine (a proposed precursor of endothelium-derived relaxing factor [EDRF]), on EDRF release from bovine pulmonary artery endothelial cells was investigated using endothelial cell-vascular smooth muscle cocultures and a superfused column containing endothelial cells grown on microcarrier beads. Cocultures were stimulated with control buffer, ATP, bradykinin, melittin, A23187, or nitroprusside in the presence and absence of varying concentrations of LNMMA (30-300 microM). LNMMA caused significant, concentration-dependent decreases in cyclic GMP accumulation in response to the endothelium-dependent dilators bradykinin, ATP, melittin, and A23187 but had no effect on control or nitroprusside-stimulated cocultures. The inhibitory effect of LNMMA on cyclic GMP accumulation was partially reversed by treatment with L-arginine, but was unaffected by D-arginine. To determine the specific site of action of LNMMA, endothelial cells on microcarrier beads were placed in a column and superfused with buffer. The effluent from the column was collected in 30-second (1.5-ml) fractions into 2-cm2 monolayer wells of vascular smooth muscle cells before and after addition of agonists (bradykinin, A23187) to the column inflow. The cyclic GMP content of each well of smooth muscle cells was determined as an index of EDRF activity. LNMMA superfused through the endothelial cell column inhibited cyclic GMP accumulation in vascular smooth muscle cells induced by bradykinin and A23187. LNMMA introduced into the effluent from the endothelial cell column had no effect on smooth muscle cyclic GMP levels. We conclude that LNMMA is an effective, specific inhibitor of EDRF production or release, and its action is specific to the endothelial cell.
Sixth International Congress on Peer Review and Biomedical Publication, September 2009
Authors: Drummond Rennie, Annette Flanagin, Fiona Godlee, Jane Smith
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 103: Array-based DNA methylation profiling of oral squamous cell carcinoma with lymph node invasion and clinical implications
Authors: Wei-Li Huang, Shu-Hao Chang, Shou-Yen Kao, Pei-Fen Su
Journal: Cancer Research (2011)

Abstract Background: Oral squamous cell carcinoma (OSCC) is the sixth common cancer and is highly mortal due to tumor recurrence and metastasis. Invasion of tumor cells into lymph nodes is one of the characters of regional metastasis. Here we assessed whether epigenetic modification of DNA methylation is correlated to OSCC regional metastasis and evaluated the potential clinical implications of DNA methylation-based biomarker. Methods: A case-control study of OSCC patients with lymph node invasion (N=8), OSCC patients without lymph node invasion (N=6), and normal oral tissues (N=2) was performed. To characterize aberrant DNA methylation in OSCC tumors with regional metastasis at diagnosis, Illumina infinium beadsarrays containing 27,578 CpG loci which cover 14,475 genes were applied. The genomic DNA of test samples was individually bisulfite-converted and subjected to beadsarray analysis. β value, the indicator of methylation status of each tested CpG locus, was derived with proper normalization. Results: Methylation β values allocated tested tissues into regional metastatic tumor, non-metastatic tumor, and control groups. A cluster of 111 CpG loci was selected based on the difference between the mean β value of OSCC tumors with and without regional metastasis. There were 69 loci and 42 loci that were hypermethylated (Δβ value ≫ 0.2) and hypomethylated (Δβ value ≪ −0.2), respectively, in OSCC with regional metastasis. Differentially methylated genes appeared to be mainly related to organ development, cell death, cell signaling, behavior, nucleic acid metabolism, and molecular transport. Several genes were further investigated for their methylation statuses by genomic bisulfite sequencing and DNA methyltransferase inhibitor reactivation in oral carcinoma cell lines with or without invasiveness. Characterization the association of hypermethylation of metastatic-associated genes and clinical pathological variables, we found combination of the hypermethylation status of a candidate gene and p16INK4A improved the prediction of lymph node invasiveness (p=0.003) and survival rate (p=0.010). Our results show the feasibility of this beadsarray analysis to identify aberrant methylation of metastatic-associated genes in OSCC as well as potential risk assessment application. The cohort for the risk assessment assay will be increased and the biological activities of candidate genes in carcinogenesis will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 103. doi:10.1158/1538-7445.AM2011-103
Lentiviral (HIV)-based RNA interference screen in human B-cell receptor regulatory networks reveals MCL1-induced oncogenic pathways
Authors: Antonio Ruiz-Vela, Mohit Aggarwal, Paloma de la Cueva, Cezary Treda, Beatriz Herreros, Daniel Martín-Pérez, Orlando Dominguez, Miguel A. Piris
Journal: Blood (2007)
Bacillus Calmette-Guérin-stimulated neutrophils release chemotaxins for monocytes in rabbit pleural spaces and in vitro.
Authors: V B Antony, S A Sahn, A C Antony, J E Repine
Journal: Journal of Clinical Investigation (1985)

Neutrophils are often seen first at sites of granulomatous inflammation but their contribution to monocyte recruitment and granuloma formation is unknown. We tested the hypothesis that neutrophils release chemotaxins which attract monocytes. We found that rapid accumulations of fluid and influxes of neutrophils followed by monocytes occurred in bacillus Calmette--Guérin (BCG)-sensitized rabbits given BCG intrapleurally but did not occur in nitrogen mustard-treated (neutropenic) BCG-sensitized rabbits given BCG intrapleurally--unless the rabbits were also given intrapleural injections of neutrophils. We also found monocyte chemotaxins in pleural spaces of control and neutrophil-reconstituted neutropenic but not in neutropenic rabbits given BCG intrapleurally. Moreover, pleural fluid monocyte chemotaxins had molecular weights (12,000-15,000 and 1,000) that were similar to molecular weights of monocyte chemotaxins present in supernatants from mixtures of neutrophils and BCG in vitro. In addition, intrapleural injection of neutrophils and BCG or supernatants from in vitro mixtures of neutrophils and BCG (but not neutrophils or BCG alone) increased the numbers of monocytes and 3H cell pellet activity in pleural fluids from untreated neutropenic rabbits or neutropenic rabbits previously injected intravenously with 3[H]methyl thymidine-labeled monocytes. Furthermore, fewer BCG were recovered from pleural fluids of BCG-sensitized control compared to neutropenic rabbits given BCG, and at autopsy 10 d after instillation of BCG, control but not neutropenic rabbits had well-defined granulomas without adhesions on their pleural surfaces. Our results suggest that BCG stimulates neutrophils to release chemotaxins that recruit monocytes, and that these responses might contribute to granuloma formation in tuberculous pleurisy.
German surgeon under investigation over organ trading
Authors: A. Tuffs
Journal: BMJ (2003)

German officials are investigating alleged organ trading in four cases of kidney transplantation carried out by a prominent surgeon.

The district attorney of Essen is looking into the case, in which kidneys were allegedly donated by Moldovan “relatives” to their “cousins” from Israel. All transplantations were carried out by the surgeon Christoph Broelsch, at Essen University Hospital and Jena University Hospital.

Last week the family of one Israeli recipient admitted in the weekly magazine Der Spiegel that it paid the Moldovan donor—who was not a …
Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma
Authors: Paula Taich, Alejandro Ceciliano, Emiliano Buitrago, Claudia Sampor, Adriana Fandino, Francisco Villasante, Evandro Lucena, Livia Romero, Guillermo L. Chantada, Paula Schaiquevich
Journal: Ophthalmology (2013)
A Double-blind Trial of a Nicotine Inhaler for Smoking Cessation
Authors: Philip Tonnesen
Journal: JAMA (1993)

To evaluate the efficacy of a new nicotine inhaler system for smoking cessation.A 1-year, randomized, double-blind, placebo-controlled study.Medical outpatient clinic with physicians experienced in smoking cessation assistance.A total of 286 volunteers who smoked at least 10 cigarettes daily recruited through a local newspaper.Subjects were randomly allocated to nicotine inhalers (n = 145) or placebo (n = 141) to be used for 3 months followed by tapering for 3 months in the context of minimal levels of advice and support.Continuous smoking abstinence at weeks 6, 12, 24, and 52, verified by measurements of carbon monoxide in expired air.Continuous smoking abstinence was significantly higher for the active nicotine inhaler group compared with the placebo inhaler group. The respective success rates were 28% and 12% after 6 weeks, 21% and 9% after 12 weeks, 17% and 8% after 6 months, and 15% and 5% after 1 year (P = .02 to .001). The mean nicotine substitution based on cotinine determinations after 2 weeks was 43% (SD, 45%) of smoking levels. The treatment was well tolerated, and no serious adverse events were reported.In this setting the nicotine inhaler appeared safe to use and increased success rates of smoking cessation attempts.
Crossprotection against nontuberculous mycobacterial infections by Mycobacterium tuberculosis memory immune T lymphocytes.
Authors: I M Orme, F M Collins
Journal: The Journal of Experimental Medicine (1986)

Adoptive immunization of T cell-deficient recipient mice with M. tuberculosis-specific memory immune T lymphocytes conferred upon these animals the ability to express significantly enhanced resistance both to the homologous infection, and to three strains of nontuberculous mycobacteria. These results support the hypothesis, therefore, that antigenic determinants possessed by the four mycobacterial strains that are relevant to the generation of protective cellular immunity are identical or closely crossreactive.
Current Management of Subdural Hematoma
Authors: Paul R. Rosenbluth
Journal: JAMA (1962)

The authors summarize experience with 100 cases in which surgery demonstrated subdural hematoma as the cause of the patient's symptoms. Spinal puncture, performed in 80 of these cases, yielded cerebrospinal fluid that was xanthochromic in 33, under increased pressure in 45, and abnormally high in protein content in 13. Spinal puncture was therefore not of great value in diagnosing this condition. Carotid and brachial angiography, on the other hand, has helped immeasurably in the diagnosis. Angiograms were taken in 63 patients, and clots located by angiography were invariably found later at surgery. Five cases in which the findings were unusual or paradoxical are described. The authors believe that the use of cerebral angiography has done away with diagnostic and frequently negative bur-hole trephinations.
Case of Fracture of the Spinous Processes of the Lumbar Vertebrae: Remarks on the Treatment of Sprained Back by "Firing"
Authors: J. Dickinson
Journal: BMJ (1852)

These, I repeat, are powerful quantities of blood, only applicable in the first stage of the-most acute and extensive inflammation in a healthy and strong constitution.The counterindication of bleeding is of higher importance with childreni than grown-np patients.A few leeches, by a mistaken indication, can, in the latter, produice a disastrous effect.Guard against leeching a
Durable Remission of Pemphigus With a Fixed-Dose Rituximab Protocol
Authors: Kara Heelan, Faisal Al-Mohammedi, Myles J. Smith, Sandra Knowles, Perla Lansang, Scott Walsh, Neil H. Shear
Journal: JAMA Dermatology (2014)

Rituximab induces B-lymphocyte apoptosis by targeting CD20 antigen and has shown efficacy in antibody-mediated autoimmune disease. Rituximab is increasingly being acknowledged as an effective and safe treatment option for pemphigus.To assess the clinical response of patients with pemphigus to rituximab using a modified fixed-dose rheumatoid arthritis protocol (1 g intravenously on days 1 and 15, followed by 500 mg intravenously if clinically warranted at 6-month intervals or repeated full dosing).A retrospective cohort study was conducted using records from a tertiary referral center for autoimmune bullous disorders. Participants included 92 patients (pemphigus vulgaris, 84 [91%], and pemphigus foliaceus, 8 [9%]) who received rituximab treatment between May 1, 2006, and August 30, 2012.The primary outcomes were time to relapse and achievement of a complete response with or without treatment at the end of the study.Median time to relapse after the first treatment cycle was 15 months (95% CI, 10.3-19.7). All patients experienced improvement. Complete remission rates with or without adjuvant treatment at final follow-up were 89% (56 patients [61%] were in complete remission without treatment and 26 patients [28%] were in complete remission during adjuvant treatment). No serious infectious adverse events occurred.The fixed-dose, modified rheumatoid arthritis protocol for rituximab was efficacious and well tolerated in patients with pemphigus. Patients who do not achieve remission after 1 cycle or patients who experience relapse benefit from further cycles of rituximab. Our results need to be confirmed in larger and controlled trials.
Pruritus in primary myelofibrosis: Clinical and laboratory correlates
Authors: Brianna E. Vaa, Alexandra P. Wolanskyj, Lindsey Roeker, Animesh Pardanani, Terra L. Lasho, Christy M. Finke, Ayalew Tefferi
Journal: American Journal of Hematology (2011)

Abstract Recent clinical trials with JAK or mammalian target of rapamycin (mTOR) inhibitors in primary myelofibrosis (PMF) have identified pruritus as one of the most treatment‐responsive disease traits. However, little is known about the prevalence of pruritus in PMF or its clinical and laboratory correlates. Among 566 consecutive patients with PMF seen at our institution, the presence or absence of pruritus was documented in 90 (16%) and 146 (26%) patients, respectively. Patients with pruritus were less likely to express MPL W515 (0% vs. 10%; P = 0.02) or leukopenia (8% vs. 24%; P = 0.002). The latter association was more pronounced in the absence of JAK2 or MPL mutations. Pruritus also clustered with marked leukocytosis (23% vs. 11%; P = 0.01) and JAK2 V617F (71% vs. 59%; P = 0.08). Pruritus did not correlate with karyotype ( P = 0.33), risk category per the Dynamic International Prognostic Scoring System (DIPSS)‐plus ( P = 0.37), DIPSS‐plus‐adjusted survival ( P = 0.41), or leukemic transformation ( P = 0.13). Plasma levels of 20 cytokines, which are known to be abnormally expressed in PMF, including IL‐1b, IL‐2R, IL‐6, IL‐8, and VEGF, were measured in 63 informative cases and showed no correlations with history of pruritus. We conclude that pruritus is relatively frequent in PMF and is prognostically irrelevant. The pathogenesis of PMF‐associated pruritus is not necessarily linked to proinflammatory cytokines but may instead involve molecules that are either granulocyte‐derived or influence granulopoiesis. The apparently differential effect of MPL vs. JAK2 mutations on pruritus requires further investigation. Am. J. Hematol. 2011. © 2011 Wiley‐Liss, Inc.
Structural and functional analysis of hypoxia-inducible factor 1
Authors: Gregg L. Semenza, Faton Agani, Greg Booth, Jo Forsythe, Narayan Iyer, Bing-Hua Jiang, Sandra Leung, Rick Roe, Charles Wiener, Aimee Yu
Journal: Kidney International (1997)

Hypoxia-inducible factor 1 (HIF-1) is a basic helix-loop-helix protein that activates transcription of hypoxia-inducible genes, including those encoding: erythropoietin, vascular endothelial growth factor, heme oxygenase-1, inducible nitric oxide synthase, and the glycolytic enzymes aldolase A, enolase 1, lactate dehydrogenase A, phosphofructokinase I, and phosphoglycerate kinase 1. Hypoxia response elements from these genes consist of a HIF-1 binding site (that contains the core sequence 5'-CGTG-3') as well as additional DNA sequences that are required for function, which in some elements include a second HIF-1 binding site. HIF-1 is a heterodimer. The HIF-1 alpha subunit is unique to HIF-1, whereas HIF-1 beta (ARNT) can dimerize with other bHLH-PAS proteins. Structural analysis of HIF-1 alpha revealed that dimerization with HIF-1 beta (ARNT) requires the HLH and PAS domains, DNA binding is mediated by the basic domain, and that HIF-1 alpha contains a carboxyl-terminal transactivation domain. Co-transfection of HIF-1 alpha and HIF-1 beta (ARNT) expression vectors and a reporter gene containing a wild-type hypoxia response element resulted in increased transcription in non-hypoxic cells and a superinduction of transcription in hypoxic cells, whereas HIF-1 expression vectors had no effect on the transcription of reporter genes containing a mutation in the HIF-1 binding site. HIF-1 alpha and HIF-1 beta (ARNT) protein levels were induced by hypoxia in all primary and transformed cell lines examined. In HeLa cells, the levels of HIF-1 alpha and HIF-1 beta protein and HIF-1 DNA-binding activity increased exponentially as cellular oxygen tension decreased, with maximum values at 0.5% oxygen and half-maximal values at 1.5 to 2% oxygen. HIF-1 alpha and HIF-1 beta (ARNT) mRNAs were detected in all human, mouse, and rat organs assayed and mRNA expression was modestly induced in rodents subjected to hypoxia. HIF-1 alpha protein levels were induced in vivo when animals were subjected to anemia or hypoxia. The HIF1A gene was mapped to human chromosome 14q21-q24 and mouse chromosome 12.