tbuckley/cabot-search huggingface dataset:
Polymorphic CAG repeats of the androgen receptor gene and rheumatoid arthritis
Authors: T. Kawasaki, T. Ushiyama, H. Ueyama, K. Inoue, K. Mori, I. Ohkubo, S. Hukuda
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> In view of the possible role of androgens in the pathogenesis of rheumatoid arthritis (RA), this study investigated the association between repeat lengths of CAG microsatellites of the androgen receptor (AR) gene and RA. <h3>METHODS</h3> The number of CAG repeats in exon 1 of the AR gene was determined in 90 men and 276 women with RA, as well as in 305 male and 332 female controls. <h3>RESULTS</h3> The male RA patients tended to have shorter repeats than the male controls (22.5 versus 23.1, p=0.07), whereas the female RA patients had similar repeats to the female controls (22.7 versus 22.9, p=0.17). Patients of both sexes were divided into younger and older age at onset groups, and compared with younger and older controls. Younger onset male RA patients had significantly shorter CAG repeat lengths than the younger male controls (21.8 versus 23.2, p=0.007) or the older onset male RA patients (21.8 versus 23.2, p=0.04). Older onset male RA and both younger and older onset female RA patients had similar CAG repeat lengths when compared with their controls. Neither seropositivity nor rheumatoid nodule positivity had a significant relation with CAG repeat lengths. <h3>CONCLUSION</h3> Shorter CAG repeats of the AR gene, presenting high levels of transactivation activity, are related to younger age onset male RA, suggesting the possible role of androgens as a modulating factor.
Use of qualitative methods alongside randomised controlled trials of complex healthcare interventions: methodological study
Authors: S. Lewin, C. Glenton, A. D Oxman
Journal: BMJ (2009)

<b>Objective</b> To examine the use of qualitative approaches alongside randomised trials of complex healthcare interventions. <b>Design</b> Review of randomised controlled trials of interventions to change professional practice or the organisation of care. <b>Data sources</b> Systematic sample of 100 trials published in English from the register of the Cochrane Effective Practice and Organisation of Care Review Group. <b>Methods</b> Published and unpublished qualitative studies linked to the randomised controlled trials were identified through database searches and contact with authors. Data were extracted from each study by two reviewers using a standard form. We extracted data describing the randomised controlled trials and qualitative studies, the quality of these studies, and how, if at all, the qualitative and quantitative findings were combined. A narrative synthesis of the findings was done. <b>Results</b> 30 of the 100 trials had associated qualitative work and 19 of these were published studies. 14 qualitative studies were done before the trial, nine during the trial, and four after the trial. 13 studies reported an explicit theoretical basis and 11 specified their methodological approach. Approaches to sampling and data analysis were poorly described. For most cases (n=20) we found no indication of integration of qualitative and quantitative findings at the level of either analysis or interpretation. The quality of the qualitative studies was highly variable. <b>Conclusions</b> Qualitative studies alongside randomised controlled trials remain uncommon, even where relatively complex interventions are being evaluated. Most of the qualitative studies were carried out before or during the trials with few studies used to explain trial results. The findings of the qualitative studies seemed to be poorly integrated with those of the trials and often had major methodological shortcomings.
Case 53-1961
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. Kibbee
Journal: New England Journal of Medicine (1961)

Presentation of Case An eighty-one-year-old man entered the hospital because of abdominal pain and pruritus. Two months previously a suprapubic prostatectomy was performed at another hospital because of urinary retention and recurrent cystitis due to benign prostatic hypertrophy. At the time of the preoperative radiologic studies a question of a renal calculus and an abdominal aneurysm was raised. The postoperative course was uneventful. One month before admission there was the onset of vague, constant abdominal distress punctuated by episodes of crampy pain in the left upper quadrant of the abdomen, with radiation to the right upper quadrant. The patient complained . . .
Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling
Authors: Larissa Lordier, Abdelali Jalil, Fréderic Aurade, Fréderic Larbret, Jerôme Larghero, Najet Debili, William Vainchenker, Yunhua Chang
Journal: Blood (2008)
Failed hip replacements.
Authors: A. J. Timperley, G. A. Gie
Journal: BMJ (1992)

Our experience with these investigations has results are comparable with those in other pubised interest in hip arthroplasty are comparable been largely restricted to adolescents with sus-lished series.The consequence of such figures, with those from a single surgeon."pected hypogonadotrophic hypogonadism, often taking into account patients' survival, is at least Villar should be supported in the call for revision in combination with growth hormone deficiency.five revision procedures per 100 primary arthro-hip surgery to be carried out by specialists.The Although hepatic, renal, and adrenocorticotrophic plasties.In 1991 we performed 56 revision hip need for revision surgery would be diminished if a reserves are expectedly higher in this age group, we arthroplasties at an estimated mean unit cost three greater proportion of the more complex primary still observe appreciable adverse manifestations, times that of a primary arthroplasty.Extrapolation hip arthroplasties and operations on patients under including nausea, sweating, and tachycardia, with of these figures suggests that every 100 primary 60 were also performed in specialist centres or by the standard doses of thyrotrophin releasing arthroplasties will result in a minimum potential surgeons with a specific interest in the technique.hormone, luteinising hormone releasing hormone, extra expenditure equivalent to 15 primary arthro- A TIMPERLEY and soluble insulin that we use in our unit.When plasties.The Swedish experience of two less G A GIE
D prostanoid receptor 2 (chemoattractant receptor–homologous molecule expressed on TH2 cells) protein expression in asthmatic patients and its effects on bronchial epithelial cells
Authors: Sally E. Stinson, Yassine Amrani, Christopher E. Brightling
Journal: Journal of Allergy and Clinical Immunology (2014)

The D prostanoid receptor 2 (DP2; also known as chemoattractant receptor-homologous molecule expressed on TH2 cells) is implicated in the pathogenesis of asthma, but its expression within bronchial biopsy specimens is unknown.We sought to investigate the bronchial submucosal DP2 expression in asthmatic patients and healthy control subjects and to explore its functional role in epithelial cells.DP2 protein expression was assessed in bronchial biopsy specimens from asthmatic patients (n = 22) and healthy control subjects (n = 10) by using immunohistochemistry and in primary epithelial cells by using flow cytometry, immunofluorescence, and quantitative RT-PCR. The effects of the selective DP2 agonist 13, 14-dihydro-15-keto prostaglandin D2 on epithelial cell migration and differentiation were determined.Numbers of submucosal DP2(+) cells were increased in asthmatic patients compared with those in healthy control subjects (mean [SEM]: 78 [5] vs 22 [3]/mm(2) submucosa, P < .001). The bronchial epithelium expressed DP2, but its expression was decreased in asthmatic patients compared with that seen in healthy control subjects (mean [SEM]: 21 [3] vs 72 [11]/10 mm(2) epithelial area, P = .001), with similar differences observed in vitro by primary epithelial cells. Squamous metaplasia of the bronchial epithelium was increased in asthmatic patients and related to decreased DP2 expression (rs = 0.69, P < .001). 13, 14-Dihydro-15-keto prostaglandin D2 promoted epithelial cell migration and at air-liquid interface cultures increased the number of MUC5AC(+) and involucrin-positive cells, which were blocked with the DP2-selective antagonist AZD6430.DP2 is expressed by the bronchial epithelium, and its activation drives epithelial differentiation, suggesting that in addition to its well-characterized role in inflammatory cell migration, DP2 might contribute to airway remodeling in asthmatic patients.
Overcoming barriers to recruitment in health research
Authors: Jenny Hewison, Andy Haines
Journal: BMJ (2006)

HIV-associated neurocognitive disorders (HAND) affects approximately 50% of HIV-infected individuals, and disruption of the blood brain barrier (BBB) has been observed in individuals with HAND. One of the underlying mechanisms of BBB breakdown is an imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), which has not been fully explored in HAND. In our present study, we used ELISA and zymography assays to examine the protein levels and enzyme activities of MMPs and/or TIMPs in plasma from a total of 59 HIV-positive individuals and 16 uninfected controls. We found that the concentration and enzyme activity of MMP-2 and MMP-9, two of the most important members of the MMP family, were increased in the plasma of HIV patients compared to HIV-negative controls. Plasma levels of TIMP-1 and TIMP-4 were not affected, while TIMP-3 was significantly increased in HIV patients. Strikingly, TIMP-2 was significantly down-regulated in HIV-1 patients. We also showed that neural cells, especially astrocytes, were able to release both MMPs and TIMPs, and such secretion was regulated by inflammatory factors like IL-1β or growth factors like TGF-β1. Furthermore, we found that TIMP-2 played a dual role on proMMP-2 activation via the ternary complex of MT1-MMP/TIMP-2/proMMP-2 on the surface of astrocytes, as low concentrations of TIMP-2 activated proMMP-2 and high concentrations inhibited proMMP-2 activity. In summary, our results demonstrate that decreased TIMP-2 found in HIV patients enhances MMP-2 activity, which is associated with BBB breakdown in HIV patients. Exogenous administration of TIMP-2 to maintain MMPs/TIMP-2 homeostasis may represent a potential therapy for HAND.
Abstract 384: Activation of Microglia in Paraventricular Nucleus of Hypothalamus: A Source of Central Cytokines Induced by Nuclear Factor-kappa B or Oxidative Stress in Hypertension
Authors: Yu-Ming Kang, Ying Ma, Yan-Lin Guo, Rong-Li He, Zhou-Wei Guo, Carrie Elks, Joseph Francis
Journal: Circulation (2008)
Abstract LB-133: Orchestrated recruitment of histone methyltransferases to DNA double strand breaks facilitates 53BP1 binding and proficient repair
Authors: Creighton T. Tuzon, Tanya M. Spektor, Lauren M. Congdon, Xiaodong Kong, Peggie Cheung, Alex J. Kuo, Kyoko Yokomori, Or Gozani, Judd C. Rice
Journal: Cancer Research (2014)

Abstract While selective binding of the tandem tudor domains of p53 binding protein 1 (53BP1) to dimethylated histone H4 lysine 20 (H4K20me2) at DNA double strand breaks (DSBs) is well-documented to be an essential event for proficient DSB repair, the enzyme(s) responsible for H4K20 methylation at DSBs remained unknown. Contrary to previous reports implicating the MMSET/NSD2 methyltransferase in this pathway, we demonstrate that MMSET is dispensable for H4K20 methylation, 53BP1 accumulation and DSB repair. Alternatively, we discovered that the PR-Set7 H4K20 monomethyltransferase (H4K20me1) is an essential component of nonhomologous end joining (NHEJ) which functions early and directly in DSB repair. PR-Set7 was found to mobilize immediately to DSBs and PR-Set7 enzymatic activity was necessary for H4K20 methylation, 53BP1 accumulation and proficient DSB repair. Identification of PR-Set7-associated proteins revealed interactions between PR-Set7 and several NHEJ repair proteins. Consistent with these findings, the rapid recruitment of PR-Set7 to induced DSBs was dependent on direct binding to the NHEJ Ku70/Ku86 heterodimer. PR-Set7-mediated H4K20me1 was found to be necessary, but not sufficient, for H4K20me2 and 53BP1 recruitment at induced DSBs and an undamaged ectopic locus. In addition, we also discovered that the Suv4-20 H4K20 dimethyltransferases mobilize to DSBs and were required for H4K20me2 and 53BP1 accumulation. Importantly, Suv4-20 was not sufficient for H4K20me2 and 53BP1 localization at induced DSBs or an undamaged ectopic locus in cells lacking a catalytically competent PR-Set7. Therefore, these results illuminate an orchestrated molecular pathway whereby PR-Set7-mediated H4K20me1 “primes” the DSB to expedite subsequent catalysis by Suv4-20 for the generation of H4K20me2 at the lesion necessary for 53BP1 binding. The collective findings identify PR-Set7 as an essential early component of NHEJ and reveal a novel temporal PR-Set7-dependent pathway that facilitates H4K20me2 and 53BP1 accumulation at DSBs necessary for proficient DSB repair. Furthermore, these results and preliminary studies indicate that small molecule inhibitors targeting PR-Set7 and/or Suv4-20 will likely be clinically effective radio- and chemo-sensitizing agents in cancer treatment. Citation Format: Creighton T. Tuzon, Tanya M. Spektor, Lauren M. Congdon, Xiaodong Kong, Peggie Cheung, Alex J. Kuo, Kyoko Yokomori, Or Gozani, Judd C. Rice. Orchestrated recruitment of histone methyltransferases to DNA double strand breaks facilitates 53BP1 binding and proficient repair. [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 LB-133. doi:10.1158/1538-7445.AM2014-LB-133
Evaluation of Patients after Acute Myocardial Infarction
Authors: Stephen E. Epstein, Sebastian T. Palmeri, Randolph E. Patterson
Journal: New England Journal of Medicine (1982)

AN important question facing physicians today is whether to recommend cardiac catheterization to the patient who has just had an acute myocardial infarction. Although it has long been recognized that information obtained from cardiac catheterization regarding left ventricular function and cardiac anatomy can provide important prognostic information, this alone has not been considered sufficient reason to catheterize all post-infarction patients. Recent reports, however, have demonstrated that coronary-artery-bypass surgery improves survival in certain subgroups of patients with stable coronary-artery disease as identified by coronary angiography. This improved survival has been demonstrated most convincingly in patients with critical narrowing of the left . . .
Abstract 596: Combination of SAHA with dietary energy restriction for breast cancer prevention
Authors: Zongjian Zhu, Weiqin Jiang, John N. McGinely, Angie Neil, Danna Steiner, Henry J. Thompson
Journal: Cancer Research (2012)

Abstract Studies of human populations and experimental models indicate that dietary energy restriction (DER) inhibits the development of breast cancer. Of the several candidate mechanisms that DER is known to affect, one that is the widely observed is the induction of class III histone deacetylase sirtuin 1 (SIRT1). Evidence is controversial as to whether induction of SIRT1 is essential for DER's cancer preventive activity or if it limits DER's effectiveness. Therefore an experiment was designed to determine if suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, would diminish or enhance the cancer preventive activity of DER. Female Sprague Dawley rats (n=30/group) were injected with 1-methyl-1-nitrosourea (50 mg/kg) at 21 days of age and 7 days thereafter were randomized to groups and fed either control diet (AIN-93G) or that diet formulation supplemented with 0.1% SAHA (w/w). Other treatment groups were 40% DER, or 0.1% SAHA+40% DER; diets were a modification of AIN93-G that assured that the only variables among groups were DER and/or SAHA. Rats were fed respective diets for 8 weeks. An additional group, 0.1% SAHA+40%DER-release, was fed 0.1% SAHA+40%DER diet for 5 weeks and released to control diet for the final 3 weeks of the experiment. Both 40%DER or 0.1%SAHA+40%DER significantly reduced mammary cancer incidence, the number of mammary adenocarcinomas per rat, and cancer burden, as well as prolonging cancer latency (p&amp;lt;0.01). After releasing rats from SAHA+DER, the number of mammary adenocarcinomas per rat was significantly lower and the cancer latency was still significantly longer than the control gp (p&amp;lt;0.05). The mechanisms of the cancer inhibition include effects on circulating factors, IGF1/IGFBP3, insulin, adiponectin, leptin, and C-reactive protein. Thus it does not appear that SIRT1 induction is not requisite for the cancer preventive activity of DER. Rather inhibition of cancer was associated with cellular AMPK activation and Akt-mTOR down regulation by SAHA+DER with additional effects being mediated via FOXO3a. Supported by PHS grant CA52626 from the National Cancer Institute. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 596. doi:1538-7445.AM2012-596
Metabolism of testosterone-14C by cultured human cells
Authors: Donna D. Shanies, Kurt Hirschhorn, Maria I. New
Journal: Journal of Clinical Investigation (1972)

The metabolism of (14)C-labeled testosterone by cultured human fibroblasts and amniotic fluid cells was investigated. Radiolabeled testosterone was incubated with the cultured cells for 48 hr, and the labeled metabolites present in the medium were subsequently identified. The major metabolic products of testosterone formed by cultured fibroblasts were Delta(4)-androstenedione, dihydrotestosterone, androsterone, and androstanediol. The amount of testosterone metabolized through each of two pathways was calculated and used to form a ratio designated the 17beta-hydroxyl/17-ketonic ratio. Fibroblasts from normal male and female children and adult females had high 17beta-hydroxyl/17-ketonic ratios indicating testosterone metabolism occurred primarily through the 17beta-hydroxyl pathway. There was change in the pattern of testosterone metabolism with age in males, i.e., adult males had much lower 17beta-hydroxyl/17-ketonic ratios than did male children. The testosterone metabolism of fibroblast cultures derived from three children with testicular feminization and their mothers was compared to normal age and sexmatched controls. Fibroblasts of children with testicular feminization metabolized testosterone predominantly through the 17-ketonic pathway and manifested a pattern of testosterone metabolism distinctly different from their sex and age matched controls. The mothers of children with testicular feminization could be distinguished from normal females by their much lower 17beta-hydroxyl/17-ketonic ratios. The much lower amounts of dihydrotestosterone and androstanediol produced by fibroblasts from patients with testicular feminization as compared with normals suggests there is a decrease in testosterone 5alpha-reductase activity in these patients. Cultured amniotic fluid cells metabolized testosterone to the same four major metabolites found in fibroblast cultures, but their activity was much lower than that of fibroblasts. Most of the amniotic fluid cell cultures metabolized testosterone largely through the 17beta-hydroxyl pathway as did fibroblasts from normal children.
LOCAL ANESTHESIA IN THE REDUCTION OF FRACTURES
Authors: IRA COHEN
Journal: JAMA (1926)

Since 1885, when Conway<sup>1</sup>first advocated the use of cocaine in the reduction of fractures and dislocations, the only reference to the subject in American medical writings is an article by Cumston,<sup>2</sup>in 1918. Conway reported three cases of Colles' fractures and one of posterior dislocation of both bones at the elbow reduced under local anesthesia. The European literature contains series of cases reported by various authors. Reclus,<sup>3</sup>in 1903, made use of the method to transport in comfort a patient with a fracture of the femur, and found that a half hour later the anesthesia was sufficient to allow of the reduction of the fracture. Lerda<sup>4</sup>reported thirty cases in 1907, and the following year Quenu<sup>5</sup>described its use in fifteen cases. Braun<sup>6</sup>detailed fifty cases in which he used local infiltration twenty-three times and either brachial or other forms of conduction anesthesia
Effects of pentoxifylline pretreatment on Kupffer cells in rat liver transplantation
Authors: Koichi Kozaki, Hiroto Egawa, Luiz Bermudez, Emmet B. Keefe, Samuel K. So, Carlos O. Esquivel
Journal: Hepatology (1995)

Previous research with pentoxifylline (PTX), a methylxanthine phosphodiesterase inhibitor, suggests that this drug may be capable of suppressing the activation of Kupffer cells and thereby help decrease liver injury after transplantation. To investigate this possibility, the current study sought to determine whether the release of O2- and tumor necrosis factor (TNF) from Kupffer cells in donor livers can be suppressed if the organs are exposed to PTX before preservation. In an in vitro experiment, rat livers were flushed with PTX (25 mg/kg body weight) in University of Washington (UW) solution or UW solution alone (control) and then and stored in UW solution for either 4 or 24 hours. Kupffer cells then were purified and their degree of activation determined by measuring O2- release and the production of TNF after lipopolysaccharide stimulation. In an in vivo experiment, a group of rats underwent orthotopic liver transplantation with grafts prepared in the same manner as in the in vitro study. TNF and aspartate transaminase (AST) were measured in blood samples taken 3 hours and 24 hours after transplantation. Compared with controls, the Kupffer cells from grafts pretreated with PTX produced significantly less O2- and TNF, and the recipients of PTX-pretreated grafts had lower levels of TNF and AST 3 hours after transplantation. The current data indicate that O2- and TNF production in liver grafts is suppressed by PTX pretreatment. Through its suppressive effect on Kupffer cells, PTX may help minimize preservation-reperfusion injury and improve graft survival.
Head and Neck Oncology: Diagnosis, Treatment, and Rehabilitation
Authors: Joseph W. Walike
Journal: JAMA (1992)

This is a user-friendly text that comprehensively covers the wide scope of head and neck oncology in a concise 500+ pages. Nearly every chapter utilizes a single-page flowsheet to graphically present the material or method of solution of the problem. This feature provides quick comprehension of sometimes difficult and complex material. The organization of chapters is excellent, and the headings within chapters make for easy and rapid reading. The editor has demanded this organization throughout so that the text has a cohesiveness sometimes lacking in multiauthored works. The material is accurate and current. The reader gets a sense of compassion throughout and an emphasis on the patient's quality of life. Medical readers will receive an accurate, appropriate, and quick pathway through the three sections of diagnosis, treatment, and rehabilitation for each tumor of the head and neck. Chapter 7 on planning is especially noteworthy and is appropriate reading for the