tbuckley/cabot-search huggingface dataset:
Molecular analysis of a major antigenic region of the 240-kD protein of Mi-2 autoantigen.
Authors: Q Ge, D S Nilasena, C A O'Brien, M B Frank, I N Targoff
Journal: Journal of Clinical Investigation (1995)

Anti-Mi-2 autoantibody is strongly associated with dermatomyositis and found in sera of 20% of patients. Mi-2 antigen contains at least eight components and previous evidence suggested that the 240-kD protein was the antigenic component for at least some sera. In this study, anti-M-2 patient sera were used to screen human thymocyte and HeLa cell lambda gt11 expression libraries, and two clones from each had plaques specifically reactive with anti-Mi-2 sera. Studies with affinity-purified antibody supported the identification of the clones. All of 44 anti-Mi-2 sera reacted with the plaques, but none of 44 control sera reacted significantly. The cDNAs were identical, and full sequencing of one revealed an open reading frame spanning a 1,054-bp insert. Rescreening the library with the cDNA yielded a 1,589-bp cDNA that continued the open reading frame. The Mi-2 cDNA hybridized to a single 7.5-8.0 kb mRNA of HeLa cells, by Northern blot. Rabbit antiserum directed at a portion of the cDNA product reacted with HeLa 240-kD Mi-2 protein. The sequence was notable for four potential zinc-fingers and several charged regions. The protein encoded by the cDNA produced in vitro reacted with only one of five of the Mi-2 sera. These findings indicate that the Mi-2 240 kD is a novel protein that is antigenic for all Mi-2 sera, and strongly suggests that a major common epitope is conformational in nature.
Hyperthermia Activates a Subset of Ataxia-Telangiectasia Mutated Effectors Independent of DNA Strand Breaks and Heat Shock Protein 70 Status
Authors: Clayton R. Hunt, Raj K. Pandita, Andrei Laszlo, Ryuji Higashikubo, Manjula Agarwal, Tetsuya Kitamura, Arun Gupta, Nicole Rief, Nobuo Horikoshi, Rajeskaran Baskaran, Ji-Hoon Lee, Markus Löbrich, Tanya T. Paull, Joseph L. Roti Roti, Tej K. Pandita
Journal: Cancer Research (2007)

Abstract All cells have intricately coupled sensing and signaling mechanisms that regulate the cellular outcome following exposure to genotoxic agents such as ionizing radiation (IR). In the IR-induced signaling pathway, specific protein events, such as ataxia-telangiectasia mutated protein (ATM) activation and histone H2AX phosphorylation (γ-H2AX), are mechanistically well characterized. How these mechanisms can be altered, especially by clinically relevant agents, is not clear. Here we show that hyperthermia, an effective radiosensitizer, can induce several steps associated with IR signaling in cells. Hyperthermia induces γ-H2AX foci formation similar to foci formed in response to IR exposure, and heat-induced γ-H2AX foci formation is dependent on ATM but independent of heat shock protein 70 expression. Hyperthermia also enhanced ATM kinase activity and increased cellular ATM autophosphorylation. The hyperthermia-induced increase in ATM phosphorylation was independent of Mre11 function. Similar to IR, hyperthermia also induced MDC1 foci formation; however, it did not induce all of the characteristic signals associated with irradiation because formation of 53BP1 and SMC1 foci was not observed in heated cells but occurred in irradiated cells. Additionally, induction of chromosomal DNA strand breaks was observed in IR-exposed but not in heated cells. These results indicate that hyperthermia activates signaling pathways that overlap with those activated by IR-induced DNA damage. Moreover, prior activation of ATM or other components of the IR-induced signaling pathway by heat may interfere with the normal IR-induced signaling required for chromosomal DNA double-strand break repair, thus resulting in increased cellular radiosensitivity. [Cancer Res 2007;67(7):3010–7]
RENAL EXTRACTION OF PARA-AMINOHIPPURATE IN INFANTS AND CHILDREN*
Authors: Philip L. Calcagno, Mitchell I. Rubin
Journal: Journal of Clinical Investigation (1963)

Earlier publications questioned the reliability of measurements of renal plasma flow in young in- fants, since the extraction ratios for para-aminohippurate (EPAH) used were those obtained in adults (1-3).It was suggested that the use of these high values for EPAH to determine renal plasma flow and filtration fraction might not be valid and could account for the high filtration fraction reported in infants under a year of age (1-5).This high fraction was interpreted to in- dicate that the rate of glomerular filtration is greater in comparison to renal plasma flow than that in adults.The present study was designed to measure EPAH in young infants in order to ar- rive at the true value for renal plasma flow and calculated filtration fraction. METHODSFifteen children between 8 days and 10 years old were studied; eight were under 3 months, and seven between 5 months and 10 years old.Pertinent clinical and labora- tory data are listed in Tables I through IV.Forty-five minutes before testing, eight of the fifteen patients were given a sedative; ' five were infants (no. 1 and 5-8) and three were older children (no. 10, 11, and 15).Inulin2 and para-aminohippurate (PAH) were administered in normal saline or 5% dextrose in water after base-line con- trol venous blood determinations were made.The diluent and the intervals from the mixing of PAH with the di- luent to the end of the test are recorded in Tables II andIII.Saline as the diluent for the PAH injection was used in four infants and in two children.Five per cent dextrose in water was the diluent in four infants and in seven children.Two infants and two children were
Gut instincts: CYP3A4 and intestinal drug metabolism
Authors: Kenneth E. Thummel
Journal: Journal of Clinical Investigation (2007)

First-pass metabolism is a common cause of incomplete and variable absolute bioavailability for an orally dosed drug. The drug-metabolizing enzyme CYP3A4 is often implicated in this process, resulting, in some cases, in systemic exposures of less than 15% of the administered dose. By creating an elegant CYP3A4-transgenic mouse model, van Herwaarden et al. show in this issue of the JCI that first-pass metabolism of the anticancer agent docetaxel by the gut wall, and not the liver, is likely to be the major cause of its low oral bioavailability in humans (see the related article beginning on page 3583). This study helps explain interpatient differences in efficacy and safety following oral therapy with approved CYP3A4 substrates and provides a powerful new tool for preclinical predictions of first-pass metabolism for new drugs in development.
Little evidence that one type of pain relief for labour is better than another, finds Cochrane review
Authors: J. Wise
Journal: BMJ (2012)

A Cochrane review has concluded that many non-drug methods of pain relief in labour, such as TENS and aromatherapy, are poorly researched and there is not enough evidence to say whether they are any more effective than placebo.

The “review of reviews” found more evidence to support the efficacy of pharmacological methods, but these do have more adverse effects. Considerable evidence exists that epidural analgesia, for example, does provide effective pain relief but it also increases the risk of forceps or ventouse being used during the birth. Epidurals also increase the risk of low blood pressure among women, motor blockade (which hinders leg movement), fever, and urine retention.

The overview included 18 systematic reviews of different interventions used to reduce pain in labour, 15 of them Cochrane reviews. A total of 312 trials were included.

Most of the evidence on non-drug interventions was based on just one or two studies and the findings are not definitive. The authors conclude, however, that there is some evidence to suggest …
Health Care Interventions to Improve the Quality of Diabetes Care in African Americans
Authors: Ignacio Ricci-Cabello, Isabel Ruiz-Pérez, Adela Nevot-Cordero, Miguel Rodríguez-Barranco, Luis Sordo, Daniela C. Gonçalves
Journal: Diabetes Care (2013)

Type 2 diabetes is a serious, costly, and potentially preventable public health problem in the U.S., and both the prevalence and incidence of diabetes have increased rapidly since the mid-1990s (1). Currently, >7% of adults in the U.S. have been diagnosed with type 2 diabetes, and diabetes-related care accounts for 11% of all U.S. health care expenditures (2).

African Americans bear a disproportionate burden from diabetes and its complications. Compared with Caucasians, African Americans are almost twice as likely to suffer from type 2 diabetes and to experience diabetes-related blindness and lower-limb amputations, and two to six times more likely to have kidney disease (3). Furthermore, these disparities are enhanced when in tandem with other axes of inequality, such as geographic region, age, or sex (4).

Health inequalities in diabetes care can be conceptualized as differences in the quality of diabetes self-management (DSM) and of the medical care received. African Americans with diabetes experience more difficulties in DSM than Caucasians (5,6). Several reasons contribute to the observed differences, namely that African Americans often present cultural beliefs about their medical care and difficulties with language or low health literacy, which interfere with the success of DSM activities. Additionally, racial disparities in health services access and delivery are also thought to contribute to the observed differences, as African Americans are less likely to have routine glycosylated hemoglobin (HbA1c) testing, lipid panels, and retinopathy screening than their Caucasian counterparts (7,8).

In the past decade, there has been a surge in the development and implementation of quality improvement interventions led by the health care sector, which aim to decrease the burden of social inequalities in diabetes care. According to the Chin et al. (9) conceptual framework, those interventions can be classified as targeted to the patients, …
Distinguishing between Hypochondriasis and Somatization Disorder: A Review of the Existing Literature
Authors: Russell Noyes, Scott Stuart, David B. Watson, Douglas R. Langbehn
Journal: Psychotherapy and Psychosomatics (2006)

A valid classification is important for further understanding of the somatoform disorders. The main disorders in this grouping – somatization disorder and hypochondriasis – have lengthy historical traditions and are defined in a contrasting manner. Various authors point to distinguishing demographic and clinical features, but there have been few direct comparisons of patients with these disorders. A review of the literature indicates those domains where differences are most likely to be found. Research assessing these may serve to refine and validate these key somatoform categories and/or dimensions.
<i> <scp>HLA</scp> ‐ <scp>B</scp> *58:01 </i> is strongly associated with allopurinol‐induced severe cutaneous adverse reactions in <scp>H</scp> an <scp>C</scp> hinese patients: a multicentre retrospective case–control clinical study
Authors: L. Cheng, Y. Xiong, C.Z. Qin, W. Zhang, X.P. Chen, J. Li, H.H. Zhou
Journal: British Journal of Dermatology (2015)

Journal Article HLA‐B*58:01 is strongly associated with allopurinol‐induced severe cutaneous adverse reactions in Han Chinese patients: a multicentre retrospective case–control clinical study Get access L. Cheng, L. Cheng Department of Clinical Pharmacology Xiangya Hospital Central South University Changsha 410008 Hunan ChinaInstitute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Changsha 410078 Hunan China Search for other works by this author on: Oxford Academic Google Scholar Y. Xiong, Y. Xiong Department of Clinical Pharmacology Xiangya Hospital Central South University Changsha 410008 Hunan ChinaInstitute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Changsha 410078 Hunan China Search for other works by this author on: Oxford Academic Google Scholar C.Z. Qin, C.Z. Qin Department of Clinical Pharmacology Xiangya Hospital Central South University Changsha 410008 Hunan ChinaInstitute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Changsha 410078 Hunan China Search for other works by this author on: Oxford Academic Google Scholar W. Zhang, W. Zhang Department of Clinical Pharmacology Xiangya Hospital Central South University Changsha 410008 Hunan ChinaInstitute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Changsha 410078 Hunan China Search for other works by this author on: Oxford Academic Google Scholar X.P. Chen, X.P. Chen Department of Clinical Pharmacology Xiangya Hospital Central South University Changsha 410008 Hunan ChinaInstitute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Changsha 410078 Hunan China Search for other works by this author on: Oxford Academic Google Scholar J. Li, J. Li Department of Dermatology Xiangya Hospital Central South University Changsha 410008 Hunan China Correspondence: Hong‐Hao Zhou and Ji Li. E‐mails: hhzhou2003@163.com; lydia.1208@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar H.H. Zhou H.H. Zhou Department of Clinical Pharmacology Xiangya Hospital Central South University Changsha 410008 Hunan ChinaInstitute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Changsha 410078 Hunan China Correspondence: Hong‐Hao Zhou and Ji Li. E‐mails: hhzhou2003@163.com; lydia.1208@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 2, 1 August 2015, Pages 555–558, https://doi.org/10.1111/bjd.13688 Published: 01 August 2015
Can Ultrasound of the Tibial Nerve Detect Diabetic Peripheral Neuropathy?
Authors: Sheila Riazi, Vera Bril, Bruce A. Perkins, Sherif Abbas, Vincent W.S. Chan, Mylan Ngo, Leif E. Lovblom, Hossam El-Beheiry, Richard Brull
Journal: Diabetes Care (2012)

Peripheral nerve imaging by portable ultrasound (US) may serve as a noninvasive and lower-cost alternative to nerve conduction studies (NCS) for diagnosis and staging of diabetic sensorimotor polyneuropathy (DSP). We aimed to examine the association between the size of the posterior tibial nerve (PTN) and the presence and severity of DSP.We performed a cross-sectional study of 98 consecutive diabetic patients classified by NCS as subjects with DSP or control subjects. Severity was determined using the Toronto Clinical Neuropathy Score. A masked expert sonographer measured the cross-sectional area (CSA) of the PTN at 1, 3, and 5 cm proximal to the medial malleolus.Fifty-five patients had DSP. The mean CSA of the PTN in DSP compared with control subjects at distances of 1 (23.03 vs. 17.72 mm(2); P = 0.004), 3 (22.59 vs. 17.69 mm(2); P < 0.0001), and 5 cm (22.05 vs. 17.25 mm(2); P = 0.0005) proximal to the medial malleolus was significantly larger. Although the area under the curve (AUC) for CSA measurements at all three anatomical levels was similar, the CSA measured at 3 cm above the medial malleolus had an optimal threshold value for identification of DSP (19.01 mm(2)) with a sensitivity of 0.69 and a specificity of 0.77 by AUC analysis.This large study of diabetic patients confirms that the CSA of the PTN is larger in patients with DSP than in control subjects, and US is a promising point-of-care screening tool for DSP.
Idiopathic Chylopericardium: ^131 I-Triolein Scan for Noninvasive Diagnosis
Authors: Stephen V. Savran, Robert A. Ratshin, James H. Shirley, Stanley M. Naguwa, Lawrence Goodman
Journal: Annals of Internal Medicine (1975)

We report idiopathic chylopericardium in a physically active, asymptomatic 29-year-old man. Preoperative diagnosis was made by external cardiac imaging after oral administration of 131-I-labeled triolein. To our knowledge this is the first report of preoperative noninvasive diagnosis of chylopericardium. After open drainage and pericardial biopsy, the patient is asymptomatic without recurrence after 8 months.
PRAVASTATIN THERAPY AMONG ALL ETHNIC GROUPS OF CARE REDUCED PRIMARY END POINT EVENTS IN CARRIERS OF THE KIF6 719ARG ALLELE, BUT NOT IN NONCARRIERS
Authors: Dov Shiffman, Marc S. Sabatine, Judy Z. Louie, Charles M. Rowland, Olga A. Iakoubova, Hannia Campos, Frank M. Sacks, James J. Devlin
Journal: Journal of the American College of Cardiology (2010)
Hepatology Principles and Practice: E Kuntz, H-D Kuntz. Berlin: Springer Verlag, colour, pp 825. ISBN 3540 42161 0
Authors: S D Taylor-Robinson
Journal: Gut (2003)

Caution with the use of cyclosporin in pregnancyWe read the article by Alstead and Nelson-Piercy with great interest. 1 We report a case (submitted for publication) of a woman with fulminant ulcerative colitis in the 29th week of pregnancy.Her disease was refractory to steroids, but she refused to have cyclosporin whilst pregnant.She therefore underwent an emergency Caesarean section and was given intravenous cyclosporin post-operatively.After 48 hours of treatment she developed severe hypertension with hypertensive encephalopathy and seizures.Although cyclosporin has been considered to be safe for both mother and foetus, we would like to highlight concerns that it is associated with potentially life threatening side effects.As a result, patients must be counselled thoroughly about the potential morbidity associated with this treatment and monitored closely.We agree with Dr Alstead in that cyclosporin should be used with extreme caution in pregnancy and the postnatal period.
Letrozole in Combination with Trastuzumab Is Superior to Letrozole Monotherapy as First Line Treatment in Patients with Hormone-Receptor-Positive, HER2- Positive Metastatic Breast Cancer (MBC) – Results of the <i>eLEcTRA</i> Trial.
Authors: J. Huober, P. Fasching, S. Paepke, E. Kubista, M. Barsoum, D. Wallwiener, N. Harbeck
Journal: Cancer Research (2009)

Abstract Background: Letrozole (LET) and trastuzumab (TRA) are established agents for the treatment of hormone-receptor (HR) positive metastatic breast cancer (MBC) patients and HER2 positive disease, respectively. The “eLEcTRA” trial was designed to compare the efficacy and safety of LET combined with TRA to LET alone in patients that are both HER2 and HR positive. Furthermore, LET alone was compared in patients with HER2 and HR positive disease vs. those with HER2 negative, HR positive tumors.Methods: In this multicenter trial, 92 pts from 32 sites in 7 countries were enrolled from 2003 to 2007. Initially, enrollment of 370 pts was planned, however, due to slow recruitment the trial was prematurely closed in 2007. Patients with HER2 and HR positive MBC were randomized to either LET alone (Arm A, n=31) or LET + TRA (Arm B, n=26) as first-line treatment. In addition, 35 patients with HER2 negative and HR positive tumors were assigned to receive LET alone as first-line treatment (Arm C). Tumor response assessments were based on RECIST. Primary endpoint was time to progression (TTP), secondary endpoints were overall response rate (ORR) and clinical benefit rate (CBR).Results: Median age in the three arms was 61 (arm A), 61,5 (arm B), and 70 years (arm C), respectively. Median TTP in the LET alone arm (A) was 3.3 months compared to 14.1 months in the LET + TRA combination arm (B) (hazard ratio=0.67; p=0.23) and 15.2 months in arm C (hazard ratio=0.71; p=0.03). CBR was 39% for arm A compared to 65% in arm B (odds ratio 3.15, CI 1.07-9.26) and 77% in arm C (odds ratio 5.34, CI 1.83-15.58), respectively. ORRs were 13% for arm A, 27% for arm B, and 11% for arm C.LVEF as cardiac safety parameter showed no change from baseline to the minimum value during the treatment for arms A and C and a slight decrease by 5% for arm B.The incidence of other cardiac adverse events was comparable in all arms (10%, 8%, and 9%). Gastrointestinal disorders or musculoskeletal and connective tissue disorders were slightly more frequent for patients receiving LET and TRA (arm B).Conclusion: The results of the eLEcTRA trial show that the combination of letrozole and trastuzumab can be safely administered and is superior to letrozole alone as first-line therapy in patients with HER2 and HR positive MBC. Our results also confirm earlier evidence that aromatase-inhibitor therapy alone is only associated with a rather short TTP in HER2 and HR positive MBC. In contrast, outcome in letrozole-treated patients with HER2 negative HR positive tumors is significantly better compared to that associated with tumors with both HR and HER2 expression.(Trial was sponsored by Novartis Pharmaceuticals) Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4094.
Statins for Ischemic Systolic Heart Failure
Authors: Frederick A. Masoudi
Journal: New England Journal of Medicine (2007)

Hydroxymethylglutaryl–coenzyme A reductase inhibitors (statins) represent one of the most important pharmacologic advances in the prevention of cardiovascular disease in decades. Since the publication of the Scandinavian Simvastatin Survival Study in 1994,1 several trials have demonstrated important benefits of statins in patients with established coronary disease. These findings have resulted in strong recommendations for the use of statins in clinical-practice guidelines.2 Statins are one of the few classes of drugs that are embedded in clinical-performance measures for coronary artery disease, which indicates that clinicians should be considered remiss if they do not prescribe these agents for all their eligible patients. . . .
Bone Loss and Hormone Therapy
Authors: AMIEL Z. RUDAVSKY
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 June 1978Bone Loss and Hormone TherapyAMIEL Z. RUDAVSKY, M.D., F.A.C.P.AMIEL Z. RUDAVSKY, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-88-6-846_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I was surprised on reading the report by Recker, Saville, and Heaney, "Effect of Estrogens and Calcium Carbonate on Bone Loss in Post-menopausal Women" (Ann Intern Med87:649-655, 1977), that there was no mention in the title, abstract, or discussion that the patients receiving hormone therapy were treated with both conjugated equine estrogen and methyltestosterone, rather than with estrogen alone. In addition, though the mean patient age at menopause was, as expected, between 46 and 50 years, the lower limit of age at menopause was reported as being 30 years, suggesting that some of the patients may... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1978Volume 88, Issue 6Page: 846-846KeywordsBone resorptionCalciumCarbonatesEstrogensHormonal therapyHormonesMenopause Issue Published: 1 June 1978 PDF DownloadLoading ...