tbuckley/cabot-search huggingface dataset:
Expression of a BTB/POZ Protein, NAC1, Is Essential for the Proliferation of Normal Cyclic Endometrial Glandular Cells and Is Up-regulated by Estrogen
Authors: Masako Ishibashi, Kentaro Nakayama, Shamima Yeasmin, Atsuko Katagiri, Kouji Iida, Naomi Nakayama, Kohji Miyazaki
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The purpose of this study was to investigate the expression and localization of NAC1, a member of the BTB/POZ gene family in the human cyclic endometrium. Experimental Design: NAC1 expression in normal cyclic endometrium was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. To elucidate the molecular mechanisms of NAC1 expression in the normal endometrium endometrial carcinoma cell lines (Ishikawa, HHUA; ER+, PR+) and primary cultured normal endometria were tested in a sex steroid induction assay and a NAC1 knockdown assay using siRNA. Results: Expression of NAC1 in glandular cells was significantly higher in the early and mid proliferative phases than in the other menstrual phases. Both NAC1 RNA and protein expression were up-regulated by treatment with 10 nmol/L 17β-Estradiol (E2) in Ishikawa, HHUA and primary cultured normal endometrial cells. The estrogen receptor antagonist ICI 182,780 significantly attenuated E2-induced NAC1 expression. NAC1 gene knockdown inhibited cell growth and induced apoptosis in Ishikawa, HHUA, and normal endometria, all of which expressed NAC1. Furthermore, NAC1 siRNA significantly abrogated estrogen-driven cellular proliferation in Ishikawa, HHUA, and primary cultured normal endometrial cells, whereas the control siRNA had no effect on cell growth in any of these cells. Conclusions: These findings suggest that NAC1 is functionally involved in E2-induced cell growth of the normal endometrial glandular cells. Because NAC1 is thought to have oncogenic potential, the current findings may provide new insight into the mechanism of estrogen induced endometrial carcinogenesis.
Parents Bereaved by Offspring Suicide
Authors: James M. Bolton, Wendy Au, William D. Leslie, Patricia J. Martens, Murray W. Enns, Leslie L. Roos, Laurence Y. Katz, Holly C. Wilcox, Annette Erlangsen, Dan Chateau, Randy Walld, Rae Spiwak, Monique Seguin, Katherine Shear, Jitender Sareen
Journal: JAMA Psychiatry (2012)

CONTEXT Suicide bereavement remains understudied and poorly understood. OBJECTIVES To examine outcomes of parents bereaved by the suicide death of their offspring and to compare these with both nonbereaved parent controls and parents who had offspring die in a motor vehicle crash (MVC). DESIGN Population-based case-control study. Suicide-bereaved parents were compared with nonbereaved matched control parents in the general population (n = 1415) and with MVC-bereaved parents (n = 1132) on the rates of physician-diagnosed mental and physical disorders, social factors, and treatment use in the 2 years after death of the offspring. Adjusted relative rates (ARRs) were generated by generalized estimating equation models and adjusted for confounding factors. SETTING Manitoba, Canada. PARTICIPANTS All identifiable parents who had an offspring die by suicide between 1996 and 2007 (n = 1415). MAIN OUTCOME MEASURES Mental and physical disorders, social factors, and treatment use. RESULTS Suicide bereavement was associated with an increased rate of depression (ARR, 2.14; 95% CI, 1.88-2.43), anxiety disorders (ARR, 1.41; 95% CI, 1.24-1.60), and marital breakup (ARR, 1.18; 95% CI, 1.13-1.23) in the 2 years after the suicide of an offspring, as compared with the 2 years prior to the death. Suicide-bereaved and MVC-bereaved parents had very few differences on predeath to postdeath outcomes. Depression rate increases were greater for MVC-bereaved parents (19.9%) compared with suicide-bereaved parents (15.9%; P = .005), whereas suicide-bereaved parents had higher rate increases of hospitalization for mental illness (P = .049). Suicide-bereaved parents were more likely than their MVC-bereaved counterparts to have depression (ARR, 1.30; 95% CI, 1.06-1.61), physical disorders (ARR, 1.32; 95% CI, 1.19-1.45), and low income (ARR, 1.34; 95% CI, 1.18-1.51) before their offspring's death. CONCLUSIONS Suicide bereavement is associated with adverse mental health and social outcomes. These consequences appear similar to those associated with MVC bereavement. Parents who lose offspring to suicide appear to be a vulnerable group even prior to their offspring's death.
Absence of VIII AHF response to adrenalin in hemophilia A
Authors: M. Elaine Eyster, Margaret Dranchak, Judy Haverstick, John S. Rogers
Journal: American Journal of Hematology (1977)

Abstract Proportionate twofold or greater increases in both Factor VIII procoagulant activity (VIII AHF) and Factor VIII‐like antigen (VIII AGN) have been observed to follow the administration of adrenalin in normal individuals. Levels of factor VIII procoagulant or clot‐promoting activity (VIII AHF) and VIII AGN were measured immediately before and one hour after the subcutaneous injection of adrenalin (0.35 ml) in ten adults with hemophilia A documented by low VIII AHF levels (ranging from 0.01‐0.25 units/ml, normal VIII AGN levels, and normal VIII VWF levels as measured by the washed‐platelet ristocetin assay). Eighteen normal adults served as controls. Results were analyzed by the paired t test. It was shown that VIII AGN increased significantly, while VIII AHF did not change, in hemophiliacs after adrenalin stimulation, regardless of the base line level. This fixed rate of VIII AHF production, release, or activation may help to explain the constancy of VIII AHF levels in individual hemophiliacs and their affected family members.
Melanoma erysipeloides: inflammatory metastatic melanoma of the skin
Authors: B.B. Tan, J.R. Marsden, D.S.A. Sanders
Journal: British Journal of Dermatology (1993)

Journal Article Melanoma erysipeloides: inflammatory metastatic melanoma of the skin Get access B.B. Tan, B.B. Tan Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar J.R. Marsden, J.R. Marsden Departments of Dermatology Dr J.R.Marsden. Search for other works by this author on: Oxford Academic Google Scholar D.S.A. Sanders D.S.A. Sanders Histopathology. Birmingham General Hospital. Birmingham B4 6NH. U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 3, 1 September 1993, Pages 327–329, https://doi.org/10.1111/j.1365-2133.1993.tb11856.x Published: 01 September 1993 Article history Accepted: 15 February 1993 Published: 01 September 1993
Treatment of xeroderma pigmentosum variant with low-dose etretinate
Authors: E. Finkeldstein, A. Lazaroc, S. Halevy
Journal: British Journal of Dermatology (1996)

Journal Article Treatment of xeroderma pigmentosum variant with low‐dose etretinate Get access E. Finkeldstein, E. Finkeldstein Department of Dermatology, Soroka Medical Centre, Facullty of Health Sciecnes, Ben‐Gurion University of the Negev, Beer‐Sheva, Israel Search for other works by this author on: Oxford Academic Google Scholar A. Lazaroc, A. Lazaroc Department of Dermatology, Soroka Medical Centre, Facullty of Health Sciecnes, Ben‐Gurion University of the Negev, Beer‐Sheva, Israel Search for other works by this author on: Oxford Academic Google Scholar S. Halevy S. Halevy Department of Dermatology, Soroka Medical Centre, Facullty of Health Sciecnes, Ben‐Gurion University of the Negev, Beer‐Sheva, Israel Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 134, Issue 4, 1 April 1996, Pages 815–816, https://doi.org/10.1111/j.1365-2133.1996.tb07005.x Published: 01 April 1996
Long-Term Persistence of Hormonal Adaptations to Weight Loss
Authors: Priya Sumithran, Luke A. Prendergast, Elizabeth Delbridge, Katrina Purcell, Arthur Shulkes, Adamandia Kriketos, Joseph Proietto
Journal: New England Journal of Medicine (2011)

After weight loss, changes in the circulating levels of several peripheral hormones involved in the homeostatic regulation of body weight occur. Whether these changes are transient or persist over time may be important for an understanding of the reasons behind the high rate of weight regain after diet-induced weight loss.We enrolled 50 overweight or obese patients without diabetes in a 10-week weight-loss program for which a very-low-energy diet was prescribed. At baseline (before weight loss), at 10 weeks (after program completion), and at 62 weeks, we examined circulating levels of leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon-like peptide 1, amylin, pancreatic polypeptide, cholecystokinin, and insulin and subjective ratings of appetite.Weight loss (mean [±SE], 13.5±0.5 kg) led to significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin (P<0.001 for all comparisons), and amylin (P=0.002) and to increases in levels of ghrelin (P<0.001), gastric inhibitory polypeptide (P=0.004), and pancreatic polypeptide (P=0.008). There was also a significant increase in subjective appetite (P<0.001). One year after the initial weight loss, there were still significant differences from baseline in the mean levels of leptin (P<0.001), peptide YY (P<0.001), cholecystokinin (P=0.04), insulin (P=0.01), ghrelin (P<0.001), gastric inhibitory polypeptide (P<0.001), and pancreatic polypeptide (P=0.002), as well as hunger (P<0.001).One year after initial weight reduction, levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss. Long-term strategies to counteract this change may be needed to prevent obesity relapse. (Funded by the National Health and Medical Research Council and others; ClinicalTrials.gov number, NCT00870259.).
Prevention of Persistent Human Papillomavirus Infection by an HPV16/18 Vaccine: A Community-Based Randomized Clinical Trial in Guanacaste, Costa Rica
Authors: Rolando Herrero, Sholom Wacholder, Ana C. Rodríguez, Diane Solomon, Paula González, Aimee R. Kreimer, Carolina Porras, John Schussler, Silvia Jiménez, Mark E. Sherman, Wim Quint, John T. Schiller, Douglas R. Lowy, Mark Schiffman, Allan Hildesheim
Journal: Cancer Discovery (2011)

Target groups for human papillomavirus (HPV) vaccination are controversial. We evaluated vaccine efficacy (VE) against 1-year persistent infection, stratified by age and sexual behavior, among young women in Costa Rica. We randomized 7,466 healthy women 18 to 25 years of age to HPV16/18 or hepatitis A vaccine (follow-up, 50.4 months). According-to-protocol (ATP) cohorts included compliant HPV-negative women; intention-to-treat (ITT) included all randomized women. ATP VE was 90.9% (95% CI, 82.0-95.9) against HPV16/18 infections, 44.5% against HPV31/33/45 (95% CI, 17.5-63.1), and 12.4% (95% CI, -3.2 to 25.6) against any oncogenic infection. Overall ITT VE against HPV16/18 infections was 49.0%, but ATP and ITT VE almost reached 100% in year 4 of follow-up. ATP efficacy against HPV16/18 was similar by age, but ITT VE was greatest among youngest women (68.9% among those 18-19 years of age; 21.8% among those 24-25 years of age) and 79.8% among virgins. Among previously unexposed women, vaccination is highly efficacious against HPV16/18 and partially against HPV31/33/45. Vaccination is most effective in women and girls before they initiate sexual activity, with programmatic and individual decision implications.
Palestine: the assault on health and other war crimes
Authors: David Katz
Journal: BMJ (2005)

Editor—The personal view by Summerfield generated considerable correspondence.1,2 However, it has not addressed the concluding analogy of the Israeli situation with that which led to suspension of the Medical Association of South Africa (MASA) from the World Medical Association (WMA). Summerfield implies that since the boycott of South African medicine helped in the fall of apartheid, a boycott of Israeli medicine should be the objective.

The issues surrounding the MASA suspension are well known and have been revisited recently.3 The complicity of the medical profession was explicit, and “apartheid medicine” itself was not “in the dock.” There may be errors of judgment in Israel, but surely not in the same league?

BMJ readers may not know what apartheid medicine entailed. I am South African born and benefited from medical education within apartheid, so maybe I should be embarrassed? Leave aside maldistribution of healthcare, malnutrition, neo-Nazi pseudogenetic race classification, and racially separate wards in teaching hospitals. Take Professor Ralph Hendrickse's testimony about autopsy, where “black” students could not view a “white” body. Only one pathologist refused to cooperate.4

It is easy to find demographic statistics and to observe comparative care in Israeli hospitals. It is not organised on such apartheid lines. Benjamin Pogrund, an anti-apartheid journalist, today works in Israeli-Palestinian dialogue. He counters the libellous equation of Israeli medicine with apartheid medicine by personal testimony of treatment in a mixed Israeli-Palestinian environment—patients, doctors, and paramedical staff—belying the conflict outside.5

My personal view is from April 2002, Passover, the time of Seder bombs, and of Jenin, in a Haifa hospital, caring for elderly relatives before and after a suicide bombing. The hospital became a frontline casualty centre. There was no difference. Shared wards, communal facilities, doctors, carers, visitors—a community where sick family members took priority, as they should.

This is not to deny inequalities of health in Israel and health problems created by war. If, however, you do not differentiate this from apartheid medicine, are you undermining not only the legitimacy of Israeli medicine, but also of Israel itself?

So I can live with being one of Summerfield's “morally corrupt” people who sense antisemitism. It is more difficult to live with this corruption of the columns of the BMJ.
RU486 (MIFEPRISTONE): Mechanisms of Action and Clinical Uses
Authors: F. Cadepond, PhD, A. Ulmann, MD, PhD, E.-E. Baulieu, MD, PhD
Journal: Annual Review of Medicine (1997)

▪ Abstract RU486 (mifepristone) has proved to be a remarkably active antiprogesterone and antiglucocorticosteroid agent in human beings. The mechanism of action involves the intracellular receptors of the antagonized hormones (progesterone and glucocorticosteroids). At the molecular level, the most important features are high binding affinity to the receptor, interaction of the phenylaminodimethyl group in the 11β-position with a specific region of the receptor binding pocket, and RU486-induced transconformation differences in the ligand-binding domain. These particularities have consequences at different steps of the receptor function as compared with agonists. However, the reasoning cannot be limited to the RU486-receptor interaction, and, for instance, there is the possibility of a switch from antagonistic property to agonist activity, depending on the intervention of other signaling pathways. It would be desirable to have derivatives with only one of the two antagonistic properties (antiprogestin, antiglucocorticosteroid) in spite of similarities between steroid structures, receptors involved, and responsive machineries in target cells. Clinically, the RU486-plus-prostaglandin method is ready to be used on a large scale and is close to being as convenient and safe as any medical method of abortion may be. The early use of RU486 as a contragestive as soon as a woman fears a pregnancy she does not want will help to defuse the abortion issue. Research should now be conducted to define an efficient and convenient contraceptive method with RU486 or other antiprogestins. The usefulness of RU486 for obstetric indications, including facilitation of difficult delivery, has to be assessed rapidly. Gynecologic trials, particularly in leiomyomata, should also be systematically continued. The very preliminary results obtained with tumors, including breast cancers, indicate that further studies are necessary.
Influence of atopy on exhaled nitric oxide in patients with stable asthma and rhinitis
Authors: CH. Gratziou, M. Lignos, M Dassiou, Ch Roussos
Journal: European Respiratory Journal (1999)

The level of exhaled NO is increased in patients with allergic asthma and seasonal rhinitis. The aim of this study was to investigate the significance of atopy on NO production in the lower airways. Measurements of exhaled NO were performed in 131 stable asthmatic patients with chronic mild asthma (95 atopics and 36 nonatopics), 72 patients with perennial rhinitis (57 atopics and 15 nonatopics) and 100 healthy controls (20 atopics and 80 non-atopics). Patients with either asthma or rhinitis had higher exhaled NO values (13.3+/-1.2 parts per billion (ppb) and 11.7+/-1.1 ppb) than control subjects (4.8+/-0.3 ppb, p&lt;0.01). Exhaled NO levels were significantly higher in atopic asthmatics (19+/-3.6 ppb) compared with nonatopic patients (5.6+/-0.8 ppb, p&lt;0.001). Similar findings were observed in patients with rhinitis (13.3+/-1.3 ppb in atopics and 5.8+/-1.2 ppb in nonatopics, p&lt;0.001). No difference was found in NO levels between atopic and nonatopic control subjects (4.8+/-0.8 ppb, and 4.5+/-0.3 ppb). In summary, this study has shown that increased exhaled NO levels are detected only in atopic patients with asthma and/or rhinitis and not in nonatopic patients. These findings may suggest that it is rather the allergic nature of airways inflammation, which is mainly responsible for the higher NO production in the lower airways.
Effects of short chain fatty acids on a new human colon carcinoma cell line (LIM1215).
Authors: R H Whitehead, G P Young, P S Bhathal
Journal: Gut (1986)

The effects of short chain fatty acids on a colon carcinoma cell line, LIM1215, have been studied. Of the four short chain fatty acids tested only butyrate at 1 mmol/l and 10 mmol/l and acetate at 10 mmol/l had significant effects on this cell line. The addition of butyrate to growth medium affected the growth rate and the production of alkaline phosphatase, dipeptidyl peptidase IV and carcinoembryonic antigen. Butyrate at a final concentration of 1 mmol/l increased the doubling time of the cells from 26 hours to 72 hours and decreased the cloning efficiency of the cells from 1.1% to 0.054%. Alkaline phosphatase concentrations increased rapidly in cells cultured in 1 mmol/l butyrate reaching peak levels after four days with alkaline phosphatase concentrations increasing more than six-fold. Levels of dipeptidyl peptidase IV and carcinoembryonic antigen were also increased after culture in butyrate containing medium. The number of alkaline phosphatase containing and dipeptidyl peptidase IV containing cells increased markedly in butyrate containing cultures. In contrast the number of mucus containing cells decreased in cultures grown in medium containing butyrate. This differentiating effect of butyrate on colon carcinoma cells may be relevant to the presence of butyrate in the colonic contents and the relationship between short chain fatty acids and fibre intake.
Effect of regional myocardial ischaemia on left ventricular isovolumic contraction
Authors: A. V. N. GOODYER, B. Y. WONG, R. LANGOU
Journal: Cardiovascular Research (1977)

In anaesthetised, open-chest dogs, global isovolumic contractility indices were reduced by acute regional ischaemia involving 12 to 14% or more of left ventricular mass. These effects were not altered by controlled reduction of blood flow to the non-ischaemic region, but were exaggerated by isoprenaline during normal perfusion of the non-ischaemic region. The results were consistent with a contraction model characterised by simple reduction of the effective length of the contractile elements.
Phase III Study of Bevacizumab Plus Docetaxel Compared With Placebo Plus Docetaxel for the First-Line Treatment of Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer
Authors: David W. Miles, Arlene Chan, Luc Y. Dirix, Javier Cortés, Xavier Pivot, Piotr Tomczak, Thierry Delozier, Joo Hyuk Sohn, Louise Provencher, Fabio Puglisi, Nadia Harbeck, Guenther G. Steger, Andreas Schneeweiss, Andrew M. Wardley, Andreas Chlistalla, Gilles Romieu
Journal: Journal of Clinical Oncology (2010)

The efficacy and safety of combining bevacizumab (7.5 and 15 mg/kg) with docetaxel as first-line therapy for human epidermal growth factor receptor 2 (HER2) -negative, locally recurrent or metastatic breast cancer (MBC) was investigated in a three-arm, placebo-controlled, phase III trial.Patients (N = 736) were randomly assigned to docetaxel 100 mg/m(2) plus either placebo or bevacizumab 7.5 or 15 mg/kg every 3 weeks. The primary end point was progression-free survival (PFS); secondary end points included best overall response, duration of response, time to treatment failure, overall survival, and safety.Combination of bevacizumab 15 mg/kg, but not 7.5 mg/kg, with docetaxel showed superior median PFS (mPFS) to placebo plus docetaxel in unstratified analysis (placebo mPFS, 8.2 months; 7.5 mg/kg mPFS, 9.0 months [hazard ratio (HR), 0.86; P = .12]; 15 mg/kg mPFS, 10.1 months [HR, 0.77; P = .006]) and stratified analysis (placebo mPFS, 8.1 months; 7.5 mg/kg mPFS, 9.0 months [HR, 0.80; P = .045]; 15 mg/kg mPFS, 10.0 months [HR, 0.67; P < .001]). Response rates in patients with measurable disease at baseline also increased with bevacizumab 15 mg/kg (46% [placebo] v 55% [7.5 mg/kg; P = .07] and 64% [15 mg/kg; P < .001]). Combination with bevacizumab had limited impact on the known toxicity profile of docetaxel.Combination of bevacizumab with docetaxel did not significantly impact on the safety profile of docetaxel. Bevacizumab 15 mg/kg every 3 weeks significantly increased PFS when combined with docetaxel as first-line therapy for MBC compared with docetaxel plus placebo.
DISTILLED WATER VERSUS SALVARSAN IN THE TREATMENT OF SYPHILIS
Authors: G. A. Stephens
Journal: BMJ (1913)

THE simple treatmiient for syplhilis lierein recommended consists of thie hiypodermic injection of 6 to 10 c.cmI. of tdistilled water every tlhree days for two to four wveeks.I was induced to give this treatment a trial as the result of somne researell work I lhadl done on surface tension, the results of which I published privately some fifteen montlhs a,go.I lhad previously published in the Practitioner al article on the Part Played by Colloids in Physiology and Pathiology, in whiichl I drew attention to the value of a consideration of suirface tension.An experiment that I carried out to shiow the effect of tle calciuni salts on surface tension is rather interestincg:Wlhen pure hydrogen peroxi(le is added to pure mercury in a cleani test tube, catalytic action occurs and oxygen is givenl off, the mercury remainiilg unaltered.This reactioni is due to ain extremely fine, film that forms on the surface of the mercury, but, on account of the tenisioni,breaks almost as soon as formed, the making and breaking beinig rhythmic.Oni adding a small qluantity of a 10 per cent.solution of pure calcium chloride to the mercury, shaling well and draiiiing it off, the mercury