tbuckley/cabot-search huggingface dataset:
82 The cholesterol-7α hydroxylase promoter factor (CPF) up-regulates the human multidrug resistance-associated protein 3 (MRP3) and is induced by bile salts in HEPG2 cells
Authors: W CHEN, L DENSON, A BOHAN, S CAI, L WANG, C SOROKA, J BOYER
Journal: Hepatology (2003)

Progressive familial intrahepatic cholestasis 1 (PFIC1) results from mutations in ATP8B1, a putative aminophospholipid flippase. Conflicting hypotheses have been proposed for the pathogenesis of PFIC1. The aim of this study was to determine whether ATP8B1 deficiency produces cholestasis by altering the activity of the farnesoid X receptor (FXR) or by impairing the structure of the canalicular membrane.ATP8B1/Atp8b1 was knocked down in human and rat hepatocytes and Caco2 cells using adenoviral and oligonucleotide small interfering RNAs.ATP8B1 messenger RNA and protein expression was greatly reduced in human and rat cells. In contrast, FXR expression and several FXR-dependent membrane transporters (bile salt export pump [BSEP], multidrug resistance-associated protein [MRP] 2) were unchanged at messenger RNA or protein levels in ATP8B1-deficient cells, whereas Mrp3 and Mrp4 were up-regulated in rat hepatocytes. FXR activity remained intact in these cells, as evidenced by 6α-ethyl chenodeoxycholic acid–mediated induction of small heterodimer partner, BSEP, and multidrug-resistant protein (MDR) 3/Mdr2. Fluorescent substrate excretion assays indicate that Bsep function was significantly reduced in Atp8b1-deficient rat hepatocytes, although Bsep remained localized to the canalicular membrane. Exposure to the hydrophobic bile acid CDCA resulted in focal areas of canalicular membrane disruption by electron microscopy and luminal accumulation of NBD-phosphatidylserine, consistent with the function of Atp8b1 as an aminophospholipid flippase.ATP8B1 deficiency predisposes to cholestasis by favoring bile acid–induced injury in the canalicular membrane but does not directly affect FXR expression, which may occur in PFIC1 as a secondary phenomenon associated with cholestasis.
Rupture of the Renal Artery After Percutaneous Transluminal Angioplasty
Authors: Jeffrey L. Kaufman
Journal: JAMA (1987)

To the Editor.—  Olin and Wholey 1 described the pathology of renal artery injury after angioplasty, but did not emphasize prevention of morbidity and mortality in the broader clinical application of this technique. At another academic institution, I observed three deaths directly related to renal artery angioplasty, two from aortic thrombosis and one from renal artery rupture. Several lessons stand out: These complications occurred with skilled angiographers, but without prior surgical consultation and at a time inconvenient for the availability of an operating room. A qualified surgeon should be available to assess these patients for major complications such as aortic thrombosis, arterial dissection, or retroperitoneal hemorrhage. Angioplasty should never be performed simply because an anatomic lesion has been discovered. If the proper diagnostic studies have not been done and absolute indications for angioplasty do not exist, the procedure should be deferred. Repeated arterial catheterization for a secondary procedure under controlled
Promoter Hypermethylation Is the Predominant Mechanism in <i>hMLH1</i> and <i>hMSH2</i> Deregulation and Is a Poor Prognostic Factor in Nonsmoking Lung Cancer
Authors: Han-Shui Hsu, Chiao-Kai Wen, Yen-An Tang, Ruo-Kai Lin, Wing-Yin Li, Wen-Hu Hsu, Yi-Ching Wang
Journal: Clinical Cancer Research (2005)

Abstract Purpose and Experimental Design: The etiologic association and prognostic significance of mismatch repair gene/protein alterations have never been examined in nonsmoking lung cancer. Therefore, we investigated protein expression and promoter hypermethylation of hMLH1 and hMSH2 genes in the tumor specimens from 105 nonsmoking female non–small cell lung cancer (NSCLC) patients. Immunohistochemistry and restriction enzyme–based multiplex PCR were used to examine the protein expression and promoter hypermethylation, respectively. The occurrence of gene/protein alteration for each gene was compared with the patients' clinicopathologic variables as well as the overall survival and cancer-specific survival rates. Results: Protein expression alteration and promoter hypermethylation were observed in 66% to 67% and 30% to 34% of tumor specimens for hMLH1 and hMSH2 genes, respectively. Loss of hMLH1 and hMSH2 protein expression was significantly associated with their promoter hypermethylation (P &amp;lt; 0.0001 and P = 0.049). The overall survival and cancer-specific survival rates were significantly lower in patients with promoter hypermethylation of hMSH2 gene than in those without hypermethylation (P = 0.038 and P = 0.004). The poor prognosis was still especially significant in adenocarcinoma (P = 0.035 and P = 0.061) and early-stage NSCLC patients (P = 0.067 and P = 0.041). Conclusion: Our data suggest that hMLH1 is the major altered mismatch repair gene involved in nonsmoking NSCLC tumorigenesis and that promoter methylation is the predominant mechanism in hMLH1 and hMSH2 deregulation. In addition, promoter methylation of the hMSH2 gene may be a potential prognostic factor in nonsmoking female lung cancer.
Abstract 4664: The effect of neoadjuvant androgen deprivation therapy on long-term outcome after radical prostatectomy
Authors: Rochelle D. Payne Ondracek, Matthew H. Hayn, Michael A. Poch, Michael J. Ray, Warren Davis, Alexandra Curtis, Hyung L. Kim, Carl D. Morrison, James R. Marshall, James L. Mohler
Journal: Cancer Research (2011)

Abstract Neoadjuvant androgen deprivation therapy (NADT) was championed for men treated with radical prostatectomy (RP) for high risk prostate cancer (CaP) in the early 1990s. Although NADT improved neither surgical margin positivity nor progression-free survival, it continues to be part of some clinical trials. The effect of NADT on long term outcome was evaluated using modern aggressiveness and failure criteria among 720 patients treated with RP at Roswell Park Cancer Institute between 1993 and 2005. Among RP patients, 125 received NADT. NCCN pre-surgery risk categories were low in 36 (29%), intermediate in 54 (43%), and high or very high in 35 (28%). Clinical and pathological aggressiveness indicators included clinical Gleason sum, clinical tumor stage (2002 TNM), highest preoperative PSA, pathological Gleason sum, pathological tumor stage (2002 TNM) and surgical margin status. Ten post-RP recurrence definitions were considered: 1) at least 1 detectable PSA, 2) at least 2 detectable PSAs, 3) PSA&amp;gt;0.2 ng/ml, 4) PSA&amp;gt;0.4 ng/ml, 5) at least 1 post RP treatment (chemotherapy, hormone, radiation), 6) PSA doubling time &amp;lt;9 months, 7) NCCN definition of failure, 8) AUA definition of failure, 9) development of metastatic CaP, 10) death from CaP. In bivariate analysis, men treated with NADT were 105% (p&amp;lt;0.0001) more likely to fail using the AUA definition, 202% (p=0.004) more likely to develop metastatic CaP, and 673% (p=0.001) more likely to die of CaP. The increased risk of recurrence persisted for NADT in multivariate analysis, despite control for all clinical and pathological parameters; the table shows data for clinical and pathological parameters that have been associated with RP failure. Analysis of hazards regression for AUA failure across NCCN risk category demonstrated that NADT was detrimental for men treated with RP, regardless of any level of risk. 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 4664. doi:10.1158/1538-7445.AM2011-4664
Registration exists for counsellors and psychotherapists
Authors: D. Tantam
Journal: BMJ (1998)

Editor—The BMJ has had a consistent policy of giving attention to mental health care. In his article on psychological treatments Richardson referred twice in his opening paragraph to the confusion that surrounds psychotherapy.1 It was disappointing to find that the article, far from dispelling this confusion, may have added to it in the minds of medical practitioners who employ or work alongside counsellors and psychotherapists. I am particularly concerned by the author's statement …
Disrupting hedgehog and WNT signaling interactions promotes cleft lip pathogenesis
Authors: Hiroshi Kurosaka, Angelo Iulianella, Trevor Williams, Paul A. Trainor
Journal: Journal of Clinical Investigation (2014)

Cleft lip, which results from impaired facial process growth and fusion, is one of the most common craniofacial birth defects. Many genes are known to be involved in the etiology of this disorder; however, our understanding of cleft lip pathogenesis remains incomplete. In the present study, we uncovered a role for sonic hedgehog (SHH) signaling during lip fusion. Mice carrying compound mutations in hedgehog acyltransferase (Hhat) and patched1 (Ptch1) exhibited perturbations in the SHH gradient during frontonasal development, which led to hypoplastic nasal process outgrowth, epithelial seam persistence, and cleft lip. Further investigation revealed that enhanced SHH signaling restricts canonical WNT signaling in the lambdoidal region by promoting expression of genes encoding WNT inhibitors. Moreover, reduction of canonical WNT signaling perturbed p63/interferon regulatory factor 6 (p63/IRF6) signaling, resulting in increased proliferation and decreased cell death, which was followed by persistence of the epithelial seam and cleft lip. Consistent with our results, mutations in genes that disrupt SHH and WNT signaling have been identified in both mice and humans with cleft lip. Collectively, our data illustrate that altered SHH signaling contributes to the etiology and pathogenesis of cleft lip through antagonistic interactions with other gene regulatory networks, including the canonical WNT and p63/IRF6 signaling pathways.
Doctors' pay is frozen for 2010-11
Authors: L. Eaton
Journal: BMJ (2010)

Most hospital doctors in England will have their pay frozen in the coming financial year in an attempt to save £3bn (€3.3bn; $4.5bn) on the public sector pay bill by 2013-14.

The BMA has slammed the decision by the prime minister, Gordon Brown. Hamish Meldrum, chairman of the BMA council, voiced particular concern over the government’s decision to overrule some of the recommendations made by the independent pay review body.

“We are well …
The Abortion Experience: Psychological and Medical Impact
Authors: Charles V. Ford
Journal: JAMA (1974)

Responding to a need for current factual information concerning abortion, the editors of the volume have compiled 29 contributions from various investigators across the United States. Some of the general conclusions reached from the multiple sources, which include some of the preeminent people in the field, indicate that abortion rates compared to live births are rising rapidly, while the number of illegal abortions has been reduced sharply where legal abortion is readily available. Firsttrimester abortion by vacuum curettage is associated with low morbidity, but experience indicates that secondtrimester abortion by current techniques has a much higher complication rate. The data indicate that approximately 50% of the women seeking abortion are single and there is a trend for women to be below 25 years of age or more than 35 years of age. There has been a gradual increase in public opinion for the acceptance of legalized abortion, particularly since the
Trial of ascorbic acid in purpura and sublingual haemorrhages.
Authors: G. Arthur, J. A. Monro, P. Poore, W. B. Rilwan, E. L. Murphy
Journal: BMJ (1967)

Childhood Depression-Frommer yet recoverable illness-in 30 children of the original 41 this had lasted for over a year, and in no fewer than eight of them for over five years.It was even more disturbing to find how long their depression had gone undetected, often despite repeated clinical examinations.As these symptoms are fairly common among children of school age, there may well be a sizable group with a handicapping yet treatable depressive illness in the school population.A personality change in a child is too easily attri- buted to " growing up," and it is too readily assumed that the attention which his difficulties attract, whether aches and pains or behaviour disorders, affords him sufficient gratification.Yet once they had recovered with treatment these children were delighted to be well, and showed no regret for any lost parental attention to vanished symptoms.In conclusion it appears plain that, despite the limitations and inaccuracies which inevitably accompany an outpatient drug trial such as this, antidepressant drugs are much more useful for the treatment of depressed children, whether with " func- tional " somatic symptoms or a " behaviour disorder," than is the phenobarbitone so often used.Much more work is needed to clarify the clinical picture of depressive illnesses seen in childhood, and to differentiate and improve this technique of treatment; but the results in this preliminary study far exceeded expectations, and suggest that such further research will be well worth while. SummaryThe clinical symptoms of childhood depression are described.A double-blind cross-over trial showed that phenelzine and chlordiazepoxide are superior to phenobarbitone and an inert capsule in treating these childhood depressions.This finding was confirmed during further periods of clinical treatment.Many children recovered rapidly from illnesses of up to five years' duration, and the diagnosis had often been missed.My thanks are due to Dr. Eliot Slater for his help and advice In the interpretation of the results, and to my colleagues in the depart- ments of paediatrics and psychological medicine, who referred patients and helped m-with this work.
Prediction and mechanism of frequent ventricular premature contractions related to haemodynamic deterioration
Authors: Kenji Kuroki, Hiroshi Tada, Yoshihiro Seo, Tomoko Ishizu, Masayuki Igawa, Hiro Yamasaki, Miyako Igarashi, Takeshi Machino, Yoshihisa Naruse, Yukio Sekiguchi, Nobuyuki Murakoshi, Kazutaka Aonuma
Journal: European Journal of Heart Failure (2012)
HDAC inhibitor therapy in autoimmunity and transplantation
Authors: Wayne W Hancock, Tatiana Akimova, Ulf H Beier, Yujie Liu, Liqing Wang
Journal: Annals of the Rheumatic Diseases (2012)

Pharmacological inhibitors of histone/protein deacetylases (HDACi) have considerable therapeutic potential as anti-inflammatory and immunosuppressive drugs. The utility of HDACi as anti-inflammatory agents is dependent upon their proving safe and effective in experimental models. Current pan-HDACi compounds are ill-suited to this role, given the broad distribution of target HDACs and their complex and multifaceted mechanisms of action. By contrast, the development of isoform-selective HDACi may provide important new tools for treatment in autoimmunity and transplantation. This review discusses which HDACs are worthwhile targets in inflammation, and the progress made towards their therapeutic inhibition, including the use of HDAC subclass and isoform-selective HDACi to promote the functions of Foxp3+ T-regulatory cells.
Systemic response to local urate crystal induced inflammation in man: a possible model to study the acute phase response.
Authors: C.W Hutton, A.J Collins, R.E Chambers, J Whicher, P.A Dieppe
Journal: Annals of the Rheumatic Diseases (1985)

The production of a systemic inflammatory response to intradermal monosodium urate crystal injection is described. A transient, self-limiting local response is associated with a systemic response detectable by a rise in the white cell count and serum amyloid A protein. The white cell change parallels the evolution of the local response, whereas the serum amyloid A response lags behind the local lesion, peaking after the local lesion is resolving. Intradermal monosodium urate injection is proposed as a possible inflammatory stimulus to explore the acute phase protein response in different disease states.
BBC told to pay Taranissi 500 000 to cover costs of changing libel defence
Authors: C. Dyer
Journal: BMJ (2008)

The High Court this week ordered the BBC to pay the obstetrician and gynaecologist Mohamed Taranissi an estimated £500 000 (€620 000; $850 000) in costs after the corporation dropped part of its defence to a libel action he is pursuing against it.

Mr Taranissi’s claim centres on a Panorama television programme, IVF Undercover, broadcast in January 2007, which he argues damaged his reputation by making defamatory allegations about his in vitro fertilisation practice. The programme, he alleges, claimed that he had been offering unnecessary and unproved therapies and operating one of his clinics without a licence.

The BBC has abandoned its reliance …
474 A one-week evaluation of salmeterol, a new long-acting beta-adrenergic aerosol, for asthma therapy
Authors: J KEMP, C BIERMAN, E BRONSKY, D COCCHETTO, D DEMARS, S JUSTUS, R LIDDLE, H ORGEL, D TINKELMAN, A VANAS
Journal: Journal of Allergy and Clinical Immunology (1991)
Rate of increase in pulmonary distensibility in a longitudinal study of smokers.
Authors: H J Colebatch, C K Ng
Journal: Thorax (1988)

To examine the hypothesis that an abnormally rapid increase in pulmonary distensibility occurs in cigarette smokers, 39 adult smokers (24 men), mean age 47 (SD 8) years, who were not disabled were studied on two occasions over a mean interval of 3.5 (SD 0.5) years. Exponential analysis of static pressure-volume data obtained during deflation of the lungs gave the exponent K, an index of distensibility. Total lung capacity (TLC) was measured in a body plethysmograph. At entry into the longitudinal study means values for K and static recoil pressure in the 39 smokers available for follow up were similar to those obtained in the original group of 101 smokers (73 men), mean age 42 (SD 11) years, in the cross sectional study. Over the interval of the study, ln K and TLC increased and FEV1 decreased at rates greater than those found in a previous longitudinal study of 34 non-smokers (24 men), mean age 42 (SD 15) years. In the longitudinal study of smokers the observed changes in K and in recoil pressure over the interval of study were greater than the values obtained from the regression slopes found in the cross sectional study of smokers. On the basis of the regression model used previously in the longitudinal study of non-smokers, the age coefficient for ln K was greater than that found in the non-smokers (p less than 0.01). The regression model also showed that the slope of ln K on age increased in older subjects. Because K is related to peripheral airspace size, a rapid rate of increase in K identifies smokers in whom airspace size is increasing abnormally rapidly. In this study the rate of increase in K and the variation between subjects was sufficient to explain the magnitude of the increased pulmonary distensibility found in cigarette smokers who present with emphysema.
Long-term Survival of Patients With AIDS, Pneumocystis carinii Pneumonia, and Respiratory Failure
Authors: Yaakov Friedman
Journal: JAMA (1991)

<h3>Objective.</h3> —To evaluate the long-term survival of patients admitted to the medical intensive care unit, Cook County Hospital, Chicago, Ill, with<i>Pneumocystis carinii</i>pneumonia and acute respiratory failure. <h3>Design.</h3> —Cohort study over a 4-year period. <h3>Setting.</h3> —Municipal teaching hospital. <h3>Patients.</h3> —Seventy-three consecutive patients who had 75 episodes of<i>P carinii</i>pneumonia and acute respiratory failure were followed up from the time of hospital admission until their deaths or the termination of the study. <h3>Outcome Measures.</h3> —Duration of survival from the time of initial hospital admission with diagnoses of<i>P carinii</i>pneumonia and acute respiratory failure. <h3>Results.</h3> —Consistent with recent reports of improved short-term outcome, the immediate hospital survival was 47% (35/75). The 1-year survival was 37% (95% confidence interval, 26% to 49%). Two patients have survived for 40 months. Almost three quarters of the patients who survived hospitalization lived for at least 1 year. <h3>Conclusions.</h3> —The long-term prognosis for patients with the acquired immunodeficiency syndrome,<i>P carinii</i>pneumonia, and acute respiratory failure is now substantially better than anticipated. Respiratory failure due to<i>P carinii</i>pneumonia does not necessarily signify the terminal phase of human immunodeficiency virus infection. Accordingly, patients with the acquired immunodeficiency syndrome,<i>P carinii</i>pneumonia, and acute respiratory failure can be appropriate candidates for life support in medical intensive care units. (<i>JAMA</i>. 1991;266:89-92)
NB Medical Examiners Implementations
Authors: Kong Meng Tan
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Dr. George Engel has addressed himself (228:579, 1974) to one of the most frustrating situations that face any society—namely, that far-reaching proposals are usually made by an elite that then manage its implementation without too much opposition from those that are affected. These proposals are usually intertwined with well-intentioned promises that they will be approached with caution and after much deliberate study. More often than not, and medical education is no exception, the constituency finds itself presented with a fait accompli. The constituency, however, must be considered partially at fault, for one finds the mass of protests arising usually after implementation of such proposals. Many people seem curiously insensitive to suggestions that could radically alter their environment. The report of the Committee on Goals and Priorities is one such comprehensive series of proposals, yet as Dr. Engel has so succinctly pointed out, few from the constituency have
THE ANTIRACHITIC ACTION OF COD LIVER OIL AND IRRADIATED ERGOSTEROL IN PARATHYROIDECTOMIZED AND THYMECTOMIZED RATS
Authors: Alwin M. Pappenheimer
Journal: The Journal of Experimental Medicine (1930)

Cod liver oil and Viosterol in therapeutic doses are antirachitic in the absence of the parathyroid gland, or of the thymus, or of both.
Psychodrama: Resolving Emotional Problems Through Role-Playing
Authors: Nancy C. Andreasen
Journal: JAMA (1977)

Lewis Yablonsky was a follower of J. L. Moreno, the founder of psychodrama, and he speaks of psychodrama with apostolic fervor. In the epilogue, Yablonsky describes Moreno's deathbed farewells to his followers, punctuated by raising his fist in a power salute. A scenario from Moreno's unpublished autobiography portrays his afterlife: After a heavenly debate on the values of psychoanalysis vs psychodrama, Freud (hitherto strangely quiet) acknowledges, "If I had lived longer, I too would most certainly have become a psychodramatist like Moreno." This book will probably not convert many others to become true believers, but it does convey an excitement about psychodrama that may be infectious. Its primary audience will be psychotherapists, particularly those interested in various forms of group therapy. Yablonsky describes the techniques of psychodrama clearly and convincingly. His points are illustrated with abundant anecdotal case material. Interested readers will be able to introduce this refined technique for
Dialogue processing: Automatic alignment or controlled understanding?
Authors: Hadas Shintel, Howard C. Nusbaum
Journal: Behavioral and Brain Sciences (2004)

Pickering & Garrod's (P&G's) mechanistic account of dialogue assumes that linguistic alignment between interlocutors takes place automatically, without using cognitive resources. However, even the most basic processes of speech perception depend on resource use. The lack of invariant mapping between input patterns and interpretations in dialogue, as in speech perception, may require controlled, rather than automatic, processing.