tbuckley/cabot-search huggingface dataset:
Hepatic androgen receptor suppresses hepatocellular carcinoma metastasis through modulation of cell migration and anoikis
Authors: Wen-Lung Ma, Cheng-Lung Hsu, Chun-Chieh Yeh, Ming-Heng Wu, Chiung-Kuei Huang, Long-Bin Jeng, Yao-Ching Hung, Tze-Yi Lin, Shuyuan Yeh, Chawnshang Chang
Journal: Hepatology (2012)

Early reports suggested androgen/androgen receptor (AR) signals promote hepatocarcinogenesis. However, all antiandrogen clinical trials failed in advanced hepatocellular carcinoma (HCC) without reasonable explanations. We examined AR functions in HCC cancer metastasis in this study. We examined hepatic AR roles in HCC metastasis by comparing liver hepatocyte AR knockout and wildtype in a carcinogen-induced HCC mouse model. We examined tumor histology, cancer metastatic risks, and cancer survival in vivo , as well as cell anoikis and migration using primary hepatic tumor culture in vitro . We also examined therapeutic potentials of AR expression combined with the molecular targeting agent sorafenib in an HCC metastasis mouse model. We found a novel cancer phenotype in which mice lacking hepatic AR developed more undifferentiated tumors and larger tumor size at the metastatic stage. These mice also died earlier with increased lung metastasis, suggesting that hepatic AR may play dual yet opposite roles to promote HCC initiation but suppress HCC metastasis. Mechanistic dissection found that hepatic AR could enhance anoikis and suppress migration of HCC cells by way of suppression of p38 phosphorylation/activation and the nuclear factor kappa B (NF-κB)/matrix metallopeptidase 9 (MMP9) pathway, respectively. In addition, the in vivo preclinical trials concluded that a combination therapy of increased AR expression and reduced multiple-kinase inhibitor (sorafenib) exhibited better therapeutic efficacy. Conclusion : Our study demonstrates that AR could orchestrate intrahepatic signaling hierarchies and cellular behaviors, consequently affect HCC progression. Results from combination therapy shed light on developing new therapeutic paradigms for battling HCC at later metastatic stages. (HEPATOLOGY 2012;56:176–185)
Role of nerves in enteric infection
Authors: R C Spiller
Journal: Gut (2002)

Peripheral and central effects of enteric infection are considered. Nerves play a vital part in the immediate response to enteric infection, promoting pathogen expulsion by orchestrating intestinal secretion and propulsive motor patterns. Laboratory studies indicate that therapeutic agents aimed at modulating the neural response can profoundly alter the outcome of infection. As our understanding of the role of nerves increases, exciting new targets for therapeutic intervention will emerge in both acute and chronic disorders induced by enteric infection.
Comparison of Adenoviruses From Species B, C, E, and F After Intravenous Delivery
Authors: Daniel Stone, Ying Liu, Zong-Yi Li, Sebastian Tuve, Robert Strauss, André Lieber
Journal: Molecular Therapy (2007)

Recent attempts to circumvent the limitations of adenovirus (Ad) vectors derived from species C serotype Ad5 have focused on the use of alternative human serotypes. These new serotypes have multiple benefits including a low prevalence of neutralizing antibodies in humans and alternate tropisms. To investigate the characteristics of alternatives to Ad5 vectors, we compared the biodistribution and safety of Ads from species B (Ad3, 11p, 35), C (Ad5), E (Ad4), and F (Ad41), or chimeric Ad5 viruses containing the Ad11 or Ad35 fibers (Ad5/11 and Ad5/35), after intravenous (IV) delivery into hCD46 transgenic mice. Our data suggest that (i) mechanisms of cell and tissue sequestration differ; (ii) levels of sequestration to lung, liver, or spleen do not correlate with toxicity; (iii) delivery of all serotypes causes activation of coagulation, possibly through platelet interaction; (iv) despite binding to the same receptor in vitro, Ad serotypes act differently in vivo; and (v) platelet depletion affects blood clearance, organ sequestration and chemokine/cytokine release of some, but not all Ad serotypes. Overall, our data indicate that Ad5-based vectors are relatively safe as compared to other serotypes. This data should be taken into consideration in future studies about the clinical use of Ad vectors.
Treatment of pulmonary exacerbations of cystic fibrosis leads to improved antioxidant status
Authors: SP Range, C Dunster, AJ Knox, FJ Kelly
Journal: European Respiratory Journal (1999)

Many cystic fibrosis (CF) patients have increased circulating levels of oxidation products and/or decreased antioxidant status. This study investigated whether treatment of pulmonary exacerbations decreased oxidative stress in CF patients. Seventeen adult patients were studied at the beginning and end of treatment with intravenous antibiotics. Plasma concentrations of the antioxidants ascorbic acid, alpha-tocopherol, uric acid and total reduced thiols, together with plasma retinol, lipid hydroperoxides, malondialdehyde and protein carbonyl levels were determined. Median (interquartile range) pretreatment and post-treatment levels were compared using the Wilcoxon signed rank test. Clinical resolution was reflected by improved spirometry. Significant increases were observed in plasma ascorbic acid (pre 30.4 (15.7-38.6) microM, post 35.2 (27.3-49.6) microM), alpha-tocopherol (pre 19.7 (13.6-25.2) microM, post 25.2 (19.3-31.6) microM) and retinol (pre 1.9 (1.5-2.5) microM, post 2.7 (1.7-3.5) microM). No change in plasma total reduced thiols occurred following treatment (pre 409 (366-420) microM, post 392 (366-423) microM), whereas uric acid fell with treatment (pre 307 (274-394) microM, post 260 (216-317) microM). Neither plasma protein carbonyls or malondialdehyde levels altered with treatment (protein carbonyls pre 0.47 (0.28-1.27), post 0.67 (0.42-0.83) nM x mg protein(-1); malondialdehyde pre 0.75 (0.53-1.18), post 0.84 (0.65-1.15) microM). Lipid hydroperoxides levels did decrease following treatment (53 (18-85) versus 17 (10-55) nM). This study demonstrated that treatment of infective exacerbations resulted in increased plasma levels of some antioxidant vitamins. No immediate change in plasma protein oxidation was observed, but lipid oxidation was decreased.
Reconfiguring acute hospitals in England
Authors: Ike Anya
Journal: BMJ (2006)

Use of Google as a diagnostic aid Bias your searchEditor-Although Google can be a valuable aid in reaching diagnoses in rare conditions, 1 the problem faced in a busy, fast-paced clinic can be the abundance of lesser quality material on the web."Biasing" or directing your search by adding the name of an online clinical knowledge base such as Emedicine can lead you to quality information more quickly; you avoid sifting through dozens of unknown journals, personal webpages, blogs, or discussion forums containing your search terms.For example, by typing "pigmented lesion+buccal" into Google you will get 55 000 hits with a vast array of very different material.However, typing "pigmented lesion+buccal+emedicine" provides only 106 hits (accessed 12 November 2006), the first being a comprehensive Emedicine review on Peutz-Jeghers syndrome. 2You get similar results by adding "BMJ" to the end of your search; in this case the top hit is an ABC of oral health article.
Emma Felicity Hounsell
Authors: C. Ball
Journal: BMJ (2013)

Emma Felicity Hounsell (nee Ball) trained in Newcastle and started her clinical career in the northeast of England. In 1998 she went on a working holiday to New Zealand, where she began her paediatric training at Tauranga Hospital. She came back to the UK for two years to complete her paediatric membership exams before returning …
Circadian rhythms, sleep, and metabolism
Authors: Wenyu Huang, Kathryn Moynihan Ramsey, Biliana Marcheva, Joseph Bass
Journal: Journal of Clinical Investigation (2011)

The discovery of the genetic basis for circadian rhythms has expanded our knowledge of the temporal organization of behavior and physiology. The observations that the circadian gene network is present in most living organisms from eubacteria to humans, that most cells and tissues express autonomous clocks, and that disruption of clock genes results in metabolic dysregulation have revealed interactions between metabolism and circadian rhythms at neural, molecular, and cellular levels. A major challenge remains in understanding the interplay between brain and peripheral clocks and in determining how these interactions promote energy homeostasis across the sleep-wake cycle. In this Review, we evaluate how investigation of molecular timing may create new opportunities to understand and develop therapies for obesity and diabetes.
Cognitive behaviour therapy in addition to antispasmodic treatment for irritable bowel syndrome in primary care: randomised controlled trial
Authors: Tom Kennedy, Roger Jones, Simon Darnley, Paul Seed, Simon Wessely, Trudie Chalder
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To assess the efficacy of cognitive behaviour therapy delivered in primary care for treating irritable bowel syndrome. <b>Design</b> Randomised controlled trial. <b>Setting</b> 10 general practices in London. <b>Participants</b> 149 patients with moderate or severe irritable bowel syndrome resistant to the antispasmodic mebeverine. <b>Interventions</b> Cognitive behaviour therapy delivered by trained primary care nurses plus 270 mg mebeverine taken thrice daily compared with mebeverine treatment alone. <b>Main outcome measures</b> Primary measures were patients9 scores on the irritable bowel syndrome symptom severity scale. Secondary measures were scores on the work and social adjustment scale and the hospital anxiety and depression scale. <b>Results</b> Of 334 referred patients, 72 were randomised to mebeverine plus cognitive behaviour therapy and 77 to mebeverine alone. Cognitive behaviour therapy had considerable initial benefit on symptom severity compared with mebeverine alone, with a mean reduction in score of 68 points (95% confidence interval 103 to 33), with the benefit persisting at three months and six months after therapy (mean reductions 71 points (109 to 32) and 11 points (20 to 3)) but not later. Cognitive behaviour therapy also showed significant benefit on the work and social adjustment scale that was still present 12 months after therapy (mean reduction 2.8 points (5.2 to 0.4)), but had an inconsistent effect on the hospital anxiety and depression scale. <b>Conclusion</b> Cognitive behaviour therapy delivered by primary care nurses offered additional benefit over mebeverine alone up to six months, although the effect had waned by 12 months. Such therapy may be useful for certain patients with irritable bowel syndrome in primary care.
The Clinical Usefulness of Hydrogen Gas as an Indicator of Left-to-Right Shunts
Authors: PAUL G. HUGENHOLTZ, THOMAS SCHWARK, R. GRIER MONROE, WALTER J. GAMBLE, ANNA J. HAUCK, ALEXANDER S. NADAS
Journal: Circulation (1963)

In 60 patients with congenital heart disease 210 observations with hydrogen gas as an indicator for left-to-right shunts were recorded at cardiac catheterization. All but nine had other definite evidence of the presence or absence of left-to-right shunting. In these nine, 21 early hydrogen arrival times formed the only conclusive evidence of left-to-right shunting. Although hydrogen and oxygen may form a highly explosive mixture, pure hydrogen used with proper precautions is a safe, reliable, and extremely simple indicator, eminently suited as a rapid screening procedure or as a supplementary tool in cases in which left-to-right shunts are difficult to prove.
OBSERVATIONS ON BREAST-FEEDING
Authors: H. W. Pooler
Journal: BMJ (1928)

r Thz RDTCAL 108 ConcluIsion .Stnnmarizing the position, morbidity in the puerperiunm is in the main due to a single cause, the Streptococcus pyofifi.c; the failuire of vaccines, a specific means of treat- mellt, is, therefore, the miiore disappointing.It appears that all but a few of our morbid cases r-ecovered spontaneously.This being so, the conclusioni follow-s that special remedies, such as vaccines, are of sub- sidiary importance in the prevention of sepsis as compared with coniservative and aseptic nmidwifery.Puerperal sepsis, being a specific disease, must be recognized as a definite clinical process to be treated like any other infectious or conita(gious malady.We are particularly indebted to Dr. Malcolm Donaldson for assistance and advice throughout the inquiry.The inauguration of the experiment on the extern district and the details of treat- ment were due in the first instance to him, and were carried out uinder his direction.To Donaldson also is due the introduction of the systematic use of sterile dressings and towels on the district anid insistence on conservative methods in the management of labour; his name in particular must therefore be associated with this paper.The extern midwifery department is grateful to Dr.Mervyn Gordon, consultinig bacteriologist to the hospital, for large supplies of vaccine, and for much helpful advice on its application.
Increased expression of mitochondrial-encoded genes in skeletal muscle of humans with diabetes mellitus.
Authors: D A Antonetti, C Reynet, C R Kahn
Journal: Journal of Clinical Investigation (1995)

Screening subtraction libraries from normal and type II diabetic human skeletal muscle, we identified four different mitochondrially encoded genes which were increased in expression in diabetes. The genes were cytochrome oxidase I, cytochrome oxidase III, NADH dehydrogenase IV, and 12s rRNA, all of which are located on the heavy strand of the mitochondrial genome. There was a 1.5- to 2.2-fold increase in the expression of these mRNA molecules relative to total RNA in both type I and type II diabetes as assessed by Northern blot analyses. Since there was approximately 50% decrease in mitochondrial DNA copy number as estimated by Southern blot analyses, mitochondrial gene expression increased approximately 2.5-fold when expressed relative to mitochondrial DNA copy number. For cytochrome oxidase I similar changes in mitochondrial gene expression were observed in muscle of nonobese diabetic and ob/ob mice, models of type I and type II diabetes, respectively. By contrast there was no change or a slight decrease in expression of cytochrome oxidase 7a, a nuclear-encoded subunit of cytochrome oxidase, and the expression of mitochondrial transcription factor 1 in human skeletal muscle did not change with type I or type II diabetes. The increased mitochondrial gene expression may contribute to the increase in mitochondrial respiration observed in uncontrolled diabetes.
A systemic type i 5 α-reductase inhibitor is ineffective in the treatment of acne vulgaris
Authors: James Leyden, Wilma Bergfeld, Lynn Drake, Frank Dunlap, Mitchel P. Goldman, Alice B. Gottlieb, Michael P. Heffernan, Janet G. Hickman, Maria Hordinsky, Michael Jarrett, Sewon Kang, Ann Lucky, Gary Peck, Tania Phillips, Marvin Rapaport, Janet Roberts, Ronald Savin, Marty E. Sawaya, Alan Shalita, Joel Shavin, James C. Shaw, Linda Stein, Daniel Stewart, John Strauss, James Swinehart, Leonard Swinyer, Diane Thiboutot, Ken Washenik, Gerald Weinstein, David Whiting, Frances Pappas, Matilde Sanchez, Lisa Terranella, Joanne Waldstreicher
Journal: Journal of the American Academy of Dermatology (2004)
Effect of bolus epinephrine on systemic hemodynamics in canine anaphylactic shock
Authors: S Mink
Journal: Cardiovascular Research (1998)

Objective: Epinephrine (Epi) is considered to be the drug of choice for anaphylactic shock (AS). However, the benefit of this drug on improving systemic hemodynamics in AS has never been shown. We used a canine ragweed model of AS to determine if an intravenous bolus of Epi hastened the recovery of hemodynamics and modified mediator release (Med) compared with no treatment (NT). Methods: In one protocol (n=8), the effects on hemodynamics of two intravenous doses of Epi (0.01 and 0.025 mg/kg) were examined for 3 h postshock in respective studies approximately three weeks apart under pentobarbital anesthesia in the same animal. In five other dogs, left ventricular (LV) mechanics were additionally determined by sonomicrometric techniques to determine changes in contractility as defined by the preload recruitable stroke–work (SW) relationship. Results: Compared with NT values, Epi treatments produced only transient increases in mean arterial pressure (MAP) and cardiac output (CO) post-challenge. By 20 min postshock, CO in the Epi studies were generally lower (p<0.05) and BP was not different from NT values. With Epi treatment, SW was reduced for a given LV end-diastolic volume compared with the control study. Epi treatments also caused relatively higher plasma thromboxane B2 concentrations postshock. Conclusion: Our findings indicate that, when given immediately postshock, bolus-Epi did not hasten recovery and caused impairment in LV mechanics in canine AS.
Australian government launches inquiry into healthcare system
Authors: C. Zinn
Journal: BMJ (1998)

The Australian federal government has launched a top level inquiry into claims by more than 200 doctors that they know patients who have died or been disabled because of breakdowns in the healthcare system.

In a surprise move the health minister, Dr Michael Wooldridge, told parliament last week that half of the 450 respondents to a survey published by the journal Australian Doctor had reported “very serious” allegations against the system. …
Comment on: Tran et al. Early Prediction of Gestational Diabetes Mellitus in Vietnam: Clinical Impact of Currently Recommended Diagnostic Criteria. Diabetes Care 2013;36:618–624
Authors: Yashdeep Gupta, Anu Gupta
Journal: Diabetes Care (2013)

We read with great interest the article by Tran et al. (1), in which the authors compared the discriminative power of prognostic models for early prediction of women at risk for the development of gestational diabetes mellitus (GDM). The research group found 5.9% prevalence of GDM by American Diabetes Association (ADA) criteria. The selective screening of women for GDM using the ADA model with a risk threshold of 3% gave 93% sensitivity for identification of women with GDM, with a 27% reduction in the number of oral glucose tolerance tests required.

If we simplify the results, it means missing 4 out of 59 cases of GDM in …
<i>Note from the Reviews Section Editorial Board</i>
Authors: George C. Prendergast, Martine Roussel, Eric Rowinsky, Dan Welch
Journal: Cancer Research (2005)

One of the new features in the Reviews Section of Cancer Research is Point-Counterpoint. In this venue, two opposing perspectives on a controversial issue of broad significance to the research community are presented. Authors submit independently and then have the opportunity to briefly rebut at the
Geographic Distribution of Heat-Related Deaths Among Elderly Persons
Authors: Beverly F. Martinez
Journal: JAMA (1989)

Mapping is a useful tool for initiating data analysis of relatively infrequent injury events and can lead to interesting hypotheses that can then be tested in further epidemiologic studies. From national death certificate data for the years 1979 through 1985, we made dot maps of fatalities due to excessive heat (<i>International Classification of Diseases</i>code E900) among persons 65 years or older. The maps show clusterings of deaths, particularly in the central, south central, and southeastern sections of the United States, to an extent not fully explained by the population density or temperature extremes. The counties principally affected were highly urbanized and, for races other than white, were relatively poor. Our maps identify counties in which heat-related health problems in the elderly are particularly severe. Public health officials in high-risk areas should undertake heat-wave contingency planning and physicians practicing in such areas should familiarize themselves with the treatment of the spectrum of heat-related illnesses. (<i>JAMA</i>. 1989;262:2246-2250)
Drugs Five Years Later
Authors: JAY S. KEYSTONE
Journal: Annals of Internal Medicine (1979)

The broad-spectrum of activity and safety of mebendazole remain, after 5 years of clinical experience, unique features of this anthelmintic. Through microtubular destruction, mebendazole kills helminths by inhibiting glucose uptake into susceptible parasites. The drug's poor absorption does not appear to affect clinical efficacy except, perhaps, in the treatment of systemic helminth infections. Mebendazole is generally considered the drug of choice for trichuriasis and has therapeutic advantages over other anthelmintics in the treatment of enterobiasis and hookworm infections. Although mebendazole is an effective agent against ascariasis, there are preferable alternatives. Among its nonapproved uses, mebendazole shows great promise in the treatment of capillariasis and hydatid disease. Further investigation is needed to establish its role in the treatment of taeniasis, Hymenolepsis nana, strongyloidiasis, trichinosis, and Dipetalonema perstans. Undoubtedly, mebendazole will find its greatest value in the treatment of patients with multiple helminth infections.This paper focuses on recent developments in the areas of mode of action and clinical efficacy of mebendazole use since its introduction in 1974. Mebendazole blocks glucose uptake by adult intestinal-dwelling nematodes and cestodes and their tissue-dwelling larvae. The drug's poor absorption does not appear to affect clinical efficacy except in the treatment of systemic helminth infections. Mebendazole has been found to be ovicidal for the eggs of roundworm, hookworm, and whipworm with the disadvantages of cost and long duration of therapy; it is also considered the best drug for the treatment of trichuriasis. Among its nonapproved uses, it shows promise in the treatment of capillariasis and hydatid disease. Further investigation is needed to establish its role in the treatment of taeniasis, Hymenolepsis nana, Strongyloidiasis, Trichinosis, and Dipetalonema perstans. Side effects such as diarrhea, abdominal pain, headache, and dizziness have been reported on rare occasions.
Familial Atrioventricular Block
Authors: Edouard Stephan
Journal: JAMA (1974)

<h3>To the Editor.—</h3> In the article, "Hereditary Progressive Atrioventricular Conduction Defect: A New Syndrome?" by Henry T. Lynch et al (225:1465, 1973), it is stated: Five families have been reported... similar to... the family under our investigation. 1. A Lebanese family was described by Stephan in 1961 (<i>Arch Mal Coeur</i>5:333, 1961). Features in common with family S include... dominant inheritance, similar age at onset, and no evidence of coronary or congenital heart disease. In family S, we have evidence of a progressive atrioventricular conduction defect culminating in a complete heart block. This evidence was lacking in Stephan's family, possibly because serial ECGs over a relatively long period of time were not available to him. But in my article, serial electrocardiograms covered periods of ten and four years in two cases. Evidence of progressive atrioventricular conduction defect was quite clear in case 2 (proband). There was a 2 to 1
CLINICAL STUDIES OF GASTRIC FUNCTION
Authors: ARTHUR L. BLOOMFIELD
Journal: JAMA (1927)

Some time ago we described a method<sup>1</sup>for the simultaneous determination in man, following a standard stimulus, of the volume of gastric secretion, the pH of the gastric juice and the motility of the stomach. In subsequent papers, studies on various phases of gastric function carried out by means of this method were reported. The present communication summarizes our various observations, and includes some further studies which have not previously been described. <h3>METHOD</h3> The method is briefly as follows: The subject should take no food during the twelve hours preceding the test. If possible, he should be under "basal" conditions; i. e., resting quietly in bed. A duodenal tube is passed to a distance which will allow the tip to reach the most dependent part of the stomach. The fasting juice is withdrawn at five minute intervals for fifteen or twenty minutes. Then, without attracting the patient's attention, 50