tbuckley/cabot-search huggingface dataset:
Both Intestinal and Hepatic Lipoprotein Production Are Stimulated by an Acute Elevation of Plasma Free Fatty Acids in Humans
Authors: Hélène Duez, Benoît Lamarche, René Valéro, Mirjana Pavlic, Spencer Proctor, Changting Xiao, Linda Szeto, Bruce W. Patterson, Gary F. Lewis
Journal: Circulation (2008)

Background— Hepatic lipoprotein production has been shown previously to be regulated by free fatty acid (FFA) flux to the liver, whereas intestinal lipoprotein production is stimulated mainly by ingested fat absorbed from the intestinal lumen. Emerging evidence indicates that intestinal lipoprotein production is increased in insulin resistance and type 2 diabetes mellitus, conditions that are associated with increased levels of circulating FFAs. Here we investigated whether short-term elevation of plasma FFAs stimulates intestinal apolipoprotein (apo) B-48– and hepatic apoB-100–containing triglyceride-rich lipoprotein (TRL) production in humans in the fed state. Methods and Results— TRL apoB-48 and apoB-100 metabolism were examined in 12 healthy men during a constant fed state. The studies were as follows, respectively: (1) Intralipid/heparin was infused intravenously immediately before and during the kinetics study to induce an ≈3-fold difference in plasma FFA compared with the saline study; (2) saline was infused intravenously as a control. ApoB-48– and apoB-100–containing TRL production and clearance were determined with a 12-hour primed constant infusion of [D3] l -leucine and multicompartmental kinetic modeling. TRL apoB-48 production rate was 69% higher in the Intralipid/heparin study than in the saline control (5.95±1.13 versus 3.53±0.58 mg/kg per day; P =0.027), and there was no significant difference in TRL apoB-48 clearance. TRL apoB-100 concentrations were also increased ( P &lt;0.001) and TRL apoB-100 production rate was 35% higher in the Intralipid/heparin study compared with saline (28±4 versus 21±3 mg/kg per day; P =0.020). Conclusions— This is the first study to demonstrate that intestinal TRL apoB-48 production is increased after short-term elevation of plasma FFAs in humans in the fed state, similar to the well-described stimulation of hepatic TRL apoB100–containing particles by FFAs.
Association analysis of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with primary biliary cirrhosis in Japanese patients
Authors: Satoru Joshita, Takeji Umemura, Kaname Yoshizawa, Yoshihiko Katsuyama, Eiji Tanaka, Minoru Nakamura, Hiromi Ishibashi, Masao Ota
Journal: Journal of Hepatology (2010)
Effect on adrenal function of topically applied clobetasol propionate (Dermovate).
Authors: C F Allenby, R A Main, R A Marsden, C G Sparkes
Journal: BMJ (1975)

Thirty-nine patients (15 outpatients and 24 inpatients) with a variety of skin diseases affecting variable areas of the body surface were treated with clobetasol propionate ointment (Dermovate). Before and after treatment the adrenal response to an intramuscular injection of tetracosactrin was rested and additional 9 am plasma cortisol levels were measured at intervals during treatment. A satisfactory initial therapeutic response was achieved in almost all cases during the trial period. When more than 50 g of ointment a week was used a significant number of patients developed adrenal suppression. WHen less than 50 g per week was used any suppression tended to be transtion. These cysts may be the cause of this condition, producing abnormal amounts of ovarian steroids which modify the pituitary response. Futher studies are needed, however, to determine this possibility.
Abstract 512: Reprogramming of the tumor microenvironment by stromal <i>Pten</i>-regulated miR-320
Authors: Agnieszka M. Bronisz, Jakub Godlewski, Julie Wallace, Anand Merchant, Gustavo Leone, Michael C. Ostrowski
Journal: Cancer Research (2011)

Abstract The tumor microenvironment is increasingly recognized as an essential collaborator for tumor cell growth and dissemination. However, our understanding of how the dialogue between stroma and tumor occurs at the molecular level is rudimentary. Recently, we showed that the genetic inactivation of Phosphatase and tensin homolog deleted on chromosome ten (Pten) in mouse mammary fibroblasts (MMFs) accelerates the initiation, progression and malignant transformation of mammary epithelial tumors and that this was associated with the activation of the transcription factor v-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2). In order to provide a molecular framework that defines how Pten deletion in MMFs, reprograms expression of other cells in the tumor microenvironment we carried out global miR profiling of Pten-/- MMFs. Among several significant changes in the miR expression profile compared with wild type MMFs, a novel and highly significant down-regulation of miR-320 was detected. We found that miR-320 in Pten-/- MMFs acted as a tumor suppressor to inhibit epithelial tumor growth in vivo, providing the first evidence for tumor suppressive functions of miRs outside the confines of the tumor cell. Proteomic analysis of the extracellular matrix showed that down-regulation of miR-320 in stromal fibroblasts induces a tumor-promoting secretome that incites profound changes in endothelial and epithelial cell phenotypes typical of malignant tumors. We found ETS2 as a direct target of miR-320 that was largely responsible for regulating the expression of the fibroblast-specific secretome. Multispectral imaging of human invasive breast carcinoma samples revealed a positive correlation between PTEN and miR-320 downregulation and negative correlation between miR-320 and ETS2 expression. Importantly, we show that expression of the miR-320/ETS2 regulated secretome can distinguish tumor stroma form normal breast stroma in breast cancer patients and can retrospectively predict patient outcome in multiple breast cancer gene expression data sets.These results extend the concept of miR function beyond the tumor cell boundary and define a network of communication between tumor fibroblasts and tumor cells that can potentially be targeted in human cancer. This work reveals miR-320 as a critical component of the Pten tumor suppressor axis that acts in stromal fibroblasts to reprogram the tumor microenvironment and curtail tumor progression. 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 512. doi:10.1158/1538-7445.AM2011-512
Co-trimoxazole in prevention of bacteriuria after prostatectomy.
Authors: N H Hills, M I Bultitude, S Eykyn
Journal: BMJ (1976)

In a prospective, double-blind trial prophylactic cotrimoxazole produced a highly significant reduction in the incidence of bacteriuria after prostatectomy. Only two out of 38 patients who received the drug developed bacteriuria compared with 19 out of 36 patients on placebo. Klebsiella-Enterobacter spp and coagulase-negative staphylococci were responsible for most infections. Although co-trimoxazole prophylaxis is obviously effective, widespread use might increase the incidence of bacterial resistance.
Coronary Nitric Oxide Production in Response to Exercise and Endothelium-Dependent Agonists
Authors: Jay H. Traverse, Yale L. Wang, Ruisheng Du, Daniel Nelson, Paul Lindstrom, Stephen L. Archer, Guangrong Gong, Robert J. Bache
Journal: Circulation (2000)

Background —Endothelium-derived nitric oxide (NO) contributes to epicardial coronary artery vasodilation during exercise. However, blockade of NO production does not impair the increase in coronary blood flow (CBF) during exercise, suggesting that NO is not obligatory for exercise-induced coronary resistance vessel dilation. In contrast, the increases in CBF produced by endothelium-dependent agonists are decreased after NO blockade. Consequently, this study was performed to determine whether the increase in coronary NO production in response to agonists is greater than that which occurs during exercise. Methods and Results —We measured the oxidation products of NO (nitrate+nitrite=NO x ) in aortic and coronary sinus plasma using chemiluminescence to assess NO x production across the coronary circulation in chronically instrumented dogs during a 3-stage treadmill exercise protocol and in response to intracoronary administration of the endothelium-dependent agonists acetylcholine (37.5 μg/min) and bradykinin (3.0 μg/min). No coronary NO x production could be detected at rest or during the first 2 stages of exercise; only at the highest level of exercise was a small increase in coronary NO x production measured. In contrast, coronary production of NO x was significantly increased in response to endothelium-dependent agonists. Conclusions —Coronary NO production in response to endothelium-dependent agonists is greater than in response to the increase in shear stress associated with exercise. These findings support previous studies suggesting that NO is not required for the coronary vasodilation that occurs in the normal heart during exercise.
Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro.
Authors: E Slatopolsky, J Finch, M Denda, C Ritter, M Zhong, A Dusso, P N MacDonald, A J Brown
Journal: Journal of Clinical Investigation (1996)

Dietary phosphorus (P) restriction is known to ameliorate secondary hyperparathyroidism in renal failure patients. In early renal failure, this effect may be mediated by an increase in 1,25-(OH)2D3, whereas in advanced renal failure, P restriction can act independent of changes in 1,25-(OH)2D3 and serum ionized calcium (ICa). In this study, we examined the effects of dietary P on serum PTH, PTH mRNA, and parathyroid gland (PTG) hyperplasia in uremic rats. Normal and uremic rats were maintained on a low (0.2%) or high (0.8%) P diet for 2 mo. PTG weight and serum PTH were similar in both groups of normal rats and in uremic rats fed the 0.2% P diet. In contrast, there were significant increases in serum PTH (130 +/- 25 vs. 35 +/- 3.5 pg/ml, P < 0.01), PTG weight (1.80 +/- 0.13 vs. 0.88 +/- 0.06 microg/gram of body weight, P < 0.01), and PTG DNA (1.63 +/- 0.24 vs. 0.94 +/- 0.07 microg DNA/gland, P < 0.01) in the uremic rats fed the 0.8% P diet as compared with uremic rats fed the 0.2% P diet. Serum ICa and 1,25-(OH)2D3 were not altered over this range of dietary P, suggesting a direct effect of P on PTG function. We tested this possibility in organ cultures of rat PTGs. While PTH secretion was acutely (30 min) regulated by medium calcium, the effects of medium P were not evident until 3 h. During a 6-h incubation, PTH accumulation was significantly greater in the 2.8 mM P medium than in the 0.2 mM P medium (1,706 +/- 215 vs. 1,033 +/- 209 pg/microg DNA, P < 0.02); the medium ICa was 1.25 mM in both conditions. Medium P did not alter PTH mRNA in this system, but cycloheximide (10 microg/ml) abolished the effect of P on PTH secretion. Thus, the effect of P is posttranscriptional, affecting PTH at a translational or posttranslational step. Collectively, these in vivo and in vitro results demonstrate a direct action of P on PTG function that is independent of ICa and 1,25-(OH)2D3.
Gateway of honor.
Authors: John H. Talbott
Journal: JAMA (1963)

The history of the American College of Physicians is a story of the rise to stature of internal medicine in this country— the culmination of the slow transition of the desire to form a scientific organization for physicians who abandoned the familiar "Physician and Surgeon" category which had prevailed since colonial times. In the latter part of the 19th century, the American Clinical and Climatological Association and the Association of American Physicians were organized for physicians who chose to devote their professional talents to internal medicine. However, membership was markedly restricted in each organization, and no pretense was made to fulfill the function in America of the Royal College of Physicians in England. In the establishment of the American College of Physicians, membership requirements included affiliation with the American Congress on Internal Medicine and the practice of medicine for a minimum of ten years. Election to Fellowship in the College
Slowing the march of the Marlboro man
Authors: R M Davis
Journal: BMJ (1994)

Slowing the march of the Marlboro man Unless current smoking patterns change cigarettes will kill 10 million people a year by 2025This week the journal reports the 40 year results from the world's longest running study of smoking and death, which finds that in Britain about half of all regular cigarette smok- ers will eventually be killed by their habit (p 901,' p 91 12).Next week more than 1000 delegates will attend the ninth world conference on tobacco and health in Paris.These provide an opportunity to take stock of the current status of tobacco and health worldwide.The World Bank estimates that the annual tobacco con- sumption will remain stable between 1990 and 2000 at 1 9 kg per person aged 15 and over.3That apparent stabil- ity masks two divergent trends: falls in tobacco use in the industrialised world and increases in developing regions.Per capita tobacco consumption is expected to fall by 17% during this decade (from 2-4 kg to 2-0 kg a year) among the 35 "established market economies" of the world.At the same time per capita consumption is predicted to rise by 12% (from 1-7 kg to 1 9 kg a year) in the 180 "demographically developing economies."Increases in con-sumption are also expected in five of the six formerly socialist economies of Europe for which the World Bank made projections.3Smoking is responsible for three million deaths a year worldwide.If current smoking patterns continue that toll will have risen to 10 million deaths a year by 2025.46Following trends in consumption, deaths attributable to tobacco will rise substantially in developing regions as deaths level off and then fall in industrialised countries.Increases in tobacco consumption in developing countries reflect the marketing activities of the multinational tobacco companies.While tobacco markets shrink in the multinationals' home countries-the United States and Britain-the companies export their products, promotions, and political pressures to Asia, Africa, Latin America, and eastern Europe.7In Taiwan free tickets to a rock concert are given to those who return empty packs ofWinston cigarettes.In the Dominican Republic the Marlboro name and colours adorn road signs.8In Moscow, where the city council has banned tobacco advertising, four adjacent, illuminated billboards advertise Western cigarettes in front of the Bolshoi Theatre.9In Bucharest the amber filters of many of
PERSISTENCE OF TETANUS ANTITOXIN IN MAN FOLLOWING ACTIVE IMMUNIZATION
Authors: P. A. T. Sneath, E. J. Kerslake
Journal: BMJ (1935)

MEDIC-AL JOURNAL and for the regulating of the time of return to work accordingly.And it should be added that the new suggestions as to the danger of certain minutely fragment- ing fibrous silicates, on which stress has been laid by W. R. Jones (1933), serves to emphasize the importance of a careful scrutiny of the stone dusts so successfully used for " stone dusting" as a precaution against explosions.It may well be that the importance given, in the past, to the presence or absence of " free silica " may have blinded us to the existence of other dangerous elements capable, equally with or in greater degree than free silica itself, of producing silicosis.
Side-effects of Vinca alkaloids.
Authors: W. G. Bradley
Journal: BMJ (1968)

psychosomatic diseases " have emotional sensitivity as their common property, and determinable specific sensitivities are found in most of them.The environment does the rest.-Iam, etc., RANYARD WEST.Church Stretton, Salop.Side-effects of Vinca Alkaloids SIR,-The findings by Dr. A. Vladutiu (22 June, p. 764) of acute dilatation of the gut in guinea-pigs receiving intraperitoneal injections of vinblastine is similar to the ex- perience of others working with this drug.Constipation, abdominal distension, and pain, sometimes sufficient to precipitate laparo- tomy, as well as acute urinary retention and loss of salivation, occasionally occur in patients receiving vinblastine,' 2 though the incidence of these complications is far greater in patients receiving the closely related alka- loid, vincristine.'' Prophylactic bulk laxa- tives and other aperients are recommended routinely for patients receiving vincristine.'Smith' found similar acute dilatation of the gut in mice treated with intraperitoneal injections of vinblastine, and moreover demonstrated degenerative changes in the myenteric plexus of the gut both in man and the mouse.This finding is in keeping with the known neurotoxicity of vinblastine, but more particularly of vincristine.'Almost certainly direct damage to the myenteric plexus causes paralysis of the gut.There is no evidence for the true ganglion-blocking action of vinblastine suggested by Dr.
The Surgeon and the HIV-Infected Patient
Authors: Kenneth W. Shewell
Journal: JAMA (1990)

<h3>To the Editor.—</h3> The recent article on litigation having to do with the acquired immunodeficiency syndrome (AIDS)<sup>1</sup>dealt with many aspects of AIDS-related discrimination. I was interested to note the many points put forward to obligate health care workers to treat AIDS patients: "The survey suggests that courts will legally enforce the professional obligation to treat HIV [human immunodeficiency virus]-infected patients" and "a decision not to treat... is likely to be viewed by the courts as medically unjustified and based on irrational fear or prejudice." The article then makes a strong case for why personnel infected with HIV may not treat patients. The American Medical Association's position is quite clear—a "physician who knows he or she is seropositive should not engage in any activity that creates a risk of transmission of the disease to others.<sup>2</sup>" The Council on Ethical and Judicial Affairs notes that "gloves cannot prevent penetrating
Trends in cutaneous malignant melanoma in Sweden 1997-2011: thinner tumours and improved survival among men
Authors: J. Lyth, H. Eriksson, J. Hansson, C. Ingvar, M. Jansson, J. Lapins, E. Månsson-Brahme, P. Naredi, U. Stierner, G. Ullenhag, J. Carstensen, C. Lindholm
Journal: British Journal of Dermatology (2014)

Both patient survival and the proportion of patients diagnosed with thin cutaneous malignant melanoma (CMM) have been steadily rising in Sweden as in most Western countries, although the rate of improvement in survival appears to have declined in Sweden at the end of the last millennium.To analyse the most recent trends in the distribution of tumour thickness (T category) as well as CMM-specific survival in Swedish patients diagnosed during 1997-2011.This nationwide population-based study included 30,590 patients registered in the Swedish Melanoma Register (SMR) and diagnosed with a first primary invasive CMM during 1997-2011. The patients were followed through 2012 in the national Cause of Death Register.Logistic and Cox regression analyses adjusting for age at diagnosis, tumour site and healthcare region were carried out. The odds ratio for being diagnosed with thicker tumours was significantly reduced (P < 0·001) and the CMM-specific survival significantly improved in men diagnosed during 2007-2011 compared with men diagnosed during 1997-2001 (hazard ratio = 0·81; 95% confidence interval 0·72-0·91; P < 0·001), while the corresponding differences for women were not significant. Women were diagnosed with significantly thicker tumours during 2002-2006 and a tendency towards decreased survival was observed compared with those diagnosed earlier (during 1997-2001) and later (during 2007-2011).In Sweden, the CMMs of men are detected earlier over time and this seems to be followed by an improved CMM-specific survival for men. Women are still diagnosed with considerably thinner tumours and they experience a better survival than men.
TRANSMISSION OF NON-A NON-B HEPATITIS TO CHIMPANZEES BY FACTOR-IX CONCENTRATES AFTER FATAL COMPLICATIONS IN PATIENTS WITH CHRONIC LIVER DISEASE
Authors: R.J. Wyke, Anthea Thornton, B. Portmann, A.J. Zuckerman, K.N. Tsiquaye, Yvette White, P.K. Das, Roger Williams
Journal: The Lancet (1979)
Postoperative Bile-Duct Strictures
Authors: Gordon A. Donaldson, Arthur W. Allen, Marshall K. Bartlett
Journal: New England Journal of Medicine (1956)

TWENTY years ago it was possible for Eliot1 to collect all 215 cases of postoperative biliary strictures reported in the literature here and abroad. In a painstaking and brilliant fashion he reviewed each case and made many observations that, if heeded over the intervening years, might have given improved results in the care of this difficult group of patients. In recent years, sizable series of cases have appeared from various clinics, some of them running into hundreds of patients, and it is of some concern whether or not the injury to bile ducts during the course of cholecystectomy has actually . . .
Gonadal Activity and Chemotherapy-Induced Gonadal Damage
Authors: Daiva R. Bajorunas
Journal: JAMA (1988)

<h3>To the Editor.—</h3> Drs Rivkees and Crawford<sup>1</sup>have reviewed the relationship of pubertal status to chemotherapyinduced gonadal damage and have concluded that the quiescent gonad of prepuberty may confer a protective effect during chemotherapy. If one could suppress germ cell proliferation and induce a quiescent gonad in the adult, then potentially the gonad might be protected from this cytotoxic drug-induced damage. Although Drs Rivkees and Crawford cite only three studies<sup>2-4</sup>and suggest that this hypothesis has been "surprisingly little-tested," there are now more than 20 studies in laboratory animals and humans testing this "germ cell suppression hypothesis."<sup>5</sup>Hodgkin's disease has been the model in the human studies because of the high curability, its occurrence during the reproductive years, and the frequent sterility caused by the combination chemothera py used for this disease. After the first report of a possible protective effect of oral contraceptives,<sup>2</sup>subsequent studies
Effect of long term lactulose ingestion on secondary bile salt metabolism in man: potential protective effect of lactulose in colonic carcinogenesis.
Authors: G P van Berge Henegouwen, S D van der Werf, A T Ruben
Journal: Gut (1987)

This study investigated whether colonic absorption of secondary bile acids, especially deoxycholate in patients with adenomas could be decreased by oral lactulose. Bile acid metabolism was studied using bile sampling and 14C-deoxycholate kinetics in patients with colonic adenomatous polyps before and after four and 12 weeks of lactulose, 60 g/day. The results indicate that lactulose decreased the deoxycholate pool size from a mean of 22.0 (SD: +/- 13.8) to 14.3 (+/- 7.6) mumol/kg (p less than 0.025). Deoxycholate absorption fell from 3.8 (+/- 2.3) to 2.9 (+/- 1.4 mumol/kg/d (ns). The biliary bile acid composition decreased significantly in deoxycholate after four and 12 weeks with a rise in primary bile acids. There was a highly significant correlation between the %-change in DCA input and the %-change in DCA pool size (r = 0.89). Intestinal transit measured by the pellet method (4.1 +/- 1.9 to 2.4 +/- 0.6 day; p less than 0.01) and faecal pH decreased, while stool frequency and weight rose significantly. Significant correlations between the %-change in gut transit time and the %-change in DCA pool size or %-change in DCA input were absent. The results show that it is possible to lower colonic secondary bile acid absorption by long term lactulose feeding. This effect can be mediated by accelerated transit and the acidification of the colonic contents.