tbuckley/cabot-search huggingface dataset:
Rapamycin (sirolimus) inhibits proliferating cell nuclear antigen expression and blocks cell cycle in the G1 phase in human keratinocyte stem cells.
Authors: A F Javier, Z Bata-Csorgo, C N Ellis, S Kang, J J Voorhees, K D Cooper
Journal: Journal of Clinical Investigation (1997)

Because the immunosuppressant rapamycin (sirolimus) blocks T cell proliferation in G1 phase, it has been proposed as a potential treatment for psoriasis, a skin disease characterized by T cell activation and keratinocyte stem cell hyperproliferation. To determine another potentially important mechanism through which rapamycin can act as an antipsoriatic agent, we tested its direct effect on keratinocyte stem cell proliferation in vitro as well as in vivo. In vivo cell cycle quiescent (G0 phase) stem cell keratinocytes in primary culture sequentially express de novo cyclin D1 and proliferating cell nuclear antigen (PCNA), prior to S phase entry, and upregulate beta1 integrin. Rapamycin inhibited the growth of keratinocytes that were leaving quiescence as well as those already in cell cycle without affecting cell viability. Although beta1 integrin(bright) expression was not affected, the number of beta1 integrin(bright) cells entering S/G2/M was significantly lowered by rapamycin. Cells treated with rapamycin exhibited decreased PCNA expression while cyclin D1 expression, which precedes PCNA expression in the cell cycle, was not affected. We found similar effects on stem cell keratinocytes in patients with psoriasis treated systemically with rapamycin. Because PCNA is required for cell cycle progression from G1 to S phase, our data indicate that inhibition of PCNA protein synthesis may be an important regulatory element in the ability of rapamycin to exert a G1 block.
279 HCV CORE-INDUCED CXCL10 SECRETION LEADS TO RECRUITMENT OF CXCR3(+) NATURAL KILLER CELLS WITH LOW CYTOTOXIC POTENTIAL
Authors: M. Eisenhardt, A. Glässner, B. Krämer, C. Körner, T. Sauerbruch, U. Spengler, J. Nattermann
Journal: Journal of Hepatology (2011)
BUILDING HEALTH BY COMMISSION
Authors: Frank G. Dickinson
Journal: JAMA (1953)

A studied attempt has been made to classify the recommendations of the Truman Commission on the Health Needs of the Nation as a middle-of-the-road program built on the solid foundation of  health insurance. This claim demands our attention before examining the many parts of the report. The recommendations on financing (I, 47-48) significantly omit the word voluntary in reference to prepayment plans or prepaid insurance. After spending almost $600,000 of National Defense funds, the commission took the wrong fork in the road, ignoring the turn marked  health insurance and drove off into an open field where the members could put the fence posts and fences wherever they pleased, thereby claiming a middle-of-the-road position. In this unbounded field of prepaid insurance or prepaid plans, not fenced in by the word voluntary, the commission could advocate almost any scheme that would provide for advance payment of the costs of illness.
Measurements of Enzymes in the Diagnosis of Acute Myocardial Infarction
Authors: MILTON W. HAMOLSKY, NATHAN O. KAPLAN
Journal: Circulation (1961)

The determination of the levels of activity of various enzymes in the blood or serum of man represents a major advance in the laboratory diagnosis of various disease states. The widespread body distribution of various enzymes at relatively large tissue activity levels in comparison to the small amounts normally in the circulation has, on the one hand, permitted the demonstration of diseased or damaged tissue by the resultant elevation of serum levels of activity. On the other hand, the generally large amounts of the clinically significant enzymes in heart, liver, skeletal muscle, kidney, brain, etc. has precluded the desired specificity of a laboratory test. At the present state of development, increases in circulating levels of various enzymes appear to be more sensitive indicators of tissue damage than previously available ones, such as the erythrocyte sedimentation rate and the C-reactive protein but it must be remembered that they are equally nonspecific. Any cause of tissue breakdown—trauma, infection, infarction, ischemia, neoplasia—may result in elevated serum levels, presumably by the release of enzyme from the damaged tissue. Thus, as with all laboratory tests, considered clinical judgment of the over-all picture remains essential. Despite this limitation, demonstration of elevated serum levels of certain enzymes (the two most useful at this time being SGOT and LDH) serves, in the proper clinical setting, as a highly valuable indicator of myocardial necrosis; failure to observe this on serial testing is an important negative finding. The SGOT activity rises promptly after myocardial infarction, permitting early confirmation. LDH, simpler to measure, affords the advantage of a more persisting abnormality (up to 10 to 14 days after infarction). In most comparative studies, LDH measurements appear to afford a greater over-all positive correlation with the ultimate diagnosis. The rapid development of this area of knowledge has already increased the diagnostic armamentarium of the clinician. Recent promise of methods to increase the specificity of the results augurs well for the future.
Erratum: Corrigendum: Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex
Authors: Froylan Calderon de Anda, Ana Lucia Rosario, Omer Durak, Tracy Tran, Johannes Gräff, Konstantinos Meletis, Damien Rei, Takahiro Soda, Ram Madabhushi, David D Ginty, Alex L Kolodkin, Li-Huei Tsai
Journal: Nature Neuroscience (2014)
Local Anaesthesia in General Surgery
Authors: H. Dodd
Journal: BMJ (1940)

Serious interest in local anaesthesia was aroused during a visit to Budapest when Professor Adam said: "I have performed over 40,000 operations under local anaesthesia and I have never had an anaesthetic fatality."He had performed a cholecystectomy, a partial gastrectomy, a thyroidectomy, and an operation for secondary empyema under local anaesthesia with sLuperlative dexterity and daintiness of surgical technique.Previously local anaesthesia had been regarded as of limited usefulness in major surgery.It had been seen used in dilettante fashion in Britain, mostly for small procedures, while in major cases it was often supplemented to such an extent that the "local " became the very junior partner of the anaesthesia.A few large operations under local anaesthetics had been witnessed, but they were not painless or convincing.The Hungarian patients, hospital and private, walked or were wheeled in chairs into the theatre (including the exophthalmic goitre patient), so that the pr-e-anaesthesia was slight.On no occasion was the
Effect of Dietary Protein Supplementation on Blood Pressure
Authors: Jiang He, Marion R. Wofford, Kristi Reynolds, Jing Chen, Chung-Shiuan Chen, Leann Myers, Deborah L. Minor, Patricia J. Elmer, Daniel W. Jones, Paul K. Whelton
Journal: Circulation (2011)

Observational studies have reported an inverse association between dietary protein intake and blood pressure (BP). We compared the effect of soy protein, milk protein, and carbohydrate supplementation on BP among healthy adults.We conducted a randomized, double-blind crossover trial with 3 intervention phases among 352 adults with prehypertension or stage 1 hypertension in New Orleans, LA, and Jackson, MS, from September 2003 to April 2008. The trial participants were assigned to take 40 g/d soy protein, milk protein, or carbohydrate supplementation each for 8 weeks in a random order. A 3-week washout period was implemented between the interventions. Three BPs were measured at 2 baseline and 2 termination visits during each of 3 intervention phases with a random-zero sphygmomanometer. Compared with carbohydrate controls, soy protein and milk protein supplementations were significantly associated with -2.0 mm Hg (95% confidence interval -3.2 to -0.7 mm Hg, P=0.002) and -2.3 mm Hg (-3.7 to -1.0 mm Hg, P=0.0007) net changes in systolic BP, respectively. Diastolic BP was also reduced, but this change did not reach statistical significance. There was no significant difference in the BP reductions achieved between soy or milk protein supplementation.The results from this randomized, controlled trial indicate that both soy and milk protein intake reduce systolic BP compared with a high-glycemic-index refined carbohydrate among patients with prehypertension and stage 1 hypertension. Furthermore, these findings suggest that partially replacing carbohydrate with soy or milk protein might be an important component of nutrition intervention strategies for the prevention and treatment of hypertension.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00107744.
CORONARY ARTERY PLAQUES IN MAINTENANCE DIALYSIS PATIENTS: HISTOPATHOLOGICAL FEATURES AND EX VIVO OPTICAL COHERENCE TOMOGRAPHY IMAGING
Authors: Hiroyuki Hao, Rika Kawakami, Takahiro Imanaka, Kenichi Fujii, Tohru Masuyama, Hatsue Ishibashi-Ueda, Seiichi Hirota
Journal: Journal of the American College of Cardiology (2014)
Pharmacology of Airway Smooth Muscle
Authors: PETER J. BARNES
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Section:ChooseTop of pageAbstract <<DIRECT AND INDIRECT EFFEC...AIRWAY SIZEPHARMACOLOGY OF BRONCHOCO...PHARMACOLOGY OF BRONCHODI...PROLIFERATIONSECRETORY FUNCTIONCELL INTERACTIONSReferencesCITING ARTICLES
Effect of aspirin on normal and cholera toxin-stimulated intestinal electrolyte transport.
Authors: R K Farris, E J Tapper, D W Powell, S M Morris
Journal: Journal of Clinical Investigation (1976)

The effect of aspirin on normal and cholera toxin-stimulated electrolyte transport has been investigated in vitro, because this drug appears to inhibit cholera toxin-induced intestinal secretion in in vivo animal models. In the Ussing chamber, 10 mM aspirin decreased the control rabbit ileal potential difference and short-circuit current by 50% and increased conductance by 28%. Bidirectional electrolyte flux determinations showed that aspirin significantly increased both Na and Cl absorption and reduced flux (which probably represents HCO3 secretion) to zero. This effect of aspirin appears to be identical to that reported to others with catecholamines as determined with similar techniques. However, alpha-adrenergic blockers did not prevent the electrical effects of aspirin, suggesting that aspirin does not have its effect through release of tissue stores of catecholamines. In the presence of aspirin, cholera toxin increased the potential difference and short-circuit current, and decreased the conductance of rabbit ileum in a fashion qualitatively similar to control tissues. However, aspirin reversed cholera toxin-stimulated Na transport from secretion to absorption, inhibited cholera toxin, induced Cl secretion by 58% and partially, but not significantly, inhibited HCO3 secretion. Thus, the inhibitory effect of aspirin on cholera toxin-induced electrolyte secretion appears to be due to aspirin-stimulated Na and Cl absorption. Although aspirin reduced tissue cyclic AMP concentrations in normal and cholera toxin-stimulated ileum, it also inhibited the electrolyte secretion induced by exogenous cyclic AMP. Thus, if aspirin's stimulatory effect on sodium and anion absorption in normal tissue and its inhibitory effect on cholera toxin-stimulated sodium and anion secretion involves a cyclic AMP-mediated system, the effect must be a step distal to cyclic AMP production or degradation. The exact mechanism of aspirin's effect on normal and cholera toxin-induced electrolyte transport, and its possible usefulness in the treatment of cholera diarrhea, remains to be determined.
A Substitute for the Arterial Pressure Catheter: Ultrasonic Detection of Arterial Motion.
Authors: Harvey Salomon
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970A Substitute for the Arterial Pressure Catheter: Ultrasonic Detection of Arterial Motion.Harvey Salomon, M.D., (Associate), Harold MassieHarvey Salomon, M.D., (Associate)Search for more papers by this author, Harold MassieSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-785_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptKorotkoff sounds have proved inadequate in the critical care situation. During shock there is insufficient acoustical energy generated to produce Korotkoff sounds. Ambient noise, hearing acuity, and the size and shape of the arm all affect the accuracy of blood pressure measurements. Therefore, the arterial catheter is used in the critical situation.A new method for indirectly measuring blood pressure solves these and reduces the need for arterial catheterization. A beam of ultrasound is directed toward the brachial artery under the standard cuff. Rapid motion of the artery wall changes the frequency of the transmitted ultrasound, and this frequency change... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cranbury, NJ. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 785-785KeywordsArterial lineArteriesBlood pressureCatheterizationCathetersCritical careHearingShockUltrasound imaging Issue Published: 1 May 1970 PDF DownloadLoading ...
Dementia: issues in early recognition and intervention in primary care
Authors: R T Woods, E. Moniz-Cook, S. Iliffe, P. Campion, M. Vernooij-Dassen, O. Zanetti, M. Franco
Journal: Journal of the Royal Society of Medicine (2003)

Changes in health policy in the UK are creating an experiment in dementia care which will be of importance to other societies and healthcare systems. A report from the Audit Commission, Forget Me Not 2002,1 concludes that general practices should make greater efforts to diagnose dementia in its early stages. Likewise the National Service Framework (NSF) for Older People2 emphasizes the need for early detection, with an enhanced role for primary care. A major challenge to implementation, however, is the observation that a substantial minority of general practitioners (GPs) are unconvinced of the benefits of early diagnosis. In the Audit Commision's survey of 8051 GPs in 73 areas of England, only 60% agreed that an early diagnosis of dementia was important—no change from the proportion in pilot data from 12 areas, collected in 1999.3 Probably, however, GP opinion has become more favourable since the publication of National Institute for Clinical Excellence (NICE) guidance on use of acetyl-cholinesterase (AChE) inhibitors for the treatment of Alzheimer's disease4—advice that may have come too late to have much impact on the full survey. A common argument is that, in the absence of effective treatment, there is nothing to be gained from early diagnosis. Forget Me Not 2002 notes that GPs who reported having received sufficient training in diagnosis and management were the ones most likely to favour early diagnosis; most GPs did not feel that they had received sufficient training. These findings may in part explain why nearly 75% of patients with moderate to severe dementia are unrecognized by primary care clinicians as having cognitive impairment.5 The Audit Commission1 points out that, if the condition is not recognized early, the patient and family commonly experience a crisis, with specialist services called in too late to establish supportive care. More positively, the NSF suggests that early diagnosis provides access to treatment, allows planning of future care and helps individuals and their families come to terms with the prognosis.
Generalized Herpes Simplex Complicating Lymphoma
Authors: Yelva L. Lynfield
Journal: JAMA (1969)

Herpes simplex virus caused an acute febrile illness with a generalized vesicular rash in an adult with advanced leukolymphosarcoma. This appeared during treatment with cyclophosphamide and prednisone. The isolation of the virus from the skin lesions by tissue culture enabled rapid diagnosis.
Social Class of Medical Students
Authors: Edwin F. Rosinski
Journal: JAMA (1965)

In a study of the social class background of students in four medical schools, it was found that approximately 12% of the students came from the lowest social classes. Approximately 54% of the total US population is classified similarly. The school with the least expensive tuition fees attracted more students from the lowest classes. It is proposed that greater financial assistance to medical students will attract a larger number of able applicants from the lowest classes. These qualified college graduates represent an untapped pool of medical school applicants.
Treatment of Functional Menstrual Disorders with Norethisterone
Authors: P. M. F. Bishop, J. C. C. de Almeida
Journal: BMJ (1960)

The introduction of 19-nortestosterone derivatives (Djerassi et al., 1954) has put a series of powerful oral progestogens at the disposal of the clinician, whereas previously the only orally active progestogen avail- able was ethinyltestosterone (ethisterone).The corresponding nor-compound, ethinyl-nortestosterone (see Formulae), was found by Hertz et al. (1954) to be five times as active by the Clauberg (1930) test, when given by the oral route to rabbits. C-CH 2OHCH //\/
Splicing of a Novel <i>Androgen Receptor</i> Exon Generates a Constitutively Active Androgen Receptor that Mediates Prostate Cancer Therapy Resistance
Authors: Scott M. Dehm, Lucy J. Schmidt, Hannelore V. Heemers, Robert L. Vessella, Donald J. Tindall
Journal: Cancer Research (2008)

Abstract The standard systemic treatment for prostate cancer (PCa) is androgen ablation, which causes tumor regression by inhibiting activity of the androgen receptor (AR). Invariably, PCa recurs with a fatal androgen-refractory phenotype. Importantly, the growth of androgen-refractory PCa remains dependent on the AR through various mechanisms of aberrant AR activation. Here, we studied the 22Rv1 PCa cell line, which was derived from a CWR22 xenograft that relapsed during androgen ablation. Three AR isoforms are expressed in 22Rv1 cells: a full-length version with duplicated exon 3 and two truncated versions lacking the COOH terminal domain (CTD). We found that CTD-truncated AR isoforms are encoded by mRNAs that have a novel exon 2b at their 3′ end. Functionally, these AR isoforms are constitutively active and promote the expression of endogenous AR-dependent genes, as well as the proliferation of 22Rv1 cells in a ligand-independent manner. AR mRNAs containing exon 2b and their protein products are expressed in commonly studied PCa cell lines. Moreover, exon 2b–derived species are enriched in xenograft-based models of therapy-resistant PCa. Together, our data describe a simple and effective mechanism by which PCa cells can synthesize a constitutively active AR and thus circumvent androgen ablation. [Cancer Res 2008;68(13):5469–77]
Michael Hague Dale
Authors: Michael Drury
Journal: BMJ (2006)

served in the Royal Army Medical Corps in Normandy, Belgium, and Rhodesia before joining his brother in general practice in Bellshill in industrial Lanarkshire.After retirement in 1978 he did locum work.He was chairman of Lanarkshire Medical Committee for 12 years.In addition to an avid interest in politics, sport, crosswords, and puddings, he supplied family, friends and neighbours with plants annually, and grew show chrysanthemums, winning many prizes locally and nationally.He was chairman of the Scottish Chrysanthemum and Dahlia Society for many years.David survived cancer three times.
The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics
Authors: Jason M. Ridlon, Jasmohan S. Bajaj
Journal: Acta Pharmaceutica Sinica B (2015)

The human body is now viewed as a complex ecosystem that on a cellular and gene level is mainly prokaryotic. The mammalian liver synthesizes and secretes hydrophilic primary bile acids, some of which enter the colon during the enterohepatic circulation, and are converted into numerous hydrophobic metabolites which are capable of entering the portal circulation, returned to the liver, and in humans, accumulating in the biliary pool. Bile acids are hormones that regulate their own synthesis, transport, in addition to glucose and lipid homeostasis, and energy balance. The gut microbial community through their capacity to produce bile acid metabolites distinct from the liver can be thought of as an "endocrine organ" with potential to alter host physiology, perhaps to their own favor. We propose the term "sterolbiome" to describe the genetic potential of the gut microbiome to produce endocrine molecules from endogenous and exogenous steroids in the mammalian gut. The affinity of secondary bile acid metabolites to host nuclear receptors is described, the potential of secondary bile acids to promote tumors, and the potential of bile acids to serve as therapeutic agents are discussed.
Effect of lifestyle intervention in patients with type 2 diabetes: A meta-analysis
Authors: Liang Chen, Jian-Hao Pei, Jian Kuang, Hong-Mei Chen, Zhong Chen, Zhong-Wen Li, Hua-Zhang Yang
Journal: Metabolism (2014)

ObjectiveThe effect of lifestyle intervention on clinical risk factors in patients with type 2 diabetes is unclear. The aim of this meta-analysis was to evaluate the effects of comprehensive lifestyle change, such as diet, exercise, and education, on clinical markers that are risk-factors for cardiovascular disease in patients with type 2 diabetes.MethodsWe searched Medline, Cochrane, EMBASE, and Google Scholar (up to August 31, 2013) for randomized controlled trials that compared standard of care (control group) with treatment regimens that included changes in lifestyle (intervention group). The primary outcome was reduction in risk factors of cardiovascular disease including body mass index (BMI), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c).ResultsA total of 16 studies were included in the meta-analysis. The standardized difference in means of change from baseline significantly favored the intervention compared with the control group in BMI (−0.29; 95% CI, −0.52 to −0.06, P = 0.014), HbA1c (−0.37; 95% CI, −0.59 to −0.14, P = 0.001), SBP (−0.16: 95% CI, −0.29 to −0.03, P = 0.016), DBP (−0.27, 95% CI = −0.41 to −0.12, P < 0.001). There was no difference between the intervention and control groups in HDL-c (0.05; 95% CI, −0.10 to 0.21; P = 0.503) and LDL-c (−0.14; 95% CI, −0.29 to 0.02; P = 0.092).ConclusionsThe meta-analysis found that lifestyle intervention showed significant benefit in risk factors that are known to be associated with development of cardiovascular disease in patients with type 2 diabetes.