tbuckley/cabot-search huggingface dataset:
Dynamin is involved in human epithelial cell vacuolation caused by the Helicobacter pylori–produced cytotoxin VacA
Authors: Junko Suzuki, Hirohide Ohnsihi, Hiroshi Shibata, Akihiro Wada, Toshiya Hirayama, Taroh Iiri, Namiki Ueda, Chiho Kanamaru, Tomohiro Tsuchida, Hirosato Mashima, Hiroshi Yasuda, Toshiro Fujita
Journal: Journal of Clinical Investigation (2001)

The Helicobacter pylori-produced cytotoxin VacA induces intracellular vacuolation. To elucidate the molecular mechanism of vacuole formation by VacA, we examined the participation of dynamin, a GTPase functioning in intracellular vesicle formation, in human HeLa cells. Immunocytochemistry revealed that endogenous dynamin was localized to vacuoles induced by VacA. In cells transiently transfected with a GTPase-defective (dominant-negative) dynamin mutant, VacA failed to induce vacuolation. In contrast, VacA did induce vacuolation in cells transiently transfected with wild-type dynamin. Furthermore, under VacA treatment, neutral red dye uptake, a parameter of VacA-induced vacuolation, was inhibited in cells stably transfected with the dominant-negative dynamin mutant. In contrast, uptake was markedly enhanced in cells stably transfected with wild-type dynamin. Moreover, VacA cytopathic effects on the viability of HeLa cells were inhibited in cells stably transfected with dominant-negative dynamin-1. Sequential immunocytochemical observation confirmed that expression of dominant-negative dynamin did not affect VacA attachment to or internalization into HeLa cells. We suggest that dynamin is involved in the intracellular vacuolation induced by VacA.
Association Between Cardiorespiratory Fitness and the Determinants of Glycemic Control Across the Entire Glucose Tolerance Continuum
Authors: Thomas P.J. Solomon, Steven K. Malin, Kristian Karstoft, Sine H. Knudsen, Jacob M. Haus, Matthew J. Laye, John P. Kirwan
Journal: Diabetes Care (2015)

OBJECTIVE Cardiorespiratory fitness (VO2max) is associated with glycemic control, yet the relationship between VO2max and the underlying determinants of glycemic control is less clear. Our aim was to determine whether VO2max is associated with insulin sensitivity, insulin secretion, and the disposition index, a measure of compensatory pancreatic β-cell insulin secretion relative to insulin sensitivity, in subjects representing the entire range of the glucose tolerance continuum. RESEARCH DESIGN AND METHODS A cohort of subjects (N = 313) with heterogeneous age, sex, BMI, and glycemic control underwent measurements of body composition, HbA1c, fasting glucose, oral glucose tolerance (OGTT), and VO2max. OGTT-derived insulin sensitivity (SiOGTT), glucose-stimulated insulin secretion (GSISOGTT), and the disposition index (DIOGTT) (the product of SiOGTT and GSISOGTT) were measured, and associations between VO2max and these determinants of glycemic control were examined. RESULTS A low VO2max was associated with high HbA1c (r = −0.33), high fasting glucose (r = −0.34), high 2-h OGTT glucose (r = −0.33), low SiOGTT (r = 0.73), and high early-phase (r = −0.34) and late-phase (r = −0.36) GSISOGTT. Furthermore, a low VO2max was associated with low early- and late-phase DIOGTT (both r = 0.41). Interestingly, relationships between VO2max and either glycemic control or late-phase GSISOGTT deteriorated across the glucose tolerance continuum. CONCLUSIONS The association between poor cardiorespiratory fitness and compromised pancreatic β-cell compensation across the entire glucose tolerance continuum provides additional evidence highlighting the importance of fitness in protection against the onset of a fundamental pathophysiological event that leads to type 2 diabetes.
Specific Expression of Cytokine Receptor-like Factor-1 and IL-27p28 in Fibroblast-Like Synoviocytes: Potential Feedback Loops to Modulate the Inflammatory Axis in Arthritis
Authors: M. Goldberg, O. Nadiv, N. Kovalchuk, G. Agar, Y. Beer, Y. Katz
Journal: Journal of Allergy and Clinical Immunology (2012)
"Photopenic" Bone Lesion Secondary to Erector Spinae Muscle Infiltration by Breast Carcinoma
Authors: ALBERTO M. EIBER, STEPHEN N. WIENER
Journal: Clinical Nuclear Medicine (1986)

A bone image demonstrating a “photopenic” vertebral lesion was found to be caused by tumor infiltration of adjacent muscle and probable secondary osseous ischemia. Magnetic resonance imaging was valuable in detecting the muscle abnormality.
Comment: Radiosensitization and the Selective Effect
Authors: Philip Rubin
Journal: JAMA (1971)

The ideal in the treatment of malignant disease is achieved when the cancer is completely eradicated and the surrounding normal tissue shows no evidence of structural or functional injury. In clinical practice, this ideal selective effect is seldom achieved; a certain degree of residual damage must be accepted as a sequel to the destruction of a lethal tumor. The extent of alterations of normal tissues that is acceptable varies in different anatomic settings, but the integrity of the vital structures must be maintained. This ideal has been described as the "selective effect" when it is applied to radiation therapy. One of the major frontiers of radiation biologic research is to make irradiation more selective. The term, "radiosensitization" has been used to describe the modification of the radiation response by agents; it broadly includes mechanisms of enhancement, such as additivity, synergism, or time dose modification. No specific radiation effect that is
Active Enforcement of Cigarette Control Laws in the Prevention of Cigarette Sales to Minors
Authors: Leonard A. Jason
Journal: JAMA (1991)

<h3>Objective.</h3> —To assess the effect that cigarette legislation would have on reducing merchant sales rates of cigarettes to minors and the affect on adolescent smoking behavior. <h3>Design.</h3> —Observational survey of merchant selling behaviors and adolescent smoking habits before and after passage of legislation. <h3>Setting.</h3> —The setting for the merchant survey was Woodridge, Ill (population 25 200), a suburban community of Chicago. The surveys were distributed to adolescents in the local junior high school. <h3>Participants.</h3> —Convenience sample of both merchants and adolescent students. <h3>Intervention.</h3> —Passage of community antismoking legislation. <h3>Main Outcome Measures.</h3> —Percentage of stores selling cigarettes to minors in Woodridge and percentage of students who had experimented with cigarettes or were regular smokers. <h3>Results.</h3> —Merchant sales rates in Woodridge decreased from a baseline of 70% before legislation to less than 5% in 1.5 years of compliance checking after legislation. Student surveys showed that the rates of cigarette experimentation and regular use of cigarettes by adolescents were reduced by over 50%. <h3>Conclusion.</h3> —Cigarette control laws can be effective in significantly reducing the rate of cigarettes sold by merchants and rates of cigarette use by adolescents. Key elements of successful legislation implementation are consistent compliance checking and heightened community awareness of the problems and prevalence of adolescent smoking. (<i>JAMA</i>. 1991;266:3159-3161)
Increased expression of granzymes A and B in fatal asthma
Authors: Raquel Annoni, Luiz Fernando F. Silva, Yvonne Nussbaumer-Ochsner, Annemarie van Schadewijk, Thais Mauad, Pieter S. Hiemstra, Klaus F. Rabe
Journal: European Respiratory Journal (2015)

Inflammatory mediators other than the classic T-helper cell type 2 (Th2)-related pathway play a role in asthma, especially in severe asthma and in exacerbations [1]. Recent studies have suggested a role for cytotoxic CD8 T-cells in lung function impairment [2], lung function decline [3] and smoking-associated asthma [4]. Increased numbers of GzmA+ and GzmB+ cells in the airways and lung parenchyma of subjects who died from asthma <http://ow.ly/IcKV7> We would like to thank G.M. Möller (Ziekenhuis Rivierenland Tiel, The Netherlands) for helpful suggestions during the study.
An Angiocardiographic Sign of Aortic Regurgitation
Authors: RENE A. ARCILLA, MAGNUS H. AGUSTSSON, ZWI STEIGER, BENJAMIN M. GASUL
Journal: Circulation (1961)

A technic of performing retrograde aortography for the study of aortic insufficiency is presented. The aortograms demonstrate the abnormal expansile movements of the aorta, and the to-and-fro motion of the opacified vascular column in the proximal portion of the aorta with systole and diastole. These phenomena were not observed in patients without aortic insufficiency. A method for calculating the stroke volume and the volume of regurgitation from these aortograms is presented.
WHAT IS THE PROGNOSTIC ASSOCIATION OF AN ELEVATED BNP AMONG HEART FAILURE PATIENTS AT THE TIME OF IMPLANTABLE CARDIOVERTER DEFIBRILLATOR IMPLANTATION?
Authors: Sanjeev P. Bhavnani, Craig Coleman, Danette Guertin, Anupam Kumar, Christopher Clyne, Jeffrey Kluger
Journal: Journal of the American College of Cardiology (2012)
Interferon-gamma and tumor necrosis factor-alpha specifically induce formation of cytomegalovirus-permissive monocyte-derived macrophages that are refractory to the antiviral activity of these cytokines.
Authors: C Söderberg-Nauclér, K N Fish, J A Nelson
Journal: Journal of Clinical Investigation (1997)

Monocytes/macrophages are key cells in the pathogenesis of human cytomegalovirus (HCMV). Although HCMV infection in monocytes is restricted to early events of gene expression, productive infection has been demonstrated in differentiated macrophages in vitro. We examined the cellular and cytokine components that are essential for HCMV replication in Concanavalin A-stimulated monocyte-derived macrophages (MDM). By negative selection, depletion of CD8+ T lymphocytes, but not CD4+ T lymphocytes, CD19+ B cells, or CD56+ NK cells, resulted in a 60-70% reduction in the number of HCMV-infected MDM, and a 4 log decrease in virus production. Neutralization of IFN-gamma and TNF-alpha, but not IL-1, IL-2, or TGF-beta, decreased production of virus by 4 logs and 2 logs, respectively. Subsequently, addition of recombinant IFN-gamma or TNF-alpha to purified monocyte cultures was sufficient to produce HCMV-permissive MDM. While IFN-gamma and TNF-alpha possess antiviral properties, addition of these cytokines to permissive MDM cultures did not affect production of HCMV. Thus, rather than inhibiting replication of HCMV, IFN-gamma and TNF-alpha specifically induce differentiation of monocytes into HCMV-permissive MDM, which are resistant to the antiviral effects of these cytokines.
Mortality Risk of Charcot Arthropathy Compared With That of Diabetic Foot Ulcer and Diabetes Alone
Authors: Min-Woong Sohn, Todd A. Lee, Rodney M. Stuck, Robert G. Frykberg, Elly Budiman-Mak
Journal: Diabetes Care (2009)

OBJECTIVE The purpose of this study was to compare mortality risks of patients with Charcot arthropathy with those of patients with diabetic foot ulcer and those of patients with diabetes alone (no ulcer or Charcot arthropathy). RESEARCH DESIGN AND METHODS A retrospective cohort of 1,050 patients with incident Charcot arthropathy in 2003 in a large health care system was compared with patients with foot ulcer and those with diabetes alone. Mortality was determined during a 5-year follow-up period. Patients with Charcot arthropathy were matched to individuals in the other two groups using propensity score matching based on patient age, sex, race, marital status, diabetes duration, and diabetes control. RESULTS During follow-up, 28.0% of the sample died; 18.8% with diabetes alone and 37.0% with foot ulcer died compared with 28.3% with Charcot arthropathy. Multivariable Cox regression shows that, compared with Charcot arthropathy, foot ulcer was associated with 35% higher mortality risk (hazard ratio 1.35 [95% CI 1.18–1.54]) and diabetes alone with 23% lower risk (0.77 [0.66–0.90]). Of the patients with Charcot arthropathy, 63% experienced foot ulceration before or after the onset of the Charcot arthropathy. Stratified analyses suggest that Charcot arthropathy is associated with a significantly increased mortality risk independent of foot ulcer and other comorbidities. CONCLUSIONS Charcot arthropathy was significantly associated with higher mortality risk than diabetes alone and with lower risk than foot ulcer. Patients with foot ulcers tended to have a higher prevalence of peripheral vascular disease and macrovascular diseases than patients with Charcot arthropathy. This finding may explain the difference in mortality risks between the two groups.
Cardiomyopathy due to Chronic Tachycardias
Authors: Larry E. Alves
Journal: JAMA (1985)

To the Editor.—  The recent article by Gillette et al 1 regarding chronic supraventricular tachycardia as a curable cause of congestive cardiomyopathy reminded us of a similar case that we treated in 1974.  Report of a Case.—  A 13-year-old girl originally presented with sustained, asymptomatic, narrow-complex, atrial tachycardia. She was treated with quinidine, 200 mg every six hours. This resulted in intermittent control of her tachycardia. When she experienced a sinus rhythm she was found to have a Wolff-Parkinson-White type B syndrome. Propranolol hydrochloride, in increasing dosages up to 40 mg every six hours, resulted in control of her arrhythmia. However, the patient subsequently developed left ventricular dilatation. She was hospitalized on Jan 28, 1975. Propranolol treatment was discontinued, and digoxin and diuretics were added to her therapeutic regimen. The quinidine dosage was increased to 200 mg every four hours to control her supraventricular tachycardia. A cardiac catheterization revealed a
Do patients cash prescriptions?
Authors: J A Winter
Journal: BMJ (1982)

and no case has yet manifested pelvic wall or suture-line disease.None of these cases has received either cytotoxic or radiotherapeutic adjuvant therapy.Our figures suggest that all but a minority of rectal cancers may be controlled locally by refinement of surgical technique.If this is so we might most profitably direct the adjuvant treatments towards the abortion of hepatic micrometastases in the manner which has been advocated by Taylor and others.2It is surely desirable that we should approach this slow-growing and often localised disease in a stepwise manner and evaluate each modality in turn.In particular trials of adjuvant therapy are unlikely to bear fruit until the surgical technique has been standardised so that we may compare like with like.
The role of secretin in the inhibition of gastric secretion by intraduodenal acid
Authors: A. S. Ward, S. R. Bloom
Journal: Gut (1974)

The effect of intraduodenal acid on pentagastrin-stimulated gastric secretion has been investigated in 12 normal subjects and 23 patients with chronic duodenal ulceration. Plasma secretin levels were monitored during each test using a highly sensitive radioimmunoassay. Significant inhibition of gastric secretion occurred in the normal subjects and duodenal ulcer patients. A significant rise in plasma secretin was observed in both groups after intraduodenal acid though there was a complete lack of correlation between the magnitude of the secretin response and the degree of gastric inhibition. Ten subjects received intraduodenal acid and a subsequent intravenous infusion of exogenous secretin (0·125-0·25 units/kg over six minutes). Gastric inhibition occurred after the acid instillation but not after secretin infusion despite plasma secretin levels greatly in excess of those produced by intraduodenal acid. These results suggest that release of secretin by itself cannot explain the gastric inhibitory response to intraduodenal acid in man.
Results of a two-year health education campaign on dietary behavior. The Stanford Three Community Study.
Authors: M P Stern, J W Farquhar, N McCoby, S H Russell
Journal: Circulation (1976)

A two-year, bilingual mass-media health education campaign was carried out in two communities with a third serving as control. In one of the two treated communities, personal couseling of high risk individuals ("intensive instruction") took place. Dietary behavior, before and after the campaigns, was assessed using a dietary questionnaire which estimated the average daily consumption by participants of cholesterol, saturated fat, and polyunsaturated fat. Both intensive instruction and the mass-media campaigns led to significant reductions (20-40%) in cholesterol and saturated fat consumption in both men and women, with intensively instructed men tending to outperform men exposed to mass-media alone. In general, the improvements in the treated communities were maintained over the two years of the study, whereas the initial small drops in the control community at the end of the first year were followed by recidivism during the second year. Polyunsaturated fat consumption fell slightly in all three communities so that increases in P/S ratios in the two treated communities were of only modest degree. Mean changes in plasma cholesterol concentration for the various cohorts under study were higly correlated with those which would have been predicted on the basis of the self-reported changes in dietary behavior. The results indicate that mass-media health education campaigns can lead to significant changes in dietary practices in the general population with potentially important public health implications.
Laryngology's Hundred-Year-Old Debt to Grand Opera
Authors: T. H. Ingalls, S. M. Hemming
Journal: New England Journal of Medicine (1955)

ON March 22, 1855, the secretary of the Royal Society of London received a communication from Manuel Garcia,1 a singing teacher, entitled "Observations on the Human Voice." The writer had observed the functioning of the larynx during the act of singing and was recording the very simple "method which I have adopted... It consists in placing a little mirror, fixed on a long handle suitably bent, in the throat of the person experimented on against the soft palate and uvula. The party ought to turn himself towards the sun so that the luminous rays falling on the little mirror may . . .
The health impacts of cold homes and fuel poverty
Authors: K. B. G. Dear, A. J. McMichael
Journal: BMJ (2011)

Three reasons to act: the health burden, inequity, and mitigation

On 12 May Michael Marmot and his team published their report, “The heath impacts of cold homes and fuel poverty,” commissioned by Friends of the Earth.1 The report highlights an obvious, well known, and largely ignored fact—that cold homes waste energy and harm their occupants—and identifies an opportunity for simultaneous gains on three fronts. By improving the thermal efficiency of British homes the government would reduce carbon dioxide (“greenhouse”) emissions, avoid a major burden of ill health, and reduce health inequity, which—as the report shows—maps closely with social and economic disadvantage. The report delivers three messages. Firstly, improving the energy efficiency of the housing stock—to spread “affordable warmth”—would bring multiple health gains, directly and through improved home finances. Secondly, fuel poverty as a result of poor housing stock causes avoidable health inequality and is unjust. Thirdly, reduced fuel use would bring environmental gains, in the short term through reduced air pollution and in the longer term in helping to mitigate climate change.

The same is true of Australia, which is perhaps often envied by inhabitants of northern Europe as a land of sand, sunshine, and seasonal tropical monsoons that bring welcome warm rains …
Thirteen cases of pyruvate kinase deficiency found in Japan
Authors: Yoji Ishida, Shiro Miwa, Hisaichi Fujii, Noboru Fujinami, Susumu Takegawa, Kunio Yamato
Journal: American Journal of Hematology (1981)

Abstract Thirteen cases of pyruvate kinase (PK) deficiency, considered to be heterozygous for different PK mutants because of no consanguinities in their parents, were characterized by the International Committee for Standardization in Haematology (ICSH) recommended methods. These deficiency cases are named PK “Kagoshima,” PK “Kyoto,” PK “Takamatsu,” PK “Abeno,” PK “Kobe,” PK “Marugame,” PK “Hoenzaka,” PK “Osaka,” PK “Motomachi,” PK “Gifu,” PK “Hiroshima” PK “Matsumoto,” and PK “Tama.” The characteristics of mutant PK enzymes suggest that the cause of chronic hemolysis depends mainly on decreased affinity for phosphoenolpyruvate, thermolability, increased inhibition by adenosine triphosphate, and low activation by fructose‐1, 6‐diphosphate.
Genomic Profiling Reveals Alternative Genetic Pathways of Prostate Tumorigenesis
Authors: Jacques Lapointe, Chunde Li, Craig P. Giacomini, Keyan Salari, Stephanie Huang, Pei Wang, Michelle Ferrari, Tina Hernandez-Boussard, James D. Brooks, Jonathan R. Pollack
Journal: Cancer Research (2007)

Abstract Prostate cancer is clinically heterogeneous, ranging from indolent to lethal disease. Expression profiling previously defined three subtypes of prostate cancer, one (subtype-1) linked to clinically favorable behavior, and the others (subtypes-2 and -3) linked with a more aggressive form of the disease. To explore disease heterogeneity at the genomic level, we carried out array-based comparative genomic hybridization (array CGH) on 64 prostate tumor specimens, including 55 primary tumors and 9 pelvic lymph node metastases. Unsupervised cluster analysis of DNA copy number alterations (CNA) identified recurrent aberrations, including a 6q15-deletion group associated with subtype-1 gene expression patterns and decreased tumor recurrence. Supervised analysis further disclosed distinct patterns of CNA among gene-expression subtypes, where subtype-1 tumors exhibited characteristic deletions at 5q21 and 6q15, and subtype-2 cases harbored deletions at 8p21 (NKX3-1) and 21q22 (resulting in TMPRSS2-ERG fusion). Lymph node metastases, predominantly subtype-3, displayed overall higher frequencies of CNA, and in particular gains at 8q24 (MYC) and 16p13, and loss at 10q23 (PTEN) and 16q23. Our findings reveal that prostate cancers develop via a limited number of alternative preferred genetic pathways. The resultant molecular genetic subtypes provide a new framework for investigating prostate cancer biology and explain in part the clinical heterogeneity of the disease. [Cancer Res 2007;67(18):8504–10]