tbuckley/cabot-search huggingface dataset:
Prolactin-Secreting Pituitary Tumors in Amenorrheic Women: A Comprehensive Study*
Authors: JANET SCHLECHTE, BARRY SHERMAN, NICHOLAS HALMI, JOHN VanGILDER, FREDERICK CHAPLER, KENNETH DOLAN, DARYL GRANNER, THERESA DUELLO, CURTIS HARRIS
Journal: Endocrine Reviews (1980)

DURING the past decade, advances in diagnostic methods have changed the amenorrhea-galactorrhea syndrome from a relative medical curiosity to a well recognized and frequently diagnosed disorder. Before the availability of a radioimmunoassay for prolactin (PRL) and sophisticated radiographic methods, patients with amenorrhea-galactorrhea were characterized by eponymic designations. The spectrum of patients now recognized as having hyperprolactinemia and PRL-secreting tumors includes postpartum amenorrhea-galactorrhea described by Chiari et al. (1) and Frommel (2), spontaneous amenorrhea-galactorrhea described by Argonz and del Castillo (3), and the amenorrhea-galactorrhea syndrome with evidence of a pituitary tumor on conventional skull x-rays described by Forbes et al. (4). The refinement of the transsphenoidal surgical approach to exploration of the sella turcica and the knowledge that amenorrheagalactorrhea and infertility can be reversed by selective surgical excision of a pituitary tumor has created n...
Correlating mind and body
Authors: T. J. Lioyd-Jones, N. Donnelly, B. Weekes
Journal: Behavioral and Brain Sciences (1995)

Abstract Gray's integration of the different levels of description and explanation in his theory is problematic: (1) The introduction of consciousness into his theorising consists of the mind-brain identity assumption, which tells us nothing new. (2) There need not be correlations between levels of description. (3) Gray's account does not extend beyond “brute” correlation. Integration must be achieved in a principled, mutually constraining way.
Abstract 5032: MK8745, an Aurora A kinase-specific inhibitor induces apoptosis in a p53-dependent manner
Authors: Jayasree S. Nair, Gary K. Schwartz
Journal: Cancer Research (2010)

Abstract Aurora kinases are mitotic serine/threonine protein kinases and are attractive novel targets for anticancer therapy. Many small molecule inhibitors are being developed and few are currently undergoing clinical trials. Aurora A kinase is essential for the successful mitotic transition. MK8745 is a novel and selective small molecule inhibitor of Aurora A kinase. Treatment of tumor cells with MK8745 (1 to 5 µM) resulted in accumulation of cells in mitosis with an increase in Aurora A expression. Despite this increase in Aurora A in the cells, dose dependent inhibition of Aurora A kinase activity was confirmed by an in vitro kinase assay using a PLK1, a specific substrate of Aurora A kinase. Also, treatment of HCT116 (p53−/−) cells ectopically overexpressing wild type p53 with MK8745 showed a decrease in phospho p53 (ser315), another known substrate of Aurora A. We then explored the mechanism by which MK8745 induces proliferation inhibition in cell lines of multiple lineages such as colon, melanoma, sarcoma and pancreatic according to p53 status. In general, the cell lines expressing wild type p53 showed a short delay in mitosis followed by cytokinesis with significant apoptosis (15%) upon exposure to MK8745. However, cell lines with null or mutant p53 underwent endoreduplication resulting in 60% polyploidy after a prolonged delay in mitosis with no apoptosis. This was further confirmed in the isogenic HCT-116 cell lines such that HCT p53−/− cells underwent polyploidy, whereas HCT p53 +/+ and the HCT p21 −/− cells underwent apoptosis. Under all of these conditions phospho histone H3 (Ser10) was not inhibited, indicating these phenotypic effects are a result of Aurora A inhibition and not Aurora B. P53 dependence for apoptosis was also confirmed in p53 null cells overexpressing wild type p53. Transient knock down of Aurora A kinase by specific SiRNA resulted in high levels of apoptosis and again showed p53 dependence. These results suggest that determining the p53 status may be important when using Aurora A kinase targeted therapies in the clinic. Further studies are underway to determine the role of p53 in the induction of apoptosis that results from inhibition of Aurora A kinase. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5032.
The genetics of physical fitness
Authors: Craig Sharp
Journal: British Journal of Sports Medicine (2000)

Bone density in elderly womenEDITOR,-In the article by Rhodes et al 1 "EVects of one year of resistance training on the relation between muscular strength and bone density in elderly women", I was surprised to see no mention of HRT status in the women in the trial.Given the relatively small number of women taking part, surely this is quite an important variable?
Diuretic treatment in decompensated cirrhosis and congestive heart failure: effect of posture.
Authors: H Ring-Larsen, J H Henriksen, C Wilken, J Clausen, H Pals, N J Christensen
Journal: BMJ (1986)

The diuretic effect of the supine position was evaluated in six patients with cirrhosis and ascites and six with congestive cardiac failure. After fasting overnight in bed the patients received bumetanide 1 mg intravenously and were then immediately randomly assigned to either bed rest in the supine position or normal daily activity in the upright position for the next six hours. Two days later the procedure was repeated, the patients being assigned to the other posture. The diuretic response was similar in patients with heart failure and cirrhosis, and was significantly greater in the supine than in the upright position: mean 1133 v 626 ml/6 h (p less than 0.01). The natriuresis was similarly larger during recumbency: mean sodium 96 v 45 mmol(mEq)/6h (p less than 0.01), and the excreted potassium in six hours was similar in both postures. The glomerular filtration rate was 100 and 66 ml/min (p less than 0.01) and heart rate 76 and 83 beats/min (p less than 0.01) in the supine and upright positions respectively. Plasma concentrations of noradrenaline, renin, and aldosterone were all raised even when the patient adopted the supine position, and a further significant rise was observed during the upright position. The results suggest that the attenuated response to intravenous bumetanide in the upright position and during normal daily activity may be due to the activation of several homeostatic mechanisms that may reduce the excretion of water and salt.
Diurnal, Seasonal, and Blood-Processing Patterns in Levels of Circulating Fibrinogen, Fibrin D-Dimer, C-Reactive Protein, Tissue Plasminogen Activator, and von Willebrand Factor in a 45-Year-Old Population
Authors: Alicja R. Rudnicka, Ann Rumley, Gordon D.O. Lowe, David P. Strachan
Journal: Circulation (2007)

Background— Circulating levels of fibrinogen, fibrin D-dimer, C-reactive protein (CRP), tissue plasminogen activator antigen (t-PA) and von Willebrand factor are associated with incident coronary heart disease. We describe cross-sectional diurnal, seasonal, and blood-processing patterns for these variables, and assess whether they represent important sources of variability that should be taken into account in epidemiological studies or for additional risk prediction in individuals. Methods and Results— A total of 9377 men and women aged 45 years were visited in their homes and blood-sampled for fibrinogen, D-dimer, CRP, t-PA, and von Willebrand factor. These variables were examined in relation to the time of blood sample collection, day of the year, and delay in processing. All variables exhibited statistically significant diurnal sinusoidality ( P ≤0.02). Our models predicted a peak rise for fibrinogen and von Willebrand factor at midday, with overall diurnal variations of 3% and 10%, respectively, after adjustment for standard cardiovascular risk factors. D-dimer exhibited a peak at 14:00 hours, CRP at 15:00 hours, and t-PA at 10:00 hours with diurnal variations of 10%, 34%, and 55%, respectively, after full adjustment. All variables except CRP showed seasonal heterogeneity. Greater delays in processing blood samples were associated with higher levels of t-PA in particular. The proportion of variation attributed to the diurnal, seasonal, and processing effects was 2% for fibrinogen and von Willebrand factor; 9% for D-dimer, 1% for CRP, and 16% for t-PA. Conclusions— Temporal variations are important sources of heterogeneity that may bias the analysis of epidemiological studies and coronary heart disease risk prediction in individuals. Sample-processing delay is particularly important for t-PA.
Limitations of thallium-201 myocardial perfusion scintigrams.
Authors: T M Mueller, M L Marcus, J C Ehrhardt, T Chaudhuri, F M Abboud
Journal: Circulation (1976)

The reliability of myocardial perfusion scintigrams with thallium-201 (201Tl) for detecting areas of hypoperfusion was assessed in 16 closed-chest dogs. Variable areas of ischemia were produced either by occluding or stenosing the left anterior descending coronary artery. Cardiac scintigrams taken in four projections were compared with regional myocardial perfusion maps. Segmental concentrations and segmental perfusions were quantitated by counting the emissions from 201Tl and the microspheres in each of 96 segments of the left ventricle. In addition, studies with a phantom were performed. The results indicate: 1) The emissions from 201Tl and from microspheres correlated well in ischemic segments (r = 0.93 +/- SE 0.02). 2) Seven of twelve ischemic hearts had definitely abnormal scintigrams and in each of these the hypoperfused zone was greater than 4.9 grams and perfusion was decreased by more than 45%. 3) In the phantom, abnormal scintigrams could be detected in the presence of lesser deficits than in the dogs. The limitation of the thallium perfusion scintigrams will be the inconsistent detection of small perfusion deficits.
Bone Mineral Density Changes in Relation to Environmental PCB Exposure
Authors: Susan Hodgson, Laura Thomas, Elena Fattore, P. Monica Lind, Tobias Alfven, Lennart Hellström, Helen Håkansson, Grazia Carubelli, Roberto Fanelli, Lars Jarup
Journal: Environmental Health Perspectives (2008)

Bone toxicity has been linked to organochlorine exposure following a few notable poisoning incidents, but epidemiologic studies in populations with environmental organochlorine exposure have yielded inconsistent results.The aim of this study was to investigate whether organochlorine exposure was associated with bone mineral density (BMD) in a population 60-81 years of age (154 males, 167 females) living near the Baltic coast, close to a river contaminated by polychlorinated biphenyls (PCBs).We measured forearm BMD in participants using dual energy X-ray absorptiometry; and we assessed low BMD using age- and sex-standardized Z-scores. We analyzed blood samples for five dioxin-like PCBs, the three most abundant non-dioxin-like PCBs, and p,p'-dichloro-phenyldichloroethylene (p,p'-DDE).In males, dioxin-like chlorobiphenyl (CB)-118 was negatively associated with BMD; the odds ratio for low BMD (Z-score less than -1) was 1.06 (95% confidence interval, 1.01-1.12) per 10 pg/mL CB-118. The sum of the three most abundant non-dioxin-like PCBs was positively associated with BMD, but not with a decreased risk of low BMD. In females, CB-118 was positively associated with BMD, but this congener did not influence the risk of low BMD in women.Environmental organochlorine exposures experienced by this population sample since the 1930s in Sweden may have been sufficient to result in sex-specific changes in BMD.
URINARY ALBUMIN-CREATININE RATIO IS RELATED WITH AUGMENTATION INDEX IN PATIENTS WITH UNCOMPLICATED ESSENTIAL HYPERTENSION
Authors: Kyu-Hyung Ryu, Seongwoo Han, Dong Ju Choi, Eung Ju Kim, Sang Ho Cho, Min Gyu Kim, Joong Hwa Chung, Sang Yeob Yim
Journal: Journal of the American College of Cardiology (2011)
Treatment with insulin pumps is no better than intensive conventional treatment
Authors: J. Barbosa
Journal: BMJ (1984)

become more important-thus explaining the common finding of young patients with acute myocardial infarction without any measurable risk factors.With the failure of multiple risk factor intervention in those at moderate risk,3 there is little immediate alternative but to focus particularly on those found to be at high risk.The yield is now partly identifiable and the motivation of physicians and in- dividuals is high.5 6 M F
Triiodothyronine enhances renal response to aldosterone in the rabbit collecting tubule.
Authors: C Barlet, A Doucet
Journal: Journal of Clinical Investigation (1987)

Since thyroid hormones and mineralocorticoids were observed to stimulate kidney Na-K-ATPase in similar sites and with similar time courses, this study was initiated to evaluate whether aldosterone is involved in the stimulation of Na-K-ATPase observed in collecting tubules 3 h after triiodothyronine (T3) administration to thyroidectomized (TX) rabbits. Results indicate that: Plasma aldosterone level decreased markedly in TX rabbits but was not restored 3 h after T3 injection; Early stimulation of Na-K-ATPase by T3 was abolished when plasma aldosterone level was suppressed by adrenalectomy or when aldosterone effects were blocked by spironolactone; Administration of aldosterone to TX rabbits mimicked the action of T3; Sensitivity of Na-K-ATPase to aldosterone markedly decreased after thyroidectomy. These results demonstrate an interaction between aldosterone and T3 in the control of Na-K-ATPase in the collecting tubule. Triiodothyronine enhances the sensitivity of Na-K-ATPase to aldosterone which, in turn, produces a stimulatory action despite the decreased plasma level observed during hypothyroidism.
Arkansas bans selling of clean urine to beat drug testing
Authors: D. Josefson
Journal: BMJ (2003)

The state of Arkansas has passed a bill that bans the sale of urine. Representative Jay Martin lobbied for and won passage of a bill to make it illegal to sell or use “clean urine” in order to pass a drug or alcohol test.

People found guilty of trafficking in urine are subject to three months' imprisonment and a fine of up to $500 (£300; €470).

Urine tests …
Efficacy of antiarrhythmic drugs in patients with arrhythmogenic right ventricular disease. Results in patients with inducible and noninducible ventricular tachycardia.
Authors: T Wichter, M Borggrefe, W Haverkamp, X Chen, G Breithardt
Journal: Circulation (1992)

Ventricular tachyarrhythmias are the major clinical manifestation of arrhythmogenic right ventricular disease. Although antiarrhythmic therapy has been widely advocated, there is only limited information available on the efficacy of antiarrhythmic drugs in these patients.The short- and long-term efficacies of various antiarrhythmic agents were retrospectively and prospectively analyzed in 81 patients (mean age, 39 +/- 14 years; range, 16-68 years; 61.7% males) with arrhythmogenic right ventricular disease. In 42 patients with inducible ventricular tachycardia during programmed ventricular stimulation, the following efficacy rates were obtained: class Ia and Ib drugs (n = 18), 5.6%; class Ic drugs (n = 25), 12%; beta-blockers (n = 8), 0%; sotalol (n = 38), 68.4%; amiodarone (n = 13), 15.4%; verapamil (n = 5), 0%; and drug combinations (n = 26), 15.4%. Only one of the 10 patients not responding to sotalol was treated effectively by amiodarone, whereas the remaining nine patients proved to be drug refractory toward all other drugs tested (3.8 +/- 2.3 drugs, including amiodarone in five cases) and underwent nonpharmacological therapy. During a follow-up of 34 +/- 25 months, three of the 31 patients (9.7%) discharged on pharmacological therapy had nonfatal recurrences of ventricular tachycardia after 0.5, 51, and 63 months, respectively. In 39 patients with noninducible ventricular tachycardia during programmed ventricular stimulation, the following efficacy rates were observed: class Ia and Ib drugs (n = 16), 0%; class Ic agents (n = 23), 17.4%; beta-blockers (n = 7), 28.6%; sotalol (n = 35), 82.8%; amiodarone (n = 4), 25%; verapamil (n = 24), 50%; and drug combinations (n = 11), 9.1%. During a follow-up of 14 +/- 13 months, four of 33 patients (12.1%) discharged on antiarrhythmic drugs had nonfatal relapses of their clinical ventricular arrhythmia.Thus, in arrhythmogenic right ventricular disease, sotalol proved to be highly effective in patients with inducible as well as noninducible ventricular tachycardia. Patients with inducible ventricular tachycardia not responding to sotalol are likely to not respond to other antiarrhythmic drugs and should be considered for nonpharmacological therapy without further drug testing. Amiodarone did not prove to be more effective than sotalol and may not be an alternative because of frequent side effects during long-term therapy, especially in young patients. Verapamil and beta-blockers were effective in a considerable number of patients with noninducible ventricular tachycardia and may be a therapeutic alternative in this subgroup. Class I agents appear to be rarely effective in the treatment of both inducible and noninducible ventricular tachycardia in arrhythmogenic right ventricular disease.
AN ANTIVIRAL SUBSTANCE FROM PENICILLIUM FUNICULOSUM
Authors: Richard E. Shope
Journal: The Journal of Experimental Medicine (1953)

Helenine is moderately stable in solution at refrigerator temperature and can be kept for long periods of time without evident loss of activity if stored frozen at the temperature of solid CO(2). It is filterable through a Seitz pad but not dialyzable. Crude SPS preparations of helenine do not lose activity when dried from the frozen state. Some conditions are described, however, which influence the preservation or inactivation of acetone-precipitated helenine when freeze-dried. Helenine is partially inactivated by exposure for 3 minutes to the temperature of a boiling water bath and is completely inactivated by autoclaving at 15 pounds' pressure for 15 minutes. The data presented suggest that helenine acts, either directly or by triggering some mechanism of the host itself, to destroy virus by a process which renders the latter non-antigenic. This effect may be exerted by action upon the virus itself or by interference with some stage in the developmental cycle of the virus. While the chemical nature of helenine is not known, the presence of a large proportion of polysaccharide in crude active preparations might suggest the possible importance of this class of substance in helenine activity. It is believed that helenine differs from the polysaccharide reported by Horsfall and McCarty and the penicillin impurity reported by Groupé and Rake to be active against certain viruses. It may be related, however, to the antiviral substance recently reported by Powell and his co-workers.
Comparison of Different Methods of Expressing Results of the Aminopyrine Breath Test
Authors: Dale A. Schoeller, Alfred L. Baker, Paul S. Monroe, Patricia S. Krager, John F. Schneider
Journal: Hepatology (1982)

Different methods of expressing the results of the aminopyrine CO2 breath test (ABT) were compared to determine the method that would be most sensitive for evaluating liver function. The patient population included health controls (n = 22); patients with mild (4), moderate (9), and severe (7) alcoholic liver disease; and patients with chronic persistent hepatitis (7), chronic active hepatitis (18), chronic active hepatitis with bridging (18), and chronic active hepatitis with cirrhosis (17). The ABT was performed with 2 micro Ci [14C]aminopyrine or 2 mg per kg [13C]aminopyrine, and the results were expressed as the instantaneous labeled CO2 excretion rates at 30, 60, 90, and 120 min after the dose, the maximum excretion rate, and the 120-min cumulative excretion. The 30-min parameter had the highest sensitivity toward moderate alcoholic hepatitis, severe alcoholic hepatitis, chronic active hepatitis with bridging, and chronic active hepatitis with cirrhosis (96%); however, when the ABT was repeated in six normal controls with 225 ml of orange juice, the 30-min rate was significantly reduced (7.8 +/- 1.3 vs. 5.6 +/- 1.2% dose per hr), and the rate of false-positive test results was increased (0 of 6 vs. 2 of 6) indicating that gastric delay influenced the 30-min parameter. The 60-min excretion rate, maximum rate, and 120-min cumulative excretion were the next most sensitive expressions of the ABT, and were not altered by the small gastric load. Of these three expressions, the 60-min parameter was the most convenient because it required fewer samples and a shorter test period.
Facilitated brain delivery of poly (ethylene glycol)–poly (lactic acid) nanoparticles by microbubble-enhanced unfocused ultrasound
Authors: Lei Yao, Qingxiang Song, Wenkun Bai, Jizhen Zhang, Deyu Miao, Mengyin Jiang, Yu Wang, Zhiyong Shen, Quanyin Hu, Xiao Gu, Meng Huang, Gang Zheng, Xiaoling Gao, Bing Hu, Jun Chen, Hongzhuan Chen
Journal: Biomaterials (2014)
Hypoxia-Inducible Factor-1α Expression Predicts a Poor Response to Primary Chemoendocrine Therapy and Disease-Free Survival in Primary Human Breast Cancer
Authors: Daniele Generali, Alfredo Berruti, Maria P. Brizzi, Leticia Campo, Simone Bonardi, Simon Wigfield, Alessandra Bersiga, Giovanni Allevi, Manuela Milani, Sergio Aguggini, Valeria Gandolfi, Luigi Dogliotti, Alberto Bottini, Adrian L. Harris, Stephen B. Fox
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To investigate the relationship of hypoxia-inducible factor-1α (HIF-1α) tumor expression in predicting the response to epirubicin and disease-free survival (DFS) in patients with breast cancer enrolled in a single institution trial of primary anthracycline and tamoxifen therapy. Experimental Design: The expression of HIF-1α was assessed by immunohistochemistry in 187 patients with T2-4 N0-1 breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin + tamoxifen as primary systemic treatment. All patients postoperatively received four cycles of the four weekly i.v. CMF regimen (cyclophosphamide, methotrexate, and 5-fluorouracil). Patients with estrogen receptor (ER)-positive primary tumors also underwent 5 years of treatment with adjuvant tamoxifen. Carbonic anhydrase IX (CAIX) was also scored as a marker of HIF activity. Results: Overall response to therapy progressively decreased with increasing tumor HIF-1α (P &amp;lt; 0.05), and HIF-1α was an independent predictor of response (P &amp;lt; 0.048). HIF-1α expression was also associated with a significantly shorter DFS (P &amp;lt; 0.02) in all patients and in ER-positive but not in ER-negative patients. Furthermore, CAIX positivity conferred a significantly shorter DFS (P = 0.02) compared with CAIX-negative tumors in patients with HIF-1α-negative tumors. Conclusions: HIF-1α expression in patients with breast cancer is a marker of poor therapy response and outcome, especially in ER-positive patients. The combination of two hypoxia markers has greater utility than assessing just one, and patients with hypoxia markers in their tumors may be suitable for administration of drugs that reduce HIF-1α expression and increase oxygen delivery to the tumor bed before starting neoadjuvant therapies.