tbuckley/cabot-search huggingface dataset:
Potentiated Sympathetic Nervous and Renin-Angiotensin Systems Reduce Nonlinear Correlation Between Sympathetic Activity and Blood Pressure in Conscious Spontaneously Hypertensive Rats
Authors: Katsufumi Sakata, Hiroo Kumagai, Motohisa Osaka, Toshiko Onami, Tomokazu Matsuura, Masaki Imai, Takao Saruta
Journal: Circulation (2002)

Patients with a reduced nonlinear component of heart rate regulation have a poorer outcome.We investigated whether a nonlinear correlation between renal sympathetic nerve activity (RSNA) and blood pressure or renal blood flow is reduced in conscious, spontaneously hypertensive rats (SHR) by comparing them with normotensive Wistar-Kyoto rats (WKY). We also determined the linearity and nonlinearity of the correlation in SHR who were given an angiotensin II receptor blocker, candesartan, orally for 2 weeks. The RSNA value was higher in SHR than in WKY, and coherence peaks of transfer function were found at 0.05 and 0.80 Hz (ie, below respiratory- and cardiac-related fluctuations). The coherence (linearity) of the transfer function was significantly higher and gain was smaller in SHR than in WKY. Because mutual information values (linear and nonlinear correlation) were similar in both strains, we found the nonlinear correlation to be lower in SHR than in WKY. Time delay values calculated by the mutual information method demonstrated that RSNA preceded blood pressure and renal blood flow by 0.5 to 1.0 s. In SHR given candesartan, the RSNA value was lower, and the linearity was lower and nonlinearity higher than SHR given vehicle.Linear correlation between RSNA and blood pressure or renal blood flow was higher in SHR than in WKY, whereas the nonlinear correlation was lower. Oral treatment with candesartan increased the nonlinearity and reduced the linearity in SHR. Increased RSNA and the renin-angiotensin system may be responsible for the lower nonlinearity and higher linearity in hypertension.
Randomized Double-Blind 2 × 2 Trial of Low-Dose Tamoxifen and Fenretinide for Breast Cancer Prevention in High-Risk Premenopausal Women
Authors: Andrea Decensi, Chris Robertson, Aliana Guerrieri-Gonzaga, Davide Serrano, Massimiliano Cazzaniga, Serena Mora, Marcella Gulisano, Harriet Johansson, Viviana Galimberti, Enrico Cassano, Simona M. Moroni, Franca Formelli, Ernst A. Lien, Giuseppe Pelosi, Karen A. Johnson, Bernardo Bonanni
Journal: Journal of Clinical Oncology (2009)

Purpose Tamoxifen and fenretinide are active in reducing premenopausal breast cancer risk and work synergistically in preclinical models. The authors assessed their combination in a two-by-two biomarker trial. Patients and Methods A total of 235 premenopausal women with pT1mic/pT1a breast cancer (n = 21), or intraepithelial neoplasia (IEN, n = 160), or 5-year Gail risk ≥ 1.3% (n = 54) were randomly allocated to either tamoxifen 5 mg/d, fenretinide 200 mg/d, their combination, or placebo. We report data for plasma insulin-like growth factor I (IGF-I), mammographic density, uterine effects, and breast neoplastic events after 5.5 years. Results During the 2-year intervention, tamoxifen significantly lowered IGF-I and mammographic density by 12% and 20%, respectively, fenretinide by 4% and 10% (not significantly), their combination by 20% and 22%, with no evidence for a synergistic interaction. Tamoxifen increased endometrial thickness principally in women becoming postmenopausal, whereas fenretinide decreased endometrial thickness significantly. The annual rate of breast neoplasms (n = 48) was 3.5% ± 1.0%, 2.1% ± 0.8%, 4.7% ± 1.3%, and 5.2% ± 1.3% in the tamoxifen, fenretinide, combination, and placebo arms, respectively, with hazard ratios (HRs) of 0.70 (95% CI, 0.32 to 1.52), 0.38 (95% CI, 0.15 to 0.90), and 0.96 (95% CI, 0.46 to 1.99) relative to placebo (tamoxifen × fenretinide adverse interaction P = .03). There was no clear association with tumor receptor type. Baseline IGF-I and mammographic density did not predict breast neoplastic events, nor did change in mammographic density. Conclusion Despite favorable effects on plasma IGF-I levels and mammographic density, the combination of low-dose tamoxifen plus fenretinide did not reduce breast neoplastic events compared to placebo, whereas both single agents, particularly fenretinide, showed numerical reduction in annual odds of breast neoplasms. Further follow-up is indicated.
Exercise modulation of growth hormone isoforms: current knowledge and future directions for the exercise endocrinologist * Commentary
Authors: B C Nindl
Journal: British Journal of Sports Medicine (2007)

Importance of growth hormone molecular heterogeneity as a partial mechanism for somatogenic adaptations to physical activity

Growth hormone (GH) exhibits a great deal of molecular heterogeneity (there are over 100 isoforms in circulation) and we are only beginning to understand how exercise influences concentrations of GH isoforms.

As the field of exercise endocrinology moves forward in the 21st century, greater recognition will be given to molecular heterogeneity that exists for many protein hormones within the paradigm of exercise and physical activity. Specifically, it is well established, but not well recognised, that GH exhibits a great deal of molecular heterogeneity, as over 100 molecular isoforms are thought to exist in the circulation. The importance of gaining a greater understanding of the exercise-mediated influences on GH molecular heterogeneity resides in the fact that the GH isoforms have diverse downstream metabolic and anabolic actions in target tissues.

The human GH-N gene expresses the main pituitary molecular mass variant in the GH family, which is the 22 kDa form. Monomeric 22 kDa GH is a 191 amino acid sequence and represents ∼21% of all circulating plasma GH. The next most prevalent form is the monomeric 20 kDa molecule, representing ∼6% of all circulating plasma GH, formed through alternative mRNA splicing during which amino acid residues 32–46 are cleaved out. GH can also undergo post-translational modification and peripheral tissue proteolytic cleavage at its site of action to form variants and aggregates (ie, dimers, trimers, pentamers, oligomers) and fragments that exist in the circulation. The existence of high-affinity and low-affinity GH-binding proteins, which are released from the pituitary and/or cleaved from the extracellular domain of the GH receptor, adds further complexity to the nature and spatial arrangement of circulating GH moieties. GH should no longer be regarded as a single hormone, but rather as a …
Polysaccharide pneumococcal vaccination: new evidence
Authors: A J Hall
Journal: Thorax (2006)

Efficacy of anti-pneumococcal vaccination in patients with COPD

The use of polysaccharide pneumococcal vaccination in elderly or high risk populations remains controversial. Evidence from less developed countries is the most persuasive in the absence of HIV, but in more developed countries the nine randomised controlled trials to date are inconclusive. They have now been the subject of some five meta-analyses1–5 and to this can be added a recent meta-analysis of both the randomised controlled trials and observational studies.6 There has even been a review of the meta-analyses!7

The most recent review is helpful because it compares the trials and the observational studies using similar quality criteria and methods of pooling results. The strongest evidence is based on pneumococcal bacteraemia as the end point. Here studies of all types—case-control, cohort and randomised controlled trials—show consistent evidence of around 50% protection. However, it remains unclear whether this represents true protection or a suppression of bacteraemia without affecting the underlying disease (pneumonia). When it comes to pneumonia, the picture is much more confusing—and here we …
Analysis of COQ2gene in multiple system atrophy
Authors: Kotaro Ogaki, Shinsuke Fujioka, Michael G Heckman, Sruti Rayaprolu, Alexandra I Soto-Ortolaza, Catherine Labbé, Ronald L Walton, Oswaldo Lorenzo-Betancor, Xue Wang, Yan Asmann, Rosa Rademakers, Neill Graff-Radford, Ryan Uitti, William P Cheshire, Zbigniew K Wszolek, Dennis W Dickson, Owen A Ross
Journal: Molecular Neurodegeneration (2014)

Loss of function COQ2 mutations results in primary CoQ10 deficiency. Recently, recessive mutations of the COQ2 gene have been identified in two unrelated Japanese families with multiple system atrophy (MSA). It has also been proposed that specific heterozygous variants in the COQ2 gene may confer susceptibility to sporadic MSA. To assess the frequency of COQ2 variants in patients with MSA, we sequenced the entire coding region and investigated all exonic copy number variants of the COQ2 gene in 97 pathologically-confirmed and 58 clinically-diagnosed MSA patients from the United States.We did not find any homozygous or compound heterozygous pathogenic COQ2 mutations including deletion or multiplication within our series of MSA patients. In two patients, we identified two heterozygous COQ2 variants (p.S54W and c.403 + 10G > T) of unknown significance, which were not observed in 360 control subjects. We also identified one heterozygous carrier of a known loss of function p.S146N substitution in a severe MSA-C pathologically-confirmed patient.The COQ2 p.S146N substitution has been previously reported as a pathogenic mutation in primary CoQ10 deficiency (including infantile multisystem disorder) in a recessive manner. This variant is the third primary CoQ10 deficiency mutation observed in an MSA case (p.R387X and p.R197H). Therefore it is possible that in the heterozygous state it may increase susceptibility to MSA. Further studies, including reassessing family history in patients of primary CoQ10 deficiency for the possible occurrence of MSA, are now warranted to resolve the role of COQ2 variation in MSA.
OBSERVATIONS ON PSYCHIATRIC SEQUELAE TO SURGICAL OPERATIONS IN WOMEN
Authors: ERICH LINDEMANN
Journal: American Journal of Psychiatry (1941)

1. Fifty-one women, aged 20 to 55, were given a neuropsychiatric examination before major abdominal surgery, with special reference to anxiety concerning the operation, history of former psychiatric difficulties, marital maladjustment and sources of environmental stress. 2. Forty patients who had no somatic complications and whose convalescences were uneventful, were reexamined after an interval of from twelve to eighteen months. 3. Twenty-five of these patients showed no change in their psychiatric status. Two patients showed relief from former psychiatric complaints. 4. Thirteen patients showed a picture of restlessness, sleeplessness, agitation and pre-occupation with depressive thought content beginning from three to four weeks after the operation and lasting more than three months. 5. The relative frequency of this postoperative condition was much higher in pelvic operations than in cholecystectomies; it occurred more frequently in persons who had had depressive episodes in their former life. 6. The incidence of this condition in our series shows no significant relationship to the presence of preoperative anxiety, to sexual maladjustments or to environmental factors as elicited in the preoperative interview. 7. Reliable predictions as to postoperative psychiatric course will be possible only after more detailed studies.
Food and Drug Interactions
Authors: C J Carr
Journal: The Annual Review of Pharmacology and Toxicology (1982)

A significant contribution could be made to patient care if nutritional biochemists, basic and clinical toxicologists, and pharmacologists in the various fields were to mount the studies needed to understand the nature of food-drug interactions. If only a small fraction of the 120 billion dollars per year spent for food or the 10 billion dollars expended for drugs were allocated for research in this area, advances might be made for the health of the nation. Changes in man's diet produce marked effects on drug metabolism. We know that changing a customary diet to one high in protein and low in carbohydrate increases the rates of metabolism of antipyrine and theophylline, and shifting to an isocaloric diet of low protein-high carbohydrate slows the rates of metabolism of these drugs. Presumably, high-protein-low carbohydrate diets in man resemble the animal studies with high protein diets that show enhanced hepatic drug metabolism. However, numerous studies emphasize the considerable individual variability to changes in human diets; some people have dramatic changes, whereas others exhibit little or no response. Similar individuality has been found in the response to enzyme induction by smoking. Numerous foods and food ingredients affect drug metabolism in human beings and apparently follow the same patterns as found in experimental animal studies with changes in the levels of cytochrome P-450 dependent monooxygenases in the liver and intestine. These changes presumably exert some protective action against environmental carcinogens, cocarcinogens, or promoters. Dietary modifications are brought about by use of weight-reducing diets, vegetarian diets, hospitalization, or post-operative regimens. These diets are often continued for long periods of time and it is likely they result in changes in the metabolism by the body of subsequently administered drugs or exposure to environmental chemicals. Methods are needed to measure inter-individual and inter-group differences in metabolism of foreign compounds in order to accurately assess dietary influences on drug metabolism and vice versa. Epidemiologic studies of rigorously selected human populations, coupled with the newer sensitive chemical analytical methods, will provide the necessary data base for these investigations.
Discordance between Sexual Behavior and Self-Reported Sexual Identity: A Population-Based Survey of New York City Men
Authors: Preeti Pathela, Anjum Hajat, Julia Schillinger, Susan Blank, Randall Sell, Farzad Mostashari
Journal: Annals of Internal Medicine (2006)

Persons reporting sexual identity that is discordant with their sexual behavior may engage in riskier sexual behaviors than those with concordant identity and behavior. The former group could play an important role in the spread of sexually transmitted diseases.To describe discordance between self-described sexual identity and behavior among men who have sex with men and associations between identity-behavior and risk behaviors.Cross-sectional, random digit-dialed telephone survey of health status and risk behaviors.New York City.Population-based sample of 4193 men.Concurrent measures of sexual identity and sexual behaviors, including number and sex of sex partners, condom use during last sexual encounter, and recent testing for HIV infection. Sex partner information was ascertained in a separate section from sexual identity; all participants were asked about the number of male sex partners and then were asked about the number of female sex partners in the past year.Of New York City men reporting a sexual identity, 12% reported sex with other men. Men who had sex with men exclusively but self-identified as heterosexual were more likely than their gay-identified counterparts to belong to minority racial or ethnic groups, be foreign-born, have lower education and income levels, and be married. These men were more likely than gay-identified men who have sex with men to report having only 1 sexual partner in the previous year. However, they were less likely to have been tested for HIV infection during that time (adjusted prevalence ratio, 0.6 [95% CI, 0.4 to 0.9]) and less likely to have used condoms during their last sexual encounter (adjusted prevalence ratio, 0.5 [CI, 0.3 to 1.0]).The survey did not sample groups that cannot be reached by using residential telephone services.Many New York City men who have sex with men do not identify as gay. Medical providers cannot rely on patients' self-reported identities to appropriately assess risk for HIV infection and sexually transmitted diseases; they must inquire about behavior. Public health prevention messages should target risky sexual activities rather than a person's sexual identity.
Endurance exercise and the production of growth hormone and haematopoietic factors in patients with anaemia
Authors: F Dimeo, W Knauf, D Geilhaupt, D Böning
Journal: British Journal of Sports Medicine (2004)

Physical activity has been shown to stimulate haematopoiesis in patients with anaemia due to chronic renal failure or haematological malignancies.To evaluate the effect of moderate exercise on the production of haematopoietically active factors.Ten patients (four men and six women, mean (SD) age 51 (10) years) with a haemoglobin concentration under 130 g/l (men) or 120 g/l (women) carried out five three minute exercise bouts at an intensity of 80% of the maximal heart rate, corresponding to a lactate concentration of 3 (0.5) mmol/l. Patients rested for three minutes between bouts. The concentrations of interleukin 6, stem cell factor, granulocyte-monocyte colony stimulating factor, granulocyte colony stimulating factor, erythropoietin, and growth hormone (GH) were evaluated before and in the eight hours after exercise.GH had risen significantly 15 minutes after exercise (1.1 (1.3) v 2.7 (2.8) ng/ml; p<0.05). No change in the concentration of the other cytokines and growth factors was observed in the eight hours after exercise.In patients with anaemia, submaximal exercise does not affect the concentration of haematopoietically active cytokines. However, it leads to an increased concentration of GH. This may be responsible for the improved haematopoiesis observed after an exercise programme in patients with chronic diseases.
Inhibition of T-antigen-binding cells by idiotypic antisera.
Authors: C A Prange, J Fiedler, D E Nitecki, C J Bellone
Journal: The Journal of Experimental Medicine (1977)

Shared idiotypy between B- and T-cell receptors specific for the antigen L-tyrosine-p-azophenyltrimethylammonium [tyr(TMA)] was studied in an antigen-binding assay using idiotypic antisera. These idiotypic reagents were prepared by inoculation of rabbits with purified anti-tyr(TMA) antibody raised in strain 13 guinea pigs. The antisera blocked 78-83% of the antigen-binding T cells (T-ABC) and 50-55% of the antigen-binding B cells (B-ABC) from tyr(TMA)-immune strain 13 and outbred lymph node cells (LNC). An excess of normal guinea pig Ig in the ABC assay did not affect the ability of the idiotypic antisera to block T- and B-ABC. Nylon wool-passed tyr(TMA)-immune LNC were trypsin treated resulting in a 75% loss of T-ABC. The trypsin-treated population was then cultured for 16 h which resulted in a return of T-ABC to 92% of pretrypsin values. 77% of these regenerated T-ABC could be blocked with idiotypic antisera. Specificity of the idiotypic antisera was tested in L-tyrosine-p-azobenzenearsonate-immune guinea pig LNC. Neither T- nor B-ABC were blocked in this heterologous system. Further blocking experiments were performed to characterize the nature of the T-ABC receptor. A variety of anti-Ig reagents, some of which block B-ABC, do not inhibit T-ABC suggesting that variable regions on T cells are not linked to Ig Constant regions.
Incidence of chemotherapy-induced amenorrhea depending on the timing of treatment by menstrual cycle phase in women with early breast cancer
Authors: S. Di Cosimo, A. Alimonti, G. Ferretti, I. Sperduti, P. Carlini, P. Papaldo, A. Fabi, A. Gelibter, M. Ciccarese, D. Giannarelli, M. Mandalà, M. Milella, E.M. Ruggeri, F. Cognetti
Journal: Annals of Oncology (2004)
CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo
Authors: Robert Passier, Hong Zeng, Norbert Frey, Francisco J. Naya, Rebekka L. Nicol, Timothy A. McKinsey, Paul Overbeek, James A. Richardson, Stephen R. Grant, Eric N. Olson
Journal: Journal of Clinical Investigation (2000)

Hypertrophic growth is an adaptive response of the heart to diverse pathological stimuli and is characterized by cardiomyocyte enlargement, sarcomere assembly, and activation of a fetal program of cardiac gene expression. A variety of Ca2+-dependent signal transduction pathways have been implicated in cardiac hypertrophy, but whether these pathways are independent or interdependent and whether there is specificity among them are unclear. Previously, we showed that activation of the Ca2+/calmodulin-dependent protein phosphatase calcineurin or its target transcription factor NFAT3 was sufficient to evoke myocardial hypertrophy in vivo. Here, we show that activated Ca2+/calmodulin-dependent protein kinases-I and -IV (CaMKI and CaMKIV) also induce hypertrophic responses in cardiomyocytes in vitro and that CaMKIV overexpressing mice develop cardiac hypertrophy with increased left ventricular end-diastolic diameter and decreased fractional shortening. Crossing this transgenic line with mice expressing a constitutively activated form of NFAT3 revealed synergy between these signaling pathways. We further show that CaMKIV activates the transcription factor MEF2 through a posttranslational mechanism in the hypertrophic heart in vivo. Activated calcineurin is a less efficient activator of MEF2-dependent transcription, suggesting that the calcineurin/NFAT and CaMK/MEF2 pathways act in parallel. These findings identify MEF2 as a downstream target for CaMK signaling in the hypertrophic heart and suggest that the CaMK and calcineurin pathways preferentially target different transcription factors to induce cardiac hypertrophy.
Spinal Cord Injury
Authors: Mark A. Young
Journal: JAMA (2005)

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