tbuckley/cabot-search huggingface dataset:
Plasma Folate, Vitamin B6, Vitamin B12, Homocysteine, and Risk of Breast Cancer
Authors: Shumin M Zhang, Walter C Willett, Jacob Selhub, David J Hunter, Edward L Giovannucci, Michelle D Holmes, Graham A Colditz, Susan E Hankinson
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: In several epidemiologic investigations, folate intake has appeared to reduce the elevated risk of breast cancer associated with moderate alcohol consumption. However, data relating plasma folate levels to breast cancer risk are sparse. We investigated the association between plasma folate and other vitamins with breast cancer in a prospective, nested case–control study. Methods: Blood samples were obtained during 1989 and 1990 from 32 826 women in the Nurses' Health Study who were followed through 1996 for the development of breast cancer. We identified 712 breast cancer case patients and selected 712 individually matched control subjects. Dietary information was obtained using food frequency questionnaires given in 1980, 1984, 1986, and 1990. Logistic regression was used to estimate the relative risks (RRs) of breast cancer (after adjustment for potential risk factors), and a generalized linear model was used to calculate the Pearson correlation coefficients between plasma estimates of folate, vitamin B6, vitamin B12, and homocysteine, and intakes of folate, vitamin B6, and vitamin B12. All statistical tests were two-sided. Results: The multivariable RR comparing women in the highest quintile of plasma folate with those in the lowest was 0.73 (95% confidence interval [CI] = 0.50 to 1.07; Ptrend = .06). The inverse association between plasma folate and breast cancer risk was highly statistically significant among women consuming at least 15 g/day (i.e., approximately 1 drink/day) of alcohol (multivariable RR = 0.11, 95% CI = 0.02 to 0.59 for highest versus lowest quintile) in contrast with that of women consuming less than 15 g/day (multivariable RR = 0.72, 95% CI = 0.49 to 1.05). The multivariable RR comparing women in the highest quintile of plasma vitamin B6 levels with those in the lowest quintile was 0.70 (95% CI = 0.48 to 1.02; Ptrend = .09). Plasma vitamin B12 levels were inversely associated with breast cancer risk among premenopausal women (multivariable RR = 0.36, 95% CI = 0.15 to 0.86 for highest versus lowest quintile) but not among postmenopausal women. Plasma homocysteine was not associated with breast cancer risk. Conclusions: Higher plasma levels of folate and possibly vitamin B6 may reduce the risk of developing breast cancer. Achieving adequate circulating levels of folate may be particularly important for women at higher risk of developing breast cancer because of higher alcohol consumption.
Local overflow and enhanced tissue content of endothelin following myocardial ischaemia and reperfusion in the pig: modulation by L-arginine
Authors: Qing-Dong Wang, Anette Hemsén, Xing-San Li, Jan M Lundberg, Yozo Uriuda, John Pernow
Journal: Cardiovascular Research (1995)

The local myocardial overflow and tissue content of endothelin-like immunoreactivity (ET-LI) during ischaemia and reperfusion as well as the coronary vascular effects of endothelin were characterised in anaesthetised pigs.Ischaemia was induced by ligation of the left anterior descending coronary artery for 45 min followed by 4 h of reperfusion. ET-LI was analysed in plasma from the anterior interventricular coronary vein and aorta for estimation of local overflow and in myocardial tissue. Endothelin analogues were given in the coronary artery for determination of local vascular effects.During reperfusion, but not during ischaemia, the veno-arterial concentration difference of ET-LI increased, resulting in a significantly increased overflow at between 10 and 120 min of reperfusion. The tissue concentration of ET-LI in the left ventricle was seven times higher in the ischaemic/reperfused area than in the non-ischaemic area: 161(SEM 30.5) v 25.3(3.8) fmol.g-1, P < 0.05. The increase in myocardial ET-LI was attenuated by 70% (P < 0.01) by coronary venous retroinfusion of the nitric oxide substrate L-arginine, whereas the overflow was unaffected. Chromatographic characterisation of the myocardial ET-LI showed that it was similar to endothelin-1. Intracoronary administration of endothelin-1, endothelin-3, and the endothelin ETB receptor agonist [Ala1,3,11,15]ET-1 evoked dose dependent coronary vasoconstriction, and reductions in left ventricular dP/dt and arterial blood pressure. Endothelin-1 was two times more potent than endothelin-3 and 10 times more potent than [Ala1,3,11,15]ET-1.Myocardial ischaemia/reperfusion evokes enhanced local overflow of ET-LI during the reperfusion period combined with an increased tissue concentration of ET-LI which is is attenuated by L-arginine. Endothelin evokes potent coronary vasoconstriction via activation of both ETA and ETB receptors.
Determinants of intrarenal Doppler indices in stable renal allografts.
Authors: B Krumme, W Grotz, G Kirste, P Schollmeyer, L C Rump
Journal: Journal of the American Society of Nephrology (1997)

Color Doppler sonography has been introduced for graft monitoring after renal transplantation. Little is known, however, about independent factors that have an impact on intrarenal Doppler indices as indicators for transplant dysfunction. Therefore, in this study, potential determinants of the resistive index (RI) and of the pulsatility index (PI) in 110 patients with stable renal allografts were studied. The mean RI and PI were 0.70 +/- 0.07 (range, 0.53 to 0.88) and 1.36 +/- 0.21 (range, 0.91 to 1.98), respectively. In multivariate regression analysis, RI and PI correlated significantly with age and arterial pulse pressure of the recipient. There was no correlation with donor age, heart rate, mean arterial blood pressure, and cyclosporine trough levels. Furthermore, parameters of kidney function, such as serum creatinine concentration, creatinine clearance rate, 51Cr-ethylenediaminetetraacetate clearance rate, and proteinuria, showed no significant correlation with the Doppler indices. The data indicate that intrarenal Doppler indices of the grafts are hemodynamic indices, primarily depending on the recipient-related vascular compliance rather than on the function of the graft. Therefore, only intraindividual comparison of the Doppler indices may be useful to detect potential changes of graft resistance during long-term follow-up.
Hamstring issues in sports: still a major clinical and research challenge
Authors: Nikos Malliaropoulos, Nicola Maffulli
Journal: British Journal of Sports Medicine (2012)

It will not be long until the Olympic 100 metre competitions. As certain as death, taxes and politicians' lies, more than one athlete's 4-year dream will vanish as his or her hamstring tears. This injury remains a great challenge in clinical practice and academic research. This issue of BJSM , with its striking cover, provides insights into the mechanisms that underpin hamstring injuries, guidance for clinical practice and suggestions for future research.

Hamstring tears occur during high-speed running but which phase of the gait cycle is the culprit? In Head to Head, Elizabeth S Chumanov and colleagues ( see page 90 ) from the Universities of Wisconsin and Melbourne provide the conventional wisdom that hamstrings are frequently injured during eccentric overload at the end of the swing phase. Serial iconoclast John W Orchard ( see page 88 ) argues that the early stance phase of sprinting is more likely the culprit but has evaded attention to date. This interesting debate might make you rethink your rehabilitation approach for hamstring injuries and it may prompt coaches to change their training prescription.

A main predictor of prognosis after acute hamstring is the mechanism of the injury. The Karolinska Institute's Carl Askling has been a pioneer in highlighting that there exist at least two distinctly different types of acute hamstring injuries. The first occurs during high-speed running and concentric muscle contraction; the injury occurs to the long head of the biceps femoris and the proximal muscle–tendon junction. The second occurs during extensive lengthening of the hamstrings, such as with high kicking, sliding tackles and …
Dual antitumour effect of 5-azacytidine by inducing a breakdown of resistance-mediating factors and epigenetic modulation
Authors: S. Venturelli, A. Berger, T. Weiland, M. Zimmermann, S. Hacker, C. Peter, S. Wesselborg, A. Konigsrainer, T. S. Weiss, M. Gregor, S. Fulda, U. M. Lauer, M. Bitzer
Journal: Gut (2010)

<h3>Background</h3> The cytokine tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown promising anticancer activity in early clinical settings by selectively inducing apoptosis in different tumour types. However, some tumour entities such as hepatocellular carcinoma (HCC) display an inherent resistance to TRAIL. A huge effort has been made to unravel strategies for a clinically applicable sensitisation of resistant cancer cells to TRAIL. Reversible epigenetic alterations such as DNA methylation play a major role in development, maintenance and resistance phenomena of tumour cells. Currently, several clinical trials are exploiting the potential of epigenetic drugs, such as 5-azacytidine (5-aza-CR) or 5-aza-2′-deoxycytidine (5-aza-dC) to break primary or secondary resistance phenomena of cancer cells. Therefore, 5-aza-CR and 5-aza-dC were investigated in the context of TRAIL resistance. <h3>Methods</h3> Alterations in proliferation, apoptosis, regulatory proteins and toxicity were investigated in TRAIL-resistant hepatoma, and also in renal, colon and pancreatic cancer cells as well as non-transformed human-derived primary hepatocytes, tissue slices isolated from human liver and non-malignant colon cells, all of which had been exposed to demethylating drugs and/or TRAIL. <h3>Results</h3> Within hours, 5-aza-CR but not 5-aza-dC sensitised in vitro cultured tumour cells to TRAIL, first by activating caspases, followed by a subsequent induction of apoptosis. This surprisingly rapid sensitisation was confirmed in vivo employing a chorioallantoic membrane assay. As a major mechanism, a 5-aza-CR-induced inhibition of cellular protein synthesis was found which led to a breakdown of tumour-protecting factors such as the antiapoptotic factor FLICE inhibitory protein (FLIP). Importantly, TRAIL and 5-aza-CR did not induce relevant toxicity or apoptosis in primary hepatocytes, liver slices from different human donors and in normal colon cells. <h3>Conclusions</h3> Molecular evidence is provided for a novel 5-aza-CR-based translational approach enabling a twofold treatment of apoptosis-resistant tumour entities, not only by an epigenetic reversion of the malignancy-associated phenotype but also by an efficient resensitisation to apoptosis-inducing substances such as TRAIL.
Pharmacologic Control of Temperature Regulation
Authors: B Cox, P Lomax
Journal: The Annual Review of Pharmacology and Toxicology (1977)

During the past two decades the physiology and pharmacology of thermoregulation have been the subjects of a considerable volume of research and numerous books and reviews. The physiologic aspects have been reviewed in detail most recently by Cabanac (1). The effects of drugs on temperature regulation have been discussed at two symposia, which resulted in books containing the proceedings (2, 3), and a third symposium in this series was held in Banff in September 1976. In reviewing this prodigious development of knowledge of the subject, any demarcation of these reports into pharmacologic is somewhat arbitrary since in many cases drugs have been used as tools to elucidate physiologic mechanisms. With respect to the actions of drugs on central thermoregulatory mechanisms, many of the compounds studied affect the CNS by modifying the activity of the several neuronal pathways that impinge on the central thermostats or that mediate the effector responses controlling body temperature. The role of the putative neuro­ transmitters involved constitutes perhaps the most debatable topic in thermoregula­ tion (4). Because there has been no recent exhaustive review of this subject we restrict the present discussion to the role of these neuroamines and the effects of drugs on their activity in the CNS. A convenient model on which to base a discussion of the role of amines in thermoregulation is the neural net described by Carlson (5). He divided the system into afferent, central, and efferent components. Of these three components there is little or no evidence for a role of amines in the afferent sensory division. Conversely there is good evidence for a role of amines in the peripheral effector part of the neural net; its pharmacology is easy to analyze and is well understood. The central compo-
CLINICAL STUDIES IN SCHIZOPHRENIA
Authors: C. MACFIE CAMPBELL
Journal: American Journal of Psychiatry (1943)

The scrutiny of this small group of patients, presenting a serious deterioration of insidious onset, reveals as outstanding factors the constitutional inadequacy of the individual patient and the unfavorable external factors which conditioned and frustrated him. Two of the patients developed pulmonary tuberculosis, but the clinical picture and course in these 2 patients were not markedly different from those of the other 7 patients. One may say that in this group the physical examination revealed no adequate cause for the onset of the deterioration. The clinical picture and course of the mental disorder in this group may be outlined as follows: The patient in adolescence or early adult life, without any adequate explanation in the way of physical illness or drastic change in the environment, begins to show a striking loss of sociability, initiative, interest and personal care. The course is as a rule steadily downwards, ending in a parasitic existence at a very low level. With the abeyance of the superior functions, with the loss of social response, of spontaneity, and of interest, there occur, perhaps as release phenomena, reactions of a lower neurological level—meaningless smiling and laughter, explosive outbursts of anger, occasional autoerotism, mannerisms and grimaces, automatic movements. Memory may be retained to a surprising extent; incoherence is frequently noted but the patient is uncommunicative. There is no special manifestation of basic urges, of underlying preoccupations, of repressed and dissociated factors. There seems to be a lack of vital energy associated with the egoistic as with the more complex social trends. The condition is one of defect rather than of conflict. In the comparative absence of tension, or turmoil, of compensatory strivings or phantasies, the clinical picture makes the impression of self-abandonment, of surrender, of acceptance of life at a lower automatic level. This surrender may be further evidence of the constitutional defect of vitality of the organism already indicated in childhood and made more manifest in face of the demands of the independent, mature, social life. The challenge of life to these underprivileged, poorly conditioned, and frustrated individuals is beyond their capacity. While others with somewhat different endowment react with hysterical or compulsive evasions, with affective slumps or sprees, with imaginative phantasies or regressive dramatisations, this group differently endowed reacts to the challenge with a simple surrender. If we continue to retain these patients within the hospitable group of schizophrenia, it may be legitimate to characterize their special type of reaction as schizophrenic "surrender." In the further analysis of the conditions of this "surrender" the inadequacy or abiotrophy of component systems of the organism requires to be investigated and evaluated.
Acute Calculous Cholecystitis
Authors: Steven M. Strasberg
Journal: New England Journal of Medicine (2008)

A 42-year-old woman presents with severe pain in the right upper quadrant, which started 15 hours earlier. She has had episodic pain in that location previously that lasted up to 2 hours. She has had one episode of vomiting with the current attack. Her temperature is 38.5°C, and the heart rate is 95 beats per minute. How should her condition be evaluated and treated?
The Ubiquitin-Like Protein FAT10 Mediates NF-κB Activation
Authors: Pengfei Gong, Allon Canaan, Bin Wang, Jeremy Leventhal, Alexandra Snyder, Viji Nair, Clemens D. Cohen, Matthias Kretzler, Vivette D'Agati, Sherman Weissman, Michael J. Ross
Journal: Journal of the American Society of Nephrology (2009)

NF-κB is a central mediator of innate immunity and contributes to the pathogenesis of several renal diseases. FAT10 is a TNF-α–inducible ubiquitin-like protein with a putative role in immune response, but whether FAT10 participates in TNF-α–induced NF-κB activation is unknown. Here, using renal tubular epithelial cells (RTECs) derived from FAT10−/− and FAT10+/+ mice, we observed that FAT10 deficiency abrogated TNF-α–induced NF-κB activation and reduced the induction of NF-κB–regulated genes. Despite normal IkBα degradation and polyubiquitination, FAT10 deficiency impaired TNF-α–induced IkBα degradation and nuclear translocation of p65 in RTECs, suggesting defective proteasomal degradation of polyubiquitinated IkBα. In addition, FAT10 deficiency reduced the expression of the proteasomal subunit low molecular mass polypeptide 2 (LMP2). Transduction of FAT10−/− RTECs with FAT10 restored LMP2 expression, TNF-α–induced IkBα degradation, p65 nuclear translocation, and NF-κB activation. Furthermore, LMP2 transfection restored IkBα degradation in FAT10−/− RTECs. In humans, common types of chronic kidney disease associated with tubulointerstitial upregulation of FAT10. These data suggest that FAT10 mediates NF-κB activation and may promote tubulointerstitial inflammation in chronic kidney diseases.
To screen or not to screen for sickle cell trait in American football?
Authors: Kimberly G Harmon, Jonathan A Drezner, Douglas J Casa
Journal: British Journal of Sports Medicine (2012)

Sickle cell trait (SCT) in America football athletes has been a topic of recent media attention. The deaths of college football athletes Ereck Plancher, Aaron O’Neil, Dale Lloyd and others as well as the recent decision of Pittsburgh Steelers safety Ryan Clark to forego a play-off game at altitude in Denver have contributed to the characterisation in the lay press of SCT as a dangerous condition. In fact, deaths in National Collegiate Athletic Association (NCAA) football players and concern from NCAA member institutions for the health and safety of student athletes led to legislation mandating all Division I athletes be screened or know their SCT status since August of 2010. On 26th January 2012, the American Society for Haematology (ASH) denounced the NCAA position. The disparity between these two positions is striking and deserves comment.

SCT is common, with 1 in 14 (7%) of blacks having SCT and up to 1 in 625 Caucasians carrying the gene. SCT is …
Diversity of Denizens of the Atherosclerotic Plaque
Authors: Peter Libby, Matthias Nahrendorf, Mikael J. Pittet, Filip K. Swirski
Journal: Circulation (2008)

T he atherosclerotic plaque typically harbors cells of several lineages whose conversations, mediated by extracellular or cell surface-associated messengers, influence decisively the biology and clinical consequences of the lesion.Early vascular biology studies defined the resting state of the endothelium, characterized by the elaboration of antithrombotic and vasodilatory mediators.The activated endothelium recruits inflammatory leukocytes, favors clot accumulation, participates in angiogenesis, and can influence the behavior of subjacent smooth muscle cells in ways that favor atherogenesis and vasoconstriction (Figure).More recently, we have come to appreciate that the endothelial cell not only can exhibit a spectrum of functions, but that some may arise postnatally from bone marrow-derived precursors. 1 Thus, the heterogeneity of endothelial cells depends not only on the mutability of their function but also on their origin.The diversity of endothelium depends not only on lineage but also location, with increasingly well-understood differences between arterial, microvascular, and venous endothelial cells.
Phase II Evaluation of Paclitaxel and Carboplatin in the Treatment of Carcinosarcoma of the Uterus: A Gynecologic Oncology Group Study
Authors: Matthew A. Powell, Virginia L. Filiaci, Peter G. Rose, Robert S. Mannel, Parviz Hanjani, Koen DeGeest, Brigitte E. Miller, Nobuyuki Susumu, Frederick R. Ueland
Journal: Journal of Clinical Oncology (2010)

Platinum and taxane compounds have demonstrated activity in uterine carcinosarcoma (malignant mixed Mullerian tumor). Ifosfamide plus paclitaxel is the regimen with established superiority based on a randomized phase III trial conducted through the Gynecologic Oncology Group. However, the toxicity, multiday schedule, and limited activity of this regimen support further development of novel regimens. Our primary objective was to estimate the antitumor activity and toxicity of paclitaxel plus carboplatin in patients with uterine carcinosarcomas.Eligible patients had advanced stage (III or IV), persistent or recurrent measurable disease, and no prior chemotherapy. Patients received paclitaxel at 175 mg/m(2) intravenously (IV) over 3 hours plus carboplatin (area under the serum concentration-time curve = 6) IV over 30 minutes every 3 weeks until disease progression or until adverse effects occurred. Common Terminology Criteria for Adverse Events v3.0 was used to grade adverse events.Fifty-five patients were entered onto the study with nine being excluded from analysis, leaving 46 evaluable for analysis. Treatment was well tolerated with expected hematologic toxicity and minimal nonhematologic grade 4 toxicity (one cardiovascular and two pain) with 59% of patients completing six or more cycles of chemotherapy. The proportions of patients with confirmed complete and partial responses were 13% and 41%, respectively, resulting in a total overall response rate of 54% (95% CI, 37% to 67%).Paclitaxel plus carboplatin demonstrates antitumor activity against uterine carcinosarcoma with acceptable toxicity and warrants further evaluation in phase III randomized trials.