tbuckley/cabot-search huggingface dataset:
Expression of heat shock proteins in the normal and stunned porcine myocardium
Authors: J. Andres, H. S Sharma, R. Knoll, J. Stahl, L. M A Sassen, P. D Verdouw, W. Schaper
Journal: Cardiovascular Research (1993)

Objective: The aim was to examine the expression of ubiquitin (Ub), 27 kDa heat shock protein (hsp27), and hsp60 mRNA in normal and briefly ischaemic and reperfused porcine myocardium: Methods: The left anterior descending coronary artery was occluded for two periods of 10 min separated by 30 min of reperfusion. After the second occlusion the myocardium was reperfused up to 210 min. Tissue from ischaemic, ischaemic-reperfused, and non-ischaemic regions of the heart was analysed by northern and slot blot hybridisation and nuclear run-on transcription assays employing radiolabelled cDNA probes for Ub, hsp27, and hsp60, as well as by western blot using monoclonal antibodies recognising Ub protein conjugates and antiserum recognising hsp27. Results: Systolic wall thickening was significantly decreased at 30 min reperfusion after both occlusions and remained depressed at longer periods of reperfusion. Using northern blot hybridisations, several mRNAs encoding Ub, 0.9 kb mRNA encoding hsp27, and 2.2 kb mRNA encoding hsp60 were detected in sham operated, non-ischaemic, and ischaemic myocardial tissues. Densitometric analysis of northern and slot blot hybridisation signals showed significant increase of basal tissue levels of Ub mRNA in stunned regions only during the 30 min of the second reperfusion period. Increased levels of hsp27 mRNA in stunned tissue were already noted at the first ischaemic period and were sustained compared to control during the subsequent periods of reperfusion. Changes in hsp60 mRNA tissue levels were not observed during ischaemia and subsequent reperfusions. Transcription of the Ub and hsp27 genes was increased during 30 and 120 min of the second reperfusion period. The transient enhancement of tissue levels of Ub mRNA was associated with temporary formation of new Ub-protein conjugates. However, the increased synthesis of mRNA encoding hsp27 was not followed by changes of hsp27 protein content in myocardial tissue. Conclusions: The findings support the hypothesis that molecular damage occurs in stunned myocardium; however, the target molecules remain to be recognised. Cardiovascular Research 1993;27:1421-1429
TRANSFER OF A FUNCTIONING HUMORAL IMMUNE SYSTEM IN TRANSPLANTATION OF T-LYMPHOCYTE-DEPLETED BONE MARROW
Authors: J.Z. Wimperis, H.G. Prentice, P. Karayiannis, M.K. Brenner, J.E. Reittie, P.D. Griffiths, A.V. Hoffbrand
Journal: The Lancet (1986)
Hypothermia in the aged.
Authors: S M Horvath, R D Rochelle
Journal: Environmental Health Perspectives (1977)

Body temperature is maintained by a balance between heat production and heat loss. Temperature regulation consequent to exposure to a cold environment appears to be modified in elderly persons. An evaluation of the physiological adjustments made by older individuals is presented. It is apparent that hypothermia can develop in the older population as a consequence of modifications in both behavioral and physiological responses to cold exposure. With the growing awareness of an energy shortage with consequent lower ambient temperatures in homes, there is a need to obtain adequate information as to the physiological capabilities and adaptive potential of elderly individuals to a cold stress.
The current use of studies on promoters and cocarcinogens in quantitative risk assessment.
Authors: J F Stara, D Mukerjee, R McGaughy, P Durkin, M L Dourson
Journal: Environmental Health Perspectives (1983)

Several of the priority pollutants discussed in EPA's Ambient Water Quality Criteria documents have been reported to have promotion or cocarcinogenic activity. For example, phenol appears to have tumor-promoting activity in mice when repeatedly applied after initiation with either 7,12-dimethyl-1,2-benzanthracene (DMBA) or benzo(a)pyrene (BaP). Similarly, it has been reported that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent promoter of liver tumors as well as a cocarcinogen. However, in developing guidelines to derive ambient water quality criteria, it became apparent that satisfactory approaches had not been developed for using promotion/cocarcinogen data in human health risk estimation, nor were available promotion and/or cocarcinogen data on individual chemicals strong enough to permit a defensible quantitative risk estimation, if such approaches had existed. For this reason, the criteria derived for pollutants with reported promotion/cocarcinogenic activities were based on approaches for carcinogenic (e.g., TCDD), toxic (e.g., fluoranthene) or organoleptic effects (e.g., 2,4-dichlorophenol). Nonetheless, with advances in studies on both the biological mechanisms and dose/response patterns of promoters and cocarcinogens, it may be possible to develop a scientifically valid quantitative approach to use this type of data for derivation of ambient water quality criteria or other risk assessments. Some progress toward this goal and the problems associated with this effort are discussed.
Community-Based Randomized Double-Blind Study of Gastrointestinal Effects and Copper Exposure in Drinking Water
Authors: Magdalena Araya, Manuel Olivares, Fernando Pizarro, Adolfo Llanos, Guillermo Figueroa, Ricardo Uauy
Journal: Environmental Health Perspectives (2004)

We assessed gastrointestinal effects in 1,365 adults exposed to either < 0.01 (controls), 2, 4, or 6 mg copper/L of drinking water for 2 months in a randomized, double-blind community-based study. The risk of symptoms increased with increasing Cu exposure and decreased with time. The best model by counting-process analysis included Cu concentration and sex. The risk of symptoms remained significantly higher in women than in men during weeks 1–4 for all concentrations tested; at week 1 comparison with the < 0.01-mg/L group showed that differences became significant in women at 4 mg/L [relative risk (RR) = 1.53; 95% confidence interval (CI), 1.02–2.05), and in men at 6 mg/L (RR = 1.9; 95% CI, 1.02–2.79). At week 2 for men and week 4 in women, the Cu concentration required to obtain significant differences on symptom report was > 6 mg Cu/L. We conclude that exposure to Cu in drinking water results in gastrointestinal symptoms, which are modulated by Cu concentration, time, and sex.
Relation between maximum time-varying elastance pressure-volume areas and myocardial oxygen consumption in dogs.
Authors: M R Starling, G B Mancini, D G Montgomery, M D Gross
Journal: Circulation (1991)

To establish whether pressure-volume areas (PVAs) calculated using the maximum time-varying elastance (Emax) have a relation with myocardial oxygen consumption (MVO2) that improves on other indexes of myocardial oxygen demand, we studied nine dogs of either sex weighing 19-39 kg, which were instrumented with a micromanometer left ventricular (LV) catheter and a Wilton-Webster coronary sinus flow catheter and had red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamics, coronary sinus flow determinations, and radionuclide angiograms were obtained under control conditions and during three to five steady-state loading conditions (mean +/- SD, 5.6 +/- 0.7). Isochronal pressure-volume data points from each pressure-volume loop were subjected to linear regression analysis to calculate Emax. The Emax relations, diastolic curves, and systolic portions of each pressure-volume loop were used to obtain calibrated PVAs. The Emax PVA (mm Hg.ml.beat-1.100 g-1) and MVO2 (ml O2.beat-1.100 g-1) values correlated in each animal (r = 0.77 to 0.99). Their slopes averaged (3.48 +/- 1.68) x 10(-5) ml O2.mm Hg-1.ml-1, and their y-axis intercepts averaged 0.07 +/- 0.04 ml O2.beat-1.100 g-1. When the MVO2 relations were compared with Emax PVA, LV systolic pressure-rate product, LV stroke work, and a modification of the LV pressure-work index, the Emax PVA, LV systolic pressure-rate product, and LV pressure-work index had similar relations with MVO2, whereas LV stroke work was a weaker index of MVO2 (p less than 0.05 versus Emax PVA). This occurred because the Emax PVA:MVO2 slopes and y-axis intercepts differed in each dog, which was due to differences in basal LV contractility. The Emax PVA:MVO2 slopes correlated with Emax (r = 0.73, p less than 0.05), and the y-axis intercepts were also weakly related to Emax (r = 0.48, p = 0.19). We conclude that the Emax PVAs calculated using data acquisition techniques that are clinically applicable have relations with MVO2 that in general do not improve on other indexes of myocardial oxygen demand in this animal preparation.
International investigation of outbreaks of foodborne disease
Authors: R. V Tauxe, J. M Hughes
Journal: BMJ (1996)

In 1992, the United States Institute of Medicine published a report entitled Emerging Infections: Microbial Threats to Health in the United States.1 The report, developed by an expert committee chaired by Drs Joshua Lederberg and Robert Shope, emphasised the fact that the world is truly a global village with respect to microbes. One factor is the change in the food industry. Foods, like many pathogens, are more likely than ever to cross national borders, and a single meal can combine products from many countries. In the United States and many other countries, importing of food from other parts of the world has increased greatly.2

One unintended consequence is that when food becomes contaminated the resulting outbreak can span continents. Indeed, Salmonella agona first spread around the world as a consequence of the use of contaminated Peruvian fish meal in chicken feed.3 More recent foodborne outbreaks of international scope include a multistate outbreak of Cyclospora cayetanenis infection in the United States and Canada related to raspberries imported from Guatemala,4 salmonellosis in the United States and several Scandinavian countries traced to alfalfa sprouts grown from imported seeds,5 6 shigellosis …
Molecular and Functional Signature of Heart Hypertrophy During Pregnancy
Authors: Mansoureh Eghbali, Rupal Deva, Abderrahmane Alioua, Tamara Y. Minosyan, Hongmei Ruan, Yibin Wang, Ligia Toro, Enrico Stefani
Journal: Circulation Research (2005)

During pregnancy, the heart develops a reversible physiological hypertrophic growth in response to mechanical stress and increased cardiac output; however, underlying molecular mechanisms remain unknown. Here, we investigated pregnancy-related changes in heart structure, function, and gene expression of known markers of pathological hypertrophy and cell stretching in mice hearts. In late pregnancy, hearts show eccentric hypertrophy, as expected for a response to volume overload, with normal left ventricular diastolic function and a moderate reduction in systolic function. Pregnancy-related physiological heart hypertrophy does not induce expression changes of known markers of pathological hypertrophy like: alpha- and beta-myosin heavy chain, atrial natriuretic factor, phospholamban, and sarcoplasmic reticulum Ca2+-ATPase. Instead, it induces the remodeling of Kv4.3 channel and increased c-Src tyrosine kinase activity, a stretch-responsive kinase. Cardiac Kv4.3 channel gene expression was downregulated by approximately 3- to 5-fold, both at the mRNA and protein levels, and was paralleled by a reduction in transient outward K+ currents, a longer action potential and by prolongation of the QT interval. Downregulation of cardiac Kv4.3 transcripts was mimicked by estrogen treatment in ovariectomized mice, and was prevented by the estrogen receptor antagonist ICI 182,780. c-Src activity increased by approximately 2-fold in late pregnancy and after estrogen treatment. We propose that, in addition to mechanical stress, the rise of estrogen toward the end of pregnancy contributes to pregnancy-related heart hypertrophy by increased c-Src activity and that the rise of estrogen is one factor that down regulates cardiac Kv4.3 gene expression providing a molecular correlate for a longer QT interval in pregnancy.
Contractile elements in stratum granulosum
Authors: Christine J. Skerrow
Journal: British Journal of Dermatology (1980)

Journal Article Contractile elements in stratum granulosum Get access Christine J. Skerrow Christine J. Skerrow University of Glasgow, Dept. of Dermatology, Anderson College Building, 56 Dumbarton Road, Glasgow, GII 6NU Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 103, Issue 1, 1 July 1980, Page 119, https://doi.org/10.1111/j.1365-2133.1980.tb15851.x Published: 01 July 1980
Research governance approval delays studies
Authors: Anne Dornhorst, Paul Chester
Journal: Journal of the Royal Society of Medicine (2009)

In the May 2009 edition of JRSM your headline article was ‘Research governance delays for a non-interventional study’ a sentiment which many researchers may share.1 The authors put the reasons for delay clearly in the arms of research and development departments (RDD) where significant variation in processes leads to variation in delay. While we do not defend the over-bureaucratic system for research approval in the UK our findings suggest that the reason for delay must be shared among those involved in the study. In 2006 we published an article which examined the delays in a similar multicentre observational study which involved 178 sites across the UK, of which 159 were hospital trusts.2 We examined the reason for delay at all sites taking more than 60 days for approval (i.e. more than the legally specified time currently required for ethics committee review).3 We found that the mean approval time was 82 days with a range of 0–259 days, thus supporting the wide variation identified by Mallick and O’Callaghan. In our analysis more than half the hospital sites took longer than 60 days (n=86, mean 126 days) to obtain local approval. We examined the source of the delay and found that of those cases taking more than 60 days, 25 (29%) were delayed at the RDD while 22 (26%) were delayed while awaiting investigators to respond to queries and 11 (13%) delayed at the trust level awaiting sign off. The remaining 28 had mixed reasons for delay beyond 60 days.

We therefore support the call for an improved approval system but would suggest that all parties involved in the approval process must be prepared to support change and act in a timely manner.
The role of the clinical tutor
Authors: D. Mabin
Journal: BMJ (1999)

A clinical tutor is accountable to, and acts on behalf of, the postgraduate dean and the chief executive in an NHS trust to oversee the provision of education for doctors in training and to ensure that this is carried out to a satisfactory standard. Many clinical tutors are, in practice if not in name, directors of medical education with a position on the trust board or trust executive committee. They are able to inform trusts about the effect of organisational changes within a trust on the training of junior doctors, and they also advise trusts on national initiatives and trends that have implications on doctors who train.

The development of the post mirrors changes in the provision of postgraduate medical education that have been brought about by government initiatives, inquiries, and legislation. The first clinical tutors and postgraduate education centres were established in hospitals in the early 1960s after concerns were raised by Sir Robert Platt, chairman of a government joint working party, about the standard of training for junior doctors in the newly created senior house officer and registrar grades. The Pickering report in 1963 recommended that within each district the provision of postgraduate medical education be supervised on behalf of the postgraduate dean by a clinical tutor, who was usually chosen from among the consultants. Subsequently, the Royal Commission on Medical Education, chaired by Lord Todd in the mid-1960s, reported that doctors in training required consultant supervision and formative assessment and that clinical tutors would coordinate the supervision of all trainees within local health districts.

The Merrison Committee of Inquiry into the Regulation of the Medical Profession in the 1970s again recommended close supervision of trainees and said that the General Medical Council should be responsible for standards of specialist education. The GMC delegated the monitoring …
Homogenized Milk and Coronary Artery Disease
Authors: Edwin L. Bierman
Journal: JAMA (1975)

There has been widespread coverage in the news media recently of the claim that the drinking of homogenized milk is a cause of excessive mortality from coronary artery disease in the United States. That this relationship might exist has been proposed by Oster,<sup>1</sup>who postulates the existence of a group of diseases caused by the depletion of<i>plasmalogen</i>in cell membranes. He includes arteriosclerosis, myocardial infarction, and angina pectoris as representative disorders with this possible origin. Plasmalogens are a type of phospholipid usually found as a component of cell membranes of muscle and of the myelin sheath of nerve fibers. The major plasmalogen of myocardium is a choline phosphatide containing an unsaturated fatty acid in a typical ester linkage and a second fatty acid as a vinyl ether,<sup>2</sup>thereby differing from the more usual phospholipid exemplified by lecithin. Fatty aldehydes or plasmals can be released from this second
Therapy-related acute myeloid leukemia and myelodysplastic syndromes in patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group
Authors: Dennis A. Eichenauer, Indra Thielen, Heinz Haverkamp, Jeremy Franklin, Karolin Behringer, Teresa Halbsguth, Beate Klimm, Volker Diehl, Stephanie Sasse, Achim Rothe, Michael Fuchs, Boris Böll, Bastian von Tresckow, Peter Borchmann, Andreas Engert
Journal: Blood (2014)
Bacterial translocation in acute and chronic portal hypertension
Authors: Eamonn M.M. Quigley, Guadalupe Garcia-Tsao
Journal: Hepatology (1994)

Patients with cirrhosis are predisposed to develop spontaneous bacteremias and peritonitis, mainly by enteric bacteria. Portal hypertension, by producing congestion and edema of the bowel wall, could increase the passage of bacteria from the intestinal lumen to regional lymph nodes to the systemic circulation or to both, a process termed bacterial translocation. The aim of this study was to investigate bacterial translocation at two stages of experimental portal hypertension: (a) acute (when shunting is minimal); and (b) chronic (when shunting is extensive and mimics the portal hypertension of cirrhosis). Rats were killed 2 days (acute) or 15 days (chronic) after partial portal vein ligation or control surgeries. Samples of mesenteric lymph nodes, blood, liver and spleen for standard bacteriological cultures and a fragment of ileum for histological examination were obtained. Two days after surgery, a significantly greater proportion of rats with acute portal hypertension (12 of 13 or 92%) had positive mesenteric lymph node cultures compared with both control groups: sham-operated (4 of 13 or 31%) and inferior vena cava-ligated (3 of 10 or 33%) animals (p < 0.01). However, 15 days after surgery no differences in translocation to mesenteric lymph nodes were found between rats with chronic portal hypertension (3 of 15 or 20%) and sham-operated controls (3 of 11 or 27%). In neither the acute nor the chronic rats were bacteria isolated from blood, spleen or liver. Rats with acute portal hypertension had significantly greater mesenteric inflammation than rats with chronic portal hypertension and control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
A5.15 Heterogeneity in plasmacytoid dendritic cell response to HIV-GP120 as a putative cause for variability in HIV musculoskeletal co-morbidity
Authors: FAH Cooles, AE Anderson, CMU Hilkens, JD Isaacs
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Musculoskeletal presentations following initial HIV infection, although variable, cause significant morbidity. gp120 is a HIV surface glycoprotein and plasmacytoid dendritic cells (pDCs) are one of the first cells to encounter gp120 aided by their high expression of CD4. pDCs produce large amounts of interferon alpha (IFN-alpha) following Toll like receptor (TLR) stimulation and their role in rheumatic disease is of increasing interest with IFN-alpha being implicated in subsets of inflammatory arthropathies. Some studies suggest an immunomodulatory role of gp120 by inhibiting pDC TLR9 induced IFN-alpha production. Given the variability in incidence of HIV associated musculoskeletal presentations we hypothesised that heterogeneity in response to gp120, and hence heterogeneity of IFN-alpha production, may contribute to variability in clinical presentation following acute HIV infection. <h3>Materials and methods</h3> Peripheral blood mononuclear cells (PBMCs) were separated from healthy donor blood samples using density centrifugation. pDCs were isolated from PBMCs by MACS magnetic isolation using the CD304<sup>+</sup> positive selection kit. Purity was measured by co-expression of CD303 and CD123 by flow cytometry. pDCs and PBMCs were both cultured in RPMI supplemented with 10% fetal calf serum +/- gp120 and CPG-A for 18 h (6 h for intracellular staining). gp120 (MN strain) and TLR9 agonist CPG-A (ODN 2216) were used at varying concentrations in these cultures. IFN-alpha production was measured by flow cytometry (intracellular IFN-a stain) or ELISA (from culture supernatant). sCD4 (10ug/ml) was included in some experiments. <h3>Results</h3> We recruited 12 healthy volunteers and pDC purity following isolation consistently &gt;90%. In both pDC and PBMC cultures gp120 by itself did not induce IFN-alpha production. However in PBMC cultures when cultured with CPG-A and gp120 66.67% of individuals (n = 8) demonstrated a dose dependant increase in IFN-alpha production when compared with CPG-A alone. However in the remaining 33.33% (n = 4) the inverse trend was seen. Similar patterns were seen for both intracellular IFN-alpha staining as well as extracellular production (ELISA). When comparing the effect of sCD4 (n = 4), an inhibitor of gp120 binding, we showed that the effects of gp120 on CPG-A induced INF-alpha production were reduced. These trends were replicated in isolated pDC cultures. <h3>Conclusions</h3> We demonstrate significant heterogeneity in response to simultaneous TLR9 signalling and exposure to gp120 in a healthy population. This may replicate heterogeneity in pDC response to acute HIV infection and TLR9 stimulation <i>in vivo</i>. This heterogeneity may, in turn, contribute to the rheumatic disease phenotype in acute HIV infection, and provide insight into novel therapeutics.