tbuckley/cabot-search huggingface dataset:
Complex Rearrangements Lead to Novel Chimeric Gene Fusion Polymorphisms at the Arabidopsis thaliana MAF2-5 Flowering Time Gene Cluster
Authors: A. L. Caicedo, C. Richards, I. M. Ehrenreich, M. D. Purugganan
Journal: Molecular Biology and Evolution (2008)

Tandem gene clusters of multigene families are rearrangement hotspots and may be a major source of novel gene formation. Here, we report on a molecular population genetic analysis of the MAF2-5 gene cluster of the model plant species, Arabidopsis thaliana. The MAF2-5 genes are a MADS-box multigene family cluster spanning ∼24 kbp on chromosome 5. We find heterogeneous evolutionary dynamics among these genes, all of which are closely related to the floral repressor, FLC, and are believed to play a role in the control of flowering time in A. thaliana. Low levels of nonsynonymous single nucleotide polymorphism (SNP) observed for MAF4 and MAF5 suggest purifying selection and conservation of function. In contrast, high levels of nonsynonymous SNPs, insertion–deletion, and rearrangements are observed for MAF2 and MAF3, including novel gene fusions that persist as a moderate-frequency polymorphism in A. thaliana. These fused genes, involving MAF2 and portions of MAF3, are expressed, resulting in the production of chimeric, alternatively spliced transcripts of MAF2. Association studies support a correlation between the described MAF2–MAF3 gene rearrangements and flowering time variation in the species. The finding that complex rearrangements within gene clusters, such as those observed for MAF2, might play a role in the generation of ecologically important phenotypic variation, emphasize the need for emerging high throughput genotyping and sequencing techniques to correctly reconstruct gene chimeras and other complex polymorphisms.
Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind, placebo-controlled trial
Authors: Molebogeng X Rangaka, Robert J Wilkinson, Andrew Boulle, Judith R Glynn, Katherine Fielding, Gilles van Cutsem, Katalin A Wilkinson, Rene Goliath, Shaheed Mathee, Eric Goemaere, Gary Maartens
Journal: The Lancet (2014)
Sarcoidosis: Speculations as to the Stages of Infection
Authors: G. E. Lewis
Journal: BMJ (1941)

TICL BRITRSHL blood loss, and may be of interest in retrospect.x hen com- pared with haemoglobin readings dLuring the phase of shock.Suggested Procedure (ai) General duties orderly or clerk to complete details on top of page 1 for each case on admission to resuscita- tion wards.(b) Nurse or traintedntutrsinig or-derly to complete sections A, B, and C under supervision.This may be done while he is waiting for the blood or plasma to warm up and while he watches it pouring in.(c) Resuscitation officer, (i) on admission, to take rapid history, do brief examination, and order treatment; (ii) introduce needle and collect blood for haemoglobin esti- mation ; (iii) later read A and B anld add any further com- ments and notes, indicating his views of the severity of the various symptoms, signs, and complaints, and ordering further treatment ; (iv) complete later notes, after two to five days if possible.(d) Nuirse or trainied nursing odlerly to accompany severe cases during operation, to supervise transfusion, and to complete operation and anaesthetic notes and records of blood loss at operation.Where possible the nurse or orderly who has resuscitated the case should be detailed for this work to ensure continuity of treatment and interest, but if one cannot be spared the co-operation of the anaesthetist shotuld be invited.Summary The desirability of a standard record card for cases of shock in E.M.S. and military hospitals is stressed.A resuscitation record card designed for practical utility and suitable for statistical research is described and illustrated.Copies of this card are readily obtainable.It was from suggestions of Lieutenant (now Major) H. W. Rodgers in January, 1940, that my blood transfuLsion record card was greatly improved.My thanks are due to Major H. L. Marriott and Captain A. Kekwick for many helpful suggestions, and to
Is self monitoring of blood pressure in pregnancy safe and effective?
Authors: J. A. Hodgkinson, K. L. Tucker, C. Crawford, S. M. Greenfield, C. Heneghan, L. Hinton, K. Khan, L. Locock, L. Mackillop, C. McCourt, M. Selwood, R. J. McManus
Journal: BMJ (2014)

Guidelines encourage the use of self monitoring of blood pressure in pregnancy, and research suggests that women prefer it. But HODGKINSON AND COLLEAGUES: explain that our enthusiasm may run ahead of the evidence and call for more research before it is routinely adopted.
Does living near heavy industry cause lung cancer in women? A case-control study using life grid interviews
Authors: R Edwards, T Pless-Mulloli, D Howel, T Chadwick, R Bhopal, R Harrison, H Gribbin
Journal: Thorax (2006)

<b>Background:</b> The incidence of lung cancer among women is high in the highly industrialised area of Teesside in north-east England. Previous research has implicated industrial pollution as a possible cause. A study was undertaken to investigate whether prolonged residence close to heavy industry is associated with lung cancer among women in Teesside. <b>Methods:</b> Two hundred and four women aged &lt;80 years with incident primary lung cancer and 339 age matched community controls were recruited to a population based case-control study. Life course residential, occupational, and active and passive smoking histories were obtained using an interviewer administered questionnaire. <b>Results:</b> The age adjusted odds ratio (OR) for lung cancer among people living &gt;25 years <i>v</i> 0 years near (within 0–5 km) heavy industry in Teesside was 2.13 (95% CI 1.34 to 3.38). After adjustment for confounding factors the OR was 1.83 (95% CI 0.82 to 4.08) for &gt;25 years or 1.10 (95% CI 0.96 to 1.26) for an additional 10 years living near industry. ORs were similar after residence near heavy industry outside Teesside was also included, and when latency was allowed for by disregarding residential exposures within the last 20 years. Adjustment for active smoking had the greatest effect on the OR. <b>Conclusions:</b> This population based study using life grid interviews for life course exposure assessment has addressed many deficiencies in the design of previous studies. The findings support those in most of the international literature of a modestly raised risk of lung cancer with prolonged residence close to heavy industry, although the confidence intervals were wide. The effect of air pollution on the incidence of lung cancer merits continued study.
Effect of Glycemic Control on Sudomotor Denervation in Type 2 Diabetes
Authors: Kai-Ren Luo, Chi-Chao Chao, Paul-Chen Hsieh, June-Horng Lue, Sung-Tsang Hsieh
Journal: Diabetes Care (2012)

OBJECTIVE Sudomotor symptoms are a common component of diabetic autonomic neuropathy, but the pathology of sudomotor innervation and its relationship with glycemic control have remained obscured. RESEARCH DESIGN AND METHODS We enrolled 42 patients (26 males and 16 females aged 56.64 ± 12.67 years) with diabetic neuropathy defined by symmetric distally predominant sensory symptoms, abnormal nerve conduction studies, and reduced intraepidermal nerve fiber density in the leg. Skin biopsies of the distal leg were immunostained with antiprotein gene product 9.5 for nerve fibers and counterstained with Congo red for sweat glands. Sweat gland innervation index (SGII) was quantified with a new computerized area-based morphometric system. RESULTS Protein gene product 9.5(+) nerve terminals surrounded secretory coils of the sweat glands in the skin of control subjects. Sudomotor denervation was present in diabetic patients, manifesting as depletion of periglandular nerve fibers with lower SGII compared with 42 age- and sex-matched control subjects (2.54 ± 1.87 vs. 4.68 ± 1.51%, P &amp;lt; 0.001). The SGII was correlated with HbA1c (P = 0.011) and was lower in patients with anhidrosis of the feet compared with those with normal sweating of the feet (0.82 ± 0.69 vs. 3.00 ± 1.81%, P = 0.001). Sudomotor denervation was concordant with cardiac autonomic dysfunction as assessed with reduced heart rate variability (P = 0.003). CONCLUSIONS Sudomotor denervation is a significant presentation of diabetic neuropathy, and the SGII was associated with HbA1c. A skin biopsy offers a structural assessment of sudomotor innervation.
Airway Strain during Mechanical Ventilation in an Intact Animal Model
Authors: Scott E. Sinclair, Robert C. Molthen, Steve T. Haworth, Christopher A. Dawson, Christopher M. Waters
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Mechanical ventilation with large tidal volumes causes ventilator-induced lung injury in animal models. Little direct evidence exists regarding the deformation of airways in vivo during mechanical ventilation, or in the presence of positive end-expiratory pressure (PEEP).
The American Diabetes Association’s 48th Annual Advanced Postgraduate Course
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2001)

This article covers symposia presented at the American Diabetes Association’s 48th Annual Advanced Postgraduate Course, which was held in New York in January 2001. Topics include management of cardiovascular disease and diabetes, management of diabetes and hypertension, estrogen therapy and cardiovascular disease, and use of ACE inhibitors. At the American Diabetes Association’s 48th Annual Advanced Postgraduate Course in New York, 19–21 January 2001, much emphasis was devoted to cardiovascular disease (CVD) management in patients with diabetes. Henry Ginsberg, New York, NY, discussed diabetic dyslipidemia as a part of the hyperglycemia syndrome and, more importantly, the insulin resistance syndrome. Central to diabetic dyslipidemia is the elevation of fatty acid levels, with consequent elevated total triglycerides, reduced HDL cholesterol levels, and normal or mildly elevated levels of LDL cholesterol of abnormal composition. Thus, triglyceride levels exceed 235 mg/dl in 9 vs. 19% of nondiabetic vs. diabetic men and are >200 mg/dl in 8 vs. 17% of women. HDL cholesterol levels <31 mg/dl are seen in 12 vs. 21% of the two groups of men, and levels <41 mg/dl are seen in 10 vs. 25% of the respective groups of women. LDL cholesterol levels are similar in individuals with and without diabetes, exceeding 190 mg/dl in 11 vs. 9% and 16 vs. 15% of men and women, respectively (1). Similarly, in the U.K. Prospective Diabetes Study (UKPDS), HDL levels were lower and triglyceride levels were higher in both men and women with diabetes, although among women with diabetes, LDL cholesterol levels were higher (2). Insulin resistance is associated with a 30–40% higher free fatty acid (FFA) level because of decreased adipocyte uptake and increased release, leading to an increase in hepatic triglyceride synthesis, with increased VLDL production. In the circulation, cholesterol ester transfer protein, which resides mainly on HDL particles, transfers cholesterol from …
Accuracy of Rapid and Point-of-Care Screening Tests for Hepatitis C
Authors: Sushmita Shivkumar, Rosanna Peeling, Yalda Jafari, Lawrence Joseph, Nitika Pant Pai
Journal: Annals of Internal Medicine (2012)

Background: 170 million persons worldwide are infected with hepatitis C, many of whom are undiagnosed. Although rapid diagnostic tests (RDTs) and point-of-care tests (POCTs) provide a time- and cost-saving alternative to conventional laboratory tests, their global uptake partly depends on their performance. Purpose: To meta-analyze the diagnostic accuracy of POCTs and RDTs to screen for hepatitis C. Data Sources: MEDLINE, EMBASE, BIOSIS, and Web of Science (1992 to 2012) and bibliographies of included articles. Study Selection: All studies evaluating the diagnostic accuracy of POCTs and RDTs for hepatitis C in adults (aged ≥18 years). Data Extraction: Two independent reviewers extracted data and critiqued study quality. Data Synthesis: Of 19 studies reviewed, 18 were meta-analyzed and stratified by specimen type (whole blood, serum, plasma, or oral fluid) or test type (POCT or RDT). Sensitivity was similarly high in POCTs of whole blood (98.9% [95% CI, 94.5% to 99.8%]) and serum or plasma (98.9% [CI, 96.8% to 99.6%]), followed by RDTs of serum or plasma (98.4% [CI, 88.9% to 99.8%]) and POCTs of oral fluid (97.1% [CI, 94.7% to 98.4%]). Specificity was also high in POCTs of whole blood (99.5% [CI, 97.5% to 99.9%]) and serum or plasma (99.7% [CI, 99.3% to 99.9%]), followed by RDTs of serum or plasma (98.6% [CI, 94.9% to 99.6%]) and POCTs of oral fluid (98.2% [CI, 92.2% to 99.6%]). Limitation: Lack of data prevented sensitivity analyses of specific tests. Conclusion: Data suggest that POCTs of blood (serum, plasma, or whole blood) have the highest accuracy, followed by RDTs of serum or plasma and POCTs of oral fluids. Given their accuracy, convenience, and quick turnaround time, RDTs and POCTs may be useful in expanding first-line screening for hepatitis C. Primary Funding Source: Canadian Institutes of Health Research.
Molecular Epidemiology: Insights Into Cancer Susceptibility, Risk Assessment, and Prevention
Authors: F. P. Perera
Journal: JNCI Journal of the National Cancer Institute (1996)

Recent molecular epidemiologic research provides compelling new evidence that environmental factors are major contributors to human cancer and that their risks are strongly influenced by genetic and aquired susceptibility. In particular, molecular epidemiology has demonstrated substantial variability in biologic response to carcinogens and suggests that certain groups—such as the very young, those with predisposing genetic traits or nutritional deficits, and even certain ethnic groups—are likely to have greater risk from selected exposures than other members of the population. This work implies that major gains in prevention of cancer, which will claim more than 554 000 American lives this year, will necessitate health and regulatory policies that protect these more susceptible groups and individuals from risks of man-made and naturally occurring environmental carcinogens. The specific implication from this research is that, to be effective in prevention, risk assessments developed in support of these policies by regulatory bodies, such as the Environmental Protection Agency, should reflect the available scientific data on individual variability in both exposure and susceptibility. [J Natl Cancer Inst 1996; 88: 496–509]
Monitoring Tumor Glucose Utilization by Positron Emission Tomography for the Prediction of Treatment Response to Epidermal Growth Factor Receptor Kinase Inhibitors
Authors: Helen Su, Claudia Bodenstein, Rebecca A. Dumont, Yann Seimbille, Steven Dubinett, Michael E. Phelps, Harvey Herschman, Johannes Czernin, Wolfgang Weber
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The mechanisms underlying the sensitivity of non–small cell lung cancer to epidermal growth factor receptor (EGFR) kinase inhibitors are complex, and there are no established markers to accurately predict treatment outcome in individual patients. Experimental Design: We investigated whether tumors responding to EGFR inhibitors can be identified by measuring treatment-induced changes in glucose utilization by positron emission tomography with the glucose analogue fluorodeoxyglucose (FDG-PET). We studied a panel of cell lines with a spectrum of sensitivity to EGFR kinase inhibitors. After incubation with the EGFR kinase inhibitor gefitinib for various time points, FDG uptake, glucose transport rates, and hexokinase activity were determined. FDG uptake in vivo was assessed by microPET imaging of tumor xenografts in mice. Results: In gefitinib-sensitive cell lines, there was a dramatic decrease in FDG uptake as early as 2 hours after treatment. Immunoblots showed the translocation of glucose transporters (GLUT3) from the plasma membrane to the cytosol; glucose transport rates were reduced 2.6-fold at this time. There was also a modest reduction of hexokinase activity. These metabolic alterations preceded changes in cell cycle distribution, thymidine uptake, and apoptosis. MicroPET studies showed an up to 55% decrease of tumor FDG uptake in sensitive xenografts within 48 hours. In contrast, gefitinib-resistant cells exhibited no measurable changes in FDG uptake, either in cell culture or in vivo. Conclusion: Glucose metabolic activity closely reflects response to gefitinib therapy. FDG-PET may be a valuable clinical predictor, early in the course of treatment, for therapeutic responses to EGFR kinase inhibitors.
Cardiovascular Effects of Endogenous Opiate Systems
Authors: J W Holaday
Journal: The Annual Review of Pharmacology and Toxicology (1983)

Opiates are among the oldest pharmacological substances known to man; their analgesic, euphoric, and addictive effects have been traditional focal points for opiate research. Without doubt, the cardiovascular effects of opiates have also been apparent to the user or abuser of opiate substances for several centuries. Persons seeking analgesic, euphoric, or antidiarrheal actions from opiate alkaloids have probably noted dizziness upon sudden st,anding due to the orthostatic hypotension these substances produce. His­ torically, however, scientific study on the cardiovascular responses to ad­ ministered opiates has lagged behind other areas of opiate research. This is understandable as, relative to doses required for their analgesic actions in humans, the cardiovascular effects of opiates are less noticeable and, indeed, undesirable. Early studies established that cardiovascular responses to morphine var­ ied among species; both autonomic and histamine-releasing properties con­ tributed to their hypotensive and bradycardic actions (1-5). Generally speaking, morphine was shown to produce prominent effects upon brain­ stem and hypothalamic centers that resulted in increased parasympathetic and decreased sympathetic tone (3-6). These effects upon autonomic out­ flow caused a depression of both heart rate and blood pressure. A resurgence of interest in opiate-cardiovascular interactions followed the discovery of endogenous opiate systems (for review see 7). A family of opioid peptides were found to be located at sites suggesting an autonomic action (8); also, opiate receptors were shown to be densely distributed in the brainstem and hypothalamus in close proximity to cardiovascular centers as well as endogenous opiate pathways (9, to). These anatomical findings
Myofibroblastic cells function as progenitors to regenerate murine livers after partial hepatectomy
Authors: M Swiderska-Syn, W K Syn, G Xie, L Krüger, M V Machado, G Karaca, G A Michelotti, S S Choi, R T Premont, A M Diehl
Journal: Gut (2013)

Smoothened (SMO), a coreceptor of the Hedgehog (Hh) pathway, promotes fibrogenic repair of chronic liver injury. We investigated the roles of SMO+ myofibroblast (MF) in liver regeneration by conditional deletion of SMO in α smooth muscle actin (αSMA)+ cells after partial hepatectomy (PH).αSMA-Cre-ER(T2)×SMO/flox mice were treated with vehicle (VEH) or tamoxifen (TMX), and sacrificed 24-96 h post-PH. Regenerating livers were analysed for proliferation, progenitors and fibrosis by qRT-PCR and quantitative immunohistochemistry (IHC). Results were normalised to liver segments resected at PH. For lineage-tracing studies, αSMA-Cre-ER(T2)×ROSA-Stop-flox-yellow fluorescent protein (YFP) mice were treated with VEH or TMX; livers were stained for YFP, and hepatocytes isolated 48 and 72 h post-PH were analysed for YFP by flow cytometric analysis (FACS).Post-PH, VEH-αSMA-SMO mice increased expression of Hh-genes, transiently accumulated MF, fibrosis and liver progenitors, and ultimately exhibited proliferation of hepatocytes and cholangiocytes. In contrast, TMX-αSMA-SMO mice showed loss of whole liver SMO expression, repression of Hh-genes, enhanced accumulation of quiescent HSC but reduced accumulation of MF, fibrosis and progenitors, as well as inhibition of hepatocyte and cholangiocyte proliferation, and reduced recovery of liver weight. In TMX-αSMA-YFP mice, many progenitors, cholangiocytes and up to 25% of hepatocytes were YFP+ by 48-72 h after PH, indicating that liver epithelial cells were derived from αSMA-YFP+ cells.Hh signalling promotes transition of quiescent hepatic stellate cells to fibrogenic MF, some of which become progenitors that regenerate the liver epithelial compartment after PH. Hence, scarring is a component of successful liver regeneration.
Nicotinic Acid, Nicotinamide, and Nicotinamide Riboside: A Molecular Evaluation of NAD<sup>+</sup> Precursor Vitamins in Human Nutrition
Authors: Katrina L Bogan, Charles Brenner
Journal: Annual Review of Nutrition (2008)

Although baseline requirements for nicotinamide adenine dinucleotide (NAD+) synthesis can be met either with dietary tryptophan or with less than 20 mg of daily niacin, which consists of nicotinic acid and/or nicotinamide, there is growing evidence that substantially greater rates of NAD+ synthesis may be beneficial to protect against neurological degeneration, Candida glabrata infection, and possibly to enhance reverse cholesterol transport. The distinct and tissue-specific biosynthetic and/or ligand activities of tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD+ precursor, nicotinamide riboside, reviewed herein, are responsible for vitamin-specific effects and side effects. Because current data suggest that nicotinamide riboside may be the only vitamin precursor that supports neuronal NAD+ synthesis, we present prospects for human nicotinamide riboside supplementation and propose areas for future research.
The effects of pilates exercise on blood pressure and selective physical fitness components in sedentary overweight females
Authors: Zeinab Omid Ali, Fahimeh Esfarjani, Effat Bambaeichi, Mohammad Marandi
Journal: British Journal of Sports Medicine (2010)

The purpose of this study was to examine the effects of 8 weeks Pilates exercise programme on blood pressure and selective physical fitness components in sedentary overweight females. Thirty sedentary overweight student females (mean ± SD; age: 26 ± 3 years, body mass: 65.9 ± 5.8 kg, height: 1.58 ± 0.08 m, BMI: 26.2 ± 1.8 kg/m 2 ) from Isfahan University participated in this study. Subjects were randomly assigned to either the experimental (n = 15) or control group (n = 15). The experimental group participated in 8 weeks Pilates class, which met for 1 h three times per week, while the control group was prevented from any sport activity and just participated in pre- and post-testing. Systolic and diastolic blood pressure, percentage of total body fat, handgrip, flexibility, aerobic power, abdominal endurance and waist circumference were assessed. There was a significant decrease in fat percentage, fat body mass and waist circumference in the experimental group after 8 weeks Pilates exercise by 7.3%, 8.5% and 4.6%, respectively (p&lt;0.05). Aerobic power, abdominal muscular endurance and hand grip in experimental group compared to control group significantly increased by 12.3%, 9.8% and 23%. In addition, flexibility consists of sit and reach and shoulder reach test in experimental group compared to control group significantly increased by 28% and 22%, respectively (p&lt;0.05). There was no significant difference between experimental and control groups in total body weight, body mass index, lean body mass and systolic and diastolic blood pressure (p&gt;0.05). It is concluded that sedentary females may experience improvement in some physical fitness components and significantly decrease in body fat and waist size following 8 weeks Pilates exercise programme.