tbuckley/cabot-search huggingface dataset:
Pressure Natriuresis in Nitric Oxide-Deficient Hypertensive Rats
Authors: LOURDES A. FORTEPIANI, ELENA RODRIGO, M. CLARA ORTÍZ, VICTORIA CACHOFEIRO, NOEMÍ M. ATUCHA, LUIS M. RUILOPE, VICENTE LAHERA, JOAQUÍN GARCÍA-ESTAN[Combining Tilde]
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Chronic inhibition of nitric oxide (NO) synthesis has been shown to result in arterial hypertension and an important blunting of the pressure diuresis and natriuresis response (PDN). The mechanisms mediating these abnormalities are not completely understood. In the present study, the role of several antihypertensive drugs to ameliorate these alterations was evaluated. The PDN relationships have been evaluated in rats chronically (8 wk) treated with the NO synthesis inhibitor N G -nitro-L-arginine methyl ester (L-NAME; 40 mg/kg per d in the drinking water). Appropriate groups of rats were simultaneously treated with the angiotensin II receptor blocker candesartan at a low (1.5 mg/kg per d) and high (2.5 mg/kg per d) dose, with the converting enzyme inhibitor captopril (60 mg/kg per d) and with the calcium channel blocker verapamil (100 mg/kg per d). Chronic treatment with L-NAME significantly elevated mean BP (163.6 ± 6.5 mmHg versus 105.1 ± 3.6 in controls), reduced GFR and renal blood flow (RBF), and shifted to the right the PDN responses. Chronic administration of low-dose candesartan, captopril, or verapamil prevented the arterial hypertension and improved renal hemodynamics, but these levels were not completely normalized. High-dose administration also improved renal hemodynamics but induced reduced BP below the levels of control animals. Despite the normalization of the elevated BP, the PDN responses of these hypertensive treated groups were not normalized, and the slopes of the respective diuretic or natriuretic responses were very similar to those of the hypertensive untreated rats. The results indicate that interruption or blockade of the reninangiotensin system and calcium channel blockade are effective treatments for the NO-deficient arterial hypertension and renal vasoconstriction. However, the PDN responses are not normalized, and this finding suggests that the antihypertensive treatment is not enough to overcome the renal alterations associated with the chronic deficiency of NO.
Health hazards in the production and processing of some fibers, resins, and plastics in Bulgaria.
Authors: M Spassovski
Journal: Environmental Health Perspectives (1976)

Results of the toxicological studies of working conditions, general and professional morbidity, and complex examinations carried out on workers engaged in the production of polyamides, polyacrylonitrile fibers, polyester fibers and poly (vinyl chloride) resin, urea-formaldehyde glue, glass fibre materials and polyurethane resins are given. An extremely high occupational hazard for workers in the production of poly (vinyl chloride) resin and porous materials from polyurethane resins and urea-formaldehyde glue has been established. Cases of vinyl chloride disease, poisoning from formaldehyde, isocyanates, and styrene were noted. Prophylactic measures were taken in Bulgaria to lessen the occupational hazard in the productions as set forth included limitation of the work day to 6 hr, free food, additional bonus and leave, and annual physical examinations of workers.
Heat shock proteins as molecular targets for intervention in atrial fibrillation
Authors: B. J.J.M. Brundel, L. Ke, A.-J. Dijkhuis, X. Qi, A. Shiroshita-Takeshita, S. Nattel, R. H. Henning, H. H. Kampinga
Journal: Cardiovascular Research (2008)

Atrial fibrillation (AF) is the most common sustained clinical tachyarrhythmia. AF is a progressive condition as demonstrated by the finding that maintenance of normal rhythm and contractile function becomes more difficult the longer AF exists. AF causes cellular stress, which induces atrial remodelling, involving reduction in the expression of L-type Ca2+ channels and structural changes (myolysis), finally resulting in contractile dysfunction. Heat shock proteins (HSPs) comprise a family of proteins involved in the protection against different forms of cellular stress. Their classical function is the prevention of toxic protein aggregation by binding to (partially) unfolded proteins. Recent investigations reveal that HSPs prevent atrial remodelling and attenuate the promotion of AF in both cellular and animal experimental models. Furthermore, studies in humans suggest a protective role for HSPs against progression from paroxysmal AF to chronic, persistent AF. Therefore, manipulation of the HSP system may offer novel therapeutic approaches for the prevention of atrial remodelling. Such approaches may contribute to the maintenance or restoration of tissue integrity and contractile function. Ultimately, this concept may offer an additional treatment strategy to delay progression towards chronic AF and/or improve the outcome of cardioversion.
Nature of Anaemia in Rheumatoid Arthritis: III. Changes in the Bone Marrow and Their Relation to Other Features of the Disease
Authors: J. Richmond, D. L. Gardner, L. M. H. Roy, J. J. R. Duthie
Journal: Annals of the Rheumatic Diseases (1956)

Two young men, were hospitalized due to acute massive blood loss with left abdominal flank pain. In both cases renal angiography showed signs of a haemorrhagic event in the left kidney, perirenal in one and subcapsular in the other. Microaneurysms indicated a diagnosis of polyarteritis nodosa, supported by renal biopsy in one case. Renal haemorrhage is an infrequent presentation of polyarteritis nodosa. Furthermore, one patient suffered also from familial Mediterranean fever, and is the fifth reported case with this combination of diseases.
Nortriptyline Versus Fluoxetine in the Treatment of Depression and in Short-Term Recovery After Stroke: A Placebo-Controlled, Double-Blind Study
Authors: Robert G. Robinson, Susan K. Schultz, Carlos Castillo, Teresa Kopel, J. Todd Kosier, R. Mark Newman, Kathryn Curdue, Gustavo Petracca, Sergio E. Starkstein
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: This study compared nortriptyline and fluoxetine with placebo in the treatment of depression and in recovery from physical and cognitive impairments after stroke. METHOD: A total of 104 patients with acute stroke enrolled between 1991 and 1997 entered a double-blind randomized study comparing nortriptyline, fluoxetine, and placebo over 12 weeks of treatment. The majority of patients were recruited from a rehabilitation hospital in Des Moines, Iowa, but other enrollment sites were also used. Both depressed and nondepressed patients were enrolled to determine whether improved recovery could be mediated by mechanisms unrelated to depression. Nortriptyline in doses of 25 mg/day gradually increased to 100 mg/day or fluoxetine in doses of 10 mg/day gradually increased to 40 mg/day or identical placebo were given over 12 weeks. Response to treatment of depression for individual patients was defined as a greater-than-50% reduction in scores on the Hamilton Rating Scale for Depression and no longer fulfilling diagnostic criteria for major or minor depression. Improved recovery for a treatment group was defined as a significantly higher mean score from baseline to end of the treatment trial, compared with patients treated with placebo, on measures of impairment in activities of daily living and levels of cognitive and social functioning. RESULTS: Nortriptyline produced a significantly higher response rate than fluoxetine or placebo in treating poststroke depression, in improving anxiety symptoms, and in improving recovery of activities of daily living as measured by the Functional Independence Measure. There was no effect of nortriptyline or fluoxetine on recovery of cognitive or social functioning among depressed or nondepressed patients. Fluoxetine in increasing doses of 10–40 mg/day led to an average weight loss of 15.1 pounds (8% of initial body weight) over 12 weeks of treatment that was not seen with nortriptyline or placebo. CONCLUSIONS: Given the doses of medication used in this study, nortriptyline was superior to fluoxetine in the treatment of poststroke depression. Demonstrating a benefit of antidepressant treatment in recovery from stroke may require the identification of specific subgroups of patients, alternative measurement scales, or the optimal time of treatment.
Long-Term Results of Heart Operations Performed by Surgeons-in-Training
Authors: Serban C. Stoica, Dimitri Kalavrouziotis, Billie-Jean Martin, Karen J. Buth, Gregory M. Hirsch, John A. Sullivan, Roger J.F. Baskett
Journal: Circulation (2008)

We investigated the association between trainees performing supervised operations and late outcomes of patients undergoing cardiac surgery.Data were prospectively collected on patients who underwent coronary artery bypass graft surgery, aortic valve replacement, or a combination of these between 1998 and 2005 at the Maritime Heart Center, Halifax, Canada. In-hospital mortality and a composite outcome of in-hospital mortality, stroke, bleeding, intra-aortic balloon pump insertion, renal failure, and sternal infection was compared between teaching (n=1054) and nonteaching cases (n=5877). Late survival and cardiovascular hospital readmissions were also examined. To adjust for baseline risk disparities, we used logistic regression for dichotomous in-hospital outcomes and Cox proportional hazards regression for survival data. Resident cases were significantly more likely to have high-risk features such as depressed ventricular function, redo operation, and urgent or emergent procedure. Resident as primary operator was not independently associated with in-hospital mortality (OR, 1.09; 95% CI, 0.75 to 1.58; P=0.66) or with the composite outcome (OR, 1.01; 95%, CI 0.82 to 1.26; P=0.90). The Kaplan-Meier event-free survival of the 2 groups was equivalent at 1, 3, and 5 years (log-rank P=0.06). By Cox regression, resident cases were not associated with late death or cardiovascular rehospitalization (hazard ratio, 1.05; 95% CI, 0.94 to 1.17; P=0.42).Cases performed by senior-level cardiac surgery residents were more likely to have greater acuity and complexity than staff surgeon-performed cases. However, clinical outcomes were similar in the short- and long-term. Allowing residents to perform cardiac surgery is not associated with adverse patient outcomes.
Diagnosing colorectal cancer in primary care
Authors: D. Weller
Journal: BMJ (2010)

Delays and suboptimal investigations mean there is much room for improvement

Earlier diagnosis of colorectal cancer, a common malignancy in the United Kingdom, improves survival. International interest in developing strategies for improving diagnosis and reducing delay is growing. The best chance of improving symptom based diagnosis resides in primary care, where most patients with cancer first present.1 In the linked systematic review (doi:10.1136/bmj.c1269), Jellema and colleagues assess the diagnostic performance of tests for colorectal cancer, either alone or in combination with symptoms.2 

Despite intensive efforts and comprehensive national cancer frameworks,3 the UK lags behind other European countries in terms of stage of presentation and survival for common cancers, including colorectal cancer.4 It has been estimated that more than 4000, or 9% of all deaths from colon cancer, could be avoided if the UK’s survival figures were in line with mean European rates.5 This has, in part, prompted a renewed emphasis on …
293 SELECTIVE GUT DECOMTAMINATION REDUCES HEPATIC EXPRESSION OF TOLL-LIKE RECEPTOR (TLR) 4 AND DEVELOPMENT OF CIRRHOSIS BUT DOES NOT PREVENT DEVELOPMENT OF HEPATOCELLULAR CARCINOMA (HCC)
Authors: F.E.Z. Mohamed, D. Dhar, N. Shah, N. Davies, A. Habtesion, T.V. Luong, A. Winstanley, A.P. Dhillon, R.P. Mookerjee, R. Jalan
Journal: Journal of Hepatology (2012)
Role of Mycoplasma Pneumoniae in Childhood Asthma
Authors: Edward G. Brooks, Vanessa Hill, Margaret Burks, Jay Peters, Harjinder Singh, Thirumalai Kannan, Schruthi Vale, Mariana Cagle, Molly Principe, Joel Barry Baseman, Pamela R. Wood
Journal: Journal of Allergy and Clinical Immunology (2013)
The relation between total joint arthroplasty and risk for serious cardiovascular events in patients with moderate-severe osteoarthritis: propensity score matched landmark analysis
Authors: B. Ravi, R. Croxford, P. C. Austin, L. Lipscombe, A. S. Bierman, P. J. Harvey, G. A. Hawker
Journal: BMJ (2013)

<b>Objective</b> To examine whether total joint arthroplasty of the hip and knee reduces the risk for serious cardiovascular events in patients with moderate-severe osteoarthritis. <b>Design</b> Propensity score matched landmark analysis. <b>Setting</b> Ontario, Canada. <b>Participants</b> 2200 adults with hip or knee osteoarthritis aged 55 or more at recruitment (1996-98) and followed prospectively until death or 2011. <b>Main outcome measure</b> Rates of serious cardiovascular events for those who received a primary total joint arthroplasty compared with those did not within an exposure period of three years after baseline assessment. <b>Results</b> The propensity score matched cohort consisted of 153 matched pairs of participants with moderate-severe arthritis. Over a median follow-up period of seven years after the landmark date (start of the study), matched participants who underwent a total joint arthroplasty during the exposure period were significantly less likely than those who did not to experience a cardiovascular event (hazards ratio 0.56, 95% confidence interval 0.43 to 0.74, P&lt;0.001). Within seven years of the exposure period the absolute risk reduction was 12.4% (95% confidence interval 1.7% to 23.1%) and number needed to treat was 8 (95% confidence interval 4 to 57 patients). <b>Conclusions</b> Using a propensity matched landmark analysis in a population cohort with advanced hip or knee osteoarthritis, this study found a cardioprotective benefit of primary elective total joint arthroplasty.
JNJ-26481585, a Novel Second-Generation Oral Histone Deacetylase Inhibitor, Shows Broad-Spectrum Preclinical Antitumoral Activity
Authors: Janine Arts, Peter King, Ann Marin, Wim Floren, Ann Belin, Lut Janssen, Isabelle Pilatte, Bruno Roux, Laurence Decrane, Ron Gilissen, Ian Hickson, Veronique Vreys, Eugene Cox, Kees Bol, Willem Talloen, Ilse Goris, Luc Andries, Marc Du Jardin, Michel Janicot, Martin Page, Kristof van Emelen, Patrick Angibaud
Journal: Clinical Cancer Research (2009)

Histone deacetylase (HDAC) inhibitors have shown promising clinical activity in the treatment of hematologic malignancies, but their activity in solid tumor indications has been limited. Most HDAC inhibitors in clinical development only transiently induce histone acetylation in tumor tissue. Here, we sought to identify a "second-generation" class I HDAC inhibitor with prolonged pharmacodynamic response in vivo, to assess whether this results in superior antitumoral efficacy.To identify novel HDAC inhibitors with superior pharmacodynamic properties, we developed a preclinical in vivo tumor model, in which tumor cells have been engineered to express fluorescent protein dependent on HDAC1 inhibition, thereby allowing noninvasive real-time evaluation of the tumor response to HDAC inhibitors.In vivo pharmacodynamic analysis of 140 potent pyrimidyl-hydroxamic acid analogues resulted in the identification of JNJ-26481585. Once daily oral administration of JNJ-26481585 induced continuous histone H3 acetylation. The prolonged pharmacodynamic response translated into complete tumor growth inhibition in Ras mutant HCT116 colon carcinoma xenografts, whereas 5-fluorouracil was less active. JNJ-26481585 also fully inhibited the growth of C170HM2 colorectal liver metastases, whereas again 5-fluorouracil/Leucovorin showed modest activity. Further characterization revealed that JNJ-26481585 is a pan-HDAC inhibitor with marked potency toward HDAC1 (IC(50), 0.16 nmol/L).The potent antitumor activity as a single agent in preclinical models combined with its favorable pharmacodynamic profile makes JNJ-26481585 a promising "second-generation" HDAC inhibitor. The compound is currently in clinical studies, to evaluate its potential applicability in a broad spectrum of both solid and hematologic malignancies.
Using Autopsy Series To Estimate the Disease “Reservoir” for Ductal Carcinoma in Situ of the Breast: How Much More Breast Cancer Can We Find?
Authors: H. Gilbert Welch
Journal: Annals of Internal Medicine (1997)

To determine how many cases of breast cancer might be found if women not known to have the disease were thoroughly examined (the disease "reservoir").MEDLINE search from 1966 to the present.Hospital-based and forensic autopsy series examining women not known to have had breast cancer during life.Observed prevalence of occult invasive breast cancer or ductal carcinoma in situ (DCIS) in which the number of women who were given a diagnosis was the numerator and the number of women examined was the denominator. For each autopsy series, we attempted to ascertain the level of scrutiny (sampling method, number of slides examined) given to the pathologic specimens.Among seven autopsy series of women not known to have had breast cancer during life, the median prevalence of invasive breast cancer was 1.3% (range, 0% to 1.8%) and the median prevalence of DCIS was 8.9% (range, 0% to 14.7%). Prevalences were higher among women likely to have been screened (that is, women 40 to 70 years of age). The mean number of slides examined per breast ranged from 9 to 275; series that reported higher levels of scrutiny tended to discover more cases of cancer.A substantial reservoir of DCIS is undetected during life. How hard pathologists look for the disease and, perhaps, their threshold for making the diagnosis are potentially important factors in determining how many cases of DCIS are diagnosed. The latter has important implications for what it means to have the disease.
SELENOPROTEIN P: An Extracellular Protein with Unique Physical Characteristics and a Role in Selenium Homeostasis
Authors: Raymond F. Burk, Kristina E. Hill
Journal: Annual Review of Nutrition (2005)

Selenoprotein P is an abundant extracellular glycoprotein that is rich in selenocysteine. It has two domains with respect to selenium content. The N-terminal domain of the rat protein contains one selenocysteine residue in a UxxC redox motif. This domain also has a pH-sensitive heparin-binding site and two histidine-rich amino acid stretches. The smaller C-terminal domain contains nine selenocysteine and ten cysteine residues. Four isoforms of selenoprotein P are present in rat plasma. They share the same N terminus and amino acid sequence. One isoform is full length and the three others terminate at the positions of the second, third, and seventh selenocysteine residues. Selenoprotein P turns over rapidly in rat plasma with the consequence that approximately 25% of the amount of whole-body selenium passes through it each day. Evidence supports functions of the protein in selenium homeostasis and oxidant defense. Selenoprotein P knockout mice have very low selenium concentrations in the brain, the testis, and the fetus, with severe pathophysiological consequences in each tissue. In addition, those mice waste moderate amounts of selenium in the urine. Selenoprotein P binds to endothelial cells in the rat, and plasma levels of the protein correlate with prevention of diquat-induced lipid peroxidation and hepatic endothelial cell injury. The mechanisms of these apparent functions remain speculative and much work on the mechanism of selenoprotein P function lies ahead. Measurement of selenoprotein P in human plasma has shown that it is depressed by selenium deficiency and by cirrhosis. Selenium supplementation of selenium-deficient human subjects showed that glutathione peroxidase activity was optimized before selenoprotein P concentration was optimized, indicating that plasma selenoprotein P is the better index of human selenium nutritional status.
MicroRNA Expression Signature and Antisense-Mediated Depletion Reveal an Essential Role of MicroRNA in Vascular Neointimal Lesion Formation
Authors: Ruirui Ji, Yunhui Cheng, Junming Yue, Jian Yang, Xiaojun Liu, He Chen, David B. Dean, Chunxiang Zhang
Journal: Circulation Research (2007)

MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate about 30% of the encoding genes of the human genome. However, the role of miRNAs in vascular disease is currently completely unknown. Using microarray analysis, we demonstrated for the first time that miRNAs are aberrantly expressed in the vascular walls after balloon injury. The aberrantly expressed miRNAs were further confirmed by Northern blot and quantitative real-time polymerase chain reaction. Modulating an aberrantly overexpressed miRNA, miR-21, via antisense-mediated depletion (knock-down) had a significant negative effect on neointimal lesion formation. In vitro, the expression level of miR-21 in dedifferentiated vascular smooth muscle cells was significantly higher than that in fresh isolated differentiated cells. Depletion of miR-21 resulted in decreased cell proliferation and increased cell apoptosis in a dose-dependent manner. MiR-21–mediated cellular effects were further confirmed in vivo in balloon-injured rat carotid arteries. Western blot analysis demonstrated that PTEN and Bcl-2 were involved in miR-21–mediated cellular effects. The results suggest that miRNAs are novel regulatory RNAs for neointimal lesion formation. MiRNAs may be a new therapeutic target for proliferative vascular diseases such as atherosclerosis, postangioplasty restenosis, transplantation arteriopathy, and stroke.
An Epilepsy/Dyskinesia-Associated Mutation Enhances BK Channel Activation by Potentiating Ca2+ Sensing
Authors: Junqiu Yang, Gayathri Krishnamoorthy, Akansha Saxena, Guohui Zhang, Jingyi Shi, Huanghe Yang, Kelli Delaloye, David Sept, Jianmin Cui
Journal: Neuron (2010)