tbuckley/cabot-search huggingface dataset:
Ischemic preconditioning suppresses the noradrenaline turnover in the rat heart
Authors: Y Takasaki
Journal: Cardiovascular Research (1998)

Objective: The mechanism by which ischemic preconditioning protects the heart is presumed to be related to the reduction of energy consumption during a subsequent myocardial infarction. Since the sympathetic nervous system enhances cardiac function and energy consumption, we investigated the relation between ischemic preconditioning and the turnover rate of noradrenaline (NA) in the rat heart. Methods: The effect of 3 cycles of 5-min occlusions of the rat left coronary artery on changes in arterial blood pressure and heart rate provoked by a subsequent 30 min of ischemia were examined until 60 min after reperfusion. The effect of 3 cycles of occlusions on the infarct size was also evaluated 60 min after reperfusion by comparing the infarcted area with the area at risk in these animals (6 per preconditioned and sham-operated group). The tissue concentration of NA during sustained ischemia was determined in the left ventricle, the intraventricular septum, and the right ventricle in the preconditioned and sham-operated groups. Changes in the turnover rate of NA after 3 cycles of occlusions were also evaluated by assessing the alpha-methyl-p-tyrosine-induced depletion of NA (n=7 per group). Results: A series of transient occlusions reduced the infarct size 60 min after a sustained ischemia for 30 min. Arterial pressure and heart rate were not affected. The concentration of NA was decreased in the left ventricle 60 min after the onset of sustained ischemia in both the preconditioned and sham-operated groups. The treatment with alpha-methyl-p-tyrosine decreased the NA concentration in all regions of the heart in the sham-operated group after 60 min. However, the treatment with alpha-methyl-p-tyrosine did not deplete the NA concentration in both the occluded and nonoccluded regions in the preconditioned group. Conclusions: Transient ischemia ameliorated the heart injury induced by a subsequent sustained ischemia, as assessed histologically. The activity of the sympathetic nervous system in all regions of the heart was reduced by transient ischemia in the left coronary vascular bed. These findings suggest that the inhibition of the sympathetic nervous system by the treatment of ischemic preconditioning takes part in the cardiac protection.
Efficacy of RAD001 (Everolimus) and Octreotide LAR in Advanced Low- to Intermediate-Grade Neuroendocrine Tumors: Results of a Phase II Study
Authors: James C. Yao, Alexandria T. Phan, David Z. Chang, Robert A. Wolff, Kenneth Hess, Sanjay Gupta, Carmen Jacobs, Jeannette E. Mares, Andrea N. Landgraf, Asif Rashid, Funda Meric-Bernstam
Journal: Journal of Clinical Oncology (2008)

Evaluate the activity of everolimus (RAD001) in combination with octreotide long-acting repeatable (LAR) in patients with advanced low- to intermediate-grade neuroendocrine tumors.Treatment consisted of RAD001 5 mg/d (30 patients) or 10 mg/d (30 patients) and octreotide LAR 30 mg every 28 days. Thirty carcinoid and 30 islet cell patients were enrolled.Intent-to-treat response rate was 20%. Per protocol, there were 13 with partial responses (22%), 42 with stable disease (SD; 70%), and five patients with progressive disease (8%). Overall median progression-free survival (PFS) was 60 weeks. Median PFS for patients with known SD at entry was longer than for those who had progressive disease (74 v 50 weeks; P < .01). Median overall survival has not been reached. One-, 2-, and 3-year survival rates were 83%, 81%, and 78%, respectively. Among 37 patients with elevated chromogranin A, 26 (70%) achieved normalization or more than 50% reduction. Most common toxicity was mild aphthous ulceration. Grade 3/4 toxicities occurring in >or= 10% of patients included hypophosphatemia (11%), fatigue (11%), and diarrhea (11%). Treatment was associated with a dose-dependent rise in lactate dehydrogenase (LDH). Those with lower than 109 U/L rise in LDH at week 4 had shorter PFS (38 v 69 weeks; P = .01). Treatment was also associated with a decrease in proliferation marker Ki-67 among patients who underwent optional paired pre- and post-treatment biopsy (P = .04).RAD001 at 5 or 10 mg/d was well tolerated in combination with octreotide LAR, with promising antitumor activity. Confirmatory studies are ongoing.
Platelet-Derived Growth Factor-AA Is an Essential and Autocrine Regulator of Vascular Endothelial Growth Factor Expression in Non–Small Cell Lung Carcinomas
Authors: Yasunori Shikada, Yoshikazu Yonemitsu, Takaomi Koga, Mitsuho Onimaru, Toshiaki Nakano, Shinji Okano, Shihoko Sata, Kazunori Nakagawa, Ichiro Yoshino, Yoshihiko Maehara, Katsuo Sueishi
Journal: Cancer Research (2005)

Abstract It is widely accepted that angiogenesis is required for tumor progression. Vascular endothelial growth factor (VEGF) is a key molecule for tumor angiogenesis; however, its expressional regulation is not well understood during all stages of tumorigenesis. Using cell lines and surgical specimens of human non–small cell lung cancers (NSCLCs), we here show that platelet-derived growth factor-AA (PDGF-AA) is an essential autocrine regulator for VEGF expression. To directly assess the expression of PDGF-AA–dependent VEGF and its roles in tumorigenesis, we stably transfected established cell lines with their antisense genes. In addition, the levels of PDGF-AA and VEGF expression in surgical sections were measured and compared with clinicopathologic findings such as tumor size and patient prognosis. PDGF-AA tightly regulated VEGF expression and had a greater effect on tumor size and patient prognosis than did VEGF in both cell lines and surgical sections. PDGF-AA expression was not seen in the atypical adenomatous hyperplasia at all, whereas VEGF was occasionally seen. Furthermore, the frequency of VEGF expression was higher in advanced NSCLCs than in precancerous lesions, which was tightly correspondent to the results for PDGF-AA. These results indicate that PDGF-AA is an important regulator of the frequency and level of VEGF expression during the transition from a precancerous lesion to advanced cancer. The PDGF-AA/VEGF axis, therefore, may be a ubiquitous autocrine system for enhancing angiogenic signals, and PDGF-AA, and its related pathways could be a more efficient target of antiangiogenic therapy for cancers than VEGF and its pathways.
A simple, inexpensive urine test of smoking.
Authors: H Peach, G A Ellard, P J Jenner, R W Morris
Journal: Thorax (1985)

Three novel colorimetric methods of detecting urinary nicotine metabolites called the barbituric acid, diethylthiobarbituric acid (DETB), and DETB extraction methods were evaluated for use as a simple, cheap, objective test of smoking. Urine samples were collected from 103 male smokers and 78 male non-smokers working at two London factories. The smokers recorded the number of cigarettes smoked over the previous 36 hours. All three methods correctly classified the smokers. The DETB extraction method had a lower false positive rate (averaging 3% on morning and afternoon urine samples) than either the DETB or the barbituric acid method (12% and 6% respectively) and was the best procedure for classifying subjects as "smokers" or "non-smokers." When a quantitative variant of the barbituric acid method was used there was a significant correlation (r = 0.85, p less than 0.001) between the ratios of urinary nicotine metabolites to creatinine and the number of cigarettes smoked. The ratios for smokers of 6-15, 16-25, and 26 or more cigarettes, however, overlapped considerably. The methods can be performed very rapidly and the reagent cost is equivalent to less than 1p per test.
Surfactant protein D in serum from patients with allergic bronchopulmonary aspergillosis
Authors: M. Krane, M. Griese
Journal: European Respiratory Journal (2003)

Surfactant protein D (SP‐D) interacts with Aspergillus fumigatus and is strongly increased in the lavage from animals with acute allergic reactions to the fungus, suggesting a central role for SP‐D. As the course of cystic fibrosis (CF) is often complicated by an allergic bronchopulmonary aspergillosis (ABPA), the authors hypothesised that SP‐D may also be increased in serum during an ABPA, potentially assisting in its diagnosis and follow-up. In 22 patients with CF (11 with ABPA, 11 matched without ABPA) and 19 control patients without a pulmonary disease, SP‐D concentrations in serum were assessed by an enzyme immunoassay. Serum SP‐D in CF patients (130±16 ng·mL −1 (mean±sem)) was significantly higher than in the controls without lung disease (66±8 ng·mL −1 ). During the whole ABPA‐episode, SP‐D level did not change significantly, despite large changes of total serum immunoglobulin E. There was a clear negative correlation between SP‐D concentration and overall lung function, i.e. forced expiratory volume in one second and forced vital capacity. Serum level of surfactant protein D may be of value to follow pulmonary function and lung injury in cystic fibrosis patients. Surfactant protein D serum levels are not helpful for the diagnosis and follow-up of an allergic bronchopulmonary aspergillosis episode, contrary to what was expected from animal experiments.
A proinflammatory role for IL-18 in rheumatoid arthritis
Authors: J. Alastair Gracie, Rosalyn J. Forsey, Woon Ling Chan, Ashley Gilmour, Bernard P. Leung, Morag R. Greer, Kristy Kennedy, Robert Carter, Xiao-Qing Wei, Damo Xu, Max Field, Alan Foulis, Foo Y. Liew, Iain B. McInnes
Journal: Journal of Clinical Investigation (1999)

IL-18 is a novel cytokine with pleiotropic activities critical to the development of T-helper 1 (Th1) responses. We detected IL-18 mRNA and protein within rheumatoid arthritis (RA) synovial tissues in significantly higher levels than in osteoarthritis controls. Similarly, IL-18 receptor expression was detected on synovial lymphocytes and macrophages. Together with IL-12 or IL-15, IL-18 induced significant IFN-γ production by synovial tissues in vitro. IL-18 independently promoted GM-CSF and nitric oxide production, and it induced significant TNF-α synthesis by CD14+ macrophages in synovial cultures; the latter effect was potentiated by IL-12 or IL-15. TNF-α and IFN-γ synthesis was suppressed by IL-10 and TGF-β. IL-18 production in primary synovial cultures and purified synovial fibroblasts was, in turn, upregulated by TNF-α and IL-1β, suggesting that monokine expression can feed back to promote Th1 cell development in synovial membrane. Finally, IL-18 administration to collagen/incomplete Freund's adjuvant–immunized DBA/1 mice facilitated the development of an erosive, inflammatory arthritis, suggesting that IL-18 can be proinflammatory in vivo. Together, these data indicate that synergistic combinations of IL-18, IL-12, and IL-15 may be of importance in sustaining both Th1 responses and monokine production in RA.
COMPARISON OF FOUR REGIMENS IN NEWLY ADMITTED FEMALE SCHIZOPHRENICS
Authors: ROBIE T. CHILDERS
Journal: American Journal of Psychiatry (1964)

A group of 80 newly admitted schizophrenics were placed at random in 4 treatment groups. Group A received ECT and had a 55% improvement rate. Group B received fluphenazine and Group C received chlorpromazine with each having a 45% improvement rate. Group D received ECT and chlorpromazine and had an 80% improvement rate.
Spontaneous autoimmunity prevented by thymic expression of a single self-antigen
Authors: Jason DeVoss, Yafei Hou, Kellsey Johannes, Wen Lu, Gregory I. Liou, John Rinn, Howard Chang, Rachel R. Caspi, Lawrence Fong, Mark S. Anderson
Journal: The Journal of Experimental Medicine (2006)

The expression of self-antigen in the thymus is believed to be responsible for the deletion of autoreactive T lymphocytes, a critical process in the maintenance of unresponsiveness to self. The Autoimmune regulator (Aire) gene, which is defective in the disorder autoimmune polyglandular syndrome type 1, has been shown to promote the thymic expression of self-antigens. A clear link, however, between specific thymic self-antigens and a single autoimmune phenotype in this model has been lacking. We show that autoimmune eye disease in aire-deficient mice develops as a result of loss of thymic expression of a single eye antigen, interphotoreceptor retinoid-binding protein (IRBP). In addition, lack of IRBP expression solely in the thymus, even in the presence of aire expression, is sufficient to trigger spontaneous eye-specific autoimmunity. These results suggest that failure of thymic expression of selective single self-antigens can be sufficient to cause organ-specific autoimmune disease, even in otherwise self-tolerant individuals.
The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots.
Authors: Leslie C Costello, Renty B Franklin
Journal: Molecular Cancer (2006)

The genetic and molecular mechanisms responsible for and associated specifically with the development and progression of malignant prostate cells are largely unidentified. In addition, despite its implication in virtually all malignant cells, the role of altered cellular metabolism as an essential factor in prostate malignancy has been largely ignored. Moreover, the intermediary metabolism of normal prostate as well as malignant prostate cells is among the least studied and most poorly understood of all mammalian cells. Some important factors, especially the role of zinc, have been identified and implicated in the development and progression of prostrate malignancy. In this review, we provide a current and updated integrated assessment of the relationships of intermediary metabolism in normal prostate and in prostate cancer. The experimental and clinical evidence that leads to the formulation of concepts of normal and malignant prostate metabolism is presented. The evidence for a concept of zinc as a tumor suppressor agent and Zip1 zinc transporter as a tumor-suppressor gene is described. The specialized function of the normal prostate glandular epithelium to produce and secrete enormously high levels of citrate involves and requires unique intermediary metabolism activities that are not generally associated with other normal mammalian cells. The accumulation of zinc by these cells is an essential factor in this unique metabolic relationship. In malignancy, the normal zinc-accumulating citrate-producing epithelial cells are metabolically transformed to citrate-oxidizing cells that lose the ability to accumulate zinc. A genetic alteration in the expression of ZIP1 zinc transporter is associated with this metabolic transformation. These genetic/metabolic relationships have important consequences on citrate-related metabolism, bioenergetics, cell proliferation and invasive capabilities of the malignant cells, which result in tumor-suppression characteristics. The genetic/metabolic relationships in normal prostate glandular epithelium are driven by the unique function to accumulate and secrete citrate. The genetic/metabolic transformation of the prostate malignant cells is driven by the metabolic/bioenergetic, growth/proliferative, and invasive/migration requirements of the malignant process. Zinc is critical to these relationships. An understanding of these genetic/metabolic relationships provides new directions and opportunities for development of regimens for the prevention and treatment of prostate cancer. Important insight into the genetic/metabolic requirements of the prostate malignant process is now evolving. Most importantly at this time, an appreciation and recognition of the genetic/metabolic significance and implications in the development of prostate malignancy is imperative; and much needed research in this area is essential. Hopefully, this review will help to achieve these goals.
Improving Diabetic Retinopathy Screening
Authors: William Jackson
Journal: Diabetes Care (2002)

The article by Gomez-Ulla et al. (1) in this issue of Diabetes Care presents a working protocol to alleviate the conundrum of providing appropriate retinal screening to an increasing diabetic population.

Despite more than 40 years of increasingly effective photocoagulation therapy and more than 30 years of advances in vitreous surgical techniques and results, diabetic retinopathy (DR) persists as a major cause of blindness in the 20- to 74-year-old population in all countries.

Despite an increasingly clear understanding of the role of systemic factors in the production and progression of DR, we are still struggling with a major visual health crisis in regard to the prevention of diabetic blindness (2–4).

Despite the improved understanding of the importance of timely diagnosis and therapy of DR, an estimated one-half of the diabetic population does not receive annual dilated examinations. Controversy exists regarding the frequency of retinal examinations for well-controlled type 2 diabetic patients without retinopathy at baseline. Type 2 diabetic patients need a dilated …
Lyell's Toxic Epidermal Necrolysis
Authors: A. Holzel
Journal: BMJ (1967)

We are surprised that in the majority of their cases the common bile duct was sufficiently dilated to allow a 2-cm.transverse incision (producing about a 1.5-cm.stoma after two-layered anastomosis) and also surprised that with a stoma that size they had no cases of cholangitis.On preliminary review, our experience is that a 2.5-cm.stoma is advisable, as recommended by Capper,' and this can be obtained in most cases only by a longitudinal incision in the common bile duct and a transverse (or, preferably, longitudinal) incision in the duodenum.The importance of the larger stoma seems to be to allow free return of duodenal contents from the common bile duct rather than to prevent stenosis, but we are investigating these points further.-Weare, etc.,
How helpful is NHS Direct? Postal survey of callers
Authors: A O'Cathain, J F Munro, J P Nicholl, E Knowles
Journal: BMJ (2000)

NHS Direct, the new 24 hour telephone advice line staffed by nurses, was established to "provide easier and faster information for people about health, illness and the NHS so that they are better able to care for themselves and their families." 1In March 1998, three first wave sites started in Lancashire, Milton Keynes, and Northumbria.As part of an extensive evaluation of this new service, 2 we surveyed callers to determine how helpful they found the advice offered.
Cloning of local growth factors involved in the determination of muscle mass
Authors: Geoffrey Goldspink
Journal: British Journal of Sports Medicine (2000)

Unlike the cells of many tissues, muscle and neuronal cells do not replicate throughout life. Therefore there has to be an effective mechanism of inducing local repair and preventing cell death. We have identified and cloned two growth factors that are expressed by muscle when it is subjected to activity which are derived from the insulin like growth factor-I (IGF-I) gene by alternative splicing.1, 2 One isoform, muscle L.IGF-I, is very similar to the liver type of IGF-I. The other is a new growth factor that could only be detected in exercised or stretched muscle. This has been called mechano growth factor (MGF) to distinguish it from liver IGF-I which has a systemic mode of action. The structure of the cDNA of this isoform indicates that it has different exons from the liver types and is not glycosylated.1 Therefore it is smaller and has a shorter half life than liver IGF-I unless it is bound to its tissue binding protein. Unlike hormones, the site and mode of action of growth factors are determined to a large extent by their specific binding proteins.

Both muscle isoforms are upregulated by stretch and overload and the evidence indicates that, during exercise, muscle L.IGF-I contributes significantly to circulating levels of IGF-I.2, 3 MGF, …
A Lecture on THE DEBILITATED CHILD
Authors: C. W. Vining
Journal: BMJ (1929)

WE are living at a time wlhen prevention of disease and tho recognitioni of its earliest -signs are being called for in nio uncertain voice, and those of us' who are specially engaged in woik l amonigst children realize only too well tho difficulties met with in the understanding and interpretation of defects in health at ani age periud whlen one, w-ould expect the problem to be in its simplest form.The system ill vogue ill this country, while it offers liberty of the subject anld free clhoice of doctor, has the disadvantage that it leaves tlhe decision as to.whlether the child neeeds miiedical attention to the palent rather than to tlhe expert.No doubt the development of the school nedical service will do a great deal to remedy this.
Psoriasis in Sri-Lanka—a computer analysis of 1366 cases
Authors: D.A. GUNAWARDENA, K.A. GUNAWARDENA, N.S. VASANTHANATHAN, J.A. GUNAWARDENA
Journal: British Journal of Dermatology (1978)

A clinical and epidemiological study of psoriasis in Sri-Lanka is presented. The prevalence in the population is estimated to be over 0.4%. The clinic incidence was 8.7%; of these 53.2% were male, and 46.8% female and 8.3% reported a family history of the disease. The mean age at onset was 25.2 years. The frequency distribution for the age at onset was bimodal with peaks at the second and fifth decades. The age at onset was significantly low in females, in patients with a family history of the disease, in those affected by weather changes and in patients whose disease was precipitated by sore throats. The existence of natural subpopulations of patients is suggested. Clinical types and complications of the disease were not essentially different from those observed in the West.
Regulation of the Proximal Tubular Sodium/Proton Exchanger NHE3 in Rats with Puromycin Aminonucleoside (PAN)-Induced Nephrotic Syndrome
Authors: Valérie Besse-Eschmann, Jelena Klisic, Vera Nief, Michel Le Hir, Brigitte Kaissling, Patrice M. Ambühl
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Excessive proteinuria due to loss of glomerular permselectivity in nephrotic syndrome can cause disturbances in renal salt and water handling with edema formation. Apart from oncotic and hydrostatic mechanisms associated with hypoalbuminemia, primary derangements in renal tubular sodium transport may contribute to the pathogenesis of nephrotic edema. Whereas there is evidence for an increase of cortical collecting duct sodium reabsorption in nephrotic rats, it remains controversial whether proximal tubule sodium transport may also be activated in this condition. The regulation of the cortical Na/H exchanger NHE3, the main pathway for Na reabsorption in the proximal tubule (PT), was investigated in rats with puromycin aminonucleoside (PAN)-induced nephrotic syndrome. PAN rats developed reduced GFR, severe proteinuria, and sodium retention within 3 d. After 10 d, immunoblots of brush border vesicles revealed a decreased abundance of NHE3 in nephrotic animals. However, the Na/H antiporter activity in the same vesicle preparations was not significantly altered. Antiporter activity normalized for NHE3 protein was increased by 88% in nephrotic animals (P = 0.025). Immunohistochemistry with the same polyclonal antibody as for immunoblots revealed a decrease of NHE3 abundance in PT. In contrast, immunoreactivity for the monoclonal antibody 2B9, which specifically recognizes the non-megalin-associated, transport-competent pool of NHE3, was higher in PAN-treated rats than in controls. In conclusion, increased sodium reabsorption might be associated with a shift of NHE3 from an inactive pool to an active pool, thus contributing to sodium retention in a state of proteinuria.
Argentaffin cells in ulcerative colitis
Authors: J. M. Skinner, R. Whitehead, J. Piris
Journal: Gut (1971)

The number of argentaffin cells have been counted in the epithelium of rectal biopsies taken from a series of patients with ulcerative colitis and a control group. The number of argentaffin cells was decreased in ulcerative colitis, but this decrease was not related either to the severity of the inflammation or to the duration of illness.