tbuckley/cabot-search huggingface dataset:
Pathogenesis of arterial hypotension in cirrhotic rats with ascites: Role of endogenous nitric oxide
Authors: Joan Clària, Wladimiro Jiménez, Josefa Ros, Mónica Asbert, Anna Castro, Vicente Arroyo, Francisca Rivera, Joan Rodés
Journal: Hepatology (1992)

Nitric oxide is a vasodilator tonically secreted by endothelial cells that is involved in the regulation of arteriolar tone. This study, which includes two protocols, was performed to investigate whether nitric oxide plays a role in the pathogenesis of arterial hypotension in cirrhosis with ascites. In protocol 1, the administration of increasing doses (25, 50, 250, 500 and 1,000 micrograms.kg-1.min-1) of the nitric oxide biosynthesis inhibitor N omega-nitro-L-arginine to 18 conscious rats with cirrhosis and ascites produced, at each dose tested, a significantly greater increase in arterial pressure than in 17 conscious control rats. At the lowest dose of N omega-nitro-L-arginine, arterial pressure significantly rose in cirrhotic rats but not in controls. In protocol 2, arterial pressure, estimated renal plasma flow, glomerular filtration rate and sodium excretion were measured in 12 cirrhotic rats with ascites and 10 control rats before and during the sequential infusion of previously selected doses of N omega-nitro-L-arginine (25, 50 and 250 micrograms.kg-1.min-1). Changes in arterial pressure reproduced those observed in protocol 1. In control rats, N omega-nitro-L-arginine caused a decrease in estimated renal plasma flow without affecting glomerular filtration rate or sodium excretion. In contrast, N omega-nitro-L-arginine administration to cirrhotic animals did not produce any appreciable renal vasoconstrictor effect, and it increased glomerular filtration rate and sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Has mortality related to alcohol decreased in Sweden?
Authors: A Romelsjo, G Agren
Journal: BMJ (1985)

In Sweden sales of alcohol dropped 17% from 1976 to 1982. Similarly, comparison of data from 1979 and 1982 shows that the mortality from cirrhosis of the liver declined appreciably, by 28% in men and 29% in women. During 1979-82 mortality from pancreatitis also declined noticeably, by 30% in men and 36% in women. By contrast, no decrease occurred in mortality from alcoholic psychosis, alcoholism, or alcohol intoxication. The decrease in mortality from cirrhosis of the liver and pancreatitis is probably explained by a decrease in the consumption of alcohol among an important subgroup of high consumers of alcohol. The lack of a decrease in mortality from alcoholic psychosis, alcoholism, and alcohol intoxication may be because such diagnoses are often made in socially deteriorated, more dependent alcoholic subjects who have not been able to reduce their consumption.
Pathogenesis of ascites and hepatorenal syndrome.
Authors: S P Wilkinson, K P Moore, V Arroyo
Journal: Gut (1991)

Ascites is one of the most common complications of cirrhosis and has a one year mortality of up to 50%.For fluid to accumulate in any clinical situation the amount of sodium ingested must exceed that excreted by the kidneys and the virtual absence of sodium from the urine of ascitic patients was first documented by Farns- worth and Krakusin in 1948.' Five years later Chart and Shipley showed such patients to have an excess of a sodium retaining hormone in their urine (later identified as aldosterone).2Four decades after these discoveries the inter-relationship between renal function, hormonal changes and ascites formation remains controversial.At the other extreme of functional renal changes up to 85% ofpatients dying with cirrhosis have renal failure and, where there is no apparent cause other than the liver disease, is termed 'hepato- renal syndrome.'In 1863 Flint noted that pro- teinuria was uncommon and kidney morphology often normal, but some patients showed a variety of renal parenchymal changes.3Hecker and Sherlock confirmed the absence of proteinuria and normal histology in many patients and reported very low urine sodium concentrations - findings of a prerenal type of uraemia.
Expression of the antigen recognized by mAb GB36 in normal skin and in skin tumours
Authors: P. HOFMAN, J.Ph. LACOUR, C. EMILIOZZI, M.J. STAQUET, B.L. HSI, B. ROSSI, J.P. ORTONNE
Journal: British Journal of Dermatology (1995)

GB36, a mouse monoclonal antibody (mAb) raised against an epithelial antigen of the human trophoblast, reacts with the epithelial basement membrane of chorionic villi; it does not react with the invasive extravillous cytotrophoblast. Expression and characterization of the antigen of GB36 (designated GBA36) were investigated in normal keratinocytes by immunoprecipitation, immunofluorescence and immunoelectron microscopic studies. Immunoprecipitation experiments demonstrated that the proteins identified on keratinocytes by mAb GB36 and a rat mAb anti-integrin alpha 6 (GoH3) were the same. Using immunofluorescence and immunoelectron microscopic methods, GBA36 was localized on the cell membrane facing the epithelial basal lamina of basal keratinocytes. GBA36 distribution in benign and malignant skin tumours was evaluated by immunostaining methods (immunofluorescence and immunoperoxidase). Analysis of tumours revealed that whereas benign epithelial tumours and intradermal naevi displayed high levels of GBA36, the expression of this antigen decreased progressively in spinocellular and basal cell carcinomas, and in cutaneous melanomas in relation to invasiveness. During cell transformation, GBA36 undergoes quantitative alterations, and expression is down-regulated. Although the functional relevance of these changes remains unknown, the correlation of decreased GBA36 expression with tumour progression may indicate a role for altered integrin expression in tissue invasion by human skin carcinoma and melanoma.
Lipid Mediators in Health and Disease: Enzymes and Receptors as Therapeutic Targets for the Regulation of Immunity and Inflammation
Authors: Takao Shimizu
Journal: The Annual Review of Pharmacology and Toxicology (2008)

Prostaglandins, leukotrienes, platelet-activating factor, lysophosphatidic acid, sphingosine 1-phosphate, and endocannabinoids, collectively referred to as lipid mediators, play pivotal roles in immune regulation and self-defense, and in the maintenance of homeostasis in living systems. They are produced by multistep enzymatic pathways, which are initiated by the de-esterification of membrane phospholipids by phospholipase A2s or sphingo-myelinase. Lipid mediators exert their biological effects by binding to cognate receptors, which are members of the G protein–coupled receptor superfamily. The synthesis of the lipid mediators and subsequent induction of receptor activity is tightly regulated under normal physiological conditions, and enzyme and/or receptor dysfunction can lead to a variety of disease conditions. Thus, the manipulation of lipid mediator signaling, through either enzyme inhibitors or receptor antagonists and agonists, has great potential as a therapeutic approach to disease. In this review, I summarize our current state of knowledge of the synthesis of lipid mediators and the function of their cognate receptors, and discuss the effects of genetic or pharmacological ablation of enzyme or receptor function on various pathophysiological processes.
Computed tomography in adult respiratory distress syndrome: what has it taught us?
Authors: P Pelosi, S Crotti, L Brazzi, L Gattinoni
Journal: European Respiratory Journal (1996)

Computed tomography (CT) has played an important role in improving our knowledge of the pathophysiology of the adult respiratory distress syndrome (ARDS), and in determining the morphological and functional relationships of different manoeuvres commonly used in the therapeutic management of this syndrome (changes in body position, application of positive end-expiratory pressure (PEEP) and mechanical ventilation). During the early phase of the disease, the ARDS lung is characterized by a homogenous alteration of the vascular permeability. Thus, oedema accumulates evenly in all lung regions with a nongravitational distribution (homogenous lung). The increased lung weight, due to increased oedema, causes a collapse of the lung regions along the vertical axis, through the transmission of hydrostatic forces (compression atelectasis). Thus, the lesions appear mainly in the dependent lung regions (dishomogeneous lung). During inspiration, at plateau pressure, the pulmonary units reopen and, if the PEEP applied is adequate, they stay open during the following expiration. Adequate PEEP is equal to or higher than the hydrostatic forces compressing that unit. Prone position is another manoeuvre which allows previously collapsed lung regions to reopen and, conversely, compresses previously aerated regions, reversing the distribution of gravitational forces. During late ARDS, there is less compression atelectasis and the lung undergoes structural changes, due to the reduced amount of oedema. This is usually associated with CO2 retention and the development of emphysema-like lesions. In conclusion, computed tomography is not only a research tool, but a useful technique which allows a better understanding of the progressive change in strategy needed to ventilate the adult respiratory distress syndrome lung at different stages of the disease.
Mammography Screening and Increased Incidence of Breast Cancer in Wisconsin
Authors: Paula M. Lantz, Patrick L. Remington, Polly A. Newcomb
Journal: JNCI Journal of the National Cancer Institute (1991)

The age-adjusted incidence of breast cancer among Wisconsin women age 40 and older has increased by almost one third since the early 1980s. To estimate what portion of the observed increase in breast cancer incidence is due to mammography screening, we developed a model of the lead-time effect of this screening test and its impact on incidence. The model incorporates annual age-specific information including 1) the expected number of cases, 2) the rate of screening, 3) the detection ratio of screening mammography, and 4) the lead time of screening mammography. For women 40 years of age and older, the model predicts a 25% increase in incidence, compared with an observed increase of 28%. Overall, mammography screening explains 74% of the difference between the expected and observed number of cases over the study period. A greater portion of the increase in incidence among postmenopausal women is attributed to mammography screening than among younger women. The increase in the use of mammography appears to account for most but not all of the increased incidence of breast cancer in Wisconsin.
Rhinoconjunctival sensitization to hydrolyzed wheat protein in facial soap can induce wheat-dependent exercise-induced anaphylaxis
Authors: Yuma Fukutomi, Yasuharu Itagaki, Masami Taniguchi, Akemi Saito, Hiroshi Yasueda, Takuya Nakazawa, Maki Hasegawa, Hiroyuki Nakamura, Kazuo Akiyama
Journal: Journal of Allergy and Clinical Immunology (2010)
Rugby World Cup 2003 injury surveillance project
Authors: J P Best, A S McIntosh, T N Savage
Journal: British Journal of Sports Medicine (2005)

Objectives: To study match injury patterns and incidence during the Rugby World Cup 2003 (RWC 2003); to compare these patterns and rates with comparative rugby injury data; and to assess differences between teams playing at different levels (eight finalists v 12 non-finalists). Methods: Data were collected prospectively during the tournament. All injuries were recorded by the 20 participating team physicians. These were submitted to the tournament medical officer. An injury was defined as an event which forced a player either to leave the field or to miss a subsequent game or both. Results: 189 injuries were recorded over 48 matches. This corresponds to 97.9 injuries per 1000 player-hours. Pool matches yielded a higher injury rate than non-pool matches. The 12 non-finalist teams sustained significantly higher injury rates than the eight finalist teams. The player positions open side flanker, inside centre, and number 8 were the most frequently injured positions. There was a low concussion rate, which may reflect under-reporting. The non-finalist teams had a higher rate of recurrent injury. Conclusions: The injury rate was higher than comparative data. Mismatches in the areas of skill, fitness, and the availability of resources for medical care of players may explain these differences.
“Apoptotic” Myocytes in Infarct Area in Rabbit Hearts May Be Oncotic Myocytes With DNA Fragmentation
Authors: Michiya Ohno, Genzou Takemura, Atsuko Ohno, Jun Misao, Yukihiro Hayakawa, Shinya Minatoguchi, Takako Fujiwara, Hisayoshi Fujiwara
Journal: Circulation (1998)

Background —Modes of cell death have been defined morphologically as apoptosis and oncosis. Infarcted myocytes have been reported to show apoptosis, as revealed by DNA fragmentation by DNA ladder and by in situ terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling (TUNEL) at the light microscopic level. We investigated whether TUNEL-positive infarcted myocytes have apoptotic or oncotic ultrastructures by using electron microscopic TUNEL, which can simultaneously observe the ultrastructure and DNA fragmentation of the same myocytes. Methods and Results —Thirty rabbits were divided into 5 groups (n=6 each) that were subjected to a sham operation or to 30-minute ischemia followed by 0-minute, 30-minute, 2-hour, or 4-hour reperfusion of a coronary artery. In the 2- and 4-hour reperfusion groups only, DNA electrophoresis showed a ladder pattern, and the light microscopic TUNEL finding was positive in the nuclei of myocytes localized in the infarcted area (6±2% and 11±3%, respectively). Electron microscopic TUNEL showed that nuclei with a significant accumulation of immunogold particles (indicating an electronic microscopic TUNEL–positive result) were observed only in the infarcted myocytes with irreversibly oncotic ultrastructures that were found in the hearts of the 2- and 4-hour reperfusion groups (41±3% and 83±4%, respectively). Irreversibly oncotic myocytes (indicated by swelling, inhomogeneously clumped chromatin in nuclei, dense bodies in mitochondria, and/or ruptured plasma membranes) were also seen in the 0- and 30-minute reperfusion groups, which did not exhibit TUNEL-positive myocytes. There was no evidence of apoptotic ultrastructures in the myocytes. Conclusions —DNA fragmentation occurs in the myocytes that had already shown irreversibly oncotic, but not apoptotic, ultrastructures with ischemia and/or reperfusion. Therefore, DNA fragmentation itself does not always mean apoptosis, and so-called apoptotic infarcted myocytes may belong to a category of cell death other than apoptosis.
Hematopoietic cells maintain hematopoietic fates upon entering the brain
Authors: Mei Massengale, Amy J. Wagers, Hannes Vogel, Irving L. Weissman
Journal: The Journal of Experimental Medicine (2005)

Several studies have reported that bone marrow (BM) cells may give rise to neurons and astrocytes in vitro and in vivo. To further test this hypothesis, we analyzed for incorporation of neural cell types expressing donor markers in normal or injured brains of irradiated mice reconstituted with whole BM or single, purified c-kit+Thy1.1loLin−Sca-1+ (KTLS) hematopoietic stem cells (HSCs), and of unirradiated parabionts with surgically anastomosed vasculature. Each model showed low-level parenchymal engraftment of donor-marker+ cells with 96–100% immunoreactivity for panhematopoietic (CD45) or microglial (Iba1 or Mac1) lineage markers in all cases studied. Other than one arborizing structure in the olfactory bulb of one BM-transplanted animal, possibly representing a neuronal or glial cell process, we found no donor-marker–expressing astrocytes or non-Purkinje neurons among &amp;gt;10,000 donor-marker+ cells from 21 animals. These data strongly suggest that HSCs and their progeny maintain lineage fidelity in the brain and do not adopt neural cell fates with any measurable frequency.
Endothelial cell injury initiates glomerular sclerosis in the rat remnant kidney.
Authors: L K Lee, T W Meyer, A S Pollock, D H Lovett
Journal: Journal of Clinical Investigation (1995)

The development of progressive glomerulosclerosis in the renal ablation model has been ascribed to a number of humoral and hemodynamic events, including the peptide growth factor, transforming growth factor-beta 1 (TGF-beta 1). An important role has also been attributed to angiotensin II (AII), which, in addition to its hemodynamic effects, can stimulate transcription of TGF-beta 1. We postulated that increased glomerular production of AII, resulting from enhanced intrinsic angiotensinogen expression, stimulates local TGF-beta 1 synthesis, activating glomerular matrix protein synthesis, and leads to sclerosis. Using in situ reverse transcription, the glomerular cell sites of alpha-1 (IV) collagen, fibronectin, laminin B1, angiotensinogen, and TGF-beta 1 mRNA synthesis were determined at sequential periods following renal ablation. The early hypertrophic phase was associated with global, but transient, increases in the mRNA for alpha-1 (IV) collagen. No changes were noted for fibronectin, TGF-beta 1, and angiotensinogen mRNAs. At 24 d after ablation, at which time sclerosis is not evident, endothelial cells, particularly in the dilated capillaries at the vascular pole, expressed angiotensinogen and TGF-beta 1 mRNAs, as well as fibronectin and laminin B1 RNA transcripts. By 74 d after ablation angiotensinogen and TGF-beta 1 mRNAs were widely distributed among endothelial and mesangial cells, and were particularly prominent in regions of evolving sclerosis. These same regions were also notable for enhanced expression of matrix protein mRNAs, particularly fibronectin. All receptor blockade inhibited angiotensinogen, TGF-beta 1, fibronectin, and laminin B1 mRNA expression by the endothelium. We conclude that, as a result of hemodynamic changes, injured or activated endothelium synthesizes angiotensinogen, triggering a cascade of TGF-beta 1 and matrix protein gene expression with resultant development of the segmental glomerular sclerotic lesion.
APPENDICEO-CAECAL INTUSSUSCEPTION
Authors: E. N. MacDermott
Journal: BMJ (1931)

<h3>Introduction</h3> The national Bowel Cancer Screening Programme (BCSP) aims to reduce mortality from bowel cancer by 16%. Screening started in Berkshire in May 2008. To achieve this it is hoped that screen detected cancers will be diagnosed at an earlier stage than those detected in the routine service. <h3>Methods</h3> A retrospective audit was carried out on all resection specimens received at one of the screening hospitals since the start of the BCSP. Cases were identified using the histopathology reporting system. Staging and tumour site information was gathered from the histopathology reports, referral route information from the cancer recording database and status in the BCSP from the bowel cancer screening computer system. Symptom profile for those patients with a positive FOBt was collected from the datasets collected at the colonoscopy assessment visit. <h3>Results</h3> Two hundred and sixty five patients had resections for cancer and the age at time of surgery ranged from 34.5 to 91.7 years. There were 146 male and 119 female patients. Of these 24 patients were referred through the BCSP following a positive FOBt (4 aged over 70 opt-ins), 3 patients had completed a FOBt with a negative result. 72 patients were in the age range covered by the BCSP and the Dukes staging in relation to their status within the programme is given in table 1 which shows a significantly increased number of Dukes A tumours in patients aged 60–70 with a positive FOBt in the BCSP (Chi squared test p &lt; 0.05). Eleven of the 20 FOBt positive patients aged 60–69 were symptomatic at the time of assessment within the programme. Three of the four over 70 opt-ins had symptoms with two Dukes B and two C1 tumours in this group <h3>Conclusion</h3> BCSP detected cancers are at a significantly earlier stage than those detected outside the programme. The three patients with a negative FOBt in the programme had more advanced tumours.
Fear of Injury With Physical Activity Is Greater in Adults With Diabetes Than in Adults Without Diabetes
Authors: Amy G. Huebschmann, Lori A. Crane, Elaine S. Belansky, Sharon Scarbro, Julie A. Marshall, Judith G. Regensteiner
Journal: Diabetes Care (2011)

Physical activity is a cornerstone of treatment for diabetes, yet people with diabetes perform less moderate and vigorous physical activity (MVPA) than people without diabetes. In contrast, whether differences in walking activity exist has been understudied. Diabetes-specific barriers to physical activity are one possible explanation for lower MVPA in diabetes. We hypothesized that people with diabetes would perform less walking and combined MVPA and would be less likely to anticipate increasing physical activity if barriers were theoretically absent, compared with people without diabetes.We surveyed 1,848 randomly selected rural Colorado adult residents by telephone from 2002 to 2004. Respondents reported weekly walking and MVPA duration and their likelihood of increasing physical activity if each of seven barriers was theoretically absent.People with diabetes (n = 129) had lower odds of walking and MVPA than people without diabetes (walking: adjusted odds ratio 0.62 [95% CI 0.40-0.95]; MVPA: adjusted odds ratio 0.60 [0.36-0.99]; ≥10 vs. <10 min/week, adjusted for age, sex, BMI, and ethnicity). Respondents with diabetes reported fear of injury as a barrier to physical activity more often than respondents without diabetes (56 vs. 39%; P = 0.0002), although this relationship was attenuated after adjusting for age and BMI (adjusted odds ratio 1.36 [0.93-1.99]).Although walking is a preferred form of activity in diabetes, people with diabetes walk less than people without diabetes. Reducing fear of injury may potentially increase physical activity for people with diabetes, particularly in older and more overweight individuals.
Childhood leukemia: electric and magnetic fields as possible risk factors.
Authors: Joseph D Brain, Robert Kavet, David L McCormick, Charles Poole, Lewis B Silverman, Thomas J Smith, Peter A Valberg, R A Van Etten, James C Weaver
Journal: Environmental Health Perspectives (2003)

Numerous epidemiologic studies have reported associations between measures of power-line electric or magnetic fields (EMFs) and childhood leukemia. The basis for such associations remains unexplained. In children, acute lymphoblastic leukemia represents approximately three-quarters of all U.S. leukemia types. Some risk factors for childhood leukemia have been established, and others are suspected. Pathogenesis, as investigated in animal models, is consistent with the multistep model of acute leukemia development. Studies of carcinogenicity in animals, however, are overwhelmingly negative and do not support the hypothesis that EMF exposure is a significant risk factor for hematopoietic neoplasia. We may fail to observe effects from EMFs because, from a mechanistic perspective, the effects of EMFs on biology are very weak. Cells and organs function despite many sources of chemical "noise" (e.g., stochastic, temperature, concentration, mechanical, and electrical noise), which exceed the induced EMF "signal" by a large factor. However, the inability to detect EMF effects in bioassay systems may be caused by the choice made for "EMF exposure." "Contact currents" or "contact voltages" have been proposed as a novel exposure metric, because their magnitude is related to measured power-line magnetic fields. A contact current occurs when a person touches two conductive surfaces at different voltages. Modeled analyses support contact currents as a plausible metric because of correlations with residential magnetic fields and opportunity for exposure. The possible role of contact currents as an explanatory variable in the reported associations between EMFs and childhood leukemia will need to be clarified by further measurements, biophysical analyses, bioassay studies, and epidemiology.