tbuckley/cabot-search huggingface dataset:
Bile ductules and stromal cells express hedgehog ligands and/or hedgehog target genes in primary biliary cirrhosis
Authors: Youngmi Jung, Shannon J. McCall, Yin‐Xiong Li, Anna Mae Diehl
Journal: Hepatology (2007)

Indian Hedgehog (Ihh) regulates tissue morphogenesis. Hedgehog (Hh) activity has been demonstrated in human cholangiocarcinoma and hepatocellular carcinoma lines, and in myofibroblasts and progenitors from adult rodent livers. We evaluated Hh pathway involvement in the response to biliary injury in primary biliary cirrhosis (PBC). Liver sections from 3 PBC patients and 3 controls without liver disease were studied. Immunohistochemistry was used to determine if cells that accumulate in PBC livers express Ihh or Hh-target genes including the Hh-receptor, Patched (Ptc), and the Hh-transcriptional activator glioblastoma (Gli) 2. Positive cells were further identified by costaining for cytokeratin (CK) 19, a biliary marker, or OV6, a hepatic progenitor marker. In all subjects, Gli2 and Ptc expression localized in portal areas. The numbers of Gli2- or Ptc-expressing cells/portal triad were each 10-fold greater in patients with PBC than in controls (P < 0.05). In PBC livers, some CK19(+) cells coexpressed Gli2 or Ptc. Many stromal fibroblastic cells were also Gli2(+). Strong Ihh expression was detected in most bile ductular cells. Scattered stromal cells also expressed Ihh. The number of Ihh(+) cells/portal triad was 6-fold greater in PBC livers than controls (P < 0.05). OV6(+) progenitors increased significantly in PBC livers, and some of these cells coexpressed Ihh, Ptc, and/or Gli2. Conclusion: This is the first direct evidence that noncancerous, adult human livers harbor several types of cells that produce and/or respond to Hh ligands. Such Hh-responsive cells accumulate during the fibroproliferative response to chronic cholestatic liver injury, suggesting a role for Hh signaling in this process. (HEPATOLOGY 2007;45:1091–1096.)
610 Pattern recognition of HCV core and NS3 proteins by innate immune cells: Role for TLR2 but not for TLR4
Authors: A DOLGANIUC, K KODYS, A KOPASZ, S OAK, P MANDREKAR, E KURTJONES, D GOLENBOCK, G SZABO
Journal: Hepatology (2003)

The release of tumor necrosis factor (TNF-α) is increased in sarcoidosis patients. TNF-α exerts its effect by binding to specific cell surface receptors. There are only fragmentary data concerning the expression of tumor necrosis factor receptors (TNFRs) on bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) lymphocytes. The aim of the study was to evaluate TNFRI (CD120a) and TNFRII (CD120b) expression on T cells and the level of soluble TNFRs in specimens of patients with different clinical manifestation and clinical outcome of sarcoidosis.We examined 49 patients with newly diagnosed pulmonary sarcoidosis. TNFRI and TNFRII density on CD4+ and CD8+ BALF and PB cells surface was estimated using monoclonal antibodies and a flow cytometry technique. The level of TNFRs in PB serum and BALF cell culture supernatant (CCS) was measured using ELISA. Immunological analyses were also performed on PB samples collected from 10 healthy volunteers.The level of soluble TNFRI (sTNFRI) in PB serum was similar in sarcoidosis patients and healthy subjects, whereas the concentration of sTNFRII in serum was significantly higher in the sarcoidosis group (P<0.001). Patients without acute symptoms of sarcoidosis, patients with radiological stage II/III as well as patients with further disease progression showed a tendency to higher levels of sTNFRs in PB serum and lower levels of sTNFRs in BALF CCS compared to Löfgren syndrome and radiological stage I subjects, and patients with spontaneous resolution of sarcoidosis.More than 80% of BALF and PB lymphocytes of sarcoidosis patients expressed both CD120a and CD120b antigens. The percentage of double-positive CD4+CD120a+ and CD4+CD120b+ cells in PB was significantly higher (P<0.005) in sarcoidosis patients than in healthy subjects. The highest percentage of CD4+CD120a+ and CD4+CD120b+ lymphocytes in BALF was determined in patients with acute disease, and in PB of patients with further spontaneous improvement.The evaluation of sTNFRs and TNFRs expression on T-helper cells may be useful in the estimation of sarcoidosis activity.
Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death
Authors: Marta A Toscano, Germán A Bianco, Juan M Ilarregui, Diego O Croci, Jorge Correale, Joseph D Hernandez, Norberto W Zwirner, Francoise Poirier, Eleanor M Riley, Linda G Baum, Gabriel A Rabinovich
Journal: Nature Immunology (2007)
Radionuclide imaging of experimental myocarditis.
Authors: W C Reeves, G L Jackson, F W Flickinger, H G Kwee, E J Schwiter, J Werner, L Whitesell, M A Biddle, G Copenhaver, B S Shaikh, R Zelis
Journal: Circulation (1981)

The ability of 67Ga citrate and 99mTc pyrophosphate cardiac imaging to detect myocarditis was assessed in an experimental rabbit model. Twenty-three rabbits were imaged approximately 72 hours after infusion of i.v. norepinephrine. Diffuse cardiac uptake was found in 13 of 15 rabbits scanned with 67Ga. Tissue distribution studies documented significant myocardial uptake of 67Ga in those with positive scans. Precordial imaging and tissue distribution studies revealed no cardiac uptake in the eight rabbits scanned with 99mTc. Histologic examination of all 23 hearts revealed qualitatively similar, typical lesions of myocarditis. This study suggests that cardiac imaging with 67Ga may be useful in the detection of myocarditis.
EXPERIMENTAL AND CLINICAL NOTES ON THE SUBARACHNOID SPACE.
Authors: DUDLEY TAIT
Journal: JAMA (1900)

From the exclusive domain of anatomy and physiology the meningeal route has made its way through the work of clinicians, to the sphere of practical medicine and surgery. To Quincke is due the credit of having demonstarted the innocuousness of subarachnoid lumbar puncture, its facility of execution, and the harmlessness of the withdrawal of a considerable amount of cerebrospinal fluid. Soon after Quincke made his original communication concerning "lumbal puncture," scores of physicians, in their enthusiasm for this new mode of relieving intradural pressure, predicted the curability of many diseases of the cerebrospinal system, previously deemed hopeless. In epilepsy, tuberculous meningitis and general paralysis many expected wonderful results. The German school, for example, singularly oblivious to the diffuse and deep cellular lesions present in tuberculosis of the meninges —the best known of all meningeal infections—adopted lumbar puncture as a logical and valuable therapeutic measure. A few doubtful cases of temporary
A pathophysiological study of the intestinal manifestations of a vasoactive intestinal peptide, calcitonin, and catecholamine-secreting tumour.
Authors: I W Booth, T R Fenton, P J Milla, J T Harries
Journal: Gut (1983)

A three year old girl with severe watery diarrhoea and a vasoactive intestinal peptide, calcitonin, and catecholamine-secreting supra-renal ganglioneuroblastoma is reported. Steady-state perfusion studies showed the jejunum to be in a net secretory state with respect to water, sodium, and chloride at low concentrations (2 mmol/l) of glucose whereas higher concentrations (56 mmol/l) reversed secretion to absorption; transmural rectal potential difference was increased (lumen negative); Na+ absorption by the rectum was impaired and secretion of potassium and bicarbonate excessive. Motility studies showed prolonged, slowly propagated migrating motor complexes with abnormal runs of non-propagated contractions in the fasting state. During perfusion with glucose, no postprandial activity occurred. These results suggest that diarrhoea results from small intestinal secretion with impaired colonic function and that tumour products may have a direct effect on intestinal motility.
Antibiotics for acute cough in primary care
Authors: A. D Hay, K. V Juttner
Journal: BMJ (2009)

Prescribing can be reduced by improving communication and measuring C reactive protein

Acute cough is the most common symptom managed by healthcare services, and it is associated with large personal, societal, and healthcare costs. In the linked randomised cluster controlled trial (doi:10.1136/bmj.b1374), Cals and colleagues assess the effects of communication skills training and the use of C reactive protein (CRP) testing on the prescription of antibiotics to patients with lower respiratory tract infection in primary care.1

The participants were older than 18 years, they had an acute (no more than four weeks’ duration) cough considered by the general practitioner to be caused by lower respiratory tract infection, and they had at least one chest symptom or sign and at least one systemic symptom or sign.2 The investigators tried to recruit patients with what most clinicians would recognise as acute bronchitis, influenza, acute exacerbations of asthma, and acute exacerbations of chronic pulmonary obstructive disease. They excluded patients who currently or recently needed antibiotics or hospital admission.

The trial used a factorial design, and the units of randomisation were individual general practitioners’ practices. Although cluster randomisation aims to prevent the control group from also receiving a group level intervention, such as communication skills training, it is not the preferred design for individual level interventions, …
Lipoprotein Oxidation and Progression of Carotid Atherosclerosis
Authors: Jukka T. Salonen, Kristiina Nyysso¨nen, Riitta Salonen, Elina Porkkala-Sarataho, Tomi-Pekka Tuomainen, Ulf Diczfalusy, Ingemar Bjo¨rkhem
Journal: Circulation (1997)

Background Epidemiological studies and animal experiments have provided evidence supporting the role of lipid peroxidation in atherogenesis and cardiovascular diseases. Direct evidence linking lipid oxidation to atherosclerotic progression in humans, however, has been lacking. We investigated the association of lipid oxidation products with the progression of early carotid atherosclerosis in hypercholesterolemic men from eastern Finland. Methods and Results Twenty subjects with a fast progression and 20 with no progression of carotid atherosclerosis in 3 years were selected from &gt;400 participants in the Kuopio Atherosclerosis Prevention Study. Progression of carotid atherosclerosis was assessed by high-resolution B-mode ultrasonography. Serum 7β-hydroxycholesterol, a major oxidation product of cholesterol in membranes and lipoproteins, and seven other cholesterol oxidation products were measured by isotope dilution–mass spectrometry, lipid hydroperoxides in LDL fluorometrically as thiobarbituric acid–reactive substances (TBARS) and oxidation susceptibility of LDL and VLDL kinetically. High concentrations of serum 7β-hydroxycholesterol (β=.47, P =.0005), cigarette smoking (β=.35, P =.0167), and LDL TBARS (β=.23, P =.0862) and an increased oxidation susceptibility of VLDL+LDL (β=.22, P =.1114) were the strongest predictors of a 3-year increase in carotid wall thickness of more than 30 variables tested in step-up least-squares regression models. A 10-variable model explained 60% of the atherosclerotic progression. In a multivariate logistic model, the risk of experiencing a fast progression increased by 80% ( P =.013) per unit (μg/L) of 7β-hydroxycholesterol. Conclusions The findings of this study provide further evidence to support an association between lipid oxidation and atherogenesis in humans.
PTU-004 Extreme hyperferritinaemia following paracetamol-induced human acute liver injury
Authors: D G Craig, A Pryde, A Conway-Morris, J Simpson, S W Walker, G J Beckett, C O Bellamy, P C Hayes, K J Simpson
Journal: Gut (2012)

<h3>Introduction</h3> Activated macrophages may play a critical role in the pathogenesis of acute liver failure (ALF). Serum ferritin (SF) is a circulating marker of macrophage activation, and heavy (H) isoforms of ferritin may have immunostimulatory effects. However, ferritin may be released from necrotic liver, confounding SF interpretation in ALF. The SF/ALT ratio may have prognostic value in non-paracetamol ALF, but has not been examined in patients with paracetamol (POD)-ALF. <h3>Methods</h3> Analysis of SF levels in acute liver injury patients admitted to a tertiary liver center, with western blotting and immunohistochemistry for ferritin isoforms. <h3>Results</h3> Retrospective database analysis revealed elevated admission SF (&gt;300 μg/l) in 109/124 (87.9%) of acute liver injury patients. Extreme SF elevations (&gt;10000 μg/l) were more common in POD (36/71, 50.7%) compared with non-POD patients (5/53, 9.4%, p&lt;0.001). Extremely elevated admission SF was confirmed in a prospective cohort of 47 POD cases (22/47, 46.8%). In both POD cohorts, admission SF was significantly higher in patients who died/were transplanted compared with spontaneous survivors (p=0.001, AUC 0.722 (95% CI 0.614 to 0.831) and in patients who developed hepatic encephalopathy (p=0.038) or the systemic inflammatory response syndrome (SIRS, p=0.008). Hyperferritinaemia correlated with proinflammatory (IL-6, Spearman9s r=0.442, p=0.006; IL-8, r=0.502, p=0.001) and antiinflammatory (IL-10; r=0.349, p=0.030) cytokine release following POD, and with organ dysfunction (SOFA; r=0.529, p&lt;0.001), but not with serum ALT (r=0.113, p=0.227). The ferritin/ALT ratio did not improve prognostic accuracy in PODs (AUC 0.706 (95% CI 0.595 to 0.817). Immunohistochemistry confirmed H and light (L) ferritin isoform expression in both normal liver tissue and explanted tissue from ALF patients. Immunoblotting of serum from POD patients with elevated SF revealed significant amounts of circulating H-ferritin, with no circulating H-ferritin observed in healthy controls. <h3>Conclusion</h3> Extreme elevations of SF are common following POD, and are associated with adverse outcomes. SF is a widely available biomarker that may have prognostic value in patients with POD-ALF and merits further evaluation in larger, prospective studies. The correlation with SIRS, organ failure and cytokinaemia and the observation of circulating H ferritin also suggests that SF may be a mediator of adverse outcome. <h3>Competing interests</h3> None declared.
PROPHYLAXIS IN EPIDEMIC CEREBROSPINAL MENINGITIS.
Authors: A. SEIBERT
Journal: JAMA (1907)

Epidemic cerebrospinal meningitis is a communicable disease. Its cause, the<i>Meningococcus intracellularis</i>, although first described by Weichselbaum twenty years ago, was not generally recognized as such until the bacteriologic work of recent epidemics had been reported on. Taking the epidemic of 1905 in the province of Upper Silesia in Germany as an example, described by Westenhoeffer,<sup>1</sup>we find that 3,102 persons were attacked and that 1,789 succumbed in this epidemic. During its course von Lingelsheim made over 3,000 tests at the bacteriologic station at Beuthen and found the meningococcus in the mucus taken from the nasopharynx in 93.8 per cent. of the patients. This coincides with the finding of Councilman, Mallory and Wright in American epidemics. Ninety per cent. of the patients were children under 15 years of age. In twenty-four healthy relatives of the patients Ostermann<sup>2</sup>found the meningococcus in the mucus taken from the nasopharynx seventeen
Prosthesis for Agenesis of the Diaphragm
Authors: J. Ordie Shaffer
Journal: JAMA (1964)

CONGENITAL HERNIA occurs in several areas of the diaphragm with varying degrees of deficiency. Aside from the retrosternal (foramen of Morgagni) and esophageal hiatal hernias, most diaphragmatic defects occur in either posterolateral portion of the diaphragm (foramen of Bockdalek). The left side is more frequently involved than the right. Rarely is the defect so large that only a rim of diaphragm exists around it. Even more rare is a complete absence of the diaphragm without even a rudimentary rim around the periphery.<sup>1</sup>Surgery has been advocated by either an abdominal or thoracic approach, with a majority favoring the abdominal approach in the newborn.<sup>2</sup>The usual partial defect permits simple approximation of the edges for repair. A larger defect is repaired by this method with greater difficulty. Complete absence (agenesis) of the diaphragm poses a new problem of replacement. A case of complete absence of the left leaf of
Recurrent Salmonella typhi Peritonitis
Authors: Robert H. K. Eng
Journal: JAMA (1980)

<i>SALMONELLA typhi</i>peritonitis is rarely seen in the United States today.<sup>1</sup>Recently the incidence of typhoid in the United States has been 0.2 cases per 100,000 people per year, with one third of the cases attributed to foreign travel.<sup>2</sup>In older series 2% of patients with typhoid had perforation of viscera and peritonitis. At the Kings County Hospital Center, four cases of typhoid were seen in 1977 and 1978. All were recent immigrants from the Caribbean. Among these patients one had peritonitis and an unusual course. <h3>Report of a Case</h3> The patient was a 19-year-old Haitian who came to the United States in January 1975. While in Haiti in November 1974, she was hospitalized for vomiting, abdominal pain, constipation, and high fevers. She was told she had typhoid fever and was treated with nasogastric tube decompression and 28 days of chloramphenicol therapy. She recovered uneventfully. Four months later,
Resting and Exercise Systolic Intervals
Authors: ARNOLD M. WEISSLER
Journal: Circulation (1972)

To the Editor:Drs. McConahay, Martin, and Cheitlin (CIRCULATION 45: 592, 1972) report their experience with measurement of systolic time intervals corrected for heart rate in normal subjects and patients with coronary artery disease.There are serious technical and conceptual problems in this paper which are pertinent to future studies attempting to test the systolic time intervals clinically.It is noteworthy that the authors chose to measure systolic time intervals from the mean of measurements made "on five consecutive cardiac cycles, each read to the nearest millisecond."All who work with systolic time-interval measurements are aware of the beatto-beat changes which result from respiratory and cycle variations.Unless an appropriate sampling of data is made, one will of necessity have wide variation in these measurements, a factor which will broaden variability in the data and obscure correlation.The measurement of the systolic time intervals to the nearest millisecond, as indicated in this paper, can be accomplished only by reading to the nearest 0.1 ml, a highly improbable technical feat unless the tracings were magnified.Further, the observations on systolic time inter- vals immediately following exercise were correct- ed for heart rate according to regression equations which were developed in resting supine subjects.To date, there is no justification for extrapolating the heart rate range of supine subjects to the exercise state for correcting intervals in this manner.One must hence raise serious doubt as to the meaning of the exercise data in this paper.From the conceptual viewpoint, there is a problem which relates to the overall meaning of the systolic time-interval determinations.In adapting systolic time-interval measurement to clinical usage, one must be cognizant that these data provide measures of cardiac performance which are not the same as other hemodynamic variables.What is pertinent to their clinical usage is the fact that these noninvasive measurements deviate from normal at the same time and in parallel with other hemodynamic measures.That
Dynamic Release and Clearance of Circulating Microparticles During Cardiac Stress
Authors: Daniel Augustine, Lisa V. Ayers, Eduardo Lima, Laura Newton, Adam J. Lewandowski, Esther F. Davis, Berne Ferry, Paul Leeson
Journal: Circulation Research (2013)

Rationale: Microparticles are cell-derived membrane vesicles, relevant to a range of biological responses and known to be elevated in cardiovascular disease. Objective: To investigate microparticle release during cardiac stress and how this response differs in those with vascular disease. Methods and Results: We measured a comprehensive panel of circulating cell-derived microparticles by a standardized flow cytometric protocol in 119 patients referred for stress echocardiography. Procoagulant, platelet, erythrocyte, and endothelial but not leukocyte, granulocyte, or monocyte-derived microparticles were elevated immediately after a standardized dobutamine stress echocardiogram and decreased after 1 hour. Twenty-five patients developed stress-induced wall motion abnormalities suggestive of myocardial ischemia. They had similar baseline microparticle levels to those who did not develop ischemia, but, interestingly, their microparticle levels did not change during stress. Furthermore, no stress-induced increase was observed in those without inducible ischemia but with a history of vascular disease. Fourteen patients subsequently underwent coronary angiography. A microparticle rise during stress echocardiography had occurred only in those with normal coronary arteries. Conclusions: Procoagulant, platelet, erythrocyte, and endothelial microparticles are released during cardiac stress and then clear from the circulation during the next hour. This stress-induced rise seems to be a normal physiological response that is diminished in those with vascular disease.
415 HIGH PREVALENCE OF CHRONIC HEPATITIS C VIRUS (HCV) INFECTION IN A GERMAN METROPOLITAN AREA: A PROSPECTIVE SCREENING ANALYSING 7683 PATIENTS
Authors: B. Schlosser, D. Domke, M. Möckel, M. Biermer, B. Fülöp, B. Wiedenmann, N. Haas, H. Bail, C. Müller, R. Tauber, T. Berg
Journal: Journal of Hepatology (2009)
Hepatic steatosis and endocannabinoids-Does it all happen within the liver?
Authors: Hermann E. Wasmuth, Christian Trautwein
Journal: Hepatology (2008)

Osei-Hyiaman D, Liu J, Zhou L, Godlewski G, Harvey-White J, Jeong WI, Bátkai S, Marsicano G, Lutz B, Buettner C, Kunos G. Hepatic CB 1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice. J Clin Invest 2008;118:3160–3169. (Reprinted with permission.) Abstract Diet-induced obesity is associated with fatty liver, insulin resistance, leptin resistance, and changes in plasma lipid profile. Endocannabinoids have been implicated in the development of these associated phenotypes, because mice deficient for the cannabinoid receptor CB(1) (CB1(−/−)) do not display these changes in association with diet-induced obesity. The target tissues that mediate these effects, however, remain unknown. We therefore investigated the relative role of hepatic versus extrahepatic CB(1) receptors in the metabolic consequences of a high-fat diet, using liver-specific CB(1) knockout (LCB1(−/−)) mice. LCB1(−/−) mice fed a high-fat diet developed a similar degree of obesity as that of wild-type mice, but, similar to CB1(−/−) mice, had less steatosis, hyperglycemia, dyslipidemia, and insulin and leptin resistance than did wild-type mice fed a high-fat diet. CB(1) agonist-induced increase in de novo hepatic lipogenesis and decrease in the activity of carnitine palmitoyltransferase-1 and total energy expenditure were absent in both CB1(−/−) and LCB1(−/−) mice. We conclude that endocannabinoid activation of hepatic CB(1) receptors contributes to the diet-induced steatosis and associated hormonal and metabolic changes, but not to the increase in adiposity, observed with high-fat diet feeding. Theses studies suggest that peripheral CB(1) receptors could be selectively targeted for the treatment of fatty liver, impaired glucose homeostasis, and dyslipidemia in order to minimize the neuropsychiatric side effects of nonselective CB(1) blockade during treatment of obesity-associated conditions.