tbuckley/cabot-search huggingface dataset:
Serum Ferritin Level Predicts Advanced Hepatic Fibrosis among U.S. Patients with Phenotypic Hemochromatosis
Authors: Elizabeth D. Morrison
Journal: Annals of Internal Medicine (2003)

Background: DNA-based HFE gene testing can confirm hereditary hemochromatosis in most people of Northern European descent. However, liver biopsy is important to detect cirrhosis. Objective: To develop noninvasive criteria to predict the presence or absence of advanced hepatic fibrosis or cirrhosis in Americans with hemochromatosis. Design: Cross-sectional study. Setting: Six tertiary care referral clinics. Patients: 182 patients with phenotypically defined hemochromatosis. Measurements: Liver histopathology and serum ferritin, aspartate aminotransferase, and alanine aminotransferase levels. Multivariate logistic regression analysis was used to examine factors associated with cirrhosis (defined as bridging fibrosis or unequivocal cirrhosis on biopsy). Results: Cirrhosis was present in 40 of 182 (22%) patients in the overall group and in 35 of 147 (24%) of C282Y homozygotes. Only 1 of 93 patients with a serum ferritin level less than 1000 g/L had cirrhosis compared with 39 of 89 patients with serum ferritin levels greater than 1000 g/L (P < 0.001). No C282Y homozygotes or C282Y/H63D compound heterozygotes with serum ferritin levels less than 1000 g/L had cirrhosis. Elevated serum aminotransferase levels (P = 0.001) and serum ferritin levels greater than 1000 g/L (P = 0.001), but not age older than 40 years (P = 0.2), were independently associated with cirrhosis. In a multivariate model, the probability of cirrhosis was 7.4% among patients with serum ferritin levels less than 1000 g/L compared with 72% among patients with serum ferritin levels greater than 1000 g/L after adjustment for age and elevated serum liver enzyme levels. Conclusions: Patients with hemochromatosis and serum ferritin levels less than 1000 g/L are unlikely to have cirrhosis. Liver biopsy to screen for cirrhosis may be unnecessary in such patients, regardless of age or serum liver enzyme levels.
Comparison of contractile mechanisms of sphingosylphosphorylcholine and sphingosine-1-phosphate in rabbit coronary artery
Authors: S.-K. Choi, D.-S. Ahn, Y.-H. Lee
Journal: Cardiovascular Research (2008)

Although stimulation with sphingosylphosphorylcholine (SPC) or sphingosine-1-phosphate (S1P) generally leads to similar vascular responses, the contractile patterns and their underlying signalling mechanisms are often distinct. We investigated the different reliance upon Ca2+-dependent and Ca2+-sensitizing mechanisms of constriction in response to SPC or S1P in coronary arteries. Contractile responses, changes in [Ca2+]i, and phosphorylation of myosin light chain phosphatase-targeting subunit (MYPT1) were measured. SPC induced a concentration-dependent sustained contraction. S1P evoked a rapid rise in force (initial transient), which was followed by a secondary sustained force. In the absence of extracellular Ca2+, the concentration dependency of constriction to SPC was shifted to the right, but with no change in maximum force, whereas S1P-induced contraction was significantly blunted. Cyclopiazonic acid (CPA) significantly decreased the initial transient force induced by S1P. In isolated single cells, S1P markedly increased [Ca2+]i, whereas only a modest elevation was noted with SPC. The S1P-induced elevation of [Ca2+]i was abolished by pre-treatment with CPA and was significantly reduced in the absence of extracellular Ca2+. In β-escin-permeabilized strips, SPC augmented pCa 6.3-induced force; this was significantly inhibited by fasudil hydrochloride. S1P induced little or no augmentation of pCa 6.3-induced force. In intact arteries, SPC-induced contraction was completely inhibited by fasudil hydrochloride. Fasudil hydrochloride had no effect on the initial transient force induced by S1P but significantly inhibited the secondary sustained force. SPC induced a several-fold increase in Thr696 and Thr853 phosphorylation of MYPT1, but S1P did not affect phosphorylation of MYPT1. Our results suggest that constriction of coronary arteries in response to the bioactive lipid S1P or SPC occurs by distinct signalling pathways. Activation of the RhoA/RhoA-associated kinase pathway and subsequent phosphorylation of MYPT1 play a key role in SPC-induced coronary contraction, whereas elevation of [Ca2+]i is crucial for S1P-induced coronary constriction.
Studies of lymphokine-activated killer (LAK) cells. I. Evidence using novel monoclonal antibodies that most human LAK precursor cells share a common surface marker.
Authors: D G Morris, H F Pross
Journal: The Journal of Experimental Medicine (1989)

Separation of LAK precursor (LAKp) cells (as defined by LAK effector generation after incubation with IL-2 for 7 d) from cells with NK activity/LGL morphology was achieved on Percoll gradients using a longer, slower centrifugation than that used for optimal NK enrichment. mAb were generated using the various Percoll fractions as the immunizing cells and used for separation and depletion studies. Two mAbs DM-1 (IgM,k) and DM-2 (IgM,k) recognizing 2-15% and 15-30% of PBL, respectively, abrogated a large proportion of LAK generative potential after complement depletion, but had little effect on NK or LAK effector activity. Cell sorting experiments indicated that the majority of LAKp cells are found within the DM-1+ population and that DM-1+ cells are not simply an accessory cell required for LAKp generation. Further, these two mAbs do not recognize cells that are responsible for generating cytotoxicity during MLC or co-culture with the PR-1 EBV lymphoblastoid cell line. Western blot analysis indicated that DM-1 and DM-2 recognize a 38,000 and 44,000 dalton moiety, respectively. The frequency of cells bearing these antigens and the intensity of cell surface staining decreased during the 7-d culture period, suggesting that these antibodies recognize determinants found only at the precursor level. These findings indicate that cells other than NK effectors or mature T cells are capable of generating a LAK cell response. These LAK precursor cells share a common differentiation surface antigen and are different from AK or antigen-specific CTL precursors. The possibility exists that these cells are identical to, or include, the NK precursor cell.
Ozone and Short-term Mortality in 95 US Urban Communities, 1987-2000
Authors: Michelle L. Bell
Journal: JAMA (2004)

Ozone has been associated with various adverse health effects, including increased rates of hospital admissions and exacerbation of respiratory illnesses. Although numerous time-series studies have estimated associations between day-to-day variation in ozone levels and mortality counts, results have been inconclusive.To investigate whether short-term (daily and weekly) exposure to ambient ozone is associated with mortality in the United States.Using analytical methods and databases developed for the National Morbidity, Mortality, and Air Pollution Study, we estimated a national average relative rate of mortality associated with short-term exposure to ambient ozone for 95 large US urban communities from 1987-2000. We used distributed-lag models for estimating community-specific relative rates of mortality adjusted for time-varying confounders (particulate matter, weather, seasonality, and long-term trends) and hierarchical models for combining relative rates across communities to estimate a national average relative rate, taking into account spatial heterogeneity.Daily counts of total non-injury-related mortality and cardiovascular and respiratory mortality in 95 large US communities during a 14-year period.A 10-ppb increase in the previous week's ozone was associated with a 0.52% increase in daily mortality (95% posterior interval [PI], 0.27%-0.77%) and a 0.64% increase in cardiovascular and respiratory mortality (95% PI, 0.31%-0.98%). Effect estimates for aggregate ozone during the previous week were larger than for models considering only a single day's exposure. Results were robust to adjustment for particulate matter, weather, seasonality, and long-term trends.These results indicate a statistically significant association between short-term changes in ozone and mortality on average for 95 large US urban communities, which include about 40% of the total US population. The findings indicate that this widespread pollutant adversely affects public health.
Changes in the distribution of laminin alpha1 chain in psoriatic skin: immunohistochemical study using confocal laser scanning microscopy
Authors: M. Vaccaro, L. Magaudda, G. Cutroneo, F. Trimarchi, O. Barbuzza, F. Guarneri, B. Guarneri
Journal: British Journal of Dermatology (2002)

Recent studies have demonstrated the presence in psoriatic skin of ultrastructural and molecular alterations in the basement membrane and an altered polarized distribution of the integrins. Previous studies have demonstrated the existence of some epithelial cell lines synthesizing only laminin beta and gamma chains that, in the absence of the laminin alpha chain, do not form a distinct basal lamina.To investigate a possible reduction/absence of the laminin alpha 1 chain in keratinocytes in psoriatic skin and to correlate this with fibronectin distribution.Using monoclonal antibodies against the laminin alpha1 chain or human plasma fibronectin and using confocal laser scanning microscopy, we evaluated the immunohistochemical expression of these two proteins in cutaneous biopsies from involved and uninvolved skin of the sacral region of 12 men with extensive chronic plaque psoriasis. Site-matched biopsies of normal skin from four men without psoriasis were used as controls.In normal skin antilaminin alpha 1 chain antibodies stained the dermal-epidermal junction in a regular and continuous manner. In involved and uninvolved psoriatic skin large regions of discontinuous immunostaining were observed, mainly at the apex of the dermal papillae; in the same regions, clusters of keratinocytes appeared markedly reactive and fibronectin was overexpressed in the papillary dermis under the interruptions of the basement membrane.The present study defines the location of the laminin alpha1 chain in involved and uninvolved psoriatic skin and suggests a possible role of the alteration of this chain, together with T-cell lymphokines and fibronectin, in the dysregulation of cell morphological processes.
Religious Coping and Life-Prolonging Care
Authors: Tomer Trevor Levin
Journal: JAMA (2009)

To the Editor: The study on religious coping and use of intensive life-prolonging care near death in patients with advanced cancer by Dr Phelps and colleagues showed that positive religious coping was associated with receipt of intensive life-prolonging medical care near death. The instrument used to measure positive religious coping, the Brief RCOPE, presupposes an image of God as someone who personally interacts with people. However, empirical research in several countries outside the United States indicates that many people have a nonpersonal image of God. Adherence to a nonpersonal image of God could result in a very different coping style, with more acceptance at the end of life and without life-prolonging medical care. Therefore, when discussing prognosis and treatment options with terminally ill patients, clinicians should not just examine whether patients adhere to a positive religious coping style but should explore their religious beliefs and values in a more balanced way. Because many clinicians feel uncomfortable discussing religious and spiritual issues at the end of life, well-developed training programs for clinicians are needed.
Endogenous calcitonin gene-related peptide mediates nonadrenergic noncholinergic depressor response to spinal cord stimulation in the pithed rat.
Authors: T Taguchi, H Kawasaki, T Imamura, K Takasaki
Journal: Circulation Research (1992)

The role of endogenous calcitonin gene-related peptide (CGRP) in the nonadrenergic noncholinergic depressor response to spinal cord stimulation was studied in the pithed rat in vivo. Pithed rats were given hexamethonium (2 mg/kg per minute i.v.) to block autonomic outflow, and mean blood pressure was artificially maintained at approximately 100 mm Hg with methoxamine (10-15 micrograms/kg per minute i.v.). Electrical stimulation of the spinal cord at the level of the lower thoracic vertebra (T9-12) caused a fall in blood pressure in a frequency-dependent (0.5-10 Hz), voltage-dependent (2.5-50 V), and pulse duration-dependent (0.25-8 msec) manner. The heart rate did not change during the depressor response. The depressor response was long lasting, and the maximum response was elicited by stimulation at 4-6 Hz. The neurotoxin tetrodotoxin (100 micrograms/kg i.v.) abolished the depressor response to spinal cord stimulation, whereas treatment with propranolol (0.5 mg/kg per minute i.v.), atropine (0.05 mg/kg per minute i.v.), or a combination of pyrilamine (0.5 mg/kg per minute i.v.) and cimetidine (0.5 mg/kg per minute i.v.) did not affect the response. In pithed rats treated with capsaicin (total dose of 500 mg/kg s.c.), spinal cord stimulation caused a slight depressor response. Exogenous CGRP, but not acetylcholine, isoproterenol, histamine, or substance P, caused a sustained fall in blood pressure that mimicked the spinal cord stimulation-induced depressor response. Continuous infusion of CGRP[8-37] (60 nmol/kg per minute i.v.), a CGRP receptor antagonist, markedly inhibited the depressor responses not only to spinal cord stimulation but also to exogenous CGRP.(ABSTRACT TRUNCATED AT 250 WORDS)
Coexistence of sick sinus rhythm and atrial flutter-fibrillation.
Authors: J A Gomes, P S Kang, M Matheson, W B Gough, N El-Sherif
Journal: Circulation (1981)

A 58-year-old man with hypertensive cardiovascular disease and atrial flutter underwent electrophysiologic studies, including multiple intra-atrial recordings and atrial stimulation. Although the surface ECG suggested the presence of atrial flutter, intra-atrial recordings demonstrated the presence of (1) sinus-like rhythm localized to an area of approximately 5 mm in and around the region of the sinus node, which was protected by entrance block; (2) flutter and/or fibrillation of the remaining parts of the right atrium; (3) fibrillation of the left atrium; and (4) transient degeneration of flutter into fibrillation at right atrial sites, with predominant flutter activity. Although a major part of the right atrium was in flutter and/or fibrillation, we could assess sinus node function by overdrive stimulation of the area of sinus node-activity. Sinus node function studied revealed an underlying sick sinus syndrome.
Recurrent epigastric pain with obscure GI bleeding; think beyond the bowel?
Authors: Maxworth Chuen-Wei Hu, Philip Victor Kaye, Ian James Beckingham, Martin Wynn James
Journal: Gut (2012)

A 74-year-old male patient presented with epigastric pain, recurrent melaena and anaemia. His medical history included myocardial infarction, rheumatoid arthritis, diet-controlled type 2 diabetes and recent endovascular infrarenal abdominal aortic aneurysm repair. He was taking aspirin, omeprazole, methotrexate and sulfasalazine. He had stopped smoking for 10 years and was a teetotaller. Upper gastrointestinal (GI) endoscopy did not demonstrate any stigmata of recent haemorrhage. No contrast leak was demonstrated on mesenteric arteriography. CT angiography also did not reveal any contrast extravasation or aortoenteric …
Comment on Tang et al. Effects of Insulin Glargine and Liraglutide Therapy on Liver Fat as Measured by Magnetic Resonance in Patients With Type 2 Diabetes: A Randomized Trial. Diabetes Care 2015;38:1339–1346
Authors: Peng-Fei Shan, Xiao-li Ji, Liuhong Wang, Ping Li, Yue-Zhong Ren
Journal: Diabetes Care (2015)

Tang et al. (1) reported that the administration of insulin glargine, but not liraglutide, reduced the liver fat burden in patients with type 2 diabetes, whereas the improvement in the liver fat fraction was not significantly different from that in the liraglutide group in a 12-week randomized trial. This is an interesting clinical study on the effects of antihyperglycemic drugs on liver fat. However, there are some concerns about this study.

First, given the different mechanisms by which insulin glargine and liraglutide therapies may reduce liver fat, the short observation period of 12 weeks may not be long enough to show the actual effects of the two agents, especially for liraglutide. …
A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: the Northern California Oncology Group trial.
Authors: D C Hohn, R J Stagg, M A Friedman, J F Hannigan, A Rayner, R J Ignoffo, P Acord, B J Lewis
Journal: Journal of Clinical Oncology (1989)

In 1983, the Northern California Oncology Group (NCOG) instituted a randomized trial of intravenous (IV) versus intraarterial (IA) floxuridine (FUDR) administered via an implantable pump for patients with colorectal cancer metastatic to the liver. The study objectives were to compare the hepatic response rate, time to hepatic progression, and toxicity for the two treatment arms. The study design, which allowed patients failing IV FUDR to crossover to the IA arm, prevents a meaningful comparative analysis of survival. Patients with liver-only metastases (N = 143) were randomized, 76 to the IV arm and 67 to the IA arm, and 115 patients (65 IV, 50 IA) were fully evaluable. Of the 65 patients in the IV arm, 28 crossed over to IA treatment after failing IV FUDR. The dose-limiting toxicity of IV FUDR was diarrhea, whereas biliary toxicity limited both the dose and duration of IA FUDR therapy. Of the first 25 patients treated with IA FUDR at a dose of .3 mg/kg/day, 10 developed radiographically evident biliary strictures, and three developed permanent jaundice. With reduction of the initial IA FUDR dose to .2 mg/kg/day, and adoption of a policy of early dosage reduction, treatment interruption, or termination of therapy for persistent elevations in alkaline phosphatase, only two further cases of serious biliary toxicity occurred. However, 26 of the 50 IA FUDR patients ultimately had therapy terminated because of drug toxicity rather than disease progression. When compared with systemic infusion, infusion into the hepatic artery greatly enhanced the antitumor activity of FUDR against colorectal liver metastases. Although biliary toxicity is the most serious limitation of this form of therapy, biliary stricture and jaundice usually can be averted through careful monitoring of liver enzymes and early dosage reduction.
Gene expression in nontumoral liver tissue and recurrence-free survival in hepatitis C virus-positive hepatocellular carcinoma
Authors: Masato Tsuchiya, Joel S. Parker, Hiroshi Kono, Masanori Matsuda, Hideki Fujii, Ivan Rusyn
Journal: Molecular Cancer (2010)

Abstract Background The goal of this study was to understand gene expression signatures of hepatocellular carcinoma (HCC) recurrence in subjects with hepatitis C virus (HCV) infection. Recurrence-free survival (RFS) following curative resection of HCC in subjects with HCV is highly variable. Traditional clinico-pathological endpoints are recognized as weak predictors of RFS. It has been suggested that gene expression profiling of HCC and nontumoral liver tissue may improve prediction of RFS, aid in understanding of the underlying liver disease, and guide individualized patient management. Frozen samples of the tumors and nontumoral liver were obtained from 47 subjects with HCV-associated HCC. Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS. Results The molecular profile of the HCV-associated HCC confirmed central roles for MYC and TGFβ1 in liver tumor development. Gene expression in tumors was found to have poor predictive power with regards to RFS, but analysis of nontumoral tissues yielded a strong predictor for RFS in late-recurring (&gt;1 year) subjects. Importantly, nontumoral tissue-derived gene expression predictor of RFS was highly significant in both univariable and multivariable Cox proportional hazard model analyses. Conclusions Microarray analysis of the nontumoral tissues from subjects with HCV-associated HCC delivers novel molecular signatures of RFS, especially among the late-recurrence subjects. The gene expression predictor may hold important insights into the pathobiology of HCC recurrence and de novo tumor formation in cirrhotic patients.
Polyarthritis and angioimmunoblastic lymphadenopathy.
Authors: N J McHugh, G J Campbell, J J Landreth, M R Laurent
Journal: Annals of the Rheumatic Diseases (1987)

Angioimmunoblastic lymphadenopathy (AILD) is a lymphoproliferative disorder with well established clinical and histological features, one of the clinical manifestations being a peripheral polyarthritis. A case of AILD with a symmetrical non-erosive peripheral polyarthritis is described, including the findings in the synovial fluid and histology of the synovium. There was a marked reduction in the number of peripheral blood T lymphocytes bearing the CDT8 phenotype in both the peripheral blood and synovial fluid. The arthritis was difficult to control, requiring large doses of corticosteroids, which produced significant side effects. Levamisole 150 mg, one day each week, was effective in controlling the arthritis and returning the numbers of CDT8 lymphocytes to normal. The aetiology of AILD is unknown, though a defect in T cell regulation, in particular T cell suppression, with a secondary B cell proliferation has been postulated. The demonstration of reduced numbers of lymphocytes bearing the CDT8 phenotype in this patient supports that theory.
Selectins and neutrophil traffic: margination and Streptococcus pneumoniae-induced emigration in murine lungs.
Authors: J P Mizgerd, B B Meek, G J Kutkoski, D C Bullard, A L Beaudet, C M Doerschuk
Journal: The Journal of Experimental Medicine (1996)

The roles of selectins in the pulmonary margination and emigration of neutrophils were investigated by using mice genetically deficient in both E- and P-selectins (E/P mutants) and/or by intravenous injections of fucoidin (inhibiting both L- and P-selectins). E/P mutants were neutrophilic (14.7 +/- 4.9 x 10(6) vs. 0.8 +/- 0.1 x 10(6) neutrophils/ml). This neutrophilia was associated with increased margination of neutrophils within pulmonary capillaries (39.7 +/- 9.4 vs. 4.6 +/- 1.1 neutrophil profiles per 100 red blood cell profiles) but no change in margination within noncapillary pulmonary microvessels. After intratracheal instillation of Streptococcus pneumoniae, lungs of E/P mutants displayed increased neutrophil emigration (564 +/- 92 vs. 116 +/- 19 neutrophils per 100 alveolar profiles), edema (5.3 +/- 1.5 vs. 1.5 +/- 0.4 microliter/g body weight), and histologic evidence of lung injury compared with those in wild-type (WT). Fucoidin treatment did not affect neutrophil emigration during streptococcal pneumonia in WT or E/P mice. During pneumonia, the number of white blood cells (WBC) tethered to or spread upon the noncapillary vessel endothelium increased in both WT and E/P lungs. These are the first data demonstrating that neutrophil margination in uninfected pulmonary capillaries does not require E- and P-selectins; that streptococcal pneumonia induces an E- and P-selectin-independent increase in WBC interactions with noncapillary endothelium; and that migration of neutrophils to alveoli can occur despite deficiency or inhibition of all of the known selectins.