tbuckley/cabot-search huggingface dataset:
Microcarcinoid tumor diagnosed with high-resolution magnification endoscopy and narrow band imaging
Authors: R. Singh, K. Yao, G. Anagnostopoulos, P. Kaye, K. Ragunath
Journal: Endoscopy (2008)

A 63-year-old patient presented with persistent dyspepsia. Endoscopy revealed an 8-mm nodule on the anterior wall of the greater curvature in the proximal part of the body of the stomach. Histological analysis demonstrated a well-differentiated tumor showing positive immunostaining with chromogranin with a background mucosa showing features of atrophic gastritis. Gastric pH and fasting serum gastrin levels were elevated. A diagnosis of a type I carcinoid tumor was made. The patient then underwent endoscopic mucosal resection with complete resection of the lesion. Follow-up endoscopy 3 months later showed a scar at the previous resection site. However, a diminutive, flat, reddened lesion measuring less than 3 mm with the appearance of an erosion was detected at a separate site on the posterior wall of the greater curvature ([Fig. 1] a). Narrow-band imaging demonstrated that, at the center of the lesion, the pit structure had disappeared ([Fig. 1] b). Magnification endoscopy with white light revealed that the subepithelial capillary network was well preserved, but underneath the epithelium, a faint yellowish hue could be seen ([Fig. 1] c). These findings were distinctly different from those of a gastric erosion or a minute gastric carcinoma. In an erosion dilated subepithelial capillaries are seen, and in the center of the erosion whitish inflammatory exudates will be visualized [1]. On the other hand, a flat early carcinoma would exhibit proliferation of the subepithelial capillaries, which would be irregular in both caliber and tortuosity [2]. Taking into consideration the patient's previous history, we suspected the lesion could have originated from an endocrine nest/microcarcinoid [3] which had grown just beneath the epithelium. The histopathological analysis of the lesion revealed a minute carcinoid tumor ([Fig. 1] d). This case illustrates the differential diagnosis between three lesions which appear very similar: an erosion, a flat early carcinoma, and a minute carcinoid, and shows the utility of high-resolution magnification endoscopy with narrow-band imaging in differentiating them.
Interallelic V(D)J trans-rearrangement within the beta T cell receptor gene is infrequent and occurs preferentially during attempted D beta to J beta joining.
Authors: J C Aster, J Sklar
Journal: The Journal of Experimental Medicine (1992)

Previous work has demonstrated that intergenic V(D)J rearrangement, a process referred to as trans-rearrangement, occurs at an unexpectedly high frequency. These rearrangements generate novel V(D)J combinations which could conceivably have some role in the normal immune system, and since they probably arise through chromosomal rearrangements akin to those associated with lymphoid neoplasia, they may also serve as a model for investigating recombinational events which underlie oncogenesis. In view of the existence of a mechanism that permits relatively frequent intergenic trans-rearrangements, it seems reasonable that interallelic trans-rearrangements involving segments belonging to each of the two alleles of a single antigen receptor gene might also occur. To determine the frequency of such rearrangements, we examined thymocytes of F1 progeny of a cross between SWR mice, which have a deletion spanning 10 of the known V beta segments, and NZW mice, which have a deletion involving all J beta 2 segments. Rearranged TCR-beta genes containing V beta segments from the NZW chromosome and J beta segments from the SWR chromosome were amplified from the DNA of F1 thymocytes with the polymerase chain reaction. Using this approach, we found that such rearrangements are relatively uncommon, being present in about 1 in 10(5) thymocytes, a frequency lower than that of V gamma/J beta intergenic trans-rearrangements. The ratio of conventional cis-rearrangement to interallelic trans-rearrangement for any particular V beta segment appears to be about 10(4):1. The structure of the junctions in all trans-rearrangements analyzed closely resembles conventional cis-rearrangements, indicating involvement of V(D)J recombinase in the ultimate joining event. However, in contrast to cis-rearrangements, a strong bias for inclusion of D beta 1 segments over D beta 2 segments was noted, suggesting that interallelic trans-rearrangement may occur preferentially during attempted D-J joining. J beta 2 segment usage in trans-rearrangements also appeared to differ from that expected from previously studied cis-rearrangements. The results have implications with respect to the events and timing of conventional cis-rearrangement during thymocyte differentiation, and the prevalence of various types of trans-rearrangements.
Loss of enteroendocrine cells in mice alters lipid absorption and glucose homeostasis and impairs postnatal survival
Authors: Georg Mellitzer, Anthony Beucher, Viviane Lobstein, Pascal Michel, Sylvie Robine, Michèle Kedinger, Gérard Gradwohl
Journal: Journal of Clinical Investigation (2010)

At least 10 enteroendocrine cell types have been identified, and the peptide hormones they secrete have diverse functions that include regulation of glucose homeostasis, food intake, and gastric emptying. Mice lacking individual enteroendocrine hormones, their receptors, or combinations of these have shed light on the role of these hormones in the regulation of energy homeostasis. However, because enteroendocrine hormones have partially overlapping functions, these loss-of-function studies produced only minor phenotypes, and none of the enteroendocrine hormones was shown to be essential for life. To examine the effect of loss of all enteroendocrine cells and hormones on energy homeostasis, we generated mice with intestinal-specific ablation of the proendocrine transcription factor neurogenin 3 (referred to herein as Ngn3Deltaint mice). Ngn3Deltaint mice were deficient for all enteroendocrine cells and hormones, and died with a high frequency during the first week of life. Mutant mice were growth retarded and had yellowish stool suggestive of steatorrhea. Subsequent analyses revealed that Ngn3Deltaint mice had impaired lipid absorption, reduced weight gain, and improved glucose homeostasis. Furthermore, intestinal epithelium of the mutant mice showed an enlarged proliferative crypt compartment and accelerated cell turnover but no changes to goblet and Paneth cell numbers. Enterocytes had shorter microvilli, but the expression of the main brush border enzymes was unaffected. Our data help unravel the role of enteroendocrine cells and hormones in lipid absorption and maintenance of the intestinal epithelium.
15N investigation into the effect of a pollutant on the nitrogen metabolism of Tetrahymena pyriformis as a model for environmental medical research.
Authors: K Arndt, D Hofmann, M Gehre, P Krumbiegel
Journal: Environmental Health Perspectives (1998)

A pilot study was performed to examine the potential of stable isotope techniques for monitoring the impact of a harmful substance on the cellular nitrogen metabolism in the ciliate species Tetrahymena pyriformis. After identical cultivation periods of control cells and toluene-exposed cells in a defined culture medium enriched with [guanidino-15N2]l-arginine, a number of nitrogen-containing pools were analyzed: 1) quantity and 15N abundance of ammonia as the end product of nitrogen metabolism in the system; 2) pattern and 15N abundances of the protein-bound amino acids in the cells; 3) pattern and 15N abundances of free amino acids in the cells; and 4) pattern and 15N abundances of the amino acids in the culture medium. In addition to 15N emission spectrometry, a new gas chromatography/combustion interface-isotope ratio mass spectrometry/mass spectrometry analytical system was used. The production and 15N content of ammonia were higher in the toluene-exposed system by 30% and 43%, respectively, indicating higher deamination rates and greater arginine consumption. The toluene-exposed cells exhibited increased 15N abundances of protein-bound amino acids in alanine, aspartic acid, glutamic acid, and tyrosine. Furthermore, structural analyses revealed the presence of N[Omega]-acetylarginine and pyrrolidonecarboxylic acid--compounds that had not previously been detected in Tetrahymena pyriformis. Differences in the 15N-enrichment of free amino acids were also evident. This new effect-monitoring system designed to investigate the impact of a pollutant on protein metabolism by using a stable isotope-labeled cell culture is a powerful tool for environmental medical research.
New drugs are taking too long to reach patients in Canada, report claims
Authors: D. Spurgeon
Journal: BMJ (2009)

Patients in Canada are being denied swift access to new drugs, because the regulatory process is too slow, says a report from the Canadian think tank the Fraser Institute.

“It takes more than 14 months, on average, for Health Canada [the federal regulatory agency] to approve new medicines as safe and effective,” claims Brett Skinner, the institute’s director of health policy and author of the report.

“And while private insurers will immediately cover those medicines, the provinces can take up to another year to decide if they will pay for the same drugs,” he said. …
Possible effect of time on renal allograft rejection.
Authors: M S Knapp, J R Cove-Smith, R Dugdale, N Mackenzie, R Pownall
Journal: BMJ (1979)

The change in plasma creatinine concentrations from decreasing values after successful renal transplantation to increasing values after the onset of rejection occurs as a sudden event. Twenty-two such episodes in 16 renal allograft recipients were studied by extrapolating sequential measurements of plasma creatinine concentrations to see when the change occurred. Seventeen of the episodes occurred between 2300 and 1100 and the rest at other times. This difference was significant. The results suggest that rejection is more common at night and apparently has a circadian rhythm, being likely to first influence creatinine clearance at around 0600.
A COMPARISON OF THE CHEMICAL ALTERATIONS IN THE BLOOD OF RATS INFECTED WITH PATHOGENIC AND NON-PATHOGENIC TRYPANOSOMES
Authors: Richard W. Linton
Journal: The Journal of Experimental Medicine (1930)

Blood samples from rats infected with Trypanosoma lewisi give normal values for lipoid phosphorus, lecithin, CO2 combining capacity, and liver glycogen. When these results are compared with the results of similar experiments with T. equiperdum infections, on the basis of the concentration of trypanosomes in the blood, it is found that the pathogenicity of the latter organism does not depend upon its numbers as affecting the blood, but that it must be in some other way injurious to the host. Whether the injury is due to a true toxin, an endotoxin, or mechanical interference is not yet known.
Aging not a death sentence; new medical insights needed
Authors: B. J. Montgomery
Journal: JAMA (1978)

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986 Pre-treatment prediction of response to interferon by cDNA microarray with high accuracy validated by cross-over study
Authors: S KANEKO, T TANAKA, M KOHARA, A DAIBA, S ITO, K KUBOTA
Journal: Hepatology (2003)

The treatment of mixed cryoglobulinemia (MC) includes several drugs steroids, cyclosporins, colchicine, plasmapheresis but given the documented association between MC and hepatitis C virus (HCV), the treatment of choice seems to be antiviral therapy. Several authors have reported the efficacy of interferon (IFN) alpha in the inhibition of HCV replication and reduction of cryoglobulin levels. The therapy with IFN as monotherapy in MC shows a complete response rate in only 10 12% of cases. Complete response to therapy using a combination of IFN plus ribavirin varies in different studies from 18% to 64% of cases. There are only two studies on the treatment of MC with peginter- feron plus ribavirin. Both studies, given the high number of complete responders, reinforce the idea that peginterferon plus ribavirin is, at present, the best avaible treatment for cryoglobulinemic syndrome. The results obtained with peginterferon combined therapy are superior to standard interferon plus ribavirin in treatment-naive patients. In fact, a sustained virological response was observed in 44% of patients; the same results were obtained for clinical (purpura and arthralgia disappearance) and biochemical (aminotransaminases normalization) responses. New drug combinations, like peginterferons plus anti-CD20 antibodies, should be considered for treatment of MC in the future.
SAP Regulates TH2 Differentiation and PKC-θ-Mediated Activation of NF-κB1
Authors: Jennifer L. Cannons, Li J. Yu, Brenna Hill, Lilia A. Mijares, Derek Dombroski, Kim E. Nichols, Anthony Antonellis, Gary A. Koretzky, Kevin Gardner, Pamela L. Schwartzberg
Journal: Immunity (2004)
Krüppel-like factor 15 activates hepatitis B virus gene expression and replication
Authors: Jie Zhou, Thomas Tan, Yongjun Tian, Bojian Zheng, J.-H. James Ou, Eric J. Huang, Benedict T.S. Yen
Journal: Hepatology (2011)

Hepatitis B virus (HBV) is a small DNA virus that requires cellular transcription factors for the expression of its genes. To understand the molecular mechanisms that regulate HBV gene expression, we conducted a yeast one-hybrid screen to identify novel cellular transcription factors that may control HBV gene expression. Here, we demonstrate that Krüppel-like factor 15 (KLF15), a liver-enriched transcription factor, can robustly activate HBV surface and core promoters. Mutations in the putative KLF15 binding site in the HBV core promoter abolished the ability of KLF15 to activate the core promoter in luciferase assays. Furthermore, the overexpression of KLF15 stimulated the expression of HBV surface antigen (HBsAg) and the core protein and enhanced viral replication. Conversely, small interfering RNA knockdown of the endogenous KLF15 in Huh7 cells resulted in a reduction in HBV surface- and core-promoter activities. In electrophoretic mobility shift and chromatin immunoprecipitation assays, KLF15 binds to DNA probes derived from the core promoter and the surface promoter. Introduction of an expression vector for KLF15 short hairpin RNA, together with the HBV genome into the mouse liver using hydrodynamic injection, resulted in a significant reduction in viral gene expression and DNA replication. Additionally, mutations in the KLF15 response element in the HBV core promoter significantly reduced viral DNA levels in the mouse serum.KLF15 is a novel transcriptional activator for HBV core and surface promoters. It is possible that KLF15 may serve as a potential therapeutic target to reduce HBV gene expression and viral replication.
Transesophageal low-energy cardioversion in an animal model of life-threatening tachyarrhythmias.
Authors: Y C Cai, S L Fan, D X Feng, S X Gan, J F Feng, Z S Kuang, Z F Li
Journal: Circulation (1989)

The purpose of this study was to determine the feasibility and efficacy of terminating life-threatening ventricular tachyarrhythmia by low-energy synchronous or asynchronous shocks delivered through a transesophageal catheter that had both an anode and a cathode. Forty-three episodes of ventricular fibrillation or flutter (Vf or VF) were provoked by transesophageal asynchronous random shocks occurring during the vulnerable period of the ventricular cycle in seven dogs and seven pigs that were healthy adults. The 43 episodes of Vf or VF were terminated by the transesophageal technique. The defibrillation energy thresholds were 23.11 +/- 6.28 J (range, 5-30 J). Seven episodes of ventricular tachycardia (VT) with a cycle length of 360 msec or less (330 +/- 27 msec) were provoked by ventricular pacing stimuli during acute myocardial ischemia resulting from delayed resuscitation in two dogs and three pigs. Five of the seven VTs had a duration of 31 seconds or more, and they were all terminated by transesophageal synchronous shocks, the cardioversion thresholds being 1.71 +/- 2.25 J (range, 0.25-5 J). Fourteen episodes of idioventricular tachycardia (IVT) with a cycle length of 400 msec or more (445 +/- 33.5 msec) spontaneously occurred after the use of adrenaline and after defibrillation in four dogs and five pigs. We also succeeded in terminating seven episodes of IVT with a duration of 34 seconds or more by the same means of treating VT, although IVT is not an indication for cardioversion in the clinical setting.(ABSTRACT TRUNCATED AT 250 WORDS)
Sex differences in peripheral vascular adrenergic receptors.
Authors: R R Freedman, S C Sabharwal, N Desai
Journal: Circulation Research (1987)

Although the incidence of many vascular diseases differs in men and women, sex differences in vascular physiology have not been extensively examined in human in vivo studies. The present study compared finger blood flow responses of normal men and women with brachial artery infusions of adrenergic agonists and with other neurally and nonneurally mediated procedures. In response to phenylephrine and clonidine, men showed significant dose-related vasoconstriction while women did not. In response to isoproterenol, men showed significant dose-related vasodilation while women did not. There were no sex differences in response to intra-arterial nitroglycerin or digoxin or to reactive hyperemia, procedures that do not act through adrenergic receptors. These data show that the sensitivity and/or density of peripheral vascular adrenergic receptors is lower in women than in men. There were no sex differences in response to reflex vasoconstriction or to intra-arterial tyramine, suggesting that neurally released norepinephrine acts at alpha-adrenergic receptors that are spatially removed from those that respond to circulating catecholamines.
Circulating Mononuclear Cells in the Obese Are in a Proinflammatory State
Authors: Husam Ghanim, Ahmad Aljada, Deborah Hofmeyer, Tufail Syed, Priya Mohanty, Paresh Dandona
Journal: Circulation (2004)

In view of the increase in plasma concentrations of proinflammatory mediators tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein (CRP) in obesity, we investigated whether peripheral blood mononuclear cells (MNC) from obese subjects are in a proinflammatory state.MNC were prepared from fasting blood samples of obese (n=16; body mass index [BMI]=37.7+/-5.0 kg/m2) and normal-weight control (n=16; BMI=23.8+/-1.9 kg/m2) subjects. Nuclear factor kappaB (NF-kappaB) binding to DNA in nuclear extracts was elevated (P<0.05) and the inhibitor of NFkappaB-beta (IkappaB-beta) was significantly lower (P<0.001) in the obese group. Reverse transcription-polymerase chain reaction revealed elevated levels of migration inhibitor factor (MIF), IL-6, TNF-alpha, and matrix metalloproteinase-9 (MMP-9) mRNA expression in the obese subjects (P<0.05). Plasma concentrations of MIF, IL-6, TNF-alpha, MMP-9, and CRP were also significantly higher. Plasma glucose, insulin, and free fatty acids (FFAs) were measured, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Plasma FFA concentration related significantly to BMI, IL-6, and TNF-alpha mRNA expression and plasma CRP levels but not to HOMA-IR. On the other hand, the inflammatory mediators were significantly related to BMI and HOMA-IR.These data show (1) for the first time that MNC in obesity are in a proinflammatory state with an increase in intranuclear NF-kappaB binding, a decrease in IkappaB-beta, and an increase in the transcription of proinflammatory genes regulated by NF-kappaB; (2) that plasma FFAs are a modulator of inflammation; and (3) that insulin resistance is a function of inflammatory mediators.
Low-level exercise testing after myocardial infarction: usefulness in enhancing clinical risk stratification.
Authors: R J Krone, J A Gillespie, F M Weld, J P Miller, A J Moss
Journal: Circulation (1985)

Of 866 patients enrolled in our multicenter study, 667 performed a low-level exercise test early after myocardial infarction, most before discharge. Excluding seven patients who died before the test could be considered, there was a 14% 1 year cardiac mortality in 192 patients who did not take the test (150 for medical and 42 for logistic reasons) compared with 5% in those who did (p less than .0001). Of those who took the test, 12% subsequently underwent bypass grafts surgery compared with 14% of those who did not (p greater than .05). Decreased mortality in the year after the infarction in those taking the test was associated with an increase in blood pressure to 110 mm Hg or higher (3% vs 18%; p less than .001), ability to complete the 9 min test (3% vs 8%; p less than .01), and the absence of couplets (4% vs 13%; p less than .05) or any ventricular ectopic depolarizations (4% vs 7%, p less than .05) before, during, or after exercise. Achievement of a blood pressure of 110 mm Hg or higher during exercise in patients with no evidence of pulmonary congestion on the chest x-ray identified a group of 454 patients (70% of those taking the test) with a 1 year cardiac mortality of 1% compared with 13% in the remaining patients (p less than .0001). Logistic models showed that the exercise test contributed independent prognostic information for cardiac death, new infarction, and bypass surgery. Results of low-level exercise testing before hospital discharge combined with clinical features of the infarction can effectively identify patients at low risk for subsequent cardiac mortality.
Endotoxin Activity and Inflammatory Markers in the Airways of Young Patients with Cystic Fibrosis
Authors: Marianne S. Muhlebach, Terry L. Noah
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Chronic endobronchial infection frequently caused by gram-negative organisms and an increased, neutrophil-dominated inflammation are characteristics of cystic fibrosis (CF). The present study examines endotoxin levels in bronchoalveolar lavage fluids of CF versus non-CF (N) control children, and correlates these with the inflammatory markers interleukin-8 and neutrophils. Fifty-five patients with CF and 56 patients without CF between the ages of 0.04 to 13.25 years were included. Infection, defined as a bacterial count above 50,000 cfu/ml, was present in 27 CF and 25 N patients. Endotoxin levels were not different between patients with and without CF (infected: 74.9 ± 12.1 EU/ml versus 51.4 ± 12.5 EU/ml, p = 0.16; noninfected: 5.9 ± 4.8 EU/ml versus 11.1 ± 4.3 EU/ml, p = 0.28). Endotoxin activity correlated to the number of gram-negative organisms in CF and N patients, and endotoxin activity per bacterial colony forming unit did not differ with various gram-negative species. Both interleukin-8 and neutrophils were positively correlated with endotoxin, but this slope was shifted toward higher levels of inflammation in CF patients. We conclude that it is unlikely that higher levels of endotoxin in the absence of viable bacteria explain the increased inflammatory response in CF.