tbuckley/cabot-search huggingface dataset:
Oral Glucose Augmentation of Insulin Secretion
Authors: Dana K. Andersen, Dariush Elahi, John C. Brown, Jordan D. Tobin, Reubin Andres
Journal: Journal of Clinical Investigation (1978)

Gastric inhibitory polypeptide, or GIP, has been postulated as the major enteric hormonal mediator of insulin release. The release of immuno-reactive GIP (IR-GIP) after oral glucose and its role in insulin release was studied in normal men by the glucose clamp technique. In 24 subjects studied with the hyperglycemic clamp, blood glucose was maintained at 125 mg/dl above basal for 2 h via a primed-continuous IV glucose infusion coupled to a servo-controlled negative feedback system. 40 g glucose per m(2) surface area was ingested at 60 min, and the blood glucose was maintained at the steady-state hyperglycemic level. Plasma IR-GIP and insulin (IRI) levels were measured throughout the 2-h period. IR-GIP levels changed little when IV glucose alone was given; the mean basal value was 305+/-34 (SEM) pg/ml. After oral glucose, IR-GIP levels began to rise within 10 min and reached a peak within 40 min of 752+/-105 pg/ml. Plasma IRI responded initially to the square wave of hyperglycemia in the typical biphasic pattern. After oral glucose, plasma IRI levels rose strikingly above the elevated levels produced by hyperglycemia alone, reaching a peak of 170+/-15 muU/ml within 45 min. The time course of the rise in IR-GIP and IRI was nearly identical. To assess whether the maintenance of euglycemia would affect this process, the euglycemic clamp was employed in 11 subjects to maintain basal blood glucose levels during a similar 2-h study. A primed-continuous insulin infusion, with a constant rate of 120 mU/m(2) per min was given together with a servo-controlled glucose infusion. This resulted in hyper-insulinemia of approximately 300 muU/ml. Glucose was ingested by six subjects at 60 min. Plasma IR-GIP responded to oral glucose similarly to the effect seen in the hyperglycemic studies. No increase in endogenous insulin release was seen despite the increase in IR-GIP when euglycemia was maintained. However, in five of seven subjects given insulin whose blood glucose concentration rose by 20 mg/dl or more after oral glucose, there was an increase in plasma insulin concentration associated with the elevation in IR-GIP. Thus, the effect of glucose-released IR-GIP on insulin secretion is dependent upon the presence of some degree of hyper-glycemia and is not inhibited in the presence of marked hyperinsulinemia.
Thrombotic risk factors and extent of liver fibrosis in chronic viral hepatitis
Authors: G V Papatheodoridis
Journal: Gut (2003)

<b>Background and aims:</b> Thrombosis of the small intrahepatic veins has been suggested to trigger liver tissue remodelling. We evaluated the prevalence of multiple thrombotic risk factors and their association with the extent of fibrosis in chronic viral hepatitis. <b>Methods:</b> Ninety consecutive patients with chronic hepatitis B or C without malignancy, a history of venous thrombosis, or antiviral/immunosuppressive therapy within the last six months were included. Thrombophilic and coagulation factors were evaluated on the liver biopsy day. <b>Results:</b> One or more thrombotic risk factors were found in 68% and ≥2 factors in 37% of patients. Higher necroinflammatory activity was independently associated with higher prothrombin time (p=0.003), alanine aminotransferase level (p=0.011), and histological staging (p=0.018). Patients with staging scores of 4–6 compared with those with scores of 0–3 more frequently had deficiency of protein C (24% <i>v</i> 3%; p=0.007), antithrombin III (28% <i>v</i> 5%; p=0.005), and plasminogen (19% <i>v</i> 2%; p=0.03), and a trend for more frequent activated protein C resistance (8% <i>v</i> 0%; p=0.075). The presence of ≥1 significant thrombotic risk factor was observed in 11/25 (44%) patients with staging scores of 4–6 and in 6/65 (9%) patients with scores of 0–3 (p&lt;0.001), being the only variable independently associated with advanced staging (odds ratio 2.4, p=0.02). <b>Conclusions:</b> Thrombotic risk factors are frequently detected in patients with chronic viral hepatitis and the presence of ≥1 significant factor is associated with more advanced fibrosis. Whether the association of such thrombophilic conditions with advanced fibrosis is a primary or secondary phenomenon and whether their development in combination with local inflammation accelerate the progression of liver fibrosis need further evaluation.
A SERUM FACTOR IN CHRONIC HYPOCOMPLEMENTEMIC NEPHRITIS DISTINCT FROM IMMUNOGLOBULINS AND ACTIVATING THE ALTERNATE PATHWAY OF COMPLEMENT
Authors: Enrique H. Vallota, Otto Götze, Hans L. Spiegelberg, Judith Forristal, Clark D. West, Hans J. Müller-Eberhard
Journal: The Journal of Experimental Medicine (1974)

Nephritic factor (C3NeF) has been isolated from plasma of patients with hypocomplementemic chronic glomerulonephritis (HCG) by ion exchange and molecular sieve chromatography. This material was further treated with solidified anti-Ig antiserum. The purified material failed to react with antiserum to human IgG, IgG3, Fab, Fc, and kappa and lambda chains, but retained full C3NeF activity. The nonidentity of C3NeF with IgG was further demonstrated by Ouchterlony analysis using anti-IgG and anti-C3NeF. Isolated C3NeF was found to be a protein with a sedimentation coefficient of 7S and a mol wt of 150,000 daltons, which on microzone electrophoresis and gel electrophoresis at pH 8.6 behaved as a γ-globulin. C3NeF is not a C1q precipitin and does not activate the classical complement pathway. Unlike cobra venom factor, it failed to enter into a complex with C3 proactivator (C3PA) when incubated with normal human serum (NHS) and then subjected to sucrose density gradient ultracentrifugation. The action of isolated C3NeF on C3 requires C3PA, C3PA convertase (C3PAse), and properdin (P). Similarly, C3PA conversion by C3NeF requires P, C3PAse, and C3. Total hemolytic activity was lost by incubation of 64 µg of C3NeF/1 ml NHS at 37°C for 30 min. Both C3a and C5a anaphylatoxin could be generated by C3NeF in serum previously depleted of anaphylatoxin inactivator. Anti-C3NeF was found to detect an antigen in all NHS tested. Treatment of NHS with solidified anti-C3NeF caused impairment of the alternate complement pathway. It failed to sustain lysis of glutathione-treated human erythrocytes initiated by inulin. It is conceivable that the normal serum constituent which is removed by anti-C3NeF constitutes the inactive precursor of C3NeF, and a heretofore unrecognized component of the alternate pathway.
Reversibility of Brainstem Damage After a Mechanical Thrombectomy
Authors: Benjamin Gory, Thomas Ritzenthaler, Roberto Riva, Norbert Nighoghossian, Francis Turjman
Journal: JAMA Neurology (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Prognostic Impact of Hypoxia-Inducible Factors 1α and 2α in Colorectal Cancer Patients
Authors: Hiroshi Yoshimura, Dipok Kumar Dhar, Hitoshi Kohno, Hirofumi Kubota, Toshiyuki Fujii, Shuhei Ueda, Shoichi Kinugasa, Mitsuo Tachibana, Naofumi Nagasue
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Angiogenesis plays an important role in a multitude of biological processes including those of tumorigenesis and cancer progression. Hypoxia is the prime driving factor for tumor angiogenesis and the family of hypoxia-inducible factors (HIFs) plays a pivotal role in this process. The role of HIF in tumor angiogenesis has been underscored in different carcinomas but yet to be reported for colorectal carcinomas. Experimental Design: In this study, we examined HIF [HIF-1α (HIF1) and HIF-2α (HIF2)] expression in 87 curatively resected colorectal carcinoma samples, and the results were correlated with clinicopathological factors, microvessel density, cyclooxygenase 2 expression, and patient prognosis. Results: HIF1 (44.8%) was more frequently expressed than HIF2 (29.9%). Most of the clinicopathological factors representing the tumor aggressiveness were significantly correlated with overexpression of HIF2 but not with HIF1 expression. HIF2 expression had direct correlation with microvessel density and cyclooxygenase 2 expression. and, in contrast, HIF1 expression had a weak but significant inverse correlation in T1 and T2 tumors only. HIF2 expression alone and the combined expression of HIF1 and HIF2 had significant impact on patient survival. In the multivariate analysis, however, only the combined expression of HIF1 and HIF2 remained independently significant. Conclusions: Taken together, our results suggest that HIF2 expression may play an important role in angiogenesis and that the combined expression of HIF1 and HIF2 may play an important role in tumor progression and prognosis of colorectal carcinomas. Therefore, HIF expression could be a useful target for therapeutic intervention.
Diffuse interstitial pneumonia and pulmonary hypertension: a novel manifestation of chronic granulomatous disease
Authors: H. Khaldi, S. Marchand-Adam, C. Kannengiesser, A. Fabre, M. P. Debray, C. Danel, M-A. Gougerot-Pocidalo, J. El Benna, M. Humbert, M. Aubier, B. Crestani
Journal: European Respiratory Journal (2009)

The present authors report the case of an adult with chronic granulomatous disease who developed an unusual lung fibrosis associated with severe pulmonary hypertension. Histological analysis of a lung biopsy showed a diffuse infiltration with pigmented macrophages without granulomas, which particularly involved the pulmonary arterial and venular walls. Clinical and histological findings were suggestive of pulmonary veno-occlusive disease. Such a clinical association has not been previously described in the literature and might be due to the persistent expression of gp91phox at a very low level. In conclusion, the present case report illustrates a novel manifestation of chronic granulomatous disease.
Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation.
Authors: M F Linton, R Gish, S T Hubl, E Bütler, C Esquivel, W I Bry, J K Boyles, M R Wardell, S G Young
Journal: Journal of Clinical Investigation (1991)

Apolipoprotein (apo) E and the two B apolipoproteins, apoB48 and apoB100, are important proteins in human lipoprotein metabolism. Commonly occurring polymorphisms in the genes for apoE and apoB result in amino acid substitutions that produce readily detectable phenotypic differences in these proteins. We studied changes in apoE and apoB phenotypes before and after liver transplantation to gain new insights into apolipoprotein physiology. In all 29 patients that we studied, the postoperative serum apoE phenotype of the recipient, as assessed by isoelectric focusing, converted virtually completely to that of the donor, providing evidence that greater than 90% of the apoE in the plasma is synthesized by the liver. In contrast, the cerebrospinal fluid apoE phenotype did not change to the donor's phenotype after liver transplantation, indicating that most of the apoE in CSF cannot be derived from the plasma pool and therefore must be synthesized locally. The apoB100 phenotype (assessed with immunoassays using monoclonal antibody MB19, an antibody that detects a two-allele polymorphism in apoB) invariably converted to the phenotype of the donor. In four normolipidemic patients, we determined the MB19 phenotype of both the apoB100 and apoB48 in the "chylomicron fraction" isolated from plasma 3 h after a fat-rich meal. Interestingly, the apoB100 in the chylomicron fraction invariably had the phenotype of the donor, indicating that the vast majority of the large, triglyceride-rich apoB100-containing lipoproteins that appear in the plasma after a fat-rich meal are actually VLDL of hepatic origin. The MB19 phenotype of the apoB48 in the plasma chylomicron fraction did not change after liver transplantation, indicating that almost all of the apoB48 in plasma chylomicrons is derived from the intestine. These results were consistent with our immunocytochemical studies on intestinal biopsy specimens of organ donors; using apoB-specific monoclonal antibodies, we found evidence for apoB48, but not apoB100, in donor intestinal biopsy specimens.
Current Status and Future Prospects for Satraplatin, an Oral Platinum Analogue
Authors: Hak Choy, Clinton Park, Min Yao
Journal: Clinical Cancer Research (2008)

Abstract Platinum drugs are major chemotherapeutic agents that are used alone or in combination with other systemic agents and/or radiation therapy in the management of many human malignancies. All three platinum drugs approved by the Food and Drug Administration, cisplatin, carboplatin, and oxaliplatin, are administrated intravenously. Satraplatin is the first orally administered platinum drug under active clinical investigation. Satraplatin and its major metabolite, JM118, have shown antineoplastic activity in in vitro, in vivo, and in clinical settings. Use of satraplatin as an alternative platinum cytotoxic agent is particularly attractive because of the convenience of administration, milder toxicity profile, lack of cross-resistance with cisplatin, theoretical advantage as a radiosensitizer, and activity in cancers historically nonresponsive to platinum drugs. The most mature clinical data for satraplatin come from the recently completed phase III trial that investigated the efficacy of satraplatin and prednisone on hormone-refractory prostate cancer patients who had failed a course of other chemotherapy agents. Preliminary reports show that the combination is statistically superior to placebo and prednisone in multiple end points, including progression-free survival, prostate-specific antigen response, objective tumor response, pain response, and duration of pain response. The difference in overall survival, however, did not reach statistical significance.
Angiotensinogen in Essential Hypertension
Authors: JEAN-MARC LALOUEL, ANDREAS ROHRWASSER, DANIEL TERREROS, TERRY MORGAN, KENNETH WARD
Journal: Journal of the American Society of Nephrology (2001)

Abstract. There is general consensus that genetic variation accounts in part for individual susceptibilities to essential hypertension. In marked contrast to classic mendelian disorders, in which genetic alterations produce a gain or loss of function, genetic determinants of essential hypertension, high blood pressure of unknown cause, are expected to be small, achieving significance through the cumulative effects of environmental exposure over the course of a lifetime. Whether and how genetic factors that contribute to common diseases can be identified remain unclear. Research on a link between angiotensinogen and essential hypertension illustrates a path that began in genetics and is now leading toward nephrology. Various challenges encountered along the way may prove to be characteristic features of genetic investigations of the pathogenesis of common diseases. The implication of a gene by statistical analysis is only the beginning of a protracted process of functional analysis at increasing levels of biologic integration. The ultimate goal is to develop an understanding of the manner in which genetic variation at a locus can affect a physiologic parameter and to extract from this inference new knowledge of significance for the prevention or treatment of disease.
Diagnostic accuracy of adipose insulin resistance index and visceral adiposity index for progressive liver histology and cardiovascular risk in nonalcoholic fatty liver disease
Authors: Giovanni Musso, Maurizio Cassader, Roberto Gambino
Journal: Hepatology (2012)

We read with interest the article by Lomonaco et al.1 reporting on the association of adipose tissue insulin resistance index (adipo-IR) with liver histology and metabolic profile in nonalcoholic fatty liver disease (NAFLD). Recently, another simple index of visceral fat function, visceral adiposity index (VAI) (see Table 1), predicted cardiometabolic risk in the general population and liver histology in chronic hepatitis C.2, 3 We assessed whether these indexes could be used for diagnostic purposes to noninvasively screen NAFLD patients at risk of progressive liver disease (i.e., nonalcoholic steatohepatitis [NASH] or advanced fibrosis) and of cardiovascular disease (CVD). Forty-one unselected otherwise healthy biopsy-proven NAFLD patients (mean ± SE age, 50 ± 3; 60% males; body mass index [BMI] 27 ± 3 kg/m2), 48% with NASH (diagnosed by Brunt criteria), 19% with advanced fibrosis), and 82 healthy controls were evaluated: besides clinically routine variables, extensively validated noninvasive markers/scores for predicting NASH (cytokeratin-18 fragments) and advanced fibrosis (NAFLD fibrosis score, FIB-4 index) were determined.4 Furthermore, circulating markers of endothelial dysfunction (E-selectin and intercellular adhesion molecule-1, ICAM-1) were measured as markers of early cardiovascular risk.5 Compared with patients with simple steatosis, NASH patients had higher adipo-IR (82,437 ± 10,158 versus 48,540 ± 6,243 mmol/L/pmol/L, P = 0.001) and VAI (2.28 ± 0.14 versus 1.54 ± 0.20, P = 0.009), and higher circulating E-selectin (45.9 ± 2.8 versus 25.3 ± 2.4 ng/mL, P = 0.008) and ICAM-1 (279.1 ± 9.3 versus 239.4 ± 8.2 ng/mL, P = 0.029). The diagnostic accuracy of adipo-IR, VAI, and other noninvasive scores is reported in Table 1. The area under receiver operating characteristics curve (AUROC) of adipo-IR for predicting NASH and advanced fibrosis was comparable to that of more extensively validated scores/markers, as was the accuracy VAI for advanced fibrosis. Both adipo-IR and VAI were superior to validated scores for predicting endothelial dysfunction. In conclusion, adipo-IR and VAI accurately predicted progressive liver histology at least as accurately as other validated noninvasive scores and, additionally, they accurately individuated NAFLD patients at increased CVD risk. Altogether, the findings by Lomonaco et al. and by our group confirm the pathogenic connections between visceral fat dysfunction and liver and cardiometabolic risk in NAFLD and prompt further independent prospective evaluation of adipose tissue dysfunction indexes for individuating NAFLD patients at increased risk of liver-related and cardiovascular complications, the major health burden of these subjects. Giovanni Musso MD*, Maurizio Cassader PhD , Roberto Gambino PhD , * Gradenigo Hospital, Turin, Italy, Department of Internal Medicine, University of Turin, Turin, Italy.
A Trial of Mass Isoniazid Preventive Therapy for Tuberculosis Control
Authors: Gavin J. Churchyard, Katherine L. Fielding, James J. Lewis, Leonie Coetzee, Elizabeth L. Corbett, Peter Godfrey-Faussett, Richard J. Hayes, Richard E. Chaisson, Alison D. Grant
Journal: New England Journal of Medicine (2014)

Tuberculosis is epidemic among workers in South African gold mines. We evaluated an intervention to interrupt tuberculosis transmission by means of mass screening that was linked to treatment for active disease or latent infection.In a cluster-randomized study, we designated 15 clusters with 78,744 miners as either intervention clusters (40,981 miners in 8 clusters) or control clusters (37,763 miners in 7 clusters). In the intervention clusters, all miners were offered tuberculosis screening. If active tuberculosis was diagnosed, they were referred for treatment; if not, they were offered 9 months of isoniazid preventive therapy. The primary outcome was the cluster-level incidence of tuberculosis during the 12 months after the intervention ended. Secondary outcomes included tuberculosis prevalence at study completion.In the intervention clusters, 27,126 miners (66.2%) underwent screening. Of these miners, 23,659 (87.2%) started taking isoniazid, and isoniazid was dispensed for 6 months or more to 35 to 79% of miners, depending on the cluster. The intervention did not reduce the incidence of tuberculosis, with rates of 3.02 per 100 person-years in the intervention clusters and 2.95 per 100 person-years in the control clusters (rate ratio in the intervention clusters, 1.00; 95% confidence interval [CI], 0.75 to 1.34; P=0.98; adjusted rate ratio, 0.96; 95% CI, 0.76 to 1.21; P=0.71), or the prevalence of tuberculosis (2.35% vs. 2.14%; adjusted prevalence ratio, 0.98; 95% CI, 0.65 to 1.48; P=0.90). Analysis of the direct effect of isoniazid in 10,909 miners showed a reduced incidence of tuberculosis during treatment (1.10 cases per 100 person-years among miners receiving isoniazid vs. 2.91 cases per 100 person-years among controls; adjusted rate ratio, 0.42; 95% CI, 0.20 to 0.88; P=0.03), but there was a subsequent rapid loss of protection.Mass screening and treatment for latent tuberculosis had no significant effect on tuberculosis control in South African gold mines, despite the successful use of isoniazid in preventing tuberculosis during treatment. (Funded by the Consortium to Respond Effectively to the AIDS TB Epidemic and others; Thibela TB Current Controlled Trials number, ISRCTN63327174.).
The <i>Justy</i> mutation identifies <i>Gon4-like</i> as a gene that is essential for B lymphopoiesis
Authors: Ping Lu, Isaiah L. Hankel, Judit Knisz, Andreas Marquardt, Ming-Yi Chiang, Johannes Grosse, Rainer Constien, Thomas Meyer, Andreas Schroeder, Lutz Zeitlmann, Umaima Al-Alem, Ann D. Friedman, Eric I. Elliott, David K. Meyerholz, Thomas J. Waldschmidt, Paul B. Rothman, John D. Colgan
Journal: The Journal of Experimental Medicine (2010)

A recessive mutation named Justy was found that abolishes B lymphopoiesis but does not impair other major aspects of hematopoiesis. Transplantation experiments showed that homozygosity for Justy prevented hematopoietic progenitors from generating B cells but did not affect the ability of bone marrow stroma to support B lymphopoiesis. In bone marrow from mutant mice, common lymphoid progenitors and pre-pro–B cells appeared normal, but cells at subsequent stages of B lymphopoiesis were dramatically reduced in number. Under culture conditions that promoted B lymphopoiesis, mutant pre-pro–B cells remained alive and began expressing the B cell marker CD19 but failed to proliferate. In contrast, these cells were able to generate myeloid or T/NK precursors. Genetic and molecular analysis demonstrated that Justy is a point mutation within the Gon4-like (Gon4l) gene, which encodes a protein with homology to transcriptional regulators. This mutation was found to disrupt Gon4l pre-mRNA splicing and dramatically reduce expression of wild-type Gon4l RNA and protein. Consistent with a role for Gon4l in transcriptional regulation, the levels of RNA encoding C/EBPα and PU.1 were abnormally high in mutant B cell progenitors. Our findings indicate that the Gon4l protein is required for B lymphopoiesis and may function to regulate gene expression during this process.
The Wilms’ tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes
Authors: H Tamaki, H Ogawa, K Ohyashiki, JH Ohyashiki, H Iwama, K Inoue, T Soma, Y Oka, T Tatekawa, Y Oji, A Tsuboi, EH Kim, M Kawakami, K Fuchigami, M Tomonaga, K Toyama, K Aozasa, T Kishimoto, H Sugiyama
Journal: Leukemia (1999)