tbuckley/cabot-search huggingface dataset:
Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation.
Authors: M Asano, M Toda, N Sakaguchi, S Sakaguchi
Journal: The Journal of Experimental Medicine (1996)

Neonatal thymectomy (NTx), especially around day 3 after birth, causes various organ-specific autoimmune diseases in mice. This report shows that: (a) T cells expressing the interleukin 2 receptor alpha chains (CD25) ontogenically begin to appear in the normal periphery immediately after day 3, rapidly increasing within 2 wk to nearly adult levels (approximately 10% of CD3+ cells, especially of CD4+ cells); (b) NTx on day 3 eliminates CD25+ T cells from the periphery for several days; inoculation immediately after NTx of CD25+ splenic T cells from syngeneic non-Tx adult mice prevents autoimmune development, whereas inoculation of CD25- T cells even at a larger dose does not; and furthermore, (c) similar autoimmune diseases can be produced in adult athymic nu/nu mice by inoculating either spleen cell suspensions from 3-d-old euthymic nu/+ mice or CD25+ cell-depleted spleen cell suspensions from older, even 1-yr-old, nu/+ mice. The CD25- populations from neonates or adults are also similar in the profile of cytokine formation. These results, taken together, indicate that one aspect of peripheral self-tolerance is maintained by CD25+ T cells that sustain potentially pathogenic self-reactive T cells in a CD25- dormant state; the thymic production of the former is developmentally programmed to begin on day 3 after birth in mice. Thus, NTx on day 3 can, at least transiently, eliminate/reduce the autoimmune-preventive CD25+ T cells, thereby leading to activation of the self-reactive T cells that have been produced before NTx.
Differential effects of oral, peripheral intravenous, and intraportal glucose on hepatic glucose uptake and insulin and glucagon extraction in conscious dogs.
Authors: T Ishida, Z Chap, J Chou, R Lewis, C Hartley, M Entman, J B Field
Journal: Journal of Clinical Investigation (1983)

The effect of equal (1.1 +/- 0.1 g/kg body wt) amounts of glucose administered orally, or by peripheral intravenous or intraportal infusion on hepatic glucose uptake and fractional hepatic extraction of insulin and glucagon was studied in conscious dogs with chronically implanted Doppler flow probes on the portal vein and hepatic artery and catheters in the portal vein, hepatic vein, carotid artery, and superior mesenteric vein. Portal vein and hepatic vein plasma flow increased only after oral glucose administration. Arterial plasma glucose increased equally to 150-160 mg/100 ml after all three routes of glucose administration. Portal vein glucose was similar after oral (195 +/- 15 mg/100 ml) and intraportal glucose infusion (215 +/- 11 mg/100 ml) and significantly higher than after peripheral intravenous glucose. Hepatic glucose uptake after oral (68 +/- 4%) and intraportal glucose administration (65 +/- 7%) significantly exceeded that after peripheral intravenous glucose infusion (23 +/- 5%). The amount of insulin above basal presented to the liver during the 180 min after oral glucose was 7.6 +/- 1.3 U, 4.3 +/- 0.6 U after intraportal glucose, and 4.1 +/- 0.6 U after peripheral intravenous glucose. Hepatic extraction of insulin increased significantly after oral glucose (42 +/- 3 to 61 +/- 4%), but was unchanged after intraportal and peripheral intravenous glucose administration. When the portal vein glucose levels achieved during peripheral intravenous glucose infusion for 90 min were maintained by a subsequent 90-min intraportal glucose infusion, hepatic glucose uptake was significantly greater during the intraportal glucose infusion. Glucagon secretion was suppressed equally after oral glucose, intraportal glucose, and peripheral intravenous glucose administration; fractional hepatic extraction of that hormone, which was significantly less than that of insulin, was unchanged. These results indicate that hepatic glucose uptake is significantly greater after oral and intraportal glucose administration than after peripheral intravenous glucose infusion. This difference is not simply related to the amount of glucose or insulin presented to the liver and the increased hepatic glucose uptake did not depend solely upon the augmented fractional hepatic extraction of insulin. Hepatic extraction of insulin and hepatic glucose uptake appear to be regulated independently.
A Prospective Study of Passive Smoking and Risk of Diabetes in a Cohort of Workers
Authors: Yasuaki Hayashino, Shunichi Fukuhara, Tomonori Okamura, Hiroshi Yamato, Hideo Tanaka, Taichiro Tanaka, Takashi Kadowaki, Hirotsugu Ueshima
Journal: Diabetes Care (2008)

OBJECTIVE—We investigated the impact of active smoking and exposure to passive smoke on the risk of developing diabetes. RESEARCH DESIGN AND METHODS—Data were analyzed from a cohort of participants in the High-Risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP) conducted in Japan from 1999 to 2004. Active and passive smoking status in the workplace was evaluated at baseline. RESULTS—Of 6,498 participants (20.9% women), a total of 229 diabetes cases were reported over a median 3.4 years of follow-up. In the workplace, compared with zero-exposure subjects, the multivariable-adjusted hazard ratios of developing diabetes were 1.81 (95% CI 1.06–3.08, P = 0.028) for present passive subjects and 1.99 (1.29–3.04, P = 0.002) for present active smokers. CONCLUSIONS—In this cohort, exposure to passive smoke in the workplace was associated with an increased risk of diabetes after adjustment for a large number of possible confounders.
Prognostic factors associated with long-term survival in previously untreated metastatic renal cell carcinoma
Authors: T.K. Choueiri, B.I. Rini, J.A. Garcia, R.C. Baz, R.M. Abou-Jawde, S.G. Thakkar, P. Elson, T.M. Mekhail, M. Zhou, R.M. Bukowski
Journal: Annals of Oncology (2006)
Effects of Erlotinib in <i>EGFR</i> Mutated Non-Small Cell Lung Cancers with Resistance to Gefitinib
Authors: Daniel B. Costa, Kim-Son H. Nguyen, Byoung C. Cho, Lecia V. Sequist, David M. Jackman, Gregory J. Riely, Beow Y. Yeap, Balázs Halmos, Joo H. Kim, Pasi A. Jänne, Mark S. Huberman, William Pao, Daniel G. Tenen, Susumu Kobayashi
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Most lung cancers with activating epidermal growth factor receptor (EGFR) mutations respond to gefitinib; however, resistance to this tyrosine kinase inhibitor (TKI) invariably ensues. The T790M mutation occurs in 50% and MET amplification in 20% of TKI-resistant tumors. Other secondary mutations (D761Y and L747S) are rare. Our goal was to determine the effects of erlotinib 150 mg/d in EGFR mutated patients resistant to gefitinib 250 mg/d, because the EGFR TKI erlotinib is given at a higher biologically active dose than gefitinib. Experimental Design: Retrospective review of 18 EGFR mutated (exon 19 deletions, L858R, and L861Q) patients that were given gefitinib and subsequently erlotinib. Seven patients had tumor resampling after TKI therapy and were analyzed for secondary EGFR mutations and MET amplification. Results: Most patients (14 of 18) responded to gefitinib with median progression-free survival of 11 months (95% confidence interval, 4-16). After gefitinib resistance (de novo or acquired), 78% (14 of 18) of these patients displayed progressive disease while on erlotinib with progression-free survival of 2 months (95% confidence interval, 2-3). Six of 7 resampled patients acquired the T790M mutation, and 0 of 3 had MET amplification. Only 1 gefitinib-resistant patient with the acquired L858R-L747S EGFR, which in vitro is sensitive to achievable serum concentrations of erlotinib 150 mg/d, achieved a partial response to erlotinib. Conclusions: In EGFR mutated tumors resistant to gefitinib 250 mg/d, a switch to erlotinib 150 mg/d does not lead to responses in most patients. These findings are consistent with preclinical models, because the common mechanisms of TKI resistance (T790M and MET amplification) in vitro are not inhibited by clinically achievable doses of gefitinib or erlotinib. Alternative strategies to overcome TKI resistance must be evaluated.
An X-ray diffraction study of chemically skinned cardiac muscle
Authors: I MATSUBARA, D W MAUGHAN, N YAGI
Journal: Cardiovascular Research (1985)

Journal Article An X-ray diffraction study of chemically skinned cardiac muscle Get access I MATSUBARA, I MATSUBARA Search for other works by this author on: Oxford Academic PubMed Google Scholar D W MAUGHAN, D W MAUGHAN **Department of Physiology and Biophysics, University of Vermont College of Medicine, Burlington, Vermont 05405, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar N YAGI N YAGI Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 19, Issue 9, September 1985, Page 514, https://doi.org/10.1093/cvr/19.9.514 Published: 01 September 1985
SOME PHYSICAL AND RADIOBIOLOGICAL PROPERTIES OF IMMUNOLOGICALLY REACTIVE MOUSE SPLEEN CELLS
Authors: David Osoba
Journal: The Journal of Experimental Medicine (1970)

Three classes of immunologically reactive cells, differing only slightly in size from each other, are required for the production of hemolysin-forming cells in culture. The three classes of cells can be detected in the normal mouse spleen by the combined use of rosette formation, velocity sedimentation, and irradiation. One class of cells (peak sedimentation velocity, 3.2 mm per hr) forms rosettes. The capacity of these cells to participate in immune responses to foreign erythrocytes is inhibited by relatively low doses of irradiation. These cells may be the immediate precursors of hemolysin-forming cells. A second class of cells (peak sedimentation velocity, 3.6 mm per hr) facilitates the production of hemolysin-forming cells by small numbers of normal spleen cells. Their facilitative activity is resistant to a relatively large dose of radiation. They do not form rosettes. The requirement of a third class of cells was deduced from the results of mixing experiments. Neither rosette-forming cells nor spleen cells largely depleted of rosette-forming cells could give rise to hemolysin-forming cells when cultured either alone or in the presence of large numbers of heavily irradiated cells. However, when rosette-forming cells, cells depleted of rosette-forming cells, and heavily irradiated cells were mixed together, hemolysin-forming cells were produced. The peak responses were found in fractions sedimenting at 4 mm per hr. Thus, it is suggested that these fractions contain a third class of cells. This class of cells does not form rosettes, but its function is inhibited by relatively low doses of radiation.
Folate Intake and Risk of Pancreatic Cancer: Pooled Analysis of Prospective Cohort Studies
Authors: Y. Bao, D. S. Michaud, D. Spiegelman, D. Albanes, K. E. Anderson, L. Bernstein, P. A. van den Brandt, D. R. English, J. L. Freudenheim, C. S. Fuchs, G. G. Giles, E. Giovannucci, R. A. Goldbohm, N. Hakansson, P. L. Horn-Ross, E. J. Jacobs, C. M. Kitahara, J. R. Marshall, A. B. Miller, K. Robien, T. E. Rohan, A. Schatzkin, V. L. Stevens, R. Z. Stolzenberg-Solomon, J. Virtamo, A. Wolk, R. G. Ziegler, S. A. Smith-Warner
Journal: JNCI Journal of the National Cancer Institute (2011)

Epidemiological studies evaluating the association between folate intake and risk of pancreatic cancer have produced inconsistent results. The statistical power to examine this association has been limited in previous studies partly because of small sample size and limited range of folate intake in some studies.We analyzed primary data from 14 prospective cohort studies that included 319,716 men and 542,948 women to assess the association between folate intake and risk of pancreatic cancer. Folate intake was assessed through a validated food-frequency questionnaire at baseline in each study. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random effects model. All statistical tests were two-sided.During 7-20 years of follow-up across studies, 2195 pancreatic cancers were identified. No association was observed between folate intake and risk of pancreatic cancer in men and women (highest vs lowest quintile: dietary folate intake, pooled multivariable RR = 1.06, 95% CI = 0.90 to 1.25, P(trend) = .47; total folate intake [dietary folate and supplemental folic acid], pooled multivariable RR = 0.96, 95% CI = 0.80 to 1.16, P(trend) = .90). No between-study heterogeneity was observed (for dietary folate, P(heterogeneity) = .15; for total folate, P(heterogeneity) = .22).Folate intake was not associated with overall risk of pancreatic cancer in this large pooled analysis.
Thoracic Aortic Aneurysm Frequency and Dissection Are Associated With Fibrillin-1 Fragment Concentrations in Circulation
Authors: Lynn M. Marshall, Eric J. Carlson, Jean O’Malley, Caryn K. Snyder, Noe L. Charbonneau, Susan J. Hayflick, Joseph S. Coselli, Scott A. LeMaire, Lynn Y. Sakai
Journal: Circulation Research (2013)

Rationale: Mutations in fibrillin-1 are associated with thoracic aortic aneurysm (TAA) in Marfan syndrome. Genome-wide association studies also implicate fibrillin-1 in sporadic TAA. Fragmentation of the aortic elastic lamellae is characteristic of TAA. Objective: Immunoassays were generated to test whether circulating fragments of fibrillin-1, or other microfibril fragments, are associated with TAA and dissection. Methods and Results: Plasma samples were obtained from 1265 patients with aortic aneurysm or dissection and from 125 control subjects. Concentrations of fibrillin-1, fibrillin-2, and fibulin-4 were measured with novel immunoassays. One hundred and seventy-four patients (13%) had aneurysms with only abdominal aortic involvement (abdominal aortic aneurysm), and 1091 (86%) had TAA. Of those with TAA, 300 patients (27%) had chronic dissection and 109 (10%) had acute or subacute dissection. Associations of fragment concentrations with TAA (versus abdominal aortic aneurysm) or with dissection (versus no dissection) were estimated with odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, sex, and smoking. Compared with controls, significantly higher percentages of aneurysm patients had detectable levels of fibrillin fragments. TAA was significantly more common (than abdominal aortic aneurysm) in the highest compared with lowest quartile of fibrillin-1 concentration (OR=2.9; 95% CI, 1.6–5.0). Relative to TAA without dissection, acute or subacute dissection (OR=2.9; 95% CI, 1.6–5.3), but not chronic dissection, was more frequent in the highest compared with lowest quartile of fibrillin-1 concentration. Neither TAA nor dissection was associated with fibrillin-2 or fibulin-4. Conclusions: Circulating fibrillin-1 fragments represent a new potential biomarker for TAA and acute aortic dissection.
Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis
Authors: M Heliovaara
Journal: Annals of the Rheumatic Diseases (2000)

Recent epidemiological studies have suggested that smoking is a risk factor for rheumatoid factor (RF) positive rheumatoid arthritis (RA). Being overweight, high serum cholesterol, and dietary factors have in some studies been found to be associated with the risk of RA. No attention, however, has been paid to coffee consumption as a risk determinant, though it is a shared covariate of the alleged risk factors.This study aimed at examining coffee consumption for its associations with RF positivity and with the risk of RA.Coffee consumption was studied, firstly, for its association with RF (sensitised sheep cell agglutination titre >/=128) in a cross sectional survey of 6809 subjects with no clinical arthritis, and secondly, for its prediction of RA in a cohort of 18 981 men and women who had neither arthritis nor a history of it at the baseline examination in 1973-76. Up to late 1989, 126 subjects of the cohort study had developed RA, of whom, 89 were positive for RF by the time of diagnosis.In the cross sectional survey the number of cups of coffee drunk daily was directly proportional to the prevalence of RF positivity. Adjusted for age and sex this association was significant (p value for linear trend, 0.008), but after further adjustment for smoking the linear trend declined below significance (p=0.06). In the cohort study there was an association between coffee consumption and the risk of RF positive RA that was not due to age, sex, level of education, smoking, alcohol intake, body mass index, or serum cholesterol. After adjustment for these potential confounders the users of four or more cups a day still had a relative risk of 2.20 (95% confidence interval 1.13 to 4.27) for developing RF positive RA compared with those drinking less. Coffee consumption did not predict the development of RF negative RA.Coffee consumption may be a risk factor for RA, possibly through mechanisms contributing to the production of RF. This hypothesis remains to be tested in further studies.
Hyperglycaemic conditions decrease cultured keratinocyte mobility: implications for impaired wound healing in patients with diabetes
Authors: C-C.E. Lan, I-H. Liu, A-H. Fang, C-H. Wen, C-S. Wu
Journal: British Journal of Dermatology (2008)

Journal Article Hyperglycaemic conditions decrease cultured keratinocyte mobility: implications for impaired wound healing in patients with diabetes Get access C‐C.E. Lan, C‐C.E. Lan Departments of Dermatology, †Microbiology and ‡Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan *Faculty of Biomedical Laboratory Science, College of Health Sciences, Kaohsiung Medical University, 100 Shih‐Chuan 1st Road, Kaohsiung 807, Taiwan Search for other works by this author on: Oxford Academic Google Scholar I‐H. Liu, I‐H. Liu Departments of Dermatology, †Microbiology and ‡Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan *Faculty of Biomedical Laboratory Science, College of Health Sciences, Kaohsiung Medical University, 100 Shih‐Chuan 1st Road, Kaohsiung 807, Taiwan Search for other works by this author on: Oxford Academic Google Scholar A‐H. Fang, A‐H. Fang Departments of Dermatology, †Microbiology and ‡Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan *Faculty of Biomedical Laboratory Science, College of Health Sciences, Kaohsiung Medical University, 100 Shih‐Chuan 1st Road, Kaohsiung 807, Taiwan Search for other works by this author on: Oxford Academic Google Scholar C‐H. Wen, C‐H. Wen Departments of Dermatology, †Microbiology and ‡Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan *Faculty of Biomedical Laboratory Science, College of Health Sciences, Kaohsiung Medical University, 100 Shih‐Chuan 1st Road, Kaohsiung 807, Taiwan Search for other works by this author on: Oxford Academic Google Scholar C‐S. Wu C‐S. Wu Departments of Dermatology, †Microbiology and ‡Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan *Faculty of Biomedical Laboratory Science, College of Health Sciences, Kaohsiung Medical University, 100 Shih‐Chuan 1st Road, Kaohsiung 807, Taiwan Correspondence: Ching‐Shuang Wu. E‐mail: m785034@kmu.edu.tw Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 159, Issue 5, 1 November 2008, Pages 1103–1115, https://doi.org/10.1111/j.1365-2133.2008.08789.x Published: 01 November 2008
Effects of Glucagon on Atrioventricular Conduction and Ventricular Automaticity in Dogs
Authors: CHARLES STEINER, ANDREW L. WIT, ANTHONY N. DAMATO
Journal: Circulation Research (1969)

The effects of glucagon, 50 µ/kg, on atrioventricular (A-V) conduction and ventricular automaticity were studied in 14 dogs. Atrial pacing was used to control the heart rate. The His bundle electrogram was recorded, and the interval from the pacing impulse (P) to the His bundle spike (H), the P-H interval, was used as a measure of A-V conduction. Ventricular automaticity was estimated in four dogs by recording vagal escape time and idioventricular rate after 60 seconds of continuous vagal stimulation. In three dogs with experimentally produced, complete heart block the effect of glucagon on idioventricular rate was estimated. When the heart rate was 250/minute, glucagon decreased the P-H interval by 30 ± 3%, from 126 ± 5 to 85 ± 5 msec ( P &lt; 0.01). When the heart rate was 310/minute, eight dogs demonstrated second-degree A-V block before glucagon; after glucagon, seven of the eight showed 1:1 A-V conduction. Glucagon increased heart rate by 38 ± 3.5%, from 148 ± 6.6 to 205 ± 8 beats/min ( P &lt;0.01). Propranolol, 2 mg/kg, did not block these effects on rate and A-V conduction. The vagal escape time and idioventricular rate with vagal stimulation and idioventricular rate in complete heart block did not change significantly after glucagon. Since glucagon profoundly increased the speed of A-V conduction without increasing ventricular automaticity, it may be useful in the treatment of A-V block especially in the presence of propranolol.
Amifostine-conjugated pH-sensitive calcium phosphate-covered magnetic-amphiphilic gelatin nanoparticles for controlled intracellular dual drug release for dual-targeting in HER-2-overexpressing breast cancer
Authors: Wei-Ming Li, Chih-Sheng Chiang, Wei-Chen Huang, Chia-Wei Su, Min-Yu Chiang, Jian-Yi Chen, San-Yuan Chen
Journal: Journal of Controlled Release (2015)
Proliferation of Airway Epithelium After Ozone Exposure
Authors: MICHAEL SALMON, HIROSHI KOTO, OONAGH T. LYNCH, EL-BDAOUI HADDAD, NICHOLAS J. LAMB, GREGORY J. QUINLAN, PETER J. BARNES, K. FAN CHUNG
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Ozone is an environmental pollutant with potent oxidizing properties. We investigated whether exposure to ozone-induced cell proliferation in the lungs of rats, and determined the effect of an antioxidant and of a glucocorticosteroid in Brown-Norway (BN) rats. Following single ozone exposure (0.5, 1.0, or 3.0 ppm for 6 h), proliferating cell nuclear antigen (PCNA) expression, as determined with immunohistochemistry, was significantly increased in the bronchial epithelium and alveolar epithelium as compared with controls exposed to filtered air with a maximal effect at 24 to 48 h (p < 0.001). Apocynin (5 mg/kg, orally), a reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, reduced the PCNA index in bronchial epithelium induced by ozone (3 ppm, 6 h) from 11.5 ± 1.3% (percent of nuclear cells expressing PCNA) to 4.4 ± 1.3% (mean ± SEM; p < 0.05). Dexamethasone (3 mg/kg, intraperitoneally) also reduced the PCNA index in bronchial epithelium, from 19.2 ± 2.3% to 10.9 ± 2.6% (p < 0.05). Dexamethasone but not apocynin inhibited ozone- induced neutrophil influx. Rats exposed repeatedly to ozone (3.0 ppm, 3 h, on three occasions 48 h apart) expressed a lower PCNA index in bronchial epithelium than did rats exposed only once at 1.9 ± 0.7% versus 6.0 ± 0.9%, respectively (p < 0.05). The proliferative epithelial response following a single exposure to ozone is modulated through oxidative and inflammatory mechanisms probably involving neutrophils.