tbuckley/cabot-search huggingface dataset:
Relationships between environmental organochlorine contaminant residues, plasma corticosterone concentrations, and intermediary metabolic enzyme activities in Great Lakes herring gull embryos.
Authors: A Lorenzen, T W Moon, S W Kennedy, G A Glen
Journal: Environmental Health Perspectives (1999)

Experiments were conducted to survey and detect differences in plasma corticosterone concentrations and intermediary metabolic enzyme activities in herring gull (Larus argentatus) embryos environmentally exposed to organochlorine contaminants in ovo. Unincubated fertile herring gull eggs were collected from an Atlantic coast control site and various Great Lakes sites in 1997 and artificially incubated in the laboratory. Liver and/or kidney tissues from approximately half of the late-stage embryos were analyzed for the activities of various intermediary metabolic enzymes known to be regulated, at least in part, by corticosteroids. Basal plasma corticosterone concentrations were determined for the remaining embryos. Yolk sacs were collected from each embryo and a subset was analyzed for organochlorine contaminants. Regression analysis of individual yolk sac organochlorine residue concentrations, or 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs), with individual basal plasma corticosterone concentrations indicated statistically significant inverse relationships for polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDDs/PCDFs), total polychlorinated biphenyls (PCBs), non-ortho PCBs, and TEQs. Similarly, inverse relationships were observed for the activities of two intermediary metabolic enzymes (phosphoenolpyruvate carboxykinase and malic enzyme) when regressed against PCDDs/PCDFs. Overall, these data suggest that current levels of organochlorine contamination may be affecting the hypothalamo-pituitary-adrenal axis and associated intermediary metabolic pathways in environmentally exposed herring gull embryos in the Great Lakes.
Tobacco and Cancer of the Tongue in Young Adults
Authors: S. P. Schantz, R. M. Byers, H. Goepfert
Journal: JAMA (1988)

<h3>To the Editor.</h3> —Reports have appeared in the literature regarding the increased mortality from tongue cancer among young adults in the United States.<sup>1,2</sup>Shemen et al<sup>1</sup>showed that an increase in head and neck cancer began in the mid-1970s and principally involved men younger than 40 years old. In light of the growing prevalence of the use of smokeless tobacco among the young adult population,<sup>3</sup>Depue<sup>2</sup>suggested a causal relationship between these two trends, but, as yet, direct evidence to support the relationship has not been provided. A review of the patient registry of The University of Texas M. D. Anderson Hospital and Tumor Institute between 1944 and 1984 also has revealed a significant increase in squamous cell carcinoma of the tongue among young adults (younger than age 40 years) (Table). The increase is both in absolute numbers and in the percentage of the total number
Efficient adenoviral gene transfer to early venous bypass grafts: comparison with native vessels
Authors: Keith M. Channon, Gregory J. Fulton, John L. Gray, Brian H. Annex, Geetha A. Shetty, Michael A. Blazing, Kevin G. Peters, Per Otto Hagen, Samuel E. George
Journal: Cardiovascular Research (1997)

Objectives: Gene therapy may provide new approaches to reduce vein graft failure following coronary or peripheral bypass surgery. The aim of this study was to investigate the relative efficacy of intraoperative adenoviral gene transfer to vein grafts, comparing transgene expression in vein grafts with that in matched native vessels in the same animal. In addition, we assessed the impact of bypass grafting on the cellular targets of gene transfer. Methods: New Zealand White rabbits underwent interposition bypass grafting of the carotid artery, using the ipsilateral external jugular vein, which was infected with an adenovirus expressing β-galactosidase immediately prior to bypass grafting (n = 16). The contralateral native jugular vein (n = 16) and carotid artery (n = 8) were infected concurrently with the same adenoviral preparation. After 3, 7 or 14 days, β-galactosidase protein expression was quantified by ELISA, and specific cell types expressing β-galactosidase were identified by X-Gal staining and by immunohistochemistry. Results: After 3 days, endothelial cells were efficiently transduced in all vessels; medial smooth muscle cells were transduced infrequently. In contrast to jugular veins after gene transfer, endothelium in vein grafts showed expression of VCAM-1 and ICAM-1, and intense inflammation with CD18+ leukocytes. Transgene expression in vein grafts at day 3 was maintained at levels approximately 50% of that in ungrafted jugular veins, but continued to decrease through day 7. Conclusions: Although vascular injury in early venous bypass grafts reduces gene transfer efficacy, significant transgene expression is maintained for at least 7 days. These findings have important implications for intraoperative gene transfer strategies in vein grafts.
PUBLIC HEALTH AND MEDICAL CARE FOR THE COMMUNITY AND THE INDIVIDUAL
Authors: Haven Emerson
Journal: JAMA (1952)

The term "health services" has been so generally used in this and previous Rural Health Conferences to describe or refer to organized provision for the sick that the true meaning of public health services has been quite overlooked or entirely disregarded. Medical care of the sick is, of course, the primary object of the practice of personal and family medicine, the relief of suffering, pain, disability, anxiety, and fear of death being the purpose of diagnosis and treatment by the physician. In spite of irregular or uneven distribution of physicians to the disadvantage of small, scattered rural population groups as compared with large cities and metropolitan populations, there are but few of our people who cannot obtain medical care of good quality. No other nation has so liberal a ratio of physicians and hospital beds in proportion to the population at large as we have, and these ratios are steadily
Analysis of Experience in Workmen's Compensation for Heart Cases
Authors: GORDON G. BERGY, DONAL R. SPARKMAN
Journal: Circulation (1966)

In this study of industrial insurance experience in cardiac cases in the State of Washington, particular attention was given to the consistency of medical opinion regarding causal relation of effort to heart attack and to the role of physicians in arriving at decisions as to such causal relationship. Four hundred thirty-one cardiac claims (53% of the total claims) submitted to the Washington State Department of Labor and Industries between 1950 and 1958 were reviewed. Twenty-one and three-tenths per cent of the claimants had documented prior heart disease. Only 6.6% had previous accepted claims for heart disease. At least 78% of all claimants whose records were studied had coronary heart disease and of the deaths, 97.8% were due to manifestations of atherosclerosis. Cardiac trauma was a rarity, occurring in 0.6% of the total and was nonfatal in all cases. In the opinion of the authors causal relationship to the work being performed was present in 71% of the "death" cases in which compensation was allowed; conversely, it was demonstrable in only 31% of the cases of living claimants in which compensation was granted. After the introduction of criteria for causal relationship by the Washington State Heart Association and internist panels, the following changes occurred: (1) The consistency of the assessment of causal relationship to accepted medical opinion improved, for (a) rejection of claims, where causal relationship to work existed, were fewer, and (b) the acceptance of claims where causal relationship was lacking, decreased. (2) The incidence of appeals decreased. Thus, criteria for guidance of physicians in the determination of causal relationship appear to be valuable, and determination of causal relationship and rating of disability may be better performed by a person other than the patient's attending physician.
Authors’ response: Importance of defining loss of response before therapeutic drug monitoring
Authors: C Steenholdt, M A Ainsworth
Journal: Gut (2015)

In his letter,1 Tan questions the use of Crohn's Disease Activity Index (CDAI) as a clinical outcome measure in our randomised controlled trial (RCT) of how to optimally handle Crohn's disease patients with symptomatic infliximab (IFX) treatment failure during ongoing IFX maintenance therapy.2 This study is hitherto the only published RCT of personalised antitumour necrosis factor-alpha (anti-TNFα) therapy where measurements of serum trough levels of drug and anti-drug antibodies (Abs) have been used to prospectively guide interventions according to proposed underlying immune-pharmacological basis for treatment failure. The study builds on our original hypothesis, which operates with IFX treatment failure caused by (1) drug immunogenicity with blockade of drug-mediated TNF-neutralisation by anti-IFX Abs and/or anti-IFX Ab-mediated increased drug clearance; (2) non-immune-mediated pharmacokinetic issues with low circulating IFX trough levels without anti-IFX Abs; or (3) in case of high circulating TNF-neutralising capacity pharmacodynamic …
Abstract B37: Monitoring kinome response to EGFR inhibition in triple negative breast cancer
Authors: Martin C. Whittle, James S. Duncan, Lee M. Graves, Gary L. Johnson
Journal: Clinical Cancer Research (2012)

Abstract Triple negative breast cancers (TNBC) are resistant to hormone therapies and HER2-targeted therapies because of their ER-negative, PR-negative, and HER2-negative status. A further lack of molecularly targeted therapies for TNBC leaves conventional cytotoxic chemotherapy as the primary course of treatment for basal-like TNBC. While TNBCs are initially sensitive to chemotherapy, resistance can quickly develop, and tumors often recur with an aggressive metastatic phenotype and poorer patient prognosis. Expression of EGFR has been linked to basal-like TNBC, and EGFR expression is significantly associated with poorer prognosis in patients. However, clinical trials targeting EGFR in TNBC have been largely unsuccessful, possibly due to TNBC cell responses that bypass targeted inhibition of EGFR. Thus, EGFR inhibition in TNBC may cause a rewiring of kinase signaling, allowing TNBC cells to evade growth arrest and/or apoptosis. Rational design of combination therapies for treating cancer entails knowing how cancer cells rewire kinase growth signaling pathways to promote proliferation and survival in the presence of molecularly targeted therapies. In this study we applied a chemical proteomic approach to define kinome response to EGFR inhibitor treatment in TNBC and identify kinases upregulated in response to EGFR inhibition. We discovered compensatory upregulation of multiple receptor tyrosine kinases in response to EGFR inhibitors that may be mediating cell growth and survival following EGFR inhibition. Our methods show that kinome response to drug treatment can be monitored and proposes a new mode for designing effective small molecule inhibitor combinations for treating cancer.
DOES THE INGESTION OF ALCOHOL INFLUENCE THE DEVELOPMENT OF ARTERIOSCLEROSIS IN FOWLS?
Authors: C. W. Nichols, M. D. Siperstein, W. Gaffey, Stuart Lindsay, I. L. Chaikoff
Journal: The Journal of Experimental Medicine (1956)

The effect of alcohol ingestion upon the development of naturally occurring and stilbestrol-induced arteriosclerosis was studied in the domestic fowl. In two experiments, a 15 per cent ethyl alcohol solution was used for drinking purposes, and in a third experiment wine containing 12 per cent of it was administered. The caloric intake of both food and alcohol was carefully controlled by pair-feeding, a glucose solution being used for drinking purposes to equalize the caloric intakes of the control birds with those of the alcohol-treated birds. A total of 224 cockrels was studied, and the period of observation for each experiment lasted 12 months. The degree of arteriosclerosis in the thoracic and abdominal aortas was determined in the gross and microscopically, and the degree of lipide infiltration was determined microscopically. The gross grading of arteriosclerotic lesions agreed closely with the microscopic analysis of intimal thickening and lipide infiltration of the arterial wall. The gross gradings were subjected to a critical statistical analysis which allowed precise statements to be made on the probability that a real effect would be overlooked. This analysis yielded no evidence that alcohol or the wine used had affected the degree of gross arteriosclerosis or lipide infiltration.
Gene therapy for cystic fibrosis: which postman, which box?
Authors: P. G Middleton, E. W F W Alton
Journal: Thorax (1998)

Since 1989 when the gene responsible for cystic fibrosis was cloned and designated the cystic fibrosis transmembrane conductance regulator (<i>CFTR</i>) gene, considerable progress has been made in the development of gene therapy for this disease. Clinical trials have already been performed using cationic liposome and adenoviral based gene transfer systems, measuring the safety and efficacy of this new form of treatment, with variable results to date. These two approaches and the current progress in airway gene delivery are discussed.
The control process is represented in both the inferior and superior parietal lobules
Authors: David E. Vaillancourt, Mary A. Mayka, Daniel M. Corcos
Journal: Behavioral and Brain Sciences (2004)

Glover postulates that the inferior parietal lobule (IPL), along with the frontal lobes and basal ganglia, mediates planning, while the superior parietal lobule (SPL), coupled with motor processes in the cerebellum, regulates the control process. We demonstrate that the control process extends beyond the cerebellum and SPL into regions hypothesized to represent planning.
Early Disturbances of Ambulatory Blood Pressure Load in Normotensive Type I Diabetic Patients With Microalbuminuria
Authors: Pierre Y Benhamou, Serge Halimi, Régis De Gaudemaris, Robert Boizel, Muriel Pitiot, Jean P Siche, Ivan Bachelot, Jean M Mallion
Journal: Diabetes Care (1992)

To compare 24-h ABP in normotensive type 1 diabetic patients with and without microalbuminuria.The study was a retrospective comparison of cases and matched control subjects. The first phase included 35 type 1 diabetic patients, normotensive by OMS criteria. The 23 patients with normoalbuminuria (< 15 micrograms/min) were compared with 12 patients with microalbuminuria (> or = 15 micrograms/min). In the second phase, the 12 microalbuminuric patients were paired by sex- and age-matched with 12 normoalbuminuric patients and 12 nondiabetic healthy control subjects. We measured casual systolic and diastolic BP and HR, 24-h ABP and AHR (recorded with a Spacelabs automatic recorder), and microalbuminuria.No correlation between microalbuminuria and casual BP was observed. Microalbuminuria was correlated significantly with diastolic 24-h APR and nocturnal systolic and diastolic ABP (r = 0.35, 0.38, and 0.33, respectively; P < 0.05) and with AHR during all time periods (24-h, r = 0.46; day, r = 0.39; night, r = 0.39; P < 0.05). Normo- and microalbuminuric patients did not differ in casual BP and HR. However, microalbuminuric patients had a significant increase in systolic 24-h ABP (119.1 +/- 8.2 vs. 113.1 +/- 8.1, P = 0.05), diastolic 24-h ABP (74.9 +/- 7.5 vs. 70.2 +/- 5.7, P = 0.04), nocturnal systolic ABP (112.8 +/- 7.1 vs. 105.8 +/- 7.9, P = 0.01), and AHR during all time periods. The same results were observed when patients were paired by age and sex.Normotensive microalbuminuric type 1 patients, although strictly comparable with normoalbuminuric patients for casual BP and HR, have an increased ABP and HR, especially during the night. This difference might reflect dysautonomia. Ambulatory measurement of BP and HR is more appropriate than casual measurements in hemodynamic studies of incipient diabetic nephropathies and could be proposed as an interesting tool for an early prediction of diabetic nephropathy.
Traumatic Rupture of Myocardium
Authors: William Bogedain
Journal: JAMA (1966)

NUMEROUS cardiac abnormalities may be produced by nonpenetrating trauma to the chest wall.<sup>1-4</sup>Accidents now rank first as a cause of death in the age group from 1 to 35. With the increasing sale of automobiles each year, it may be anticipated that the total number of cardiac injuries due to nonpenetrating trauma may also increase, and all physicians should be aware of the importance of early diagnosis. Lives may be saved by earlier recognition and surgical repair of cardiac tears or rupture from nonpenetrating trauma. Very little has been added to the literature since the reports of Beck and Bright<sup>5,6</sup>and Kissane et al<sup>7,8</sup>of their clinical and experimental work regarding nonpenetrating traumatic pathology to the heart. In a report from the Armed Forces Institute of Pathology in 1958, Parmley et al<sup>9</sup>described traumatic rupture of the heart. One of the most important single case
Lactate dehydrogenase isoenzymes in the human hypertrophic heart
Authors: N. W. REVIS, R. Y. THOMSON, A. J. V. CAMERON
Journal: Cardiovascular Research (1977)

Lactate dehydrogenase isoenzymes have been measured in human hearts at autopsy. As compared with normal hearts, hypertrophic hearts and ischaemic hypertrophic hearts showed a shift in the isoenzyme distribution. This shift appeared to be more closely associated with an increase in the relative proportion of fibrous tissue than with changes in the myocardial cells.
Lyngbyatoxin A, A Cyanobacteria Dervived Aquatic Toxin, Induces Expression Of Pro-inflammatory Cytokines Including Il-4 And Il-5 By Human PBMC
Authors: J.W. Caldwell, D. Kellogg, L. Isakson, S. Watkins, A. Reich, A. Foss, J. Sleasman
Journal: Journal of Allergy and Clinical Immunology (2010)
Defective aquaporin-2 trafficking in nephrogenic diabetes insipidus and correction by chemical chaperones.
Authors: B K Tamarappoo, A S Verkman
Journal: Journal of Clinical Investigation (1998)

Five single-point aquaporin-2 (AQP2) mutations that cause non-X-linked nephrogenic diabetes insipidus (NDI) were characterized to establish the cellular defect and to develop therapeutic strategies. In Xenopus oocytes expressing AQP2 cRNAs, single-channel water permeabilities of mutants L22V, T126M, and A147T were similar to that of wild-type AQP2, whereas R187C and C181W were nonfunctional. In [35S]methionine pulse-chase experiments in transiently transfected CHO cells, half-times for AQP2 degradation were approximately 4 h for wild-type AQP2 and L22V, and mildly decreased for T126M (2.7 h), C181W (2.4 h), R187C (2.0 h), and A147T (1.8 h). Immunofluorescence showed three distinct AQP2-staining patterns: plasma membrane and endosomal staining (wild-type, L22V), endoplasmic reticulum (ER) staining (T126M > A147T approximately R187C), or a mixed pattern of reticular and perinuclear vesicular staining. Immunoblot of fractionated vesicles confirmed primary ER localization of T126M, R187C, and A147T. To determine if the AQP2-trafficking defect is correctable, cells were incubated with the "chemical chaperone" glycerol for 48 h. Immunoblot showed that glycerol produced a nearly complete redistribution of AQP2 (T126M, A147T, and R187C) from ER to membrane/endosome fractions. Immunofluorescence confirmed the cellular redistribution. Redistribution of AQP2 mutants was also demonstrated in transfected MDCK cells, and using the chaperones TMAO and DMSO in place of glycerol in CHO cells. Water permeability measurements indicated that functional correction was achieved. These results indicate defective mammalian cell processing of mutant AQP2 water channels in NDI, and provide evidence for pharmacological correction of the processing defect by chemical chaperones.
Is there a genetic factor in flecainide toxicity?
Authors: J. Beckmann, R. Hertrampf, U. Gundert-Remy, G. Mikus, A. S. Gross, M. Eichelbaum
Journal: BMJ (1988)

Thirdly, we measured the pressure in 31 bottles used by ward nurses at this hospital.Subsequently 52 patients were specifically asked not to inject air.After using a whole bottle they completed a questionnaire and recorded whether they found this to be easier, whether they found it difficult to draw up insulin, and whether air bubbles were a problem.In the first study the mean pressure fell rapidly to below -39 9 kPa after 3 ml insulin was withdrawn and subsequently fell more gradually to -58-5 kPa.No difficulty was experienced either in withdrawing the plunger or with air bubbles.In the second study pressures in 31 of the 81 bottles were close to atmospheric pressure (±0 07 kPa) (figure).The pressure was -13-3 kPa or less in 24 bottles, being below -39 9 kPa in 15, which suggested that air had not been injected before insulin was withdrawn.There was no significant difference in mean age, duration of treatment, or insulin dose between the 24 patients who provided these bottles and the remaining 57.The pressure in the 31 bottles used by nurses was below -13-3 kPa in 23 (figure), and values above -0 7 kPa were found in only four.The questionnaires from the 52 patients who did not add air showed that 42 found it easier, 47 found no difficulty in withdrawing insulin, and 40 did not find that air bubbles were a problem.
Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer.
Authors: L M Sollid, G Markussen, J Ek, H Gjerde, F Vartdal, E Thorsby
Journal: The Journal of Experimental Medicine (1989)

Typing of DNA from 94 unrelated children with celiac disease (CD) with HLA-DQA1 and -DQB1 allele-specific oligonucleotide probes revealed that all but one (i.e., 98.9%) may share a particular combination of a DQA1 and a DQB1 gene. These genes are arranged in cis position on the DR3DQw2 haplotype and in trans position in DR5DQw7/DR7DQw2 heterozygous individuals. Thus, most CD patients may share the same cis- or trans-encoded HLA-DQ alpha/beta heterodimer.