tbuckley/cabot-search huggingface dataset:
Effects of structure on binding to the 2,3,7,8-TCDD receptor protein and AHH induction--halogenated biphenyls.
Authors: S Safe, S Bandiera, T Sawyer, B Zmudzka, G Mason, M Romkes, M A Denomme, J Sparling, A B Okey, T Fujita
Journal: Environmental Health Perspectives (1985)

The quantitative structure-activity relationships (QSARs) for polychlorinated biphenyl (PCB) congeners have been determined by comparing the EC50 values for three in vitro test systems, namely, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction in rat hepatoma H-4-II-E cells and competitive binding avidities to the rat cytosolic receptor protein (using 2,3,7,8-tetrachlorodibenzo-p-dioxin as a radioligand). For several PCB congeners that are in vivo inducers of rat hepatic microsomal AHH, there was a linear correlation between the -log EC50 values for receptor and the -log EC50 values for AHH (or EROD) induction; moreover, a comparable linear relationship was observed between the -log EC50 values for AHH and EROD induction. Previous in vivo studies have shown that the most active PCB congeners 3,3',4,4'-tetra-, 3,4,4',5-tetra-, 3,3',4,4',5-penta-, and 3,3',4,4',5,5'-hexachlorobiphenyl, cause many of the biologic and toxic effects reported for the highly toxic halogenated aryl hydrocarbon, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Moreover, the monoortho-substituted homologs of the four coplanar PCBs also elicit comparable in vivo biologic and toxic responses. It was evident from the QSARs for PCBs that there was an excellent correspondence between the in vivo and in vitro potencies of the individual PCB congeners. The effects of substituents on both receptor binding and AHH/EROD induction was determined for a series of 4'-substituted (X)-2,3,4,5-tetrachlorobiphenyls (where X = H, Cl, Br, I, OH, OCH3, NO2, COCH3, F, CF3, CH3, C2H5, i-C3H7, n-C4H9 and t-C4H9). Not unexpectedly, there was a linear relationship between the -log EC50 values for AHH and EROD induction, and these results confirm that both enzymatic oxidations are catalyzed by the same cytochrome P-450 isozyme(s). The effects of substituent structure on receptor binding for 12 substituents was subjected to multiple regression analysis which correlates the relative binding affinities of the compounds with the physical chemical characteristics of the substituents. The analysis gave the following equation: log (1/EC50) = 1.53 sigma + 1.47 pi + 1.09 HB + 4.08 for n = 12, s = 0.18, r = 0.978; where n is the number of substituents, s is the standard deviation, r is the correlation coefficient, and sigma = electronegativity, pi = hydrophobicity (log P) and HB = hydrogen bonding capacity for the substituent groups.(ABSTRACT TRUNCATED AT 400 WORDS)
Impaired contraction and relaxation in skin resistance arteries from patients with congestive heart failure
Authors: J A Angus, C P Ferrier, K Sudhir, D M Kaye, G L Jennings
Journal: Cardiovascular Research (1993)

The aim was to determine the pharmacological reactivity of human small resistance arteries in patients with cardiac failure.Small arteries (< 300 microns internal diameter) were removed from gluteal skin biopsy specimens and mounted in a double myograph for isometric force recording.Arteries from six patients with congestive heart failure contracted to only 65% of the maximum response recorded in nine arteries from normal volunteers when activated by potassium chloride (124 mM), noradrenaline (1 microM), or both. The lesser contraction in congestive heart failure vessels with no significant shift in sensitivity (EC50) was also observed in concentration-response studies with noradrenaline, angiotensin I, and angiotensin II. The concentration-contraction curves for serotonin showed only 40% of the maximum contractility to K+ in normal arteries, and this ratio was similar in congestive heart failure arteries. Normal arteries precontracted with noradrenaline (1 microM) relaxed in response to sodium nitroprusside, calcitonin gene related peptide, and the endothelium dependent agonist acetylcholine; in congestive heart failure vessels there was a marked loss of the relaxation response only to acetylcholine.These results suggest that in chronic congestive heart failure skin resistance arteries have impaired contraction responses probably independent of any receptor down regulation. The loss of endothelium dependent vasodilatation to acetylcholine suggests that EDRF release is impaired. These changes may well play an important role in the disturbances of peripheral vascular function associated with heart failure.
Quality of Hamburger's Book
Authors: JOEL I. HAMBURGER
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 May 1973Quality of Hamburger's BookJOEL I. HAMBURGER, M.D.JOEL I. HAMBURGER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-794 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: When one has the temerity to write a book entitled Hyperthyroidism: Concept and Controversy, one must expect criticism. Indeed, to stimulate polemic was one of my objectives. Thus, Young's unfavorable review (Ann Intern Med 78:166-167, 1973) might be useful.I regretfully share Young's opinion that students and practitioners (barring special interest) might not value technical details of radioiodine uptake. However, 8% of my referred patients come to me because of laboratory errors, often the result of lack of appreciation of one or more of the points cited. Furthermore, some readers may also do testing; for them methods...References1. WALDSTEINSLODKIKAGANIEC SSG: A clinical study of thyroid storm. Ann Intern Med 52:626-642, 1960 LinkGoogle Scholar2. HAMBURGER J: Management of the pregnant hyperthyroid. The argument against combined antithyroid-thyroid therapy. Obstet Gynecol 40:114-117, 1972 CrossrefMedlineGoogle Scholar3. SELENKOW H: Antithyroid-thyroid therapy of thyrotoxicosis during pregnancy. Obstet Gynecol 40:117-121, 1972 CrossrefMedlineGoogle Scholar4. ENGBRING N: Critique on the use of combined therapy versus antithyroid drugs alone in hypertension during pregnancy. Obstet Gynecol 40:121-122, 1972 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Northland Thyroid Laboratory, P.C. Southfield, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1973Volume 78, Issue 5Page: 794-795KeywordsHyperthyroidismResearch laboratories Issue Published: 1 May 1973 PDF DownloadLoading ...
The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic: preparation for severe respiratory emergency outbreaks
Authors: Nicolò Patroniti, Alberto Zangrillo, Federico Pappalardo, Adriano Peris, Giovanni Cianchi, Antonio Braschi, Giorgio A. Iotti, Antonio Arcadipane, Giovanna Panarello, V. Marco Ranieri, Pierpaolo Terragni, Massimo Antonelli, Luciano Gattinoni, Fabrizio Oleari, Antonio Pesenti
Journal: Intensive Care Medicine (2011)
BH3-only protein bid participates in the Bcl-2 network in healthy liver cells
Authors: Hayato Hikita, Tetsuo Takehara, Takahiro Kodama, Satoshi Shimizu, Atsushi Hosui, Takuya Miyagi, Tomohide Tatsumi, Hisashi Ishida, Kazuyoshi Ohkawa, Wei Li, Tatsuya Kanto, Naoki Hiramatsu, Lothar Hennighausen, Xiao‐Ming Yin, Norio Hayashi
Journal: Hepatology (2009)

Bcl-2 homology domain 3 (BH3)-only protein Bid is posttranslationally cleaved by caspase-8 into its truncated form (tBid) and couples with stress signals to the mitochondrial cell death pathway. However, the physiological relevance of Bid is not clearly understood. Hepatocyte-specific knockout (KO) of Bcl-xL leads to naturally-occurring apoptosis despite co-expression of Mcl-1, which shares a similar anti-apoptotic function. We generated Bcl-xL KO, Bcl-xL/Bid double KO, Bcl-xL/Bak double KO, Bcl-xL/Bax double KO, and Bcl-xL/Bak/Bax triple KO mice and found that hepatocyte apoptosis caused by Bcl-xL deficiency was completely dependent on Bak and Bax, and surprisingly on Bid. This indicated that, in the absence of Bid, Bcl-xL is not required for the integrity of differentiated hepatocytes, suggesting a complicated interaction between core Bcl-2 family proteins and BH3-only proteins even in a physiological setting. Indeed, a small but significant level of tBid was present in wild-type liver under physiological conditions. tBid was capable of binding to Bcl-xL and displacing Bak and Bax from Bcl-xL, leading to release of cytochrome c from wild-type mitochondria. Bcl-xL–deficient mitochondria were more susceptible to tBid-induced cytochrome c release. Finally, administration of ABT-737, a pharmacological inhibitor of Bcl-2/Bcl-xL, caused Bak/Bax-dependent liver injury, but this was clearly ameliorated with a Bid KO background. Conclusion: Bid, originally considered to be a sensor for apoptotic stimuli, is constitutively active in healthy liver cells and is involved in the Bak/Bax-dependent mitochondrial cell death pathway. Healthy liver cells are addicted to a single Bcl-2–like molecule because of BH3 stresses, and therefore special caution may be required for the use of the Bcl-2 inhibitor for cancer therapy. (HEPATOLOGY 2009.)
Isotopic Studies on Collagen Degradation and the Urine Excretion of Hydroxyproline *
Authors: Darwin J. Prockop
Journal: Journal of Clinical Investigation (1964)

Although marked changes in collagen can be observed in a number of clinical conditions, ini- tial studies of the metabolic turnover of collagen suggested that this protein was metabolically more stable than other body proteins and that perhaps it was metabolically inert.After injecting glycine-C14 into rats, Neuberger, Slack (2), and Perrone (3) found that much less radioactivity was incorporated into collagen than into liver pro- teins.In addition, they found that the small amount of glycine-Cl" that did enter collagen dis- appeared with a half-life of over six weeks in young rats and longer in old rats.Subsequently, a number of investigators (4, 5) demonstrated rapid turnover rates in the small amount of "solu- ble" collagen which can be extracted from most tissues and is a precursor of insoluble collagen.Significant degradation of collagen, however, was not evident in studies performed directly on nor- mal tissues.Recently, Lindstedt and Prockop (6) attempted to study the metabolic turnover of collagen by injecting proline-Cl" into rats and then following the specific activity of urine hydroxyproline-C14.Since nearly all the hydroxyproline in vertebrates is found in collagen, and since the only source of this amino acid appears to be the hydroxylation of "bound" proline in situ (7, 8), the decay of urine hydroxyproline-C14 was assumed to reflect the degradation in vivo of collagen or its immediate precursors.The results suggested that although most of body collagen is metabolically stable, there are forms that are both synthesized and degraded rapidly under normal conditions.
The Relationship between Childhood Wheezing and Overweight Status as a Function of the Proinflammatory Mediators IL-6 and Leptin in a High-Risk Birth Cohort
Authors: S.L. Friedlander, D.J. Mueller, Z. Zhang, K.A. Roberg, E.L. Anderson, M.D. Evans, R.E. Gangnon, H.J. Lai, J.E. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2006)
Dose-response relationships and time course of the response to systemic beta adrenoreceptor agonists in infants with bronchopulmonary disease.
Authors: R Kraemer, P Birrer, M H Schoni
Journal: Thorax (1988)

The lung function response to three doses of salbutamol 0.075 mg/kg given at 10 minute intervals by gastric tube was studied in 31 infants aged 2-22 months with bronchopulmonary disease (eight after the respiratory distress syndrome, 15 with wheezy bronchitis, and eight with cystic fibrosis). Lung function was measured by whole body plethysmography. Seven of 31 infants had normal lung function and 10 of the remaining 24 had an increase in thoracic gas volume (TGV), 10 an increase in airway resistance (Raw), and four an increase in both the TGV and Raw. The response of TGV and Raw to salbutamol was analysed by circular statistics, enabling analysis of coupled, directional data. Thirty minutes after administration of the first dose of salbutamol there was a reduction in TGV or Raw in 21 of the 24 infants, 11 showing a decrease in TGV ("volume responder") and 10 a fall in Raw ("flow responder"). These results indicate that in most infants with bronchopulmonary disease an improvement in lung function can be documented after systemic administration of beta agonists if both TGV and Raw are measured.
LIGATION OF THE ANGULAR VEIN IN INFECTIONS OF THE UPPER LIP
Authors: C. A. ROEDER
Journal: JAMA (1928)

It is well recognized today that infections of the upper lip—particularly of the carbuncular type—are always to be considered most seriously; and furthermore that in the most virulent infections no form of treatment has proved efficacious in even a bare majority of instances. The superficial infections of the upper lip and adjacent structures on the lateral portion of the nose as a rule resolve without serious results; but the deeper infections, particularly in the upper lip, wherein the subcutaneous tissues become involved—the area in which the veins lie—are far too often followed by a fatality as the result of a septic cavernous sinusitis and meningitis.  It is practically impossible, at present, to state in the early stages of an infection of the upper lip how far the process will proceed; and it is well known that the most serious appearing infections have resulted in recovery, with or without good treatment,
Tregs control the development of symptomatic West Nile virus infection in humans and mice
Authors: Marion C. Lanteri, Katie M. O’Brien, Whitney E. Purtha, Mark J. Cameron, Jennifer M. Lund, Rachel E. Owen, John W. Heitman, Brian Custer, Dale F. Hirschkorn, Leslie H. Tobler, Nancy Kiely, Harry E. Prince, Lishomwa C. Ndhlovu, Douglas F. Nixon, Hany T. Kamel, David J. Kelvin, Michael P. Busch, Alexander Y. Rudensky, Michael S. Diamond, Philip J. Norris
Journal: Journal of Clinical Investigation (2009)

West Nile virus (WNV) causes asymptomatic infection in most humans, but for undefined reasons, approximately 20% of immunocompetent individuals develop West Nile fever, a potentially debilitating febrile illness, and approximately 1% develop neuroinvasive disease syndromes. Notably, since its emergence in 1999, WNV has become the leading cause of epidemic viral encephalitis in North America. We hypothesized that CD4+ Tregs might be differentially regulated in subjects with symptomatic compared with those with asymptomatic WNV infection. Here, we show that in 32 blood donors with acute WNV infection, Tregs expanded significantly in the 3 months after index (RNA+) donations in all subjects. Symptomatic donors exhibited lower Treg frequencies from 2 weeks through 1 year after index donation yet did not show differences in systemic T cell or generalized inflammatory responses. In parallel prospective experimental studies, symptomatic WNV-infected mice also developed lower Treg frequencies compared with asymptomatic mice at 2 weeks after infection. Moreover, Treg-deficient mice developed lethal WNV infection at a higher rate than controls. Together, these results suggest that higher levels of peripheral Tregs after infection protect against severe WNV disease in immunocompetent animals and humans.
The Doctor-Patient Relationship
Authors: WILLIAM G. BISSELL
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 April 1982The Doctor-Patient RelationshipWILLIAM G. BISSELLWILLIAM G. BISSELLSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-96-4-527 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The December issue had a most interesting combination of articles (1, 2). Both address the importance of understanding and applying the powerful, so-called nonspecific placebo effects and other psychologically mediated effects that can benefit our patients. Dr. Sox's cautionary remarks were reasonable, but several comments are in order.First, in light of increased consumer pressure, we must remember that our patients deserve the best medical care, whether or not that conforms to what they expect or desire. Thus, although patients may have come to expect prescriptions and diagnostic tests, these should be given only when needed and...References1. JENSEN P. The doctor-patient relationship: headed for impasses or improvement? Ann Intern Med. 1981;95:769-71. LinkGoogle Scholar2. SOX H, MARGULIES I, and SOX C. Psychologically mediated effect of diagnostic tests. Ann Intern Med. 1981;95:680-5. LinkGoogle Scholar3. BALINT M. The Doctor, His Patient, and the Illness. 2nd ed. New York: International Universities Press; 1972. Google Scholar4. ETIENNE P. Adverse effects of medical and psychiatric work-up in six demented geriatric patients. Am J Psychiatry. 1981;138:520-1. CrossrefMedlineGoogle Scholar1. SOX H, MARGULIES I, and SOX C. Psychologically mediated effects of diagnostic tests. Ann Intern Med. 1981:95:680-4. LinkGoogle Scholar2. SACKETT D. Clinical diagnosis and the clinical laboratory. Clin Invest Med. 1978:1:37-43. MedlineGoogle Scholar3. MCWHINNEY I. Beyond diagnosis: an approach to the integration of behavioral science and clinical medicine. N Engl J Med. 1972:387:384-7. CrossrefGoogle Scholar4. HAYNES R, SACKETT D, and TAYLOR D. Increased absenteeism from work after detection and labeling of hypertensive patients. N Engl J Med. 1978:299:741-4. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: WILLIAM G. BISSELL PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1982Volume 96, Issue 4Page: 527-528 ePublished: 1 December 2008 Issue Published: 1 April 1982 PDF downloadLoading ...
Adrenalectomy ameliorates ablative nephropathy in the rat independently of corticosterone maintenance level
Authors: Zhi Yun Quan, Mackenzie Walser, Gary S. Hill
Journal: Kidney International (1992)

The roles of the adrenal gland and of dietary protein level in ablative nephropathy in the rat were examined by comparing adrenalectomized rats, replaced with corticosterone at low physiological (1 and 2) or high physiological (3 and 4) levels with intact rats (5 and 6). All groups were subjected to 5/6 nephrectomy and followed 12 weeks on a regular diet (2, 4 and 6) or a reduced protein diet (1, 3 and 5). Groups 1, 2, 5 and 6 all grew at the same rate but groups 3 and 4 grew less, though food intake was nearly the same in all. Higher dietary protein, higher corticosterone maintenance level, and the presence of intact adrenal glands all increased proteinuria significantly. Extracellular fluid volume (82Br space) was identical in all groups at 8 and 12 weeks, because the animals were given a choice of water or saline to drink. Mortality was highest (50%) in Group 6 and lowest (11%) in Group 1, but these differences were not significant. Final inulin clearance was significantly improved by adrenalectomy when non-survivors were scored as having zero clearance, but not if the analysis was limited to survivors. It was not affected by diet or by corticosterone level. Renal histopathological scores were also improved significantly by adrenalectomy and by protein restriction, but were not influenced by corticosterone level. Thus adrenalectomy and dietary protein restriction independently ameliorate ablative nephropathy, but corticosterone replacement level has no effects, except on proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of pneumothorax or pleural effusion on pulmonary function.
Authors: J J Gilmartin, A J Wright, G J Gibson
Journal: Thorax (1985)

The effects of pneumothorax or pleural effusion on respiratory function as measured by the commonly applied tests were investigated by studying 13 patients (six with pneumothorax, seven with effusion) with and, as far as possible, without air or fluid in the pleural cavity. Measurements included spirometric volumes, carbon monoxide transfer factor (TLCO), and KCO by the single breath method, maximum expiratory flow-volume curves, and subdivisions of lung volume estimated by both inert gas dilution and body plethysmography. In patients with pneumothorax "pleural volume" was estimated as the difference between lung volumes measured by dilution and thoracic gas volume measured by plethysmography. In patients with effusion the change in "pleural volume" was equated with the volume of fluid subsequently aspirated. "Total thoracic capacity" (TTC) was estimated by adding total lung capacity (TLC) measured by dilution and "pleural volume." Both effusion and pneumothorax produced a restrictive ventilatory defect with reductions of vital capacity, functional residual capacity, and TLC. In the patients with effusion TTC fell after aspiration, suggesting that the pleural fluid produced relative expansion of the chest wall as well as compression of the lung. In patients with pneumothorax, however, there was no difference in TTC with and without air in the pleural space. In the presence of pleural air or fluid there was a slight decrease in TLCO and increase in KCO, with a small but significant increase in the rate of lung emptying during forced expiration.
Association of adherence to lifestyle recommendations and risk of colorectal cancer: a prospective Danish cohort study
Authors: H. Kirkegaard, N. F. Johnsen, J. Christensen, K. Frederiksen, K. Overvad, A. Tjonneland
Journal: BMJ (2010)

<b>Objectives</b> To evaluate the association between a simple lifestyle index based on the recommendations for five lifestyle factors and the incidence of colorectal cancer, and to estimate the proportion of colorectal cancer cases attributable to lack of adherence to the recommendations. <b>Design</b> Prospective cohort study. <b>Setting</b> General population of Copenhagen and Aarhus, Denmark. <b>Participants</b> 55 487 men and women aged 50-64 years at baseline (1993-7), not previously diagnosed with cancer. <b>Main outcome measure</b> Risk of colorectal cancer in relation to points achieved in the lifestyle index (based on physical activity, waist circumference, smoking, alcohol intake, and diet (dietary fibre, energy percentage from fat, red and processed meat, and fruits and vegetables)) modelled through Cox regression. <b>Results</b> During a median follow-up of 9.9 years, 678 men and women had colorectal cancer diagnosed. After adjustment for potential confounders, each additional point achieved on the lifestyle index, corresponding to one additional recommendation that was met, was associated with a lower risk of colorectal cancer (incidence rate ratio 0.89 (95% confidence interval 0.82 to 0.96). In this population an estimated total of 13% (95% CI 4% to 22%) of the colorectal cancer cases were attributable to lack of adherence to merely one additional recommendation among all participants except the healthiest. If all participants had followed the five recommendations 23% (9% to 37%) of the colorectal cancer cases might have been prevented. Results were similar for colon and rectal cancer, but only statistically significant for colon cancer. <b>Conclusions</b> Adherence to the recommendations for physical activity, waist circumference, smoking, alcohol intake, and diet may reduce colorectal cancer risk considerably, and in this population 23% of the cases might be attributable to lack of adherence to the five lifestyle recommendations. The simple structure of the lifestyle index facilitates its use in public health practice.