tbuckley/cabot-search huggingface dataset:
Hepatic glucagon metabolism. Correlation of hormone processing by isolated canine hepatocytes with glucagon metabolism in man and in the dog.
Authors: W A Hagopian, H S Tager
Journal: Journal of Clinical Investigation (1987)

We have found that canine and rat hepatocytes convert (125I)iodoTyr10-glucagon to a peptide metabolite lacking the NH2-terminal three residues of the hormone. The peptide is released into the cell incubation medium and its formation is unaffected by a variety of lysosomotropic or other agents. Use of specific radioimmunoassays and gel filtration demonstrated in both normal subjects and in chronic renal failure patients a plasma peptide having the properties of the hormone fragment identified by cell studies. Studies of the dog revealed a positive gradient of the fragment across the liver and no differential gradient of the fragment and glucagon across the kidney. We conclude that the glucagon fragment arises from the cell-mediated processing of the hormone on a superficial aspect of the hepatocyte, the glucagon fragment identified during experiments in vitro represents the cognate of a peptide formed during the hepatic metabolism of glucagon in vivo, and measurement of the fragment by COOH-terminal radioimmunoassays could lead to an understimulation of hepatic glucagon extraction.
Quality of life in thalassemia: A comparison of SF‐36 results from the thalassemia longitudinal cohort to reported literature and the US norms
Authors: A. Sobota, R. Yamashita, Y. Xu, F. Trachtenberg, P. Kohlbry, D.A. Kleinert, P.J. Giardina, J.L. Kwiatkowski, D. Foote, V. Thayalasuthan, J.B. Porter, A.A. Thompson, L. Schilling, C.T. Quinn, E.J. Neufeld
Journal: American Journal of Hematology (2010)

Thalassemia is a chronic, inherited blood disorder, which, in its most severe form, causes life-threatening anemia. Advances in treatment have led to increased life expectancy however the need for chronic blood transfusions and chelation therapy remains a significant burden for patients. Our study compared health related quality of life (HRQOL) from the Thalassemia Clinical Research Network's (TCRNs) Thalassemia Longitudinal Cohort (TLC) study to US norms and assessed association with clinical variables. There were 264 patients over age 14 who completed the Medical Outcomes Study 36-Item Short Form Health Survey version 2 (SF36v2) baseline assessment. When compared to US norms, TLC patients had statistically significant (P < 0.05) worse HRQOL on five of the eight subscales (physical functioning, role-physical, general health, social functioning, and role-emotional) and on both summary scales (physical component summary and mental component summary). Women, older patients, and those with more disease complications and side effects from chelation reported lower HRQOL. In general, adolescents and adults with thalassemia report worse HRQOL than the US population, despite contemporary therapy. The SF-36 should become a standard instrument for assessing HRQOL in thalassemia to determine predictors of low HRQOL which may be better addressed by a multidisciplinary team.
Fraud in science.
Authors: L Altman, L Melcher
Journal: BMJ (1983)

Instances of research fraud such as the John Darsee case have raised questions about the incidence of fraud in scientific research and the willingness of the biomedical establishment to acknowledge and correct the problem. There is no consensus among scientists and editors of medical journals about how widespread data falsification is, whether it can be identified and controlled through the traditional peer review process, and whether or not it should be a matter of public concern. The authors conclude that fraud in science is a complex issue which requires more attention from researchers, administrators, and editors than it now receives.
Myocardial Reperfusion Injury
Authors: Derek M. Yellon, Derek J. Hausenloy
Journal: New England Journal of Medicine (2007)

Lethal reperfusion injury is a paradoxical type of myocardial injury caused by the restoration of coronary blood flow after an ischemic episode. This review focuses on the mechanisms of the injury, on attempts to protect the heart against it, and on promising new approaches to cardioprotection during percutaneous coronary intervention.
Intrasplenic hepatocellular transplantation corrects hepatic encephalopathy in portacaval-shunted rats
Authors: Joaquim Ribeiro, Bernard Nordlinger, François Ballet, Luc Cynober, Colette Coudray-Lucas, Marielle Baudrimont, Claire Legendre, Roland Delelo, Yves Panis
Journal: Hepatology (1992)

The aim of this work was to evaluate the effect of intrasplenic hepatocellular transplantation on hepatic encephalopathy in an experimental model of chronic liver failure induced by end-to-side portacaval shunt in the rat. Inbred male Wistar Furth rats were divided into three groups: rats subjected to portacaval shunt (n = 10), rats subjected to portacaval shunt and intrasplenic hepatocellular transplantation of 10 7 hepatocytes isolated from livers of syngeneic rats (n = 10) and sham-operated rats (n = 10). Behavior tests were performed in a blind fashion at 3 wk, at 2 mo and at 3 mo after surgery. Spontaneous activity and nose-poke exploration by individual rats were studied in automated open field boxes equipped with infrared cells. Each cell beam interruption was automatically recorded on a microcomputer and transformed into a score index (counts/hour). Plasma levels of amino acids, ammonia and total biliary acids were measured. Portacaval shunt rats showed reduced spontaneous activity and nose-poke exploration scores. Intrasplenic hepatocellular transplantation significantly increased spontaneous activity after 2 mo and improved nose-poke exploration after 3 wk. At 3 mo, spontaneous activity and nose-poke exploration in portacaval shunt/intrasplenic hepatocellular transplantation rats were not significantly different from those of sham rats. Increases in plasma ammonia levels after portacaval shunt were not corrected. Amino acid imbalance and bile acid concentration in plasma were partially corrected by intrasplenic hepatocellular transplantation. These data show that intrasplenic hepatocellular transplantation can correct the neurological symptoms of hepatic encephalopathy in an experimental model of chronic liver failure and suggest that intrasplenic hepatocellular transplantation might be of therapeutic interest in chronic liver failure. (Heratology 1992;15:12-18).
Save our souls
Authors: D. Spence
Journal: BMJ (2009)

Let’s dispense with the normal pleasantries: what the hell is going to happen to all our recently qualified general practitioners? Locum work is drying up, out of hours rota sessions are full, the only permanent jobs are salaried positions, and GP partnerships seem to be coming to an end. Why is all this happening?

The reasons are several. In the mid-1990s a shortage of doctors led to an expansion of medical schools’ intake; this expanded cohort of doctors is now completing specialist training. Furthermore, after the Modernising Medical Careers (MMC) debacle in 2007 a …
Urinary 16-Androsten-3 -ol, 17-Oxosteroids and Mental Illness
Authors: B. W. L. Brooksbank, W. Pryse-Phillips
Journal: BMJ (1964)

immediately be referred for expert opinion even if she has no symptoms.All women of child-bearing age with a mitral valve diameter of 1.5 cm. or less require close supervision, and if they become pregnant it is safest to undertake valvotomy.
Nosocomial transmission of Mycobacterium bovis resistant to 11 drugs in people with advanced HIV-1 infection
Authors: Antonio Guerrero, Javier Cobo, Jesús Fortün, Enrique Navas, Carmen Quereda, Angel Asensio, José Cañón, Jesús Blazquez, Enrique Gómez-Mampaso
Journal: The Lancet (1997)
The best time to die (to help fellow taxpayers)
Authors: Robert A Da Prato
Journal: BMJ (2007)

In previous studies, heroin was shown to engender cocaine-like discriminative stimulus (DS) effects; however, the mechanisms underlying the cocaine-like effects of heroin are unknown. The present study evaluated the extent to which the shared DS effects of heroin and cocaine involve common monoaminergic mechanisms of action. In squirrel monkeys discriminating cocaine (0.3 mg/kg) from saline, heroin engendered full or partial substitution for cocaine in three of four monkeys. Pretreatment with the selective dopamine transport inhibitor 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine (GBR 12909) dose dependently enhanced the cocaine-like DS effects of heroin in these three monkeys as well as the DS effects of cocaine in all subjects. Neither talsupram, a noradrenergic transport inhibitor, nor prazosin, a noradrenergic antagonist selective for α-1 receptors, systematically altered the cocaine-like DS effects of heroin at doses that enhanced (talsupram) or attenuated (prazosin) the DS effects of cocaine. Pretreatment with the serotonin uptake inhibitor citalopram similarly failed to alter the cocaine-like DS effects of heroin at doses that attenuated the DS effects of cocaine. Altogether, these findings suggest that heroin shares DS effects with cocaine in a subset of monkeys, and these cocaine-like effects are mediated at least in part by enhanced dopaminergic activity. Unlike the DS effects of cocaine itself, however, the cocaine-like DS effects of heroin do not appear to involve either noradrenergic or serotonergic mechanisms.
Requirement of Nuclear Factor-κB in Angiotensin II– and Isoproterenol-Induced Cardiac Hypertrophy In Vivo
Authors: Christian Freund, Ruth Schmidt-Ullrich, Anthony Baurand, Sandra Dunger, Wolfgang Schneider, Peter Loser, Amina El-Jamali, Rainer Dietz, Claus Scheidereit, Martin W. Bergmann
Journal: Circulation (2005)

Background— In vitro experiments have proposed a role of nuclear factor-κB (NF-κB), a transcription factor, in cardiomyocyte hypertrophy and protection against apoptosis. Currently, the net effect on cardiac remodeling in vivo under common stress stimuli is unclear. Methods and Results— We have generated mice with cardiomyocyte-restricted expression of the NF-κB super-repressor IκBαΔN (ΔN MHC ) using the Cre/lox technique. ΔN MHC mice displayed an attenuated hypertrophic response compared with control mice on infusion of angiotensin II (Ang II) or isoproterenol by micro-osmotic pumps, as determined by echocardiography (left ventricular wall dimensions: control plus Ang II, ×1.5±0.1 versus sham; ΔN MHC plus Ang II, ×1.1±0.1 versus sham; P &lt;0.05; n≥9), heart weight, and histological analysis. Real-time reverse-transcriptase polymerase chain reaction showed significantly reduced expression of hypertrophy markers β-myosin heavy chain and atrial natriuretic peptide in Ang II–treated ΔN MHC mice ( P &lt;0.05 versus control plus Ang II; n=4). Neither cardiomyocyte apoptosis nor left ventricular dilatation was observed. In cultured adult rat cardiomyocytes, NF-κB DNA binding activity was increased by both Ang II– and interleukin-6–related cytokines. The latter are known to be released by cardiac fibroblasts on Ang II stimulation and thus could locally increase the NF-κB response of cardiomyocytes. Finally, results from in vitro and in vivo experiments suggest a role for NF-κB in the regulation of prohypertrophic interleukin-6 receptor gp130 on mRNA levels. Conclusions— These results indicate that targeted inhibition of NF-κB in cardiomyocytes in vivo is sufficient to impair Ang II– and isoproterenol-induced hypertrophy without increasing the susceptibility to apoptosis.
Enhanced Intrarenal Angiotensinogen Contributes to Early Renal Injury in Spontaneously Hypertensive Rats
Authors: Hiroyuki Kobori, Yuri Ozawa, Yuki Suzaki, Akira Nishiyama
Journal: Journal of the American Society of Nephrology (2005)

This study was performed to determine whether augmented intrarenal angiotensinogen may contribute to the enhanced renal angiotensin II (Ang II) and associated tissue injury in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto rats (WKY) were maintained on a normal diet and killed at either 7 or 14 wk of age. Two groups of SHR received either an Ang II type 1 receptor blocker (ARB; olmesartan, 5 mg/d) or a triple therapy (hydralazine 7.5 mg/d, reserpine 0.15 mg/d, and hydrochlorothiazide 3 mg/d [HRH]) during weeks 7 through 14. Systolic BP and renal Ang II were significantly increased in SHR-14 (n = 8) compared with WKY-7, WKY-14, and SHR-7 (n = 8 each), and ARB treatment prevented these increases (n = 8). However, whereas HRH treatment prevented the development of hypertension in SHR, this combination therapy failed to decrease renal Ang II (n = 8). With the use of urine samples or fixed renal sections, renal injuries in rats were quantified in a semiautomated manner by the following six parameters: (1) urinary excretion rate of total protein, (2) glomerular sclerosis, (3) interstitial expansion, (4) and (5) numbers of monocytes/macrophages in interstitium or glomeruli, and (6) arterial proliferation. Angiotensinogen mRNA and protein levels in kidney cortex, measured by real-time reverse transcriptase—PCR and Western blot analysis, respectively, and all six parameters of renal damage were changed in parallel, and ARB treatment also prevented these increases. However, HRH treatment failed to prevent these increases. These results indicate that SHR have enhanced intrarenal angiotensinogen production that contributes to increased Ang II levels leading to the development of hypertension and renal injury in this strain.
Histiocytic sarcoma of the thyroid
Authors: Javier Munoz, Bertha E. Sanchez, Ding Wang
Journal: American Journal of Hematology (2011)

A 74-year-old smoker male presented with a rapidly enlarging right neck mass, hoarseness, and dysphagia. Thyroid biopsies obtained by open surgery showed a diffuse proliferation of discohesive sheets of large oval and polygonal cells (figure 1 panel A) with round to oval vesicular nuclei. A thorough pathological investigation excluded an epithelial, melanocytic, myeloid, or lymphoid origin hence the morphologic and immunohistochemical findings of positive hemoglobin scavenger receptor or CD163 (figure 1 panel B) and CD68 markers were most consistent with histiocytic sarcoma (HS) [1]. Computed tomography (CT) revealed a locally advanced thyroid mass producing significant deviation of the trachea (figure 1 panel C), and several lung nodules. The patient was started on concurrent radiotherapy to the thyroid and intravenous chemotherapy with cisplatin and doxorubicin with improvement of his presenting symptoms. Interval CT (figure 1 panel D) months after completion of therapy showed a decrease in size of the thyroid mass although there was an increase in size of the lung nodules. Because of the mixed radiological response seen, a CT-guided lung biopsy revealed synchronous poorly differentiated nonsmall cell lung carcinoma. As there are no consensus guidelines for the management of HS due to its rarity, an extensive discussion with the patient took place, and it was decided to commence agents with proven activity against lung cancer with hopes of also achieving some response on his HS of the thyroid. Palliative chemotherapy was given with six cycles of carboplatin, etoposide, and bevacizumab with clinical and radiological stability of lung lesions and his thyroid mass, the latter as documented by positron emission tomography with actual decrease on fluorodeoxyglucose uptake and size of thyroid HS from 8 cm (panel E) to 6.9 cm (figure 1 panel F) in diameter and improvement of the deviation of his trachea. His lung involvement was eventually worsened; hence, the patient was subsequently switched to pemetrexed and bevacizumab until his performance status declined to the point that the patient opted for hospice care ∼16 months after his initial diagnosis. A diagnosis of HS implies a high mortality risk due to rapidly progressive disease despite the use of several chemotherapy agents that usually produce minimal response rates [2]. Our case emphasizes the need for further research in this uncommon disease, which carries dismal prognosis. Panel A, Hematoxylin-eosin staining. Panel B, CD163 marker. Panel C and D, computed tomography of the chest showing a thyroid mass with deviation of trachea, and a lung mass. Panel E and F, positron emission tomography showing decrease on fluorodeoxyglucose uptake and size of thyroid mass.
III. A Field Trial in Young School Children
Authors: Warren Winkelstein
Journal: JAMA (1962)

A concentrated, alum-containing, formalin-inactivated measles virus vaccine was used in a double-blind field trial conducted among school children. The dosage schedule consisted of 0.5 ml. of either vaccine (330 children) or placebo (319 children), intramuscularly, followed by a second such dose a week later, and a final injection 21 days after that. Most children completed their series on schedule. Subsequent observation disclosed a decrease in measles of 96% if only cases noted 14 or more days after the third dose were considered. If all cases that occurred after the first dose were counted, then the protection amounted to about 65%. The vaccinated group had a marked decrease in school absenteeism.
Is Bone&amp;ndash;Wax&lt;sup&gt;&amp;reg;&lt;/sup&gt; an Injectable Urologic Material?
Authors: Kursat Aksu, Ramazan Asci, Saban Sarikaya, Recep Buyukalpelli, A. Faik Yilmaz, Levent Yildiz, Bedri Kandemir
Journal: European Urology (2001)
Accumulated body burden and endogenous release of lead in employees of a lead smelter.
Authors: D E Fleming, D Boulay, N S Richard, J P Robin, C L Gordon, C E Webber, D R Chettle
Journal: Environmental Health Perspectives (1997)

Bone lead levels for 367 active and 14 retired lead smelter workers were measured in vivo by X-ray fluorescence in May-June 1994. The bone sites of study were the tibia and calcaneus; magnitudes of concentration were used to gauge lead body burden. Whole blood lead readings from the workers generated a cumulative blood lead index (CBLI) that approximated the level of lead exposure over time. Blood lead values for 204 of the 381 workers were gathered from workers returning from a 10-month work interruption that ended in 1991; their blood level values were compared to their tibia and calcaneus lead levels. The resulting relations allowed constraints to be placed on the endogenous release of lead from bone in smelter works. Calcaneus lead levels were found to correlate strongly with those for tibia lead, and in a manner consistent with observations from other lead industry workers. Relations between bone lead concentration and CBLI demonstrated a distinctly nonlinear appearance. When the active population was divided by date of hire, a significant difference in the bone lead-CBLI slope emerged. After a correction to include the component of CBLI existing before the workers' employment at the smelter was made, this difference persisted. This implies that the transfer of lead from blood to bone in the workers has changed over time, possibly as a consequence of varying exposure conditions.
Release of Ca2+ from the endoplasmic reticulum is not the mechanism for bile acid-induced cholestasis and hepatotoxicity in the intact rat liver.
Authors: G C Farrell, S K Duddy, G E Kass, J Llopis, A Gahm, S Orrenius
Journal: Journal of Clinical Investigation (1990)

The hypothesis that monohydroxy bile acids exert their cholestatic and hepatotoxic effects via a sustained elevation of cytosolic [Ca2+] was tested in the isolated perfused rat liver. Infusion of the specific inhibitor of microsomal Ca2+ sequestration, 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) (25 microM for 10 min) produced efflux of Ca2+ from the liver and a sustained (20 min) increase in cytosolic [Ca2+] as indicated by the threefold increase in hepatic glucose output. Release of the endoplasmic reticular Ca2+ pool was demonstrated by the complete abolition of vasopressin- and phenylephrine-induced Ca2+ exchange between the liver and perfusate. Despite the profound perturbation of intracellular Ca2+ homeostasis produced by tBuBHQ, there was no decrease in bile flow and no evidence of hepatocellular injury (for 60 min), as indicated by lactate dehydrogenase release. In contrast, lithocholic acid (25 microM for 10 or 30 min) or taurolithocholic acid (5 microM for 10 or 30 min) produced an 80-90% inhibition of bile flow and a progressive increase in perfusate lactate dehydrogenase activity. During and after bile acid infusion, there was no change in Ca2+ fluxes between liver and perfusate, no stimulation of glucose output from the liver, and hormone-stimulated Ca2+ responses were preserved. It is concluded that the mechanisms for bile acid-induced cholestasis and hepatotoxicity in the intact liver are not attributable to changes in intracellular Ca2+ homeostasis, and especially not to prolonged release or depletion of Ca2+ sequestered in the endoplasmic reticulum.
Towards elucidation of the drug release mechanism from compressed hydrophilic matrices made of cellulose ethers. I. Pulse-field-gradient spin-echo NMR study of sodium salicylate diffusivity in swollen hydrogels with respect to polymer matrix physical structure
Authors: Carmen Ferrero, Danielle Massuelle, Damien Jeannerat, Eric Doelker
Journal: Journal of Controlled Release (2008)
Enhanced hepatic delivery of siRNA and microRNA using oleic acid based lipid nanoparticle formulations
Authors: Xinmei Wang, Bo Yu, Wei Ren, Xiaokui Mo, Chenguang Zhou, Hongyan He, HuLiang Jia, Lu Wang, Samson T. Jacob, Robert J. Lee, Kalpana Ghoshal, L. James Lee
Journal: Journal of Controlled Release (2013)
<i>β</i><sub>2</sub>‐ADR haplotypes/polymorphisms associate with bronchodilator response and total IgE in grass allergy
Authors: G. Woszczek, M. Borowiec, A. Ptasinska, S. Kosinski, R. Pawliczak, M. L. Kowalski
Journal: Allergy (2005)

Association and linkage studies of beta2-adrenergic receptor (beta2-ADR) polymorphisms in relation to the expression of asthmatic phenotypes and immune regulatory mechanisms have shown inconsistent results. In order to analyse the relevance of particular combinations of single nucleotide polymorphisms (SNPs) or haplotypes of beta2-ADR gene to bronchial asthma, bronchodilator response and total immunoglobulin E (IgE) we determined by direct DNA sequencing five SNPs (in positions: -47, -20, 46, 79, 252) in a group of 180 Caucasian subjects (110 patients with grass allergy and 70 nonatopic controls). The eight different beta2-ADR haplotypes were identified, with three the most common of them representing 92% of the studied cohort. Significantly higher (pcor = 0.0045) bronchodilator response was observed in patients with homozygotic genotype 46A/A in comparison with respective homo- and hetero-zygotes. There was no significant difference in bronchodilator response when beta2-ADR haplotypes were analysed. Significantly higher (pcor = 0.0005) total IgE levels were found in patients with beta2-ADR haplotype -47T/-20T/46A/79C/252G and homozygotic carriers of 46A (pcor = 0.0015) and 79C (pcor = 0.003) genotypes. No significant associations were found in regards to asthmatic phenotype and atopy. These results indicate that depending on phenotype studied, either an individual beta2-ADR SNP or beta2-ADR haplotype might affect disease manifestation.