tbuckley/cabot-search huggingface dataset:
Immunoelectron microscopy identification of early proliferating cells in rat liver tissue during hyperplasia induced by lead nitrate
Authors: Koshilya Rijhsinghani, Ho-Soon H. Choi, Leroy A. Burton, Fiorenzo Paronetto, Nicola Tavoloni
Journal: Hepatology (1993)

Recent studies have suggested that hepatic stem cells may be involved in at least some forms of liver epithelial growth. To obtain further information on this controversial hypothesis, we treated rats with lead nitrate to induce liver growth and identified the cells undergoing early DNA synthesis by bromodeoxyuridine immunohistochemistry, using both light and electron microscopic detection methods. Eight hours after an intravenous injection of lead nitrate 100 μmol/kg, DNA synthesis was detected in a few scattered hepatocytes and in nonparenchymal cells in portal connective tissue. At the light microscopic level, identification of nonparenchymal cells was limited to bile duct epithelial cells. Other cell types were also labeled, but their identity could not be established. At the ultrastructural level, however, four types of nonparenchymal cells were identified as containing bromodeoxyuridine immunogold particles. These four types included bile duct epithelial cells, fibroblasts, macrophages and nondescript periductular cells. These periductular cells displayed certain ultrastructural features of bile duct cells but did not line a lumen or display microvilli on their apical membrane, nor did they reside within the bile duct basement membrane. Because proliferation of nonparenchymal cells in portal areas preceded that of hepatocytes, it is suggested that the former reaction reflects a direct mitogenic effect of lead nitrate and not an adaptive growth response secondary to parenchymal enlargement. However, whether DNA synthesis in periductular cells or bile duct cells reflects activation of hepatic stem cells cannot be established from the present morphological observations. If so, such a progenitor compartment must be dormant because it does not seem to play a functional role in this and other forms of adult liver epithelial growth. (HEPATOLOGY 1993;17:685–692.)
Health-Related Quality-of-Life Results From Multinational Clinical Trials of Insulin Lispro: Assessing benefits of a new diabetes therapy
Authors: James G Kotsanos, Louis Vignati, William Huster, Carol Andrejasich, Mary Beth Boggs, Alan M Jacobson, David Marrero, Susan D Mathias, Donald Patrick, Sunita Zalani, James Anderson
Journal: Diabetes Care (1997)

To compare health-related quality of life (HRQOL) in patients with diabetes receiving insulin lispro with patients receiving regular human insulin (Humulin R).We performed two randomized comparative studies over a 6-month period (3 months per treatment). Primary analyses used crossover baseline to 3-month changes in HRQOL scores. Ninety-three principal investigators in Canada, France, Germany, and the U.S. participated in these studies. One HRQOL crossover study included 468 patients with type I diabetes; the other HRQOL crossover study included 474 patients with type II diabetes. In both studies, patients were taking insulin at least 2 months before enrollment. Primary outcomes included two generic HRQOL domains, energy/fatigue and health distress, and two diabetes-specific domains, treatment satisfaction and treatment flexibility. Thirty secondary outcomes included both generic and diabetes-specific measures. Secondary outcome domains were controlled for multiplicity in the analyses.Primary analyses showed that treatment satisfaction scores (P < 0.001) and treatment flexibility scores (P = 0.001) were higher for insulin lispro in type I diabetic patients. No other significant treatment differences were detected using the data from these 6-month crossover studies.Treatment satisfaction and treatment flexibility were significantly improved in patients with type I diabetes using insulin lispro. Other HRQOL findings were comparable for insulin lispro and regular human insulin. Insulin lispro appears to have a measurable impact on lifestyle benefits in patients with type I diabetes, as demonstrated by increased treatment satisfaction and treatment flexibility.
Hypoglycemia Screening During Sleep
Authors: Samuel Eichold
Journal: JAMA (1965)

To the Editor:—  The central nervous system requires cellular glucose for neurological function. With low blood glucose, cellular level in the CNS falls and neurological response is similarly affected. Measure of this by light response on the retina is of value in insulin-treated diabetics to rule out hypoglycemia during sleep. The problem of hypoglycemic shock during the hours of sleep for those who require exogenous insulin in the management of diabetes mellitus has plagued since the advent of insulin. Signs such as perioral pallor, sweating, restless movements, or unusual vocal activity are not always present. They may represent more than mild hypoglycemia! To awaken an individual to ascertain his status is disturbing, to say the least. Most families seek to avoid this vexing action despite their deep concern.  At Camp Seale Harris, full chemical control of the child with diabetes is carefully sought. Many campers have had little chemical control
Book Review Birth Day: A Pediatrician Explores the Science, the History, and the Wonder of Childbirth By Mark Sloan. 370 pp. New York, Ballantine Books, 2009. $25. 978-0-345-50286-5 (cloth); 978-0-345-51293-2 (e-book).
Authors: Phillip G. Stubblefield
Journal: New England Journal of Medicine (2009)
Detection of Drug-Resistant Tuberculosis by Xpert MTB/RIF in Swaziland
Authors: Elisabeth Sanchez-Padilla, Matthias Merker, Patrick Beckert, Frauke Jochims, Themba Dlamini, Patricia Kahn, Maryline Bonnet, Stefan Niemann
Journal: New England Journal of Medicine (2015)

Rapid diagnosis of drug-resistant tuberculosis is important in determining proper management. This letter reports on limitations of the Xpert MTB/RIF assay in determining rifampin resistance in tuberculosis isolates in Swaziland.
A PREDICTORS OF RECURRENT CHEST PAIN IN PATIENTS WITH VASOSPASTIC ANGINA ON 3-YEAR CLINICAL OUTCOMES
Authors: Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Yoonjee Park, akkala goud, Sunki Lee, Ji Bak Kim, Sung Il Im, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong-Seog Seo, Dong Joo Oh, Taehoon Ahn
Journal: Journal of the American College of Cardiology (2014)
Spain's tougher line on smoking in public places spreads to other countries
Authors: A. G. Rada
Journal: BMJ (2011)

The new Spanish law on smoking in public places, which came into force on 2 January ( BMJ 2010;341:c7429, doi:10.1136/bmj.c7429), is already having an effect on other countries’ laws, the World Health Organization has said. 

Armando Peruga, programme manager of WHO’s Tobacco Free Initiative, said, “Spain changing the model and sending the message that it [a soft approach to smoking in public places] doesn’t work is a severe blow for the tobacco industry. The health minister of …
Naltrexone, an opioid receptor antagonist, attenuates liver fibrosis in bile duct ligated rats
Authors: M R Ebrahimkhani, S Kiani, F Oakley, T Kendall, A Shariftabrizi, S M Tavangar, L Moezi, S Payabvash, A Karoon, H Hoseininik, D A Mann, K P Moore, A R Mani, A R Dehpour
Journal: Gut (2006)

The aim of this study was to investigate the hypothesis that the opioid system is involved in the development of hepatic fibrosis.The effect of naltrexone (an opioid receptor antagonist) on hepatic fibrosis in bile duct ligated (BDL) or sham rats was assessed by histology and hepatic hydroxyproline levels. Liver matrix metalloproteinase 2 (MMP-2) was measured by zymography, and alpha smooth muscle actin (alpha-SMA) and CD45 (leucocyte common antigen) by immunohistochemistry. The redox state of the liver was assessed by hepatic glutathione (GSH)/oxidised glutathione (GSSG) and S-nitrosothiol levels. Subtypes of opioid receptors in cultured hepatic stellate cells (HSCs) were characterised by reverse transcriptase-polymerase chain reaction, and the effects of selective delta opioid receptor agonists on cellular proliferation, tissue inhibitor of metalloproteinase 1 (TIMP-1), and procollagen I expression in HSCs determined.Naltrexone markedly attenuated the development of hepatic fibrosis as well as MMP-2 activity (p<0.01), and decreased the number of activated HSCs in BDL rats (p<0.05). The development of biliary cirrhosis altered the redox state with a decreased hepatic GSH/GSSG ratio and increased concentrations of hepatic S-nitrosothiols, which were partially or completely normalised by treatment with naltrexone, respectively. Activated rat HSCs exhibited expression of delta1 receptors, with increased procollagen I expression, and increased TIMP-1 expression in response to delta(1) and delta(2) agonists, respectively.This is the first study to demonstrate that administration of an opioid antagonist prevents the development of hepatic fibrosis in cirrhosis. Opioids can influence liver fibrogenesis directly via the effect on HSCs and regulation of the redox sensitive mechanisms in the liver.
Air Pollution—Critical Choices
Authors: Frank W. Barton
Journal: JAMA (1970)

What do you want, good air or good comfort? Parodying a familiar slogan describes the current dilemma of citizens in New York city. Added to their 1970 summer doldrums, stagnant air loaded with sulfur oxides and particulate pollution caused New Yorkers public annoyance, insults to their sense perceptions, and respiratory difficulties. Officially reported to be the worst in the country, New York's air has three times as much sulfur dioxide as the federal government considers safe for human life. New York city also experienced this summer its worst power shortage since the 1965 Northeast blackout. Two massive generators broke down, reducing power capacity by 17%. Emergency plans to conserve electricity called for the subway system to use a third fewer trains and to run them at half speed.  Opposition from a number of sources has delayed for years a plan of the utility company to build a pumped-storage hydroelectric plant
No mucosal involvement in a patient with paraneoplastic pemphigus associated with thymoma and myasthenia gravis
Authors: S.E. Lee, T. Hashimoto, S-C. Kim
Journal: British Journal of Dermatology (2008)

Conflicts of interest: none declared. Sir, Myasthenia gravis (MG) can be accompanied by skin disorders, including pemphigus, vitiligo and alopecia areata, all of which are immunologically mediated.1 The coincidence of MG and paraneoplastic pemphigus (PNP) is rare, but some patients with MG, thymoma and PNP have been reported.2 We report a patient with PNP associated with alopecia areata, invasive thymoma and MG. The most unusual clinical feature of our case was that there was no mucosal involvement. A 44‐year‐old Korean woman was admitted to the Department of Neurology in September 1996, because of a 20‐day history of diplopia and a 7‐day history of ptosis. Under the impression of third nerve palsy, she received pulsed methylprednisolone for 5 days, and the ptosis and diplopia improved. In August 1997, she was re‐admitted due to muscle weakness for 15 days and alopecia for 2 months. A positive neostigmine test, Jolly test, and increased titre of antibodies to acetylcholine receptor (11·1 nmol L−1) confirmed the diagnosis of MG. Chest computed tomography revealed a 4‐cm mediastinal mass consistent with thymoma. Physical examination revealed multiple alopecic patches on the scalp (Fig. 1a). Biopsy from an alopecic lesion revealed mild lymphocytic infiltration around hair follicles, compatible with nonscarring alopecia. Direct immunofluorescence (DIF) on an alopecic patch and normal skin showed IgG and C3 deposits along the basement membrane zone and keratinocyte cell surfaces (Fig. 1d). Indirect immunofluorescence (IIF) using human skin substrates showed circulating IgG antibodies that bound to the surface of keratinocytes at a titre of 1 : 1280. IIF performed on rat bladder and monkey oesophagus was also positive (Fig. 1e). Immunoblotting analysis using extracts of human epidermis detected envoplakin (210 kDa) and periplakin (190 kDa). We performed desmoglein (Dsg) enzyme‐linked immunosorbent assay, but could not detect any anti‐Dsg3 or anti‐Dsg1 IgG antibodies in the patient's serum.
Allergenic Activity of a Major Grass Pollen Allergen Is Elevated in the Presence of Nasal Secretion
Authors: ALBRECHT BUFE, KIRSTEN GEHLHAR, GABRIELE SCHRAMM, MAX SCHLAAK, WOLF-MEINHARD BECKER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Phl p5 is a major allergen of timothy grass and causes rhinitis and bronchial asthma in nearly all patients allergic to grass pollen. The biochemical processing of this molecule by the nasal mucosa at its first encounter and possible changes of its biologic activity are unknown. Two isoforms of the allergen were expressed in Escherichia coli and subsequently purified. Conversion of these preparations to various forms with molecular size between 10 and 20 kD in the presence of nasal secretion was observed. Surprisingly, in skin prick test assays with allergic patients the mixture of converted peptides caused significantly higher allergic response when compared with the parent protein. Allergenic activity of the recombinant N-terminal Phl p5a and the C-terminal Phl p5b as measured by skin prick test and histamine release assays was significantly higher than that of the respective parent molecules. Using pancreatic rather than nasal secretion, Phl p5b was completely degraded and its allergenicity was almost completely reduced. Proteolytic degradation converts Phl p5 to defined fragments with increased allergenicity. Complete degradation of Phl p5 on the mucosa could be a preventive strategy to destroy its potency for the induction of an allergic response.
Combination of gemcitabine and cisplatin for biliary tract cancer: A platform to build on
Authors: Nataliya Razumilava, Gregory J. Gores
Journal: Journal of Hepatology (2010)

Background: There is no established standard chemotherapy for patients with locally advanced or metastatic biliary tract cancer. We initially conducted a randomized, phase 2 study involving 86 patients to compare cisplatin plus gemcitabine with gemcitabine alone. After we found an improvement in progression free survival, the trial was extended to the phase 3 trial reported here. Methods: We randomly assigned 410 patients with locally advanced or metastatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer to receive either cisplatin (25 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter on days 1 and 8, every 3 weeks for eight cycles) or gemcitabine alone (1000 mg per square meter on days 1, 8, and 15, every 4 weeks for six cycles) for up to 24 weeks. The primary end point was overall survival. Results: After a median follow-up of 8.2 months and 327 deaths, the median overall survival was 11.7 months among the 204 patients in the cisplatin-gemcitabine group and 8.1 months among the 206 patients in the gemcitabine group (hazard ratio, 0.64; 95% confidence interval, 0.52-0.80; p <0.001). The median progression-free survival was 8.0 months in the cisplatin-gemcitabine group and 5.0 months in the gemcitabine-only group (p <0.001). In addition, the rate of tumor control among patients in the cisplatin-gemcitabine group was significantly increased (81.4% vs. 71.8%, p = 0.049). Adverse events were similar in the two groups, with the exception of more neutropenia in the cisplatin-gemcitabine group; the number of neutropenia-associated infections was similar in the two groups. Conclusions: As compared with gemcitabine alone, cisplatin plus gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity. Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer.
Use leftover Tamiflu to grit icy roads, MP suggests
Authors: Z. Kmietowicz
Journal: BMJ (2010)

An MP has said that unused supplies of oseltamivir (Tamiflu) pills left over from the swine flu pandemic that never quite happened in the United Kingdom could be used to grit icy roads.

Paul Flynn, Labour MP for Newport West, filed an early day motion in the House of Commons on 20 January to highlight concerns about the intended mass use of oseltamivir in the UK.

In it Mr Flynn says he was “surprised” by a recent BMJ systematic review highlighting the fact …
Family Practice in Evolution
Authors: John P. Geyman
Journal: New England Journal of Medicine (1978)

Family practice has developed in direct response to the public need for primary care with the elements of comprehensiveness, continuity and accessibility. This specialty represents a re-emphasis of the generalist role in medicine, with particular concern for the family as the unit of care. Since the American Board of Family Practice was formed nine years ago, the first phase of development has been completed. Teaching programs in family medicine have been effectively established at undergraduate and graduate levels throughout the country in both university and community settings. Refinement of teaching programs and initiation of a strong ongoing research effort are now required. The continued successful evolution of family practice as a foundation of primary care in the United States is essential to extend the highest possible quality of care to the entire population at a cost that can be afforded in a society with limited resources for health care.
Efficacité et complications de la photothérapie dynamique dans le cancer de l'œsophage superficiel: comparaison du traitement en première intention et du traitement de rattrapage pour récidive locale ou échec de la radio-chimiothérapie
Authors: S Lecleire, F Di Fiore, M Antonietti, E Ben Soussan, P Hochain, E Lerebours, P Michel, P Ducrotte
Journal: Endoscopy (2008)

Introduction: La photothérapie dynamique (PDT) est actuellement l'une des options thérapeutiques de première intention chez les malades atteints de cancer de l'œsophage superficiel. Récemment, la PDT été employée comme un traitement de rattrapage après une récidive locale ou un échec de la radio-chimiothérapie (RCT). (1)
G-Rich DNA Suppresses Systemic Lupus
Authors: Prashant S. Patole, Daniel Zecher, Rahul D. Pawar, Hermann-Josef Gro[Combining Diaeresis]ne, Detlef Schlo[Combining Diaeresis]ndorff, Hans-Joachim Anders
Journal: Journal of the American Society of Nephrology (2005)

Whereas the role of immune complexes in mediating renal cell and immune cell activation is well established, the contribution of sequence-specific immunomodulatory actions of the chromatin part remains unclear. Toll-like receptor-9 (TLR-9) mediates immunostimulatory effects of unmethylated microbial CpG-DNA. It was hypothesized that hypomethylated CpG-DNA in vertebrates may have similar effects and may contribute to disease progression in lupus nephritis. A synthetic G-rich DNA, known to block CpG-DNA effects, was used in this study. In macrophages, G-rich DNA suppressed CpG-DNA-but not LPS-induced production of CCL5 in a dose-dependent manner. Injections of G-rich DNA suppressed lymphoproliferation induced by CpG-DNA injections in mice. In MRL(lpr/lpr) mice with lupus nephritis, labeled G-rich DNA co-localized to glomerular immune complexes and was taken up into endosomes of TLR-9-positive infiltrating macrophages. Eleven-week-old MRL(lpr/lpr) mice that received injections of either saline or G-rich DNA for 13 wk revealed decreased lymphoproliferation and less autoimmune tissue injury in lungs and kidneys as compared with saline-treated controls. G-rich DNA reduced the levels of serum dsDNA-specific IgG2a as well as the renal immune complex deposits. This was consistent with the blocking effect of G-rich DNA on CpG-DNA-induced proliferation of B cells that were isolated from MRL(lpr/lpr) mice. As oligodeoxyribonucleotide 2114-treated MRL(lpr/lpr) mice were not exposed to exogenous CpG-DNA, these effects should relate to a blockade of CpG motifs in endogenous DNA. It is concluded that adjuvant activity of self-DNA contributes to the pathogenesis of lupus nephritis. Modulating the CpG-DNA-TLR-9 pathway may offer new opportunities for the understanding and treatment of lupus.
Polymorphisms in human histamine receptor H4 gene are associated with atopic dermatitis
Authors: B. Yu, Y. Shao, J. Zhang, X.L. Dong, W.L. Liu, H. Yang, L. Liu, M.H. Li, C.F. Yue, Z.Y. Fang, C. Zhang, X.P. Hu, B.C. Chen, Q. Wu, Y.W. Chen, W. Zhang, J. Wan
Journal: British Journal of Dermatology (2010)

Atopic dermatitis (AD) is a chronic skin disease affecting more than 15% of children and 2% of adults. A strong connection between genetic factors and AD has been described for a long time. Histamine receptor H4 (HRH4) has been shown to be related to different kinds of allergic and autoimmune disorders. However, an association between HRH4 and AD has not yet been reported.To examine a possible association between HRH4 and AD.Genomic DNA from 301 patients with AD and 313 healthy controls was extracted and three exons of HRH4 were sequenced.We found three new single nucleotide polymorphisms (SNPs) in HRH4 which were significantly associated with AD: ss142022671 [odds ratio (OR) 1.87, 95% confidence interval (CI) 1.24-2.81; P = 0.002], ss142022677 (OR 4.40, 95% CI 2.42-8.00; P = 1.5 x 10(-7)) and ss142022679 (OR 4.26, 95% CI 2.38-7.61; P = 1.3 x 10(-7)). The SNPs ss142022677 and ss142022679 were found to be in strong linkage disequilibrium (D' = 0.98; r(2) = 0.92). Two-SNP haplotype analysis (ss142022677 and ss142022679) showed that the major AA haplotype was protective against AD (OR 0.22, 95% CI 0.12-0.40; P = 3.1 x 10(-8)) and the minor TT haplotype was significantly associated with AD (OR 4.13, 95% CI 2.27-7.54; P = 6.6 x 10(-7)). In addition, in a three-SNP haplotype analysis (ss142022671, ss142022677 and ss142022679), the major TAA haplotype was protective against AD (OR 0.46, 95% CI 0.31-0.69; P = 0.0001), while the complementary ATT haplotype was found to be significantly associated with AD (OR 3.81, 95% CI 2.03-7.14; P = 8.3 x 10(-6)).Polymorphisms of ss142022671, ss142022677 and ss142022679 in HRH4 are associated with AD.