tbuckley/cabot-search huggingface dataset:
Calcitonin gene-related peptide modulates interleukin-13 in circulating cutaneous lymphocyte-associated antigen-positive T cells in patients with atopic dermatitis
Authors: C. Antúnez, M.J. Torres, S. López, R. Rodriguez-Pena, M. Blanca, C. Mayorga, L.F. Santamaría-Babi
Journal: British Journal of Dermatology (2009)

Neuropeptides (NPs) may play an important role in the pathogenesis of atopic dermatitis (AD) by regulating immune responses and contributing to the cross-talk between the immune and nervous systems.To assess the ability of NPs to influence interleukin (IL)-13 and interferon (IFN)-gamma production and the expression of the activation marker HLA-DR in skin memory T cells [cutaneous lymphocyte-associated antigen (CLA)+ T cells] from patients with AD with severe, chronic lesions and intense pruritus, and from nonatopic controls.Cells were cultured in the presence and absence of different NPs, calcitonin gene-related peptide (CGRP), somatostatin (SOM) and substance P (SP). IL-13 and IFN-gamma production and HLA-DR expression were measured in both CLA+ and CLA- T-cell subsets by flow cytometry.CGRP increased IL-13 production in peripheral blood mononuclear cells from patients with AD (P < 0.05), with no changes detected in the presence of SOM or SP. These patients with AD had a lower expression of CGRP receptor compared with controls (P < 0.05). Memory T cells incubated with CGRP also showed an increase in IL-13 (P < 0.05) and HLA-DR (P < 0.05) in CLA+ T cells from patients with AD compared with controls, but not in CLA- T cells. Patients with a higher production of IL-13 were those with higher total IgE and percentage of skin area involved. Furthermore, the IL-13/IFN-gamma ratio was increased in patients with AD after cells were cultured with CGRP (P < 0.05).Our results suggest an immunomodulatory role of CGRP towards a Th2 pattern in CLA+ T cells, which may contribute to exacerbating clinical symptoms in patients with AD.
Valsartan reduced diabetes but not CV events in patients with impaired glucose tolerance and CV risk factors
Authors: Michael Farkouh
Journal: Annals of Internal Medicine (2010)

ACP Journal Club15 June 2010Valsartan reduced diabetes but not CV events in patients with impaired glucose tolerance and CV risk factorsMichael Farkouh, MD, MScMichael Farkouh, MD, MScMount Sinai Medical Center, New York, New York, USA (M.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-12-201006150-02009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationThe NAVIGATOR Study Group. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362:1477-90. https://pubmed.ncbi.nlm.nih.gov/20228403Clinical Impact RatingsGIM/FP/GP: Cardiology: Endocrinology: References1 Knowler WC, Fowler SE, Hamman RF, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374:1677-86. [PMID: 19878986] Google Scholar2 Gerstein HC, Yusuf S, Bosch J, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368:1096-105. [PMID: 16997664] Google Scholar3 Bosch J, Yusuf S, Gerstein HC, et al. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006;355:1551-62. [PMID: 16980380] Google Scholar4 Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358:580-91. [PMID: 18256393] Google Scholar5 Montori VM, Isley WL, Guyatt GH. Waking up from the DREAM of preventing diabetes with drugs. BMJ. 2007;334:882-4. [PMID: 17463460] Google Scholar6 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33:S62-9. [PMID: 20042775] Google Scholar Author, Article, and Disclosure InformationAffiliations: Mount Sinai Medical Center, New York, New York, USA (M.F.)This article was published at Annals.org on 1 June 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoNateglinide did not reduce diabetes or CV events in patients with impaired glucose tolerance and CV risk factors Michael Farkouh Metrics 15 June 2010Volume 152, Issue 12Page: JC6-9KeywordsBlood plasmaCardiovascular disease riskGlucoseGlucose intoleranceHospitalizationsHypertensionMedical risk factorsMyocardial infarctionRevascularizationUnstable angina ePublished: 15 June 2010 Issue Published: 15 June 2010 CopyrightCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Functional analysis of hepatitis B virus reactivating in hepatitis B surface antigen-negative individuals
Authors: Meike Hass, Charles Hannoun, Tatyana Kalinina, Gunhild Sommer, Christoph Manegold, Stephan Günther
Journal: Hepatology (2005)

Abstract The biological properties of latent or occult hepatitis B virus (HBV) have been poorly characterized as a result of the extremely low virus concentration. This report describes the phenotype of HBV reactivating in two patients after an HBsAg-negative latency period. One patient had latent HBV infection for at least 12 years without detectable viremia and symptoms of liver disease. Several full-length HBV genomes were cloned at reactivation, sequenced, and functionally tested by transfection into HuH7 cells. Genomes from both patients showed a low replication phenotype. It was caused at the level of RNA encapsidation or HBV DNA synthesis, but was not attributable to uncommon mutations in the terminal protein domain of P protein. A substantial subpopulation (≈50%) of genomes from one patient did not express pre-S2/S mRNA and HBsAg. Site-directed mutagenesis identified a single G-A mutation within the S gene (position 458) to be responsible for this effect. The G458A mutation was also effective if the S gene was placed under control of a heterologous promoter. Furthermore, nuclear run-on transcription showed that the G458A mutation acts at the posttranscriptional level. The mutation affected a 5′ splice site and prevented splicing of the pre-S2/S mRNA from position 458 to 1305. In conclusion , HBV latency may be characterized by viruses with reduced replication competence and antigen expression. In one patient, HBsAg expression was terminated by an as yet undescribed posttranscriptional mechanism. A single mutation inactivated a 5′ splice site that is obviously essential for pre-S2/S mRNA accumulation. Supplementary material for this article can be found on the Hepatology website ( http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html ). (Hepatology 2005;42:93–103.)
Nazi Medicine and the Nuremberg Trials: From Medical War Crimes to Informed Consent
Authors: Boleslav L Lichterman
Journal: BMJ (2005)

P aul Weindling is a renowned expert on medicine in Nazi Germany. His new book is the third in “an informal trilogy on German medical atrocities.” The preceding two were Health, Race and German Politics between National Unification and Nazism 1870-1945 (published in 1989) and Epidemics and Genocide in Eastern Europe (published in 2000).

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Palgrave Macmillan, £60, pp 496 ISBN 1 4039 3911 X http://www.palgrave.com/

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The current book is in three parts. The first gives an outline of coercive experimentation in Nazi Germany, which Weindling divides into four overlapping phases.

The first phase (1939-41), which he calls the neurological, was linked to the euthanasia programme (code named T4) that provided a testing ground for the killing techniques that would later be used in the “final solution.” Hitler's decree authorising euthanasia coincided with Germany's invasion of Poland. The programme targeted the elimination of adult patients in mental institutions and resulted in the execution—chiefly by gassing—of more than 70 000 people.

The second phase, from 1939 to 1944, was the large scale experiments on sterilisation and human reproduction (a direct continuation of the 1933 Sterilisation Law, which was administered through the genetic health courts). About 400 000 people with …

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Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia
Authors: Davide Rossi, Hossein Khiabanian, Valeria Spina, Carmela Ciardullo, Alessio Bruscaggin, Rosella Famà, Silvia Rasi, Sara Monti, Clara Deambrogi, Lorenzo De Paoli, Jiguang Wang, Valter Gattei, Anna Guarini, Robin Foà, Raul Rabadan, Gianluca Gaidano
Journal: Blood (2014)
The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan
Authors: Zhuo Wang, Juan Pascual-Anaya, Amonida Zadissa, Wenqi Li, Yoshihito Niimura, Zhiyong Huang, Chunyi Li, Simon White, Zhiqiang Xiong, Dongming Fang, Bo Wang, Yao Ming, Yan Chen, Yuan Zheng, Shigehiro Kuraku, Miguel Pignatelli, Javier Herrero, Kathryn Beal, Masafumi Nozawa, Qiye Li, Juan Wang, Hongyan Zhang, Lili Yu, Shuji Shigenobu, Junyi Wang, Jiannan Liu, Paul Flicek, Steve Searle, Jun Wang, Shigeru Kuratani, Ye Yin, Bronwen Aken, Guojie Zhang, Naoki Irie
Journal: Nature Genetics (2013)

The unique anatomical features of turtles have raised unanswered questions about the origin of their unique body plan. We generated and analyzed draft genomes of the soft-shell turtle (Pelodiscus sinensis) and the green sea turtle (Chelonia mydas); our results indicated the close relationship of the turtles to the bird-crocodilian lineage, from which they split ∼267.9-248.3 million years ago (Upper Permian to Triassic). We also found extensive expansion of olfactory receptor genes in these turtles. Embryonic gene expression analysis identified an hourglass-like divergence of turtle and chicken embryogenesis, with maximal conservation around the vertebrate phylotypic period, rather than at later stages that show the amniote-common pattern. Wnt5a expression was found in the growth zone of the dorsal shell, supporting the possible co-option of limb-associated Wnt signaling in the acquisition of this turtle-specific novelty. Our results suggest that turtle evolution was accompanied by an unexpectedly conservative vertebrate phylotypic period, followed by turtle-specific repatterning of development to yield the novel structure of the shell.
Interrelationships among zinc, copper, lead, and cadmium in food, feces, and organs of humans.
Authors: K Tsuchiya, S Iwao
Journal: Environmental Health Perspectives (1978)

Concentrations of zinc, copper, lead, and cadmium were determined in 20 samples of food collected over a period of 20 days, 221 samples of feces collected over a period of 5 days from 19 males, 17 females, and 11 children and 85 samples each of renal cortex and liver from autopsied human cadavers in order to investigate the relationships among the four metals and among the various martices. In food the highest correlation was observed between copper and zinc (0.34). In feces the highest correlation was also between copper and zinc (0.45). In the highest correlation between cadmium and zinc (0.33), but that in the renal cortex was between copper and cadmium (0.52). These findings suggest that the relationships among the concentrations of the four metals in food and feces are almost equal to each other, but differ greatly from the concentrations in human organs due to the differing metabolic actions of the metals once they are absorbed into the body. In addition, it was observed that zinc and cadmium concentrations in the renal cortex increase with age, but copper and lead concentrations do not show much variation with age.
Breast screening in Britain and Sweden.
Authors: G. Sanders, H. G. Pledger
Journal: BMJ (1988)

resolve with the onset of bone marrow regeneration.Nevertheless, the facial tissue had been extensively damaged and in the process of healing the facial wound underwent dehiscence to produce a large oral fistula.This required reconstructive surgery with skin grafting, which was successful.The patient received further chemotherapy without any serious infective complications.These two cases complement the atypical ones described by Dr Weinbren and colleagues.The first emphasises how lethal an infection with P aeruginosa can be in the neutropenic patient, although the pulmonary embolus may have contributed to his death.The second illustrates that even if the infection can be controlled long enough to allow haemopoietic recovery the subsequent tissue breakdown and healing process may still lead to major clinical problems.The importance of good oral hygiene and mouth care to prevent colonisation and infection gaining a foothold cannot be overemphasised.
Cigarette Smoking and Blood Lipids
Authors: Alfred Kershbaum, Samuel Bellet
Journal: JAMA (1964)

A NUMBER OF recent epidemiological studies have shown that a positive relationship exists between cigarette smoking and coronary heart disease<sup>1-3</sup>and between cigarette smoking and elevated serum lipids.<sup>4-7</sup>While these statistical associations may suggest a cause and effect relationship between smoking and coronary disease and smoking and lipid abnormalities, observations of an experimental nature are necessary to determine whether this actually exists. Since blood lipid variations have been generally accepted as an important factor in atherogenesis, an investigation of the effect of cigarette smoking and nicotine administration on lipid metabolism was undertaken to help clarify the relationship of smoking and coronary heart disease. In the present report several phases of this investigation will be discussed: (1) the effect of cigarette smoking and nicotine on free fatty acids (FFA),<sup>8,9</sup>(2) the importance of the adrenal glands and sympathetic nervous system in the FFA response to smoking,<sup>10</sup>(3)
Treatment of Primary Hemochromatosis With Deferoxamine
Authors: Neal Young
Journal: JAMA (1979)

IN PATIENTS with hemochromatosis, congestive heart failure is usually intractable and often heralds rapid deterioration and death.<sup>1</sup>In some cases of primary hemochromatosis, vigorous phlebotomy therapy has resulted in the relief of heart failure and prolonged life.<sup>1</sup>In patients in whom hemochromatosis is secondary to transfusion therapy or in those in whom hemochromatosis accompanies anemia, therapy with the iron-chelating agent deferoxamine mesylate has been employed to reverse tissue damage.<sup>2</sup>This report describes a patient with hereditary hemochromatosis and coincident β-thalassemia trait who had complete reversal of congestive heart failure, pericarditis, and cardiac arrhythmias while receiving deferoxamine. <h3>Report of a Case</h3> A 37-year-old man was admitted to the Clinical Center of the National Institutes of Health for treatment of severe congestive heart failure. Dyspnea with exertion developed in 1942 when he was 13 years old; he was found to be mildly anemic, and therapy was begun with ferrous sulfate,
Influence of Hydrochloric Acid on Gastric Secretion and Emptying in Patients with Duodenal Ulcer
Authors: J. N. Hunt
Journal: BMJ (1957)

VISCERAL LESIONS IN HERPES ZOSTER BMJso 681 viscus, innervated by the corresponding nerve roots, which results in inflammatory lesions and spasm in the case of the hollow organs.This suggests that, in addi- tion to the sympathetic and parasympathetic pathways, there exists a third nerve pathway by which visceral activity may be altered.
Role of self-instruction and self-testing in teaching pathology.
Authors: R C Curran, E L Jones
Journal: BMJ (1977)

resemble many oral medications in shape, being cylinders 11 mm in diameter and 3-5 mm in height.It is therefore not surprising that the inebriated or senile patient, the diabetic with impaired vision, or the patient attempting to take an oral medication in the dark might mistake these tablets for an oral medicine.If additional studies find that accidental ingestion of these pills is as common as our experience suggests, alternative methods of urine testing should be considered for patients who are likely to ingest these tablets accidentally-for example, alcoholic or senile patients or patients with visual or language problems, especially if they are taking many tablets.The manufacturer might also consider changing the size and shape of the tablets to lessen the likelihood of their being mistaken for oral medications.We thank Dr Fred Kern jun for his helpful suggestions and
Soluble CD40 ligand induces endothelial dysfunction in human and porcine coronary artery endothelial cells
Authors: Changyi Chen, Hong Chai, Xinwen Wang, Jun Jiang, Md Saha Jamaluddin, Dan Liao, Yuqing Zhang, Hao Wang, Uddalak Bharadwaj, Sheng Zhang, Min Li, Peter Lin, Qizhi Yao
Journal: Blood (2008)
FAMILIAL MAMMARY TUMORS IN THE RABBIT
Authors: Harry S. N. Greene
Journal: The Journal of Experimental Medicine (1939)

The clinical histories of two different types of familial mammary cancer in the rabbit have been described. In one type, the first clinical sign of breast abnormality was a sudden and intense engorgement and thereafter the disorder passed through stages of cyst formation and benign neoplasia to cancer with metastasis. In the second type, neoplasia originated in clinically normal breast tissue and there was no history of antecedent mammary abnormality.
Loss of the signaling adaptor TRAF1 causes CD8+ T cell dysregulation during human and murine chronic infection
Authors: Chao Wang, Ann J. McPherson, R. Brad Jones, Kim S. Kawamura, Gloria H.Y. Lin, Philipp A. Lang, Thanuja Ambagala, Marc Pellegrini, Thomas Calzascia, Nasra Aidarus, Alisha R. Elford, Feng Yun Yue, Elisabeth Kremmer, Colin M. Kovacs, Erika Benko, Cecile Tremblay, Jean-Pierre Routy, Nicole F. Bernard, Mario A. Ostrowski, Pamela S. Ohashi, Tania H. Watts
Journal: The Journal of Experimental Medicine (2011)

The signaling adaptor TNFR-associated factor 1 (TRAF1) is specifically lost from virus-specific CD8 T cells during the chronic phase of infection with HIV in humans or lymphocytic choriomeningitis virus (LCMV) clone 13 in mice. In contrast, TRAF1 is maintained at higher levels in virus-specific T cells of HIV controllers or after acute LCMV infection. TRAF1 expression negatively correlates with programmed death 1 expression and HIV load and knockdown of TRAF1 in CD8 T cells from viral controllers results in decreased HIV suppression ex vivo. Consistent with the desensitization of the TRAF1-binding co-stimulatory receptor 4-1BB, 4-1BBL–deficient mice have defects in viral control early, but not late, in chronic infection. TGFβ induces the posttranslational loss of TRAF1, whereas IL-7 restores TRAF1 levels. A combination treatment with IL-7 and agonist anti–4-1BB antibody at 3 wk after LCMV clone 13 infection expands T cells and reduces viral load in a TRAF1-dependent manner. Moreover, transfer of TRAF1+ but not TRAF1− memory T cells at the chronic stage of infection reduces viral load. These findings identify TRAF1 as a potential biomarker of HIV-specific CD8 T cell fitness during the chronic phase of disease and a target for therapy.
BCR-ABL kinase is dead; long live the CML stem cell
Authors: Alexander Perl, Martin Carroll
Journal: Journal of Clinical Investigation (2010)

Chronic myeloid leukemia (CML) is a hematopoietic disease characterized by expansion of myeloid blood cells. It is caused by the t(9;22) chromosomal translocation that results in the expression of the fusion tyrosine kinase BCR-ABL. Tyrosine kinase inhibitor (TKI) therapy has led to long-term remissions, but patients remain BCR-ABL+. There is agreement that TKIs do not kill CML stem cells; however, it is controversial whether this is because of a lack of BCR-ABL kinase inhibition in CML stem cells or because CML stem cells do not require BCR-ABL for survival. In this issue of the JCI, Corbin and colleagues provide definitive evidence that BCR-ABL is kinase active in CML stem cells and that TKIs inhibit this kinase activity without affecting CML stem cell survival. Rather, CML stem cells revert to a normal dependence on cytokines for survival and proliferation. These results demonstrate that the CML stem cell is not BCR-ABL addicted and have important implications for developing curative therapeutic approaches to CML.
Bone-Marrow Hypoplasia Following Use of Chloramphenicol Eye Drops
Authors: Robert L. Rosenthal
Journal: JAMA (1965)

THE DEVELOPMENT of bone-marrow hypoplasia, depression of erythropoiesis, and aplastic anemia following ingestion of chloramphenicol have been well documented. 1 This report presents the previously undescribed development of marrow hypoplasia following the use of chloramphenicol eye drops in a patient with a family history of fatal aplastic anemia produced by ingestion of chloramphenicol.  Report of a Case  A 36-year-old white male, director of personnel, presented with complaints of intermittent epistaxis for three months, daily bleeding of the gums for three weeks, and weakness for one week. His history revealed the use of chloramphenicol eye drops, 0.5% in an aqueous solution, prescribed when he complained that his eyes appeared reddened. For the past 23 months, he used these eye drops on an average of two out of three days, estimating that the original prescription was refilled about 25 times without medical supervision. The eye drops produced no local inflammation or evidence
Effect of an oral gold compound, auranofin, on non-specific bronchial hyperresponsiveness in mild asthma.
Authors: M Honma, G Tamura, K Shirato, T Takishima
Journal: Thorax (1994)

A recent double blind clinical trial in Japan has shown that auranofin (6 mg/day) is a useful treatment for patients with moderate to severe asthma. To investigate the mechanism of action of auranofin the bronchial responsiveness to inhaled methacholine has been studied in well controlled asthmatic subjects.Nineteen adult asymptomatic asthmatic subjects received auranofin (3 mg orally twice a day) or inactive placebo in random order for 12 weeks in a double blind fashion. Bronchial responsiveness to inhaled methacholine and pulmonary function tests were measured at the same time on different days before, and six and 12 weeks after, each treatment.Non-specific bronchial hyperresponsiveness 12 weeks after treatment with auranofin was decreased compared with that before treatment with auranofin and 12 weeks after treatment with inactive placebo, although the treatment did not improve pulmonary function tests.Non-specific bronchial hyperresponsiveness 12 weeks after treatment with auranofin is decreased in a group of mild asymptomatic asthmatic patients with normal lung function.
Infusion of methyl tertiary butyl ether in bile ducts of rabbits.
Authors: W R Murray
Journal: Gut (1989)

Infusion of methyl tertiary butyl ether in bile ducts of rabbits SIR,-I was interested to read the paper from Professor Tritapepe's group (Gut 1989; 30: 206-12). 1 feel it is important to emphasise that this work has little or no bearing on previously published human in vivo studies on the use of methyl tertiary butyl ether