tbuckley/cabot-search huggingface dataset:
A novel “humanized mouse” model for autoimmune hepatitis and the association of gut microbiota with liver inflammation
Authors: Muhammed Yuksel, Yipeng Wang, Ningwen Tai, Jian Peng, Junhua Guo, Kathie Beland, Pascal Lapierre, Chella David, Fernando Alvarez, Isabelle Colle, Huiping Yan, Giorgina Mieli‐Vergani, Diego Vergani, Yun Ma, Li Wen
Journal: Hepatology (2015)

Autoimmune hepatitis (AIH) in humans is a severe inflammatory liver disease characterized by interface hepatitis, the presence of circulating autoantibodies, and hyper-gammaglobulinemia. There are two types of AIH, type 1 (AIH-1) and type 2 (AIH-2), characterized by distinct autoimmune serology. Patients with AIH-1 are positive for anti-smooth muscle and/or antinuclear autoantibodies, whereas patients with AIH-2 have anti-liver kidney microsomal type 1 and/or anti-liver cytosol type 1 autoantibodies. Cytochrome P4502D6 is the antigenic target of anti-liver kidney microsomal type 1, and formiminotransferase cyclodeaminase is the antigenic target of anti-liver cytosol type 1. It is known that AIH, both types 1 and 2, is strongly linked to the human leukocyte antigen (HLA) alleles -DR3, -DR4, and -DR7. However, direct evidence of the association of HLA with AIH is lacking. We developed a novel mouse model of AIH using the HLA-DR3 transgenic mouse on the nonobese-diabetic background by immunization of HLA-DR3- and HLA-DR3+ nonobese-diabetic mice with a DNA plasmid, coding for human cytochrome P4502D6/formiminotransferase cyclodeaminase fusion protein. Immunization with cytochrome P4502D6/formiminotransferase cyclodeaminase leads to a sustained elevation of alanine aminotransferase, development of antinuclear autoantibodies and anti-liver kidney microsomal type 1/anti-liver cytosol type 1 autoantibodies, chronic immune cell infiltration, and parenchymal fibrosis on liver histology in HLA-DR3+ mice. Immunized mice also showed an enhanced T helper 1 immune response and paucity of the frequency of regulatory T cells in the liver. Moreover, HLA-DR3+ mice with exacerbated AIH showed reduced diversity and total load of gut bacteria.Our humanized animal model has provided a novel experimental tool to further elucidate the pathogenesis of AIH and to evaluate the efficacy and safety of immunoregulatory therapeutic interventions in vivo.
Sensitivity and specificity of the American College of Rheumatology 1987 criteria for the diagnosis of rheumatoid arthritis according to disease duration: a systematic literature review and meta-analysis
Authors: F Banal, M Dougados, C Combescure, L Gossec
Journal: Annals of the Rheumatic Diseases (2008)

To evaluate the ability of the widely used ACR set of criteria (both list and tree format) to diagnose RA compared with expert opinion according to disease duration.A systematic literature review was conducted in PubMed and Embase databases. All articles reporting the prevalence of RA according to ACR criteria and expert opinion in cohorts of early (<1 year duration) or established (>1 year) arthritis were analysed to calculate the sensitivity and specificity of ACR 1987 criteria against the "gold standard" (expert opinion). A meta-analysis using a summary receiver operating characteristic (SROC) curve was performed and pooled sensitivity and specificity were calculated with confidence intervals.Of 138 publications initially identified, 19 were analysable (total 7438 patients, 3883 RA). In early arthritis, pooled sensitivity and specificity of the ACR set of criteria were 77% (68% to 84%) and 77% (68% to 84%) in the list format versus 80% (72% to 88%) and 33% (24% to 43%) in the tree format. In established arthritis, sensitivity and specificity were respectively 79% (71% to 85%) and 90% (84% to 94%) versus 80% (71% to 85%) and 93% (86% to 97%). The SROC meta-analysis confirmed the statistically significant differences, suggesting that diagnostic performances of ACR list criteria are better in established arthritis.The specificity of ACR 1987 criteria in early RA is low, and these criteria should not be used as diagnostic tools. Sensitivity and specificity in established RA are higher, which reflects their use as classification criteria gold standard.
Bronchoalveolar Lavage Cells and Proteins in Patients with the Acquired Immunodeficiency Syndrome
Authors: Young Kr, Rankin Ja, Naegel Gp, Paul Es, Reynolds Hy
Journal: Annals of Internal Medicine (1985)

Several components of cellular and humoral immunity were examined in bronchoalveolar lavage fluid and blood of 15 patients with the acquired immunodeficiency syndrome, and the results were compared to data from 25 healthy controls (including 5 asymptomatic homosexual men). Compared with that of controls, bronchoalveolar lavage fluid from patients tended to have more lymphocytes and significantly more neutrophils; a lower OKT4/OKT8 ratio, due to an increase in total OKT8 cells; and normal total OKT4 cell counts, despite a significant decrease in numbers of OKT4 cells in peripheral blood. Patients also had significantly more IgG-releasing cells and higher IgG levels than controls in lavage fluid. These data show that, in the lung lining fluid of patients with the acquired immunodeficiency syndrome, significant alterations in cellular and humoral immunity exist that differ in several important respects from immunity in controls and from corresponding changes in patients' peripheral blood.
Phylogenetically related, clinically different: human papillomaviruses 6 and 11 variants distribution in genital warts and in laryngeal papillomatosis
Authors: J.M. Godínez, S. Nicolás-Párraga, V.N. Pimenoff, B. Mengual-Chuliá, N. Muñoz, F.X. Bosch, G.I. Sánchez, J. McCloskey, I.G. Bravo
Journal: Clinical Microbiology and Infection (2013)
Regulation of L-Type Calcium Channel and Delayed Rectifier Potassium Channel Activity by p <sup>21</sup> -Activated Kinase-1 in Guinea Pig Sinoatrial Node Pacemaker Cells
Authors: Yunbo Ke, Ming Lei, Thomas P. Collins, Stevan Rakovic, Paul A.D. Mattick, Michiko Yamasaki, Mark S. Brodie, Derek A. Terrar, R. John Solaro
Journal: Circulation Research (2007)

Phosphorylation of ion channels plays an important role in the regulation of cardiac function, but signaling mechanisms controlling dephosphorylation are not well understood. We have tested the hypothesis that p(21)-activated kinase-1 (Pak1), a serine-threonine protein kinase regulated by Ras-related small G proteins, regulates sinoatrial node (SAN) ion channel activity through a mechanism involving protein phosphatase 2A. We report a novel role of Pak1-mediated signaling in attenuating isoproterenol-induced enhancement of L-type Ca(2+) current (I(CaL)) and delayed rectifier potassium current (I(K)) in guinea pig SAN pacemaker cells. We demonstrate that in guinea pig SAN: (1) there is abundant expression of endogenous Pak1 in pacemaker cells; (2) expression of constitutively active Pak1 depresses isoproterenol-induced upregulation of I(CaL) and I(K); (3) inhibition of protein phosphatase 2A increases the enhancement of I(K) and I(CaL) by isoproterenol in Ad-Pak1-infected cells; (4) protein phosphatase 2A coimmunoprecipitates with endogenous Pak1 in SAN tissue; and (5) expression of constitutively active Pak1 suppresses the chronotropic action of isoproterenol on pacemaker activity of intact SAN preparations. In conclusion, our data demonstrate that a Pak1 signaling pathway exists in cardiac pacemaker cells and that this novel pathway plays a role in the regulation of ion channel activity.
Minor Physical Anomalies, Dermatoglyphic Asymmetries, and Cortisol Levels in Adolescents With Schizotypal Personality Disorder
Authors: Dana Davis Weinstein, Donald Diforio, Jason Schiffman, Elaine Walker, Robert Bonsall
Journal: American Journal of Psychiatry (1999)

A relationship between schizotypal personality disorder and schizophrenia has been documented in behavioral genetic studies, and there are similarities in the cognitive deficits and brain abnormalities associated with these disorders. Adolescents with schizotypal personality disorder are of particular interest because the postpubertal period is a critical one for the development of a DSM axis I disorder. It is likely that some schizotypal adolescents will remain stable over time, some will improve, and a subgroup will develop schizophrenia. This study tested the hypotheses that, like schizophrenic patients, schizotypal adolescents manifest an elevated rate of minor physical and dermatoglyphic anomalies, both of which suggest prenatal neurodevelopmental abnormalities. Cortisol release is also of interest because of evidence that the hypothalamic-pituitary-adrenal axis may influence the behavioral expression of vulnerability to schizophrenia.Minor physical anomalies, dermatoglyphic asymmetries, and salivary cortisol levels were measured in three groups of adolescents: 20 with schizotypal personality disorder, 20 with other personality disorders, and 26 with no disorder. Assessments began at noon, and four saliva samples were obtained at hourly intervals.The schizotypal personality disorder group showed more minor physical anomalies and dermatoglyphic asymmetries than the normal comparison group and higher cortisol levels than both of the other groups. Group differences in cortisol level were most pronounced at the beginning of the evaluation. Cortisol level and age were positively correlated.The findings support the assumption that schizotypal personality disorder is associated with perturbations in fetal neurodevelopment and, under some circumstances, a heightened cortisol response.
Phase Ib study of weekly mammalian target of rapamycin inhibitor ridaforolimus (AP23573; MK-8669) with weekly paclitaxel
Authors: C. Sessa, D. Tosi, L. Viganò, J. Albanell, D. Hess, M. Maur, S. Cresta, A. Locatelli, R. Angst, F. Rojo, N. Coceani, V.M. Rivera, L. Berk, F. Haluska, L. Gianni
Journal: Annals of Oncology (2009)
Presymptomatic differences in Toll-like receptor function in infants who have allergy
Authors: Susan L. Prescott, Paul Noakes, Bonita W.Y. Chow, Liza Breckler, Catherine A. Thornton, Elysia M. Hollams, May Ali, Anita H.J. van den Biggelaar, Meri K. Tulic
Journal: Journal of Allergy and Clinical Immunology (2008)
Molecular imaging of gliomas with PET: Opportunities and limitations
Authors: C. la Fougere, B. Suchorska, P. Bartenstein, F.-W. Kreth, J.-C. Tonn
Journal: Neuro-Oncology (2011)

Neuroimaging enables the noninvasive evaluation of glioma and is considered to be one of the key factors for individualized therapy and patient management, since accurate diagnosis and demarcation of viable tumor tissue is required for treatment planning as well as assessment of treatment response. Conventional imaging techniques like MRI and CT reveal morphological information but are of limited value for the assessment of more specific and reproducible information about biology and activity of the tumor. Molecular imaging with PET is increasingly implemented in neuro-oncology, since it provides additional metabolic information of the tumor, both for patient management as well as for evaluation of newly developed therapeutics. Different molecular processes have been proposed to be useful, like glucose consumption, expression of amino acid transporters, proliferation rate, membrane biosynthesis, and hypoxia. Thus, PET might help neuro-oncologists gain further insights into tumor biology by "true molecular imaging" as well as understand treatment-related phenomena. This review describes the method of PET acquisition as well as the tracers used to image biological processes in gliomas. Furthermore, it considers the clinical impact of PET on the use of currently available radiotracers, which were shown to be potentially valuable for discrimination between neoplastic and nonneoplastic tissue, as well as on tumor grading, determinination of treatment response, and providing an outlook toward further developments.
Endocrinopathy and Spastic Paraplegia
Authors: FUMITOSHI SHIOMI
Journal: Annals of Internal Medicine (1979)

Letters1 February 1979Endocrinopathy and Spastic ParaplegiaFUMITOSHI SHIOMI, M.D.FUMITOSHI SHIOMI, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-90-2-280_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I read with interest "Abnormal Function of Endocrine Pancreas and Anterior Pituitary in Friedreich's Ataxia" (1). The neurodegenerative system disorders are occasionally accompanied by endocrinopathies (2, 3), but the participation of hypothalamus had not been established clearly.Recently, we studied another example of the association of motor disturbance and endocrinopathies. Our patients were three siblings 30, 28, and 25 years old with dwarfism, hypogonadism, spastic paraplegia, atypical retinal degeneration, and mental retardation. They were not obese and had no digital anomaly. These physical abnormalities are consistent with the Laurence-Moon syndrome (4) or Laurence-Moon-Hutchinson syndrome (5). The sella...References1. BIRDTURNERSUMIBIERMAN TJSE: Abnormal function of endocrine pancreas and anterior pituitary in Friedreich's ataxia. Studies in a family. Ann Intern Med 88:478-481, 1978 LinkGoogle Scholar2. LAURENCEMOON JR: Four cases of "retinitis pigmentosa" occurring in the same family, and accompanied by general imperfections of development. Ophthalmol Rev 2:32-41, 1966 Google Scholar3. KAPUSCINSKI W: Ueber familiäre Adelhautentartung mit ataktischen Störungen. Ber Dtsch Ophthalmol Ges 50:13-19, 1934 Google Scholar4. MCKUSICK V: Mendelian Inheritance in Man. Catalogs of Autosomal Dominant, Autosomal Recessive, and X-Linked Phenotypes. Baltimore and London, the Johns Hopkins University Press, 1975 Google Scholar5. FRANCESCHETTIKLEIN AD: Les manifestations tapétorétiniennes et leur importance clinique et génétique. Rev Otoneuroophtalmol 20:109-128, 1948 Google Scholar6. FERRIERSTONE PE: Familial pituitary dwarfism. Pediatrics 43:858-865, 1969 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: FUMITOSHI SHIOMI, M.D.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1979Volume 90, Issue 2Page: 280-280KeywordsAtaxiaHypogonadismHypothalamusIntellectual disabilityOverweightPancreasParaplegia ePublished: 1 December 2008 Issue Published: 1 February 1979 PDF downloadLoading ...
The proliferation of cells in the dermal infiltrate of lichen planus lesions
Authors: J.‐M. Lachapelle, M. Brassinne
Journal: British Journal of Dermatology (2006)

The proliferation of mononuclcar cells infiltrating the dermis in lichen planus lesions was studied in five untreated patients. A biopsy of a lesion was made in each patient. Thin slices of the specimens were incubated for 60 min in the presence of 3H thymidine (3HT), fixed and radioautographed. The mean value of the 3HT labelling index (±SE) was 2.87±0.14%. This labelling index (LI) is relatively high; it is not statistically different from the LI encountered in the dermal infiltrate of allergic contact dermatitis (P>0.45), but is three to four times higher than in psoriasis or irritant dermatitis. The proliferative cells are most probably lymphoblasts. A biopsy of another lichen planus lesion was made in two of the five patients 60 min after a local injection of 10 μCi of 3HT. Imprints of lesions were treated histochemically for Naphthol AS-D acetate esterase(s) identification, a useful method for distinguishing monocytes (many cytoplasmic granules) and lymphocytes (few if any granules). The imprints were then radioautographed. No 3HT-labelled cells contained more than one or two cytoplasmic granules, which suggests that they are of lymphocytic origin. The biological significance of this lymphoblastic proliferation still remains hypothetical.
Her-2/neu Expression in Prostate Cancer
Authors: Joan Carles, Josep Lloreta, Marta Salido, Albert Font, Marta Suarez, Veronica Baena, Miquel Nogue, Montserrat Domenech, Xavier Fabregat
Journal: Clinical Cancer Research (2004)

The clinical effects of targeting Her-2/neu in prostate carcinoma are not known. This study explores the feasibility of molecular profiling to determine the correlation between Her-2/neu expression and hormonal sensitivity. Patients with progressive androgen-independent prostate carcinoma were eligible to participate in the study. Her-2/neu expression was assessed on pretreatment tissue specimens and on bone marrow obtained in progressive androgen-independent disease. Her-2/neu expression was evaluated by immunohistochemistry and by fluorescence in situ hybridization in a consecutive series of 26 progressive androgen-independent prostate cancer patients. Twenty four bone marrow biopsy specimens and 16 prostate biopsies from 26 patients were analyzed. These biopsies were categorized by androgen sensitivity at the time of the biopsy. In total, 90% of specimens from bone marrow were Her-2/neu positive, and 10% of the specimens were Her-2/neu negative. Of the prostate biopsies, all were from patients with androgen-dependent disease. Three of 13 androgen-dependent prostate biopsies (23%) overexpressed Her-2/neu. Of the 10 tumor samples analyzed by fluorescence in situ hybridization, genomic amplification of the Her-2/neu locus was not detected in any of the metastatic prostate tumors. Her-2/neu expression varies with the clinical state of patients with prostate carcinoma: Accurate Her-2/neu profiling requires sampling metastatic tissue in patients with metastatic disease. Her-2/neu sampling from metastatic prostate carcinoma is not feasible until more reliable and practical methods can be developed.
Experts question government delays in improving end of life care
Authors: A. O'Dowd
Journal: BMJ (2010)

National efforts to improve care at the end of life should be speeded up to maintain the progress made in some parts of England, it has been claimed.

The health policy think tank the King’s Fund has warned against a loss of momentum on England’s end of life care programme in a new report published this week and has questioned the government’s intention to leave a review of this area until 2013.

Around 500 000 people die each year in England. More than half (55%) of deaths occur in hospital and only 20% at home. The government has said that several surveys have shown that most people’s preference is to die at home.

The government announced on 18 October in its consultation …
Cytochrome P450 Genetic Polymorphisms and the Response to Prasugrel
Authors: Jessica L. Mega, Sandra L. Close, Stephen D. Wiviott, Lei Shen, Richard D. Hockett, John T. Brandt, Joseph R. Walker, Elliott M. Antman, William L. Macias, Eugene Braunwald, Marc S. Sabatine
Journal: Circulation (2009)

Background— Both clopidogrel and prasugrel require biotransformation to active metabolites by cytochrome P450 (CYP) enzymes. Among persons treated with clopidogrel, carriers of reduced-function CYP2C19 alleles have significantly lower levels of active metabolite, diminished platelet inhibition, and higher rates of adverse cardiovascular events. The effect of CYP polymorphisms on the clinical outcomes in patients treated with prasugrel remains unknown. Methods and Results— The associations between functional variants in CYP genes, plasma concentrations of active drug metabolite, and platelet inhibition in response to prasugrel were tested in 238 healthy subjects. We then examined the association of these genetic variants with cardiovascular outcomes in a cohort of 1466 patients with acute coronary syndromes allocated to treatment with prasugrel in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38 trial. Among the healthy subjects, no significant attenuation of the pharmacokinetic or the pharmacodynamic response to prasugrel was observed in carriers versus noncarriers of at least 1 reduced-function allele for any of the CYP genes tested ( CYP2C19 , CYP2C9 , CYP2B6 , CYP3A5 , and CYP1A2 ). Consistent with these findings, in subjects with acute coronary syndromes treated with prasugrel, no significant associations were found between any of the tested CYP genotypes and risk of cardiovascular death, myocardial infarction, or stroke. Conclusions— Common functional CYP genetic variants do not affect active drug metabolite levels, inhibition of platelet aggregation, or clinical cardiovascular event rates in persons treated with prasugrel. These pharmacogenetic findings are in contrast to observations with clopidogrel, which may explain, in part, the different pharmacological and clinical responses to the 2 medications.
Effects of oral salt loading on beta-adrenergic receptor responsiveness in normal and hypertensive subjects
Authors: M. VOLPE, B. TRIMARCO, B. RICCIARDELLI, L. SACCA, B. UNGARO, F. RENGO, M. CONDORELLI
Journal: Cardiovascular Research (1982)

The effect of oral salt loading (400 mmol per day of NaCl for 7 days) on cardiac and pancreatic beta-receptor responsiveness has been evaluated in 12 patients with established essential hypertension and in seven age-matched control subjects. Cardiac beta-receptor responsiveness was evaluated by assessing the dose of isoprenaline which increased a stable heart rate by 25% (chronotropic dose 25%, CD 25%). Pancreatic beta-receptor responsiveness was measured by the incremental areas of insulin secretion induced by iv infusion of increasing amounts of isoprenaline. Before salt load, CD 25% was significantly higher in hypertensives compared with controls (7.84 +/- 1.34 micrograms vs 3.9 +/- 0.48 micrograms, P less than 0.05) while there was no difference in the isoprenaline-induced insulin secretion between the two groups of subjects. After salt loading, CD 25% was significantly reduced in hypertensive patients but was not modified in normal subjects. Therefore, the difference in CD 25% was no longer detectable between the two groups (5.5 +/- 1.42 micrograms vs 3.2 +/- 0.48 micrograms in normal subjects and in hypertensives, respectively, NS). Furthermore, salt loading failed to induce any change in isoprenaline-induced insulin secretion in either groups. These results support the existence of a relationship between sodium intake and adrenergic beta-receptor responsiveness in human hypertension.
A comparison of latex slide tests for rheumatoid factors.
Authors: D J Lea, D J Ward
Journal: Annals of the Rheumatic Diseases (1972)

OBJECTIVE--To determine the prognosis in patients with diphtherial myocarditis and bradyarrhythmias and to assess the results of ventricular pacing in those with third degree atrioventricular block. DESIGN--Case series. SETTING--Referral department of cardiology in a teaching hospital. PATIENTS--Twenty four out of 46 patients admitted with diphtherial myocarditis over 10 years had bradyarrhythmias. Six had sinus bradycardia, 15 atrioventricular or intraventricular conduction disturbances, and three atrioventricular dissociation. MAIN OUTCOME MEASURE--Death rate. RESULTS--Eleven patients died (46%): all seven patients with third degree atrioventricular block, the patient with bifascicular block, and three of the six patients with bundle branch block. Seven died of cardiogenic shock and four of ventricular fibrillation. All nine patients with sinus bradycardia or atrioventricular dissociation survived. CONCLUSION--Conduction system disturbances in patients with diphtherial myocarditis are markers of severe myocardial damage and a poor prognosis. In addition, ventricular pacing does not improve survival.