tbuckley/cabot-search huggingface dataset:
Relationship of bacterial and viral infections to exacerbations of asthma.
Authors: C W Clarke
Journal: Thorax (1979)

Fifty-one asthmatic patients were followed for up to 18 months. During this time 111 exacerbations of wheeze were recorded. Involvement by pathogenic respiratory bacteria and viruses was looked for directly by culture and indirectly by antibody studies. Proof of infection was found in only 12 (10.8%) of the 111 exacerbations. Only eight patients provided sputum samples. Potential bacterial pathogens were found in four. Viruses were isolated in four of 27 exacerbation specimens; significant rises in specific viral antibody titres occurred in three. Six patients developed precipitating antibody to respiratory bacteria over the study but only one in relation to an exacerbation. The study therefore indicated that the great majority of exacerbations of asthma in these patients were not due to respiratory tract infection.
Feedback Regulation of Cholesterol Biosynthesis
Authors: LAWRENCE W. WHITE
Journal: Circulation Research (1972)

Regulation of hepatic cholesterol biosynthesis is thought to occur at the step involving formation of mevalonate from 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA); this reaction is catalyzed by HMG-CoA reductase. Oral administration of cholestyramine, an agent that interferes with cholesterol reabsorption and is associated with a compensatory increase in hepatic cholesterol synthesis, was used to evaluate feedback regulation of cholesterol biosynthesis. Liver slices and cell-free fractions were prepared from control rats and rats fed 3% cholestyramine for 3-7 days. Cholestyramine feeding was associated with a four- to eightfold increase in incorporation of [ 14 C]acetate into cholesterol and mevalonate. However, there was no effect on incorporation of [ 14 C]acetate into CO 2 , fatty acids, or acetoacetate or on incorporation of [ 14 C]mevalonate into cholesterol, indicating stimulation at an early regulatory site prior to mevalonate formation. In fractionated liver homogenates, incorporation of [ 14 C] acetate, [ 14 C]acetyl-CoA, and [ 14 C]HMG-CoA into mevalonate increased markedly following cholestyramine administration. In the absence of microsomes, incorporation of [ 14 C]acetate and [ 14 C]acetyl-CoA into HMG was also increased. Changes in incorporation of [ 14 C]acetate into HMG, mevalonate, and cholesterol corresponded to changes in product synthesis. I concluded that (1) interruption of the enterohepatic circulation of cholesterol causes a release of feedback inhibition of cholesterol synthesis, (2) mevalonate synthesis catalyzed by HMG-CoA condensing enzyme and HMG-CoA reductase, and (3) HMG-CoA condensing enzyme, by limiting the availability of HMG-CoA, may have an important regulatory function in cholesterol biosynthesis.
Case-Control Study of the D2 Dopamine Receptor Gene and Smoking Status in Lung Cancer Patients
Authors: Margaret R. Spitz, Huihui Shi, Fang Yang, Karen Suchanek Hudmon, Hong Jiang, Robert M. Chamberlain, Christopher I. Amos, Ying Wan, Xifeng Wu, Paul Cinciripini, Waun K. Hong
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Interindividual differences in the structure and expression of the dopamine receptor genes affect dopamine availability and may be the genetic basis for variation in vulnerability to tobacco smoking. In this study, prevalences of polymorphisms in the TaqIA allele (A1 and A2) and the TaqIB allele (B1 and B2) of the D2 dopamine receptor gene in 157 lung cancer case patients and 126 control subjects were determined to assess whether individuals homozygous or heterozygous for the less common A1 and B1 alleles are more vulnerable to nicotine addiction. Methods: Case and control subjects were accrued from an ongoing epidemiologic study. Blood samples were collected from them and subjected to molecular genetic analyses. Subjects were interviewed to obtain relevant information. Current and former smokers were administered a questionnaire to quantify their addiction to nicotine. Results: The combined B1B2 genotypes appeared to be more prevalent in ever smokers than in never smokers among case patients (30.3% versus 13.3%; two-sided P = .233) and among control subjects (30.9% and 0%; two-sided P = .02); statistically significant differences were not observed among those with A1 genotypes. Statistically significant correlations between the presence of the A1 and B1 alleles were observed (r = .73 for case subjects and r = .76 for control subjects; two-sided P<.001). Individuals with rarer genotypes reported having been substantially younger at the time of smoking initiation (statistically significant for both A1 and B1) and having attempted to quit smoking fewer times (statistically significant for only A1). Conclusion: Variant alleles of the D2 dopamine receptor gene may play a role in determining nicotine addiction, although the associations between the at-risk genotypes and measures of nicotine addiction were not entirely consistent.
Reduction of hepatitis B surface antigen levels and hepatitis B surface antigen seroclearance in chronic hepatitis B patients receiving 10 years of nucleoside analogue therapy
Authors: Wai-Kay Seto, Danny Ka-Ho Wong, James Fung, Fung-Yu Huang, Ching-Lung Lai, Man-Fung Yuen
Journal: Hepatology (2013)

The profile and clinical significance of serum hepatitis B surface antigen (HBsAg) levels during long-term nucleoside analogue (NA) therapy in chronic hepatitis B (CHB) is undetermined. From 1994 to 2002, 322 Chinese CHB patients were started on lamivudine in our center. Patients were recruited if they were continuously treated with lamivudine for at least 10 years and maintained favorable virologic responses throughout therapy (HBV DNA <2,000 IU/mL). HBsAg and HBV DNA levels were measured serially, and the predictability of HBsAg kinetics in determining NA-related HBsAg seroclearance was determined. Seventy patients were recruited, of which 43 (61.4%) were hepatitis B e antigen (HBeAg)-positive. Fifty-two (74.3%) patients had undetectable viremia (HBV DNA <20 IU/mL) during therapy. Fifteen (21.4%) patients were followed up for 15 years. The median rate of HBsAg reduction was 0.104 log IU/mL/year, with no significant difference found when comparing patients who were HBeAg-positive versus HBeAg-negative, were genotype B versus C, and had detectable versus undetectable viremia during therapy (all P > 0.05). Seven (10%) patients achieved HBsAg seroclearance, and when compared with the remaining 63 patients, had significantly lower median baseline HBsAg levels (P = 0.012) and a greater median rate of HBsAg reduction (P < 0.001). Baseline HBsAg levels and the rate of HBsAg reduction achieved an area under the receiver operating characteristic curve of 0.860 (P = 0.004; 95% confidence interval [CI], 0.742-0.978) and 0.794 (P = 0.018; 95% CI, 0.608-0.979), respectively. Baseline HBsAg <1,000 IU/mL and on-treatment reduction of HBsAg >0.166 log IU/mL/year were optimal cutoff levels in predicting subsequent HBsAg seroclearance (negative predictive values, 98.1% and 97.8%, respectively).Low baseline HBsAg levels and greater rate of HBsAg reduction achieved high predictive values for predicting HBsAg seroclearance, strengthening the prognostic role of HBsAg measurements during NA therapy.
Dysfunctional Transforming Growth Factor-β Receptor II Accelerates Prostate Tumorigenesis in the TRAMP Mouse Model
Authors: Hong Pu, Joanne Collazo, Elisabeth Jones, Dustin Gayheart, Shinichi Sakamoto, Adam Vogt, Bonnie Mitchell, Natasha Kyprianou
Journal: Cancer Research (2009)

The contribution of a dysfunctional transforming growth factor-beta type II receptor (TGF beta RII) to prostate cancer initiation and progression was investigated in an in vivo mouse model. Transgenic mice harboring the dominant-negative mutant TGF-beta type II receptor (DNTGF beta RII) in mouse epithelial cell were crossed with the TRAMP prostate cancer transgenic mouse to characterize the in vivo consequences of inactivated TGF-beta signaling on prostate tumor initiation and progression. Histopathologic diagnosis of prostate specimens from the TRAMP+/DNTGF beta RII double transgenic mice revealed the appearance of early malignant changes and subsequently highly aggressive prostate tumors at a younger age, compared with littermates TRAMP+/Wt TGF beta RII mice. Immunohistochemical and Western blotting analysis revealed significantly increased proliferative and apoptotic activities, as well as vascularity and macrophage infiltration that correlated with an elevated vascular endothelial growth factor and MCP-1 protein levels in prostates from TRAMP+/DNTGF beta RII+ mice. An epithelial-mesenchymal transition (EMT) effect was also detected in prostates of TRAMP+/DNTGF beta RII mice, as documented by the loss of epithelial markers (E-cadherin and beta-catenin) and up-regulation of mesenchymal markers (N-cadherin) and EMT-transcription factor Snail. A significant increase in the androgen receptor mRNA and protein levels was associated with the early onset of prostate tumorigenesis in TRAMP+/DNTGF beta RII mice. Our results indicate that in vivo disruption of TGF-beta signaling accelerates the pathologic malignant changes in the prostate by altering the kinetics of prostate growth and inducing EMT. The study also suggests that a dysfunctional TGF beta RII augments androgen receptor expression and promotes inflammation in early stage tumor growth, thus conferring a significant contribution by TGF-beta to prostate cancer progression.
Assessment of disability and quality of life in elderly patients with heart failure: data from the IN‐CHF — Nursing Study
Authors: D. Del Sindaco, G. Pulignano, A.P. Maggioni, M.C. Barbieri, M.A. Semproli, R. Betti, B. Albanese, A. Di Cunzolo, A. Ponzetta, C. Opasich
Journal: European Journal of Heart Failure (2000)
Lower Risk of Cancer in Patients on Metformin in Comparison With Those on Sulfonylurea Derivatives
Authors: Rikje Ruiter, Loes E. Visser, Myrthe P.P. van Herk-Sukel, Jan-Willem W. Coebergh, Harm R. Haak, Petronella H. Geelhoed-Duijvestijn, Sabine M.J.M. Straus, Ron M.C. Herings, Bruno H.Ch. Stricker
Journal: Diabetes Care (2011)

Numerous studies have suggested a decreased risk of cancer in patients with diabetes on metformin. Because different comparison groups were used, the effect magnitude is difficult to estimate. Therefore, the objective of this study was to further analyze whether, and to what extent, use of metformin is associated with a decreased risk of cancer in a cohort of incident users of metformin compared with users of sulfonylurea derivatives.Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. The association between the risk of cancer in those using metformin compared with those using sulfonylurea derivatives was analyzed using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant.Use of metformin was associated with a lower risk of cancer in general (hazard ratio 0.90 [95% CI 0.88-0.91]) compared with use of sulfonylurea derivatives. When specific cancers were used as end points, similar estimates were found. Dosage-response relations were identified for users of metformin but not for users of sulfonylurea derivatives.In our study, cumulative exposure to metformin was associated with a lower risk of specific cancers and cancer in general, compared with cumulative exposure to sulfonylurea derivatives. However, whether this should indeed be seen as a decreased risk of cancer for the use of metformin or as an increased risk of cancer for the use sulfonylurea derivatives remains to be elucidated.
Pig Domestication and Human-Mediated Dispersal in Western Eurasia Revealed through Ancient DNA and Geometric Morphometrics
Authors: Claudio Ottoni, Linus Girdland Flink, Allowen Evin, Christina Geörg, Bea De Cupere, Wim Van Neer, László Bartosiewicz, Anna Linderholm, Ross Barnett, Joris Peters, Ronny Decorte, Marc Waelkens, Nancy Vanderheyden, François-Xavier Ricaut, Canan Çakırlar, Özlem Çevik, A. Rus Hoelzel, Marjan Mashkour, Azadeh Fatemeh Mohaseb Karimlu, Shiva Sheikhi Seno, Julie Daujat, Fiona Brock, Ron Pinhasi, Hitomi Hongo, Miguel Perez-Enciso, Morten Rasmussen, Laurent Frantz, Hendrik-Jan Megens, Richard Crooijmans, Martien Groenen, Benjamin Arbuckle, Nobert Benecke, Una Strand Vidarsdottir, Joachim Burger, Thomas Cucchi, Keith Dobney, Greger Larson
Journal: Molecular Biology and Evolution (2012)

Zooarcheological evidence suggests that pigs were domesticated in Southwest Asia ∼8,500 BC. They then spread across the Middle and Near East and westward into Europe alongside early agriculturalists. European pigs were either domesticated independently or more likely appeared so as a result of admixture between introduced pigs and European wild boar. As a result, European wild boar mtDNA lineages replaced Near Eastern/Anatolian mtDNA signatures in Europe and subsequently replaced indigenous domestic pig lineages in Anatolia. The specific details of these processes, however, remain unknown. To address questions related to early pig domestication, dispersal, and turnover in the Near East, we analyzed ancient mitochondrial DNA and dental geometric morphometric variation in 393 ancient pig specimens representing 48 archeological sites (from the Pre-Pottery Neolithic to the Medieval period) from Armenia, Cyprus, Georgia, Iran, Syria, and Turkey. Our results reveal the first genetic signatures of early domestic pigs in the Near Eastern Neolithic core zone. We also demonstrate that these early pigs differed genetically from those in western Anatolia that were introduced to Europe during the Neolithic expansion. In addition, we present a significantly more refined chronology for the introduction of European domestic pigs into Asia Minor that took place during the Bronze Age, at least 900 years earlier than previously detected. By the 5th century AD, European signatures completely replaced the endemic lineages possibly coinciding with the widespread demographic and societal changes that occurred during the Anatolian Bronze and Iron Ages.
Subcutaneous Haemorrhages in Rheumatoid Patients treated with Prednisone
Authors: G. M. Nashelsky, C. J. Smyth
Journal: Annals of the Rheumatic Diseases (1958)

The occurrence of these ecchymotic lesions has usually been listed among the other side-effects of therapy with these newer steroid substances.Boland (1956) reported that 24 of seventy patients (34 per cent.)receiving prednisone and prednisolone developed subcutaneous haemorrhages, but the report by Denko and Schroeder (1957) is the only detailed study of this toxic manifestation to these steroids.They observed a 20 per cent.incidence of purpuric lesions in a series of 75 patients who received these drugs.Similar lesions were previous- ly observed in patients receiving the original or older steroid preparations (cortisone, hydrocortisone, and corticotropin); however, it has been our experience that this bleeding tendency has appeared with increased frequency since the introduction of the so-called delta-l or meta drugs.The purpose of this report is to call attention to these purpuric lesions and to summarize some studies that have been carried out in an effort to explain the mechan- ism of their production. Clinical ObservationsIn the past 12 months, 44 patients under treatment for rheumatoid arthritis at the Arthritis Clinic of the University of Colorado Medical Centre have been observed who developed superficial haemorrhagic
Discovery of novel transcripts and gametophytic functions via RNA-seq analysis of maize gametophytic transcriptomes
Authors: Antony M Chettoor, Scott A Givan, Rex A Cole, Clayton T Coker, Erica Unger-Wallace, Zuzana Vejlupkova, Erik Vollbrecht, John E Fowler, Matthew MS Evans
Journal: Genome biology (2014)

Abstract Background Plant gametophytes play central roles in sexual reproduction. A hallmark of the plant life cycle is that gene expression is required in the haploid gametophytes. Consequently, many mutant phenotypes are expressed in this phase. Results We perform a quantitative RNA-seq analysis of embryo sacs, comparator ovules with the embryo sacs removed, mature pollen, and seedlings to assist the identification of gametophyte functions in maize. Expression levels were determined for annotated genes in both gametophytes, and novel transcripts were identified from de novo assembly of RNA-seq reads. Transposon-related transcripts are present in high levels in both gametophytes, suggesting a connection between gamete production and transposon expression in maize not previously identified in any female gametophytes. Two classes of small signaling proteins and several transcription factor gene families are enriched in gametophyte transcriptomes. Expression patterns of maize genes with duplicates in subgenome 1 and subgenome 2 indicate that pollen-expressed genes in subgenome 2 are retained at a higher rate than subgenome 2 genes with other expression patterns. Analysis of available insertion mutant collections shows a statistically significant deficit in insertions in gametophyte-expressed genes. Conclusions This analysis, the first RNA-seq study to compare both gametophytes in a monocot, identifies maize gametophyte functions, gametophyte expression of transposon-related sequences, and unannotated, novel transcripts. Reduced recovery of mutations in gametophyte-expressed genes is supporting evidence for their function in the gametophytes. Expression patterns of extant, duplicated maize genes reveals that selective pressures based on male gametophytic function have likely had a disproportionate effect on plant genomes.
A 3-D model-based registration approach for the PET, MR and MCG cardiac data fusion
Authors: Timo Mäkelä, Quoc Cuong Pham, Patrick Clarysse, Jukka Nenonen, Jyrki Lötjönen, Outi Sipilä, Helena Hänninen, Kirsi Lauerma, Juhani Knuuti, Toivo Katila, Isabelle E. Magnin
Journal: Medical Image Analysis (2003)
Pulmonary hypertension associated with benfluorex exposure
Authors: Laurent Savale, Marie-Camille Chaumais, Vincent Cottin, Emmanuel Bergot, Irène Frachon, Grégoire Prevot, Christophe Pison, Claire Dromer, Patrice Poubeau, Nicolas Lamblin, Gilbert Habib, Martine Reynaud-Gaubert, Arnaud Bourdin, Olivier Sanchez, Pascale Tubert-Bitter, Xavier Jaïs, David Montani, Olivier Sitbon, Gérald Simonneau, Marc Humbert
Journal: European Respiratory Journal (2012)

Benfluorex was marketed in France until 2009, despite its similar pharmacological properties with fenfluramine and its derivatives known to be a cause of pulmonary arterial hypertension (PAH). The aim of this study is to report clinical and haemodynamic characteristics for patients suffering from pulmonary hypertension (PH) associated with benfluorex exposure that had been identified by the French PAH Network. 85 cases of PH associated with benfluorex exposure were identified by the French PAH Network from June 1999 to March 2011. Of these, 70 patients had confirmed pre-capillary PH. The median duration of exposure was 30 months, with a median of 108 months between start of exposure and diagnosis of the pulmonary vascular disease. 33% of all patients also had prior exposure to fenfluramine or dexfenfluramine, and an additional risk factor for PH was identified in 20 (30%) out of 70 patients with pre-capillary PH. A quarter of patients in this current series showed coexisting PH and mild-to-moderate cardiac valve involvement. The results of our study, together with the accumulated data regarding the known toxic effects of fenfluramine and dexfenfluramine, strongly suggest that benfluorex exposure is a potent trigger for PAH.
Serologic monitoring of disease and treatment in a patient with pulmonary aspergilloma.
Authors: J F Tomee, T S van der Werf, J P Latge, G H Koeter, A E Dubois, H F Kauffman
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Disease progression and efficacy of fungistatic treatment in pulmonary aspergilloma (PA) are difficult to monitor. The usefulness of chest tomography, IgG-ELISA serology, double immunodiffusion, and IgG-immunoblotting was assessed in monitoring disease progression and efficacy of itraconazole treatment during a 9-yr follow-up of a patient with two exacerbations of PA. A rise in IgG-ELISA titer coincided with a recrudescence of clinical symptoms, whereas a decrease after treatment paralleled clinical improvement. IgG-binding to a 32-kD serine protease and to 60- and 94-kD proteins produced with collagen-containing culture medium closely corresponded with IgG-ELISA titers. IgG-binding to a 40-kD metalloprotease remained at very low levels until symptoms and fungal growth became well advanced, when a sharp rise was seen. Responses to all antigens rapidly diminished after the start of successful treatment with itraconazole. Serology may be a useful adjunct in the monitoring of disease progression and the efficacy of itraconazole treatment in patients with PA. IgG-binding to individual fungal proteins shows subtle differences in kinetics. Immunologic responses to fungal proteases raised with collagen-containing culture media may reflect fungal proteolytic involvement during disease progression and treatment more closely than responses to proteins raised with conventional media.
Human keratin diseases: the increasing spectrum of disease and subtlety of the phenotype-genotype correlation
Authors: A D Irvine, W H I Mclean
Journal: British Journal of Dermatology (1999)

Keratins are obligate heterodimer proteins that form the intermediate filament cytoskeleton of all epithelial cells. Keratins are tissue and differentiation specific and are expressed in pairs of types I and II proteins. The spectrum of inherited human keratin diseases has steadily increased since the causative role of mutations in the basal keratinocyte keratins 5 and 14 in epidermolysis bullosa simplex (EBS) was first reported in 1991. At the time of writing, mutations in 15 epithelial keratins and two trichocyte keratins have been associated with human diseases which include EBS, bullous congenital ichthyosiform erythroderma, epidermolytic palmoplantar keratoderma, ichthyosis bullosa of Siemens, diffuse and focal non‐epidermolytic palmoplantar keratoderma, pachyonychia congenita and monilethrix. Mutations in extracutaneous keratins have been reported in oral white sponge naevus and Meesmann's corneal dystrophy. New subtleties of phenotype–genotype correlation are emerging within the keratin diseases with widely varying clinical presentations attributable to similar mutations within the same keratin. Mutations in keratin‐associated proteins have recently been reported for the first time. This article reviews clinical, ultrastructural and molecular aspects of all the keratin diseases described to date and delineates potential future areas of research in this field.