tbuckley/cabot-search huggingface dataset:
Reduced serum levels of immunoreactive erythropoietin in patients with cirrhosis and chronic anemia
Authors: Massimo Siciliano, Daniele Tomasello, Alessandro Milani, Bianca Maria Ricerca, Sergio Storti, Lodovico Rossi
Journal: Hepatology (1995)

Chronic anemia is frequently observed in patients affected by cirrhosis. To investigate the possible role of erythropoietin (Epo) in the pathogenesis of anemia in cirrhosis, we measured the immunoreactive Epo levels and the respective hemoglobin (Hb) concentrations in 48 anemic and nonanemic cirrhotic patients and in a control group of healthy subjects and patients with iron-deficiency anemia. Epo concentrations were determined in serum using a sensitive enzyme immunoassay. The regression curve between Epo values and Hb concentrations showed a significant inverse exponential trend both in cirrhotic patients (r = -.55; P < .0001) and controls (r = -.92; P < .0001). In a semilogarithmic plot, the line slope obtained in cirrhotic patients was significantly lower (P < .005) than that of controls, suggesting a blunt Epo response to anemia in cirrhosis. Moreover, covariance analysis showed that the Epo levels for a given degree of anemia were further reduced in the patients with a more severe disease, suggesting a close relation between cirrhosis and the mechanisms involved in the derangement of the Epo feedback system. Finally, the Epo concentrations measured in the cirrhotic patients without anemia did not significantly differ from Epo values obtained in healthy subjects. An impaired Epo response may play a role in maintaining low Hb concentrations in cirrhotic patients with anemia. However, the evidence of a residual Epo response to anemia in cirrhosis and the presence of normal basal Epo levels in nonanemic cirrhotic patients do not support an inadequate Epo secretion as one of the primary causes of anemia in cirrhosis.
P12 Role of Interferon gamma release assay (QuantiFERON-TB Gold In Tube) in blood in the diagnostic work up of active tuberculosis in a high TB prevalence region
Authors: S. Kumar, D. Gupta, I. Verma, S. K. Jindal, R. Agarwal
Journal: Thorax (2011)

<h3>Objective</h3> To study the role of Interferon gamma release assay (IGRA) (QuantiFERON–TB Gold In Tube) in blood in the diagnostic work up of active tuberculosis (TB) in a high TB prevalence region. <h3>Design</h3> Prospective, comparative group study. <h3>Setting</h3> Subjects presenting to the services of the Pulmonary Medicine Department of a large tertiary care teaching hospital in northern India. <h3>Methods</h3> We prospectively enrolled, 30 cases of smear or histopathology proven newly diagnosed tuberculosis (18 pulmonary (PTB) and 12 extra-pulmonary (EPTB)) patients controls along with 30 healthy controls. All cases and controls underwent Tubercular Skin Test (TST) using 0.1 mL (1 tuberculin units) of purified protein derivative RT23 and IGRA using QuantiFERON-TB-Gold In Tube assay (QFT) in blood. For TST an induration ≥10 mm was taken as positive. QFT testing was performed and interpreted as per manufacturer9s (Cellestis) instructions. <h3>Results</h3> We studied 30 patients of active tuberculosis (18 PTB and 12 EPTB) and 30 healthy controls (14 men and 13 women, mean age 35.03±13.23 years). TST positivity had a sensitivity of 83.33% and 66.67% and specificity of 60% for both categories for the diagnosis of active PTB and EPTB respectively. In contrast QFT positivity had a sensitivity of 61.11% and 58.33% and specificity of 50% for the diagnosis of active PTB and EPTB respectively. <h3>Conclusions</h3> In this study the QFT-IGRA had a limited overall usefulness in the diagnosis of active pulmonary and extrapulmonary TB. QFT, thus can neither be taken as rule in nor rule out test in a high TB prevalence region like India. TST with all its limitation probably will continue to serve a useful purpose. Larger prospective studies are needed in high incidence countries to determine the sensitivity and specificity of IGRAs, their ability to serve as useful rule-out test for active TB.
Automatically controlled continuous positive airway pressure. A bright past, a dubious future
Authors: D.O. Rodenstein
Journal: European Respiratory Journal (2000)

Before the scientific medical community became aware that obstructive sleep apnoea was an extremely prevalent disorder, SULLIVAN et al. [1] described what is still the best treatment available for this disorder: continuous positive airway pressure (CPAP) applied through the nose during sleep. The common endpoint of obstructive sleep apnoea, obstructive sleep hypopnoea and upper airway resistance syndrome is an increase in pharyngeal resistance occurring during sleep, leading to increased efficient or inefficient respiratory efforts that usually terminate with an arousal reaction [2]. When respiratory efforts are inefficient, hypoxia and hypercapnia develop during the period of increased pharyngeal resistance until sleep is interrupted, whereas, when respiratory efforts are efficient, hypoxia and hypercapnia are avoided. Nevertheless, the extraordinary effort necessary to sustain ventilation also leads to an arousal reaction [3]. Nasal CPAP acts essentially as a pneumatic splint pushing apart the walls of the pharynx and allowing normal spontaneous ventilation by the patients. In spite of its cumbersome nature, the treatment is so efficient that up to 80% of patients to whom it is proposed accept and comply with treatment for many years [4]. However, side-effects are not uncommon, and some patients discontinue therapy as time goes by. The continuous positive pressure necessary to ensure a good nights sleep varies from patient to patient in an individual and poorly predictable way. This makes the individual titration of pressure necessary. Usually this is done during a full or split polysomnographic night, using a trial and error process in which the pressure is slowly increased until apnoeas, hypopnoeas, snoring, episodes of flow limitation and/or arousals are abolished. Drops in saturation may persist when they are due to obesity in addition to sleep apnoea. In such cases, correction of apnoeas does not completely normalize oxygen saturation during the night. The means of titrating the pressure varies from centre to centre and there is no unique well-accepted way of performing titration. In the early years of CPAP, suppression of apnoeas was the main end-point of titration; hypopnoeas came later, and snoring, flow limitation and arousals were incorporated as targets for abolition in later years [5].
Temporally Regulated and Tissue-Specific Gene Manipulations in the Adult and Embryonic Heart Using a Tamoxifen-Inducible Cre Protein
Authors: Dawinder S. Sohal, Mai Nghiem, Michael A. Crackower, Sandra A. Witt, Thomas R. Kimball, Kevin M. Tymitz, Josef M. Penninger, Jeffery D. Molkentin
Journal: Circulation Research (2001)

Abstract —The advent of conditional and tissue-specific recombination systems in gene-targeted or transgenic mice has permitted an assessment of single gene function in a temporally regulated and cell-specific manner. Here we generated transgenic mice expressing a tamoxifen-inducible Cre recombinase protein fused to two mutant estrogen-receptor ligand-binding domains (MerCreMer) under the control of the α-myosin heavy chain promoter. These transgenic mice were crossed with the ROSA26 lacZ-flox –targeted mice to examine Cre recombinase activity and the fidelity of the system. The data demonstrate essentially no Cre-mediated recombination in the embryonic, neonatal, or adult heart in the absence of inducing agent but &gt;80% recombination after only four tamoxifen injections. Expression of the MerCreMer fusion protein within the adult heart did not affect cardiac performance, cellular architecture, or expression of hypertrophic marker genes, demonstrating that the transgene-encoded protein is relatively innocuous. In summary, MerCreMer transgenic mice represent a tool for temporally regulated inactivation of any loxP-targeted gene within the developing and adult heart or for specifically directing recombination and expression of a loxP-inactivated cardiac transgene in the heart.
<i>N</i>-acetyltransferase 1 and 2 polymorphisms in<i>para</i>-substituted arylamine-induced contact allergy
Authors: G.A. Westphal, K. Reich, T.G. Schulz, C. Neumann, E. Hallier, A. Schnuch
Journal: British Journal of Dermatology (2000)

Abstract Sensitization to arylamines such as p-phenylenediamine is frequently diagnosed in patients with allergic contact dermatitis. Reactive metabolites of p-phenylenediamine might be produced in the skin by O-acetylation of N-hydroxylamines catalysed by local N-acetyltransferases (NATs). In this study, we tested whether genetic polymorphisms of NATs, which are known to affect enzyme activity, may influence the susceptibility to para-substituted arylamine-induced contact eczema. Using polymerase chain reaction and restriction enzyme analysis, the distribution of polymorphisms of NAT1 and NAT2 was investigated in 88 patients sensitized to para-substituted aryl compounds and 123 healthy controls. NAT2 rapid acetylators, i.e. carriers of the NAT2*4 wild-type allele, were more common in the contact allergy (44%) than in the healthy control group [30%; P = 0·042, odds ratio 1·9 (95% confidence interval, CI 1·05–3·27)]. Slow acetylators carrying the NAT2*5b/2*6a genotype were significantly less frequent among patients [13% vs. 38% in controls; P = 0·009, odds ratio 0·39 (95% CI 0·19–0·78)]. The carriage rate of the NAT1*10 allele, which is supposed to encode for a rapid NAT1 phenotype, was not significantly different between patients and controls [43% vs. 36%; odds ratio 1·5 (95% CI 0·88–2·68)]. Interactions between NAT2*4 and NAT1*10 were suggested by the increased frequency of the NAT2*4/NAT1*10 haplotype in patients (27%) compared with controls [15%; P = 0·039, odds ratio 2·1 (95% CI 1·04–4·04)]. As the NAT1 and NAT2 encoding genes are located in close proximity on chromosome 8p22, the latter finding could at least partly be due to genetic linkage. In fact, a linkage disequilibrium between NAT2*4 and NAT1*10 was observed in the contact allergy (P = 0·0025) and in the control group (P = 0·042). Our data indicate an association between the NAT2*4/NAT1*10 haplotype and contact sensitization to para-substituted aryl compounds. Therefore, acetylation may either enhance contact sensitization or NAT2*4 and NAT1*10 might be linked to an unknown susceptibility factor.
A long-term study of threshold values and output characteristics of cardiac pacemakers.
Authors: G G Jaros, P Marchand, M Milner, I W Obel
Journal: Thorax (1967)

<h3>Summary</h3> Eukaryotic genes generate multiple mRNA transcript isoforms though alternative transcription, splicing, and polyadenylation. However, the relationship between human transcript diversity and protein production is complex and not well understood at a global level. We fractionated a polysome profile and reconstructed transcript isoforms from each fraction, which we term Transcript Isoforms in Polysomes sequencing (TrIP-seq). Analysis of these data revealed regulatory features that control ribosome occupancy and the resulting translational output of each transcript isoform. We extracted a panel of 5′ and 3′ untranslated regions that control protein production from an unrelated gene in cells over a 100-fold range. Select 5′ untranslated regions exert robust translational control between cell lines, while 3′ untranslated regions can confer cell-type-specific expression. These results expose the large dynamic range of transcript-isoform-specific translational control, identify isoform-specific sequences that control protein output in human cells, and demonstrate that transcript isoform diversity must be considered when relating RNA and protein levels.
Scleroderma, primary biliary cirrhosis, and Sjogren's syndrome after cosmetic breast augmentation with silicone injection: a case report of possible human adjuvant disease.
Authors: Y Okano, M Nishikai, A Sato
Journal: Annals of the Rheumatic Diseases (1984)

A 52-year-old woman developed scleroderma, primary biliary cirrhosis, and Sjögren9s syndrome after cosmetic silicone injections. These conditions may possibly represent 9human adjuvant disease9.
Prediction of severity of acute pancreatitis: an alternative approach.
Authors: S T Fan, T K Choi, E C Lai, J Wong
Journal: Gut (1989)

Admission laboratory data of 203 patients suffering from acute pancreatitis were analysed to search for a simpler method of prediction of severity than the traditional multifactor prognostic scoring system. By discriminant analysis, admission serum urea and plasma glucose were identified to be factors with independent significance in predicting severity. If the presence of either factor higher than the cutoff point (urea greater than 7.4 mmol/l, glucose greater than 11.0 mmol/l) was considered as an indication of severe disease, then the sensitivity of this method was 75.0%, specificity 80.3% and the accuracy 79.3%. The predictive ability of this method was comparable with the Glasgow multifactor scoring system when the latter was also used to grade severity of our patients. It has the advantage, however, of simplicity and the ability of predicting severity at the time of admission.
Autoimmune Antibodies and Recurrence-Free Interval in Melanoma Patients Treated With Adjuvant Interferon
Authors: Marna G. Bouwhuis, Stefan Suciu, Sandra Collette, Steinar Aamdal, Wim H. Kruit, Lars Bastholt, Ulrika Stierner, François Salès, Poulam Patel, Cornelis J. A. Punt, Micaela Hernberg, Alain Spatz, Timo L. M. ten Hagen, Johan Hansson, Alexander M. M. Eggermont
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundAppearance of autoantibodies and clinical manifestations of autoimmunity in melanoma patients treated with adjuvant interferon (IFN)-α2b was reported to be associated with improved prognosis. We assessed the association of the appearance of autoantibodies after initiation of treatment with recurrence-free interval in two randomized trials that compared intermediate doses of IFN with observation for the treatment of melanoma patients.
Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behçet's disease
Authors: Yun Jong Lee, Yukihiro Horie, Graham R Wallace, Yong Seok Choi, Ji Ah Park, Ji Yong Choi, Ran Song, Young-Mo Kang, Seong Wook Kang, Han Joo Baek, Nobuyoshi Kitaichi, Akira Meguro, Nobuhisa Mizuki, Kenichi Namba, Susumu Ishida, Jinhyun Kim, Edyta Niemczyk, Eun Young Lee, Yeong Wook Song, Shigeaki Ohno, Eun Bong Lee
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To identify non-major histocompatibility complex susceptible genes that might contribute to Behçet9s disease (BD). <h3>Methods</h3> We performed a genome-wide association study using DNA samples from a Korean population consisting of 379 BD patients and 800 controls. A replication study was performed in a Japanese population (363 BD patients and 272 controls). To evaluate the functional implication of the target single nucleotide polymorphisms (SNP), gene expression levels in peripheral T cells, allele-specific modulation of promoter activity and biological effect of mRNA knockdown were investigated. <h3>Results</h3> We found a novel association of BD to the <i>GIMAP</i> locus, mapped to chromosome 7q36.1 (rs1608157, p=6.01×10<sup>−8</sup> in a minor allele dominant model; rs11769828, allele based p=1.60×10<sup>−6</sup>). A fine mapping study identified an association with four additional SNP: rs1522596 (OR=1.45, p=7.70×10<sup>−6</sup>) in <i>GIMAP4</i>; rs10266069 (OR=1.32, p=2.67×10<sup>−4</sup>) and rs10256482 (OR=1.27, p=5.27×10<sup>−4</sup>) in <i>GIMAP2</i>; and rs2286900 (OR=1.61, p=3.53×10<sup>−5</sup>) in <i>GIMAP1</i> areas. Replication study using DNA samples from the Japanese population validated the significant association between BD and the <i>GIMAP</i> locus. The <i>GIMAP4</i> promoter construct plasmid with the minor allele of rs1608157 displayed significantly lower activity than one with the major allele. Moreover, CD4 T cells from BD patients showed a lower level of <i>GIMAP4</i> mRNA, and <i>GIMAP4</i> knockdown was protective against Fas-mediated apoptosis. <h3>Conclusions</h3> These results suggest that a <i>GIMAP</i> cluster is a novel susceptibility locus for BD, which is involved in T-cell survival, and T-cell aberration can contribute to the development of BD.
Systemic treatments for basal cell carcinoma (BCC): the advent of dermato-oncology in BCC
Authors: F.R. Ali, J.T. Lear
Journal: British Journal of Dermatology (2013)

Basal cell carcinoma (BCC) is the most common cancer in the U.K. and its incidence is increasing. Vismodegib, a hedgehog pathway inhibitor, has recently been licensed by the U.S. Food and Drug Administration for treatment of advanced BCC. Phase 2 trials have demonstrated efficacy in cases of locally advanced and metastatic BCC, as well as cases of hereditary basal cell naevus (Gorlin) syndrome. Side-effects are frequent and considerable and include myalgia, taste disturbance, alopecia, weight loss and fatigue. Further research is needed to investigate means of circumventing these side-effects, and longitudinal data are required to assess the long-term benefits of, and the nature of resistance to, this novel class of agents. Alternative hedgehog inhibitors are currently in clinical development. We review the current data pertaining to this novel treatment modality and discuss its likely future role in the management of BCC.
Accuracy of the Phonocardiogram in Assessing Severity of Aortic and Pulmonic Stenosis
Authors: RAUL GAMBOA, PAUL G. HUGENHOLTZ, ALEXANDER S. NADAS
Journal: Circulation (1964)

A critical evaluation was made of the reliability of three easily obtainable phonocardiographic criteria in the estimation of ventricular peak pressure in congenital pulmonic and aortic valvular stenosis. In 50 patients with pulmonic stenosis the Q-ejection click interval showed a significant inverse relationship to peak pressure (r=–0.77, p &lt;0.001), while no significant relationship existed in aortic stenosis (r = 0.40, p &lt;0.5). The timing of the peak magnitude of the murmur again related significantly to the right ventricular pressure (r = 0.72, p &lt; 0.001) and with the log of pulmonary valve area (r=–0.72, p &lt;0.001). In contrast no significant relationships existed in aortic stenosis. The degree of splitting also reflected the severity of right ventricular hypertension (r = 0.84, p &lt;0.001), while this measurement in aortic stenosis proved quite variable and did not reflect ventricular peak pressure. The significance of a combination of these criteria in predicting the severity of right ventricular hypertension and in obviating the need for cardiac catheterization is stressed. An explanation for the mechanism underlying the observed changes is given. Q-ejection click interval in particular constitutes an indirect but sensitive way (r =–0.90, p &lt; 0.001) of estimating the rate of pressure development (dp/dt) in the hypertrophied right ventricle.
The Fruitless Gene in Nasonia Displays Complex Sex-Specific Splicing and Contains New Zinc Finger Domains
Authors: R. C. Bertossa, L. van de Zande, L. W. Beukeboom
Journal: Molecular Biology and Evolution (2009)

The transcription factor Fruitless exerts a broad range of functions during Drosophila development, the most apparent of which is the determination of sexual behavior in males. Although fruitless sequences are found in other insect orders, little is known about fruitless structure and function outside Diptera. We have performed a thorough analysis of fruitless transcripts in the haplo-diploid wasp Nasonia vitripennis and found both sex-specific and non–sex-specific transcripts similar to those found in Drosophila. In Nasonia, however, a novel, large fruitless transcript is present in females only. Putative binding sites for sex-specific splicing factors found in Nasonia fruitless and doublesex as well as Apis mellifera doublesex transcripts were sufficient to identify a corresponding female-specific fruitless exon in A. mellifera, suggesting that similar factors in both hymenopteran species could be responsible for sex-specific splicing of both genes. Furthermore, new C2H2 zinc finger domains found in Nasonia fruitless transcripts were also identified in the fruitless locus of major holometabolous insect species but not in drosophilids. Conservation of important domains and sex-specific splicing in Diptera and Hymenoptera support the hypothesis that fruitless is an ancient gene and has conserved functions in insects. Considerable divergences in other parts of the gene are expected to underlie species-specific differences and may help to explain diversity observed in insect sexual behaviors.
Promoter Methylation of <i>DAL-1/4.1B</i> Predicts Poor Prognosis in Non–Small Cell Lung Cancer
Authors: Shinji Kikuchi, Daisuke Yamada, Takeshi Fukami, Mari Masuda, Mika Sakurai-Yageta, Yuko N. Williams, Tomoko Maruyama, Hisao Asamura, Yoshihiro Matsuno, Masataka Onizuka, Yoshinori Murakami
Journal: Clinical Cancer Research (2005)

DAL-1/4.1B is an actin-binding protein originally identified as a molecule whose expression is down-regulated in lung adenocarcinoma. We have previously shown that a lung tumor suppressor, TSLC1, associates with DAL-1, suggesting that both proteins act in the same cascade. The purpose of this study is to understand the molecular mechanisms and clinical significance of DAL-1 inactivation in lung cancer.We studied aberration of the DAL-1 in 103 primary non-small cell lung cancers (NSCLC) and 18 lung cancer cells. Expression and allelic and methylation status of DAL-1 was examined by reverse transcription-PCR, microsatellite analysis, and bisulfite sequencing or bisulfite single-strand conformational polymorphism, respectively.Loss of DAL-1 expression was strongly correlated with promoter methylation in lung cancer cells, whereas DAL-1 expression was restored by a demethylating agent, 5-aza-2'-deoxycytidine. The DAL-1 promoter was methylated in 59 (57%) primary NSCLC tumors, 37% of which were associated with loss of heterozygosity around the DAL-1 on chromosomal region 18p11.3. In squamous cell carcinomas, DAL-1 methylation was observed in 9 of 10 tumors at stage I, whereas the incidence of methylation gradually increased in adenocarcinomas as they progressed [13 of 36 (36%), 4 of 12 (33%), 14 of 17 (82%), and 3 of 3 (100%) tumors at stages I, II, III, and IV, respectively; P = 0.0026]. Furthermore, in adenocarcinomas, disease-free survival and overall survival were significantly shorter in patients with tumors harboring the methylated DAL-1 (P = 0.0011 and P = 0.045, respectively).DAL-1 methylation is involved in the development and progression of NSCLC and provides an indicator for poor prognosis.