tbuckley/cabot-search huggingface dataset:
Impact of the Hypoxia-Inducible Factor-1 α (<i>HIF1A</i>) Pro582Ser Polymorphism on Diabetes Nephropathy
Authors: Harvest F. Gu, Xiaowei Zheng, Norhashimah Abu Seman, Tianwei Gu, Ileana Ruxandra Botusan, Vivekananda Gupta Sunkari, Ezarul Faradianna Lokman, Kerstin Brismar, Sergiu-Bogdan Catrina
Journal: Diabetes Care (2012)

Hypoxia plays a major pathogenic role in diabetic nephropathy (DN). We have investigated in this study the effect of hypoxia-inducible factor 1 α subunit (HIF1A) genetic polymorphisms on the development of DN.In 1,165 American type 1 diabetic patients with and without DN selected from the Genetics of Kidneys in Diabetes (GoKinD) study, the HIF1A genetic polymorphisms were genotyped with TaqMan allelic discrimination. The regulation of HIF-1α in the kidneys of diabetic mice was appreciated by immunohistochemistry, and the effect HIF1A Pro582Ser polymorphism on HIF-1α sensitivity to glucose was evaluated in vitro.We identified a protective association between HIF1A Pro582Ser polymorphism and DN in male subjects. We also provided mechanistic insights that HIF-1α is repressed in the medulla of diabetic mice despite hypoxia and that Pro582Ser polymorphism confers less sensitivity to the inhibitory effect of glucose during a hypoxic challenge.The current study demonstrates for the first time that HIF1A Pro582Ser polymorphism has an effect on DN, possibly by conferring a relative resistance to the repressive effect of glucose on HIF-1α.
Morphological types of hepatocellular hyalin in Indian childhood cirrhosis: an ultrastructural study.
Authors: N C Nayak, S Roy
Journal: Gut (1976)

Morphological variants of intrahepatocytic hyalin in Indian childhood cirrhosis have been analysed by electron microscopy.This structure, morphologically identical with Mallory's alcoholic hyalin, is encountered in three different forms.The most common one is composed of randomly orientated fibrils.The next common type is composed of smudgy homogeneous or finely granular material, while the least common type consists of parallel fibrils with gentle curves giving a 'finger-print' appearance.Fragmented endoplasmic reticulum and ribosomes were frequently asso- ciated with hyalin suggesting that these organelles contribute to their formation.
Overall intelligence and localized brain damage
Authors: Dahlia W. Zaidel
Journal: Behavioral and Brain Sciences (2007)

Abstract Overall mean performance on intelligence tests by brain-damaged patients with focal lesions can be misleading in regard to localization of intelligence. The widely used WAIS has many subtests that together recruit spatially distant neural “centers,” but individually the subtests reveal localized functions. Moreover, there are kinds of intelligence that defy the localizationist approach inferred from brain damage.
Use of risk assessment instruments to predict violence and antisocial behaviour in 73 samples involving 24 827 people: systematic review and meta-analysis
Authors: S. Fazel, J. P. Singh, H. Doll, M. Grann
Journal: BMJ (2012)

<b>Objective</b> To investigate the predictive validity of tools commonly used to assess the risk of violence, sexual, and criminal behaviour. <b>Design</b> Systematic review and tabular meta-analysis of replication studies following PRISMA guidelines. <b>Data sources</b> PsycINFO, Embase, Medline, and United States Criminal Justice Reference Service Abstracts. <b>Review methods </b>We included replication studies from 1 January 1995 to 1 January 2011 if they provided contingency data for the offending outcome that the tools were designed to predict. We calculated the diagnostic odds ratio, sensitivity, specificity, area under the curve, positive predictive value, negative predictive value, the number needed to detain to prevent one offence, as well as a novel performance indicator—the number safely discharged. We investigated potential sources of heterogeneity using metaregression and subgroup analyses. <b>Results</b> Risk assessments were conducted on 73 samples comprising 24 847 participants from 13 countries, of whom 5879 (23.7%) offended over an average of 49.6 months. When used to predict violent offending, risk assessment tools produced low to moderate positive predictive values (median 41%, interquartile range 27-60%) and higher negative predictive values (91%, 81-95%), and a corresponding median number needed to detain of 2 (2-4) and number safely discharged of 10 (4-18). Instruments designed to predict violent offending performed better than those aimed at predicting sexual or general crime. <b>Conclusions</b> Although risk assessment tools are widely used in clinical and criminal justice settings, their predictive accuracy varies depending on how they are used. They seem to identify low risk individuals with high levels of accuracy, but their use as sole determinants of detention, sentencing, and release is not supported by the current evidence. Further research is needed to examine their contribution to treatment and management.
Effect of pilocarpine on propranolol-induced bronchoconstriction in asthma.
Authors: M Okayama, T Shen, J Midorikawa, J T Lin, H Inoue, T Takishima, K Shirato
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

To investigate whether increased release of acetylcholine may be involved in propranolol-induced bronchoconstriction (PIB), the inhibitory effect of pilocarpine (Pilo), an agonist of M2-muscarinic receptors that in 11 stable asthmatic subjects. The bronchial responsiveness to Pilo was also measured in terms of Dmin, defined as the cumulative dose at the point where respiratory resistance (Rrs) began to increase. In PIB, the maximum increase in Rrs (Rrs max) after stopping inhalation for 1 min was measured. Atropine reversed PIB. After pilocarpine pretreatment at a dose equal to Dmin, Rrs max divided by baseline Rrs decreased significantly from 206.6 +/- 61.1 to 163.0 +/- 42.6% (mean +/- SD) (p = 0.001). The ratio of PIB (Rrs max/baseline Rrs) with Pilo to PIB without Pilo correlated inversely according to the pretreatment dose (Dmin) of Pilo (p < 0.05). These results suggest increased release of acetylcholine in PIB and that M2-muscarinic receptors are at least in part functioning in stable asthmatic airways.
Granulocyte macrophage colony stimulating factor as adjuvant therapy for resected stage III/IV melanoma: Retrospective review of a single institutional experience
Authors: T. A. Patel, M. Baweja, W. Maples, S. Markovic
Journal: Journal of Clinical Oncology (2007)

19002 Background: Preliminary data suggesting positive clinical outcome in patients treated with adjuvant granulocyte macrophage colony stimulating factor (GM-CSF) following surgical resection of stage III/IV melanoma already exist (Spitler et al). A compassionate use protocol for the treatment of such patients with the “Spitler” regimen (GM-CSF administered at 250 mcg/day s.c. for 14 days of a 28 day cycle) has been ongoing at Mayo Clinic. Herein we present a retrospective review. Methods: Between 1998 and 2006, data was collected from 30 patients rendered disease free by surgery who received adjuvant GM-CSF. GM-CSF was administered per the “Spitler” regimen, although one patient received a reduced dose of 125mcg/day. The Kaplan-Meier approach was used to estimate relapse free survival. Results: Thirty patients (14 Female) with a median age of 53 and excellent performance status were evaluated. Most patients had resected stage III melanoma (Stage II/III/IV: 1/20/9). Median followup was 33 months (3–96). Twenty one patients were treated with GM-CSF for at least 12 months. Overall, relapse-free survival at 1 year was estimated to be 69% (95% confidence interval (CI) of 54% to 88%), reducing to 44% (95% CI of 29% to 67%) at 3 years. According to stage, relapse free survival at 1 year was 70% (III) and 63% (IV), and at 3 years was 54% (III), and 13% (IV). Among the 21 patients completing at least 1 year of therapy, relapse free survival at 3 years was 52%. Seventeen patients relapsed (III/IV: 10/7). Six of these patients were retreated and only two relapsed. Toxicities were grade 1 with most common being injection site rash (23%), asthenia (17%), myalgia (17%), and fever (7%). One patient required dose modification for elevated liver function tests. Conclusions: Although limited in scope, our data further support a potential beneficial effect of adjuvant GM-CSF in resected stage III/IV melanoma. Recurrences in the treated population were often localized and amenable to further surgical treatment. The clinical relevance of this strategy is currently being prospectively tested (E4697, now closed to accrual). No significant financial relationships to disclose.
Unusual microbes in asthma exacerbation: Alcaligenes xylosoxidans and Leishmania
Authors: B. Robibaro, G-C. Funk, G. Dekan, D. Demetriou, R. Ziesche, S. Winkler, L.H. Block
Journal: European Respiratory Journal (2009)

Asthma is a chronic inflammatory condition characterised by a variable degree of airflow limitation. Exacerbations during the course of asthma often occur due to environmental factors or infectious, mostly viral, aetiology. The present study reports the case of a 61-yr-old male with severe asthma hospitalised due to increasing respiratory distress. Since recovery was delayed despite anti-obstructive/anti-inflammatory and antibiotic therapy, further diagnostic procedures, including bronchoscopy, were performed in order to attempt to identify the cause of the worsening respiratory condition. The surprising finding consisted of a rare coincidence of concomitant infection with the bacterial pathogen Alcaligenes xylosoxidans, grown from bronchoalveolar lavage fluid, and the protozoan parasite Leishmania spp., revealed by histopathological examination of bronchial mucosal biopsy specimens. This is the first report of an isolated bronchial mucosal involvement of Leishmania in an HIV-negative asthma patient following brief exposure in Leishmania-endemic regions. Further, to the best of the present authors' knowledge, this represents the first description of A. xylosoxidans in asthma, although it is questionable whether it was an infection or colonisation. The present observation identifies previously unreported microbial pathogens associated with asthma exacerbation. Further, the report highlights the importance of obtaining a thorough travel history and applying invasive diagnostic procedures in circumstances of treatment failure, even under unfavourable conditions.
Foundation trusts revel in new powers, report says
Authors: Rebecca Coombes
Journal: BMJ (2005)

Foundation trusts are making the most of their freedoms to invest in new facilities and beds but are not outperforming ordinary NHS trusts, a review by the Healthcare Commission concluded this week.The review, the first of its kind and the result of visits to the first 20 foundation trusts, also found that four trusts were projecting large deficits of more than £3m ($5.3m; €4.4m).The commission concludes that, overall, foundation trusts had "hit the ground running" and have wasted no time exercising new freedoms to borrow money and to speed up decisions on opening new wards and operating theatres.For example, it took just 11 weeks for the University Hospital Birmingham NHS Foundation Trust to plan additional wards and modular theatres-whereas it would possibly have taken two and a half years for the plan to go through the strategic health authority's processes, the Commission said.(See p 59.)
Bronchial Mucosal Immunoreactivity of Sensory Neuropeptides in Severe Airway Diseases
Authors: PASCAL CHANEZ, DAVID SPRINGALL, ANTONIO M. VIGNOLA, ANNE MORADOGHI-HATTVANI, JULIA M. POLAK, PHILIPPE GODARD, JEAN BOUSQUET
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Neuropeptides act on most of the components of the bronchial environment. They influence bronchomotor tone and bronchial vascular caliber and permeability. To investigate the nonadrenergic, noncholinergic system within the airways in asthma and chronic bronchitis, we performed endobronchial biopsies in 16 normal human volunteers, 49 patients with asthma of varying severity, including 16 patients treated with oral corticosteroids, and 13 patients with chronic bronchitis. Frozen sections of biopsies stained with specific antibodies against the neural marker PGP 9.5, vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) were analyzed for the presence of nerves through indirect immunofluorescence. Nerves were present in most of the biopsies and were found within and below the epithelium and adjacent to smooth muscle, glands, and blood vessels. By comparison with those in normal subjects, the numbers of VIP-immunoreactive nerves were not significantly decreased in patients with asthma and chronic bronchitis, but NPY-immunoreactive nerves were significantly decreased in the smooth muscle of these latter two groups of patients (p < 0.005). There was no correlation between disease severity and the number of nerves found in the biopsies. This study does not confirm previous findings in autopsy material of some defects in sensory and VIP-containing nerves in severe asthma.
Opposing Effects of Androgen Deprivation and Targeted Therapy on Prostate Cancer Prevention
Authors: Shidong Jia, Xueliang Gao, Sang Hyun Lee, Sauveur-Michel Maira, Xiaoqiu Wu, Edward C. Stack, Sabina Signoretti, Massimo Loda, Jean J. Zhao, Thomas M. Roberts
Journal: Cancer Discovery (2012)

Abstract Prostate cancer is an ideal target for chemoprevention. To date, chemoprevention clinical trials with 5α-reductase inhibitors have yielded encouraging yet ultimately confounding results. Using a preclinical mouse model of high-grade prostatic intraepithelial neoplasia (HG-PIN) induced by PTEN loss, we observed unprecedented deteriorating effects of androgen deprivation, in which surgical castration or MDV3100 treatment accelerated disease progression of the otherwise stable HG-PIN to invasive castration-resistant prostate cancer (CRPC). As an alternative, targeting the phosphoinositide 3-kinase (PI3K) signaling pathway via either genetic ablation of genes encoding PI3K components or pharmacologic inhibition of the PI3K pathway reversed the PTEN loss–induced HG-PIN phenotype. Finally, concurrent inhibition of the PI3K and mitogen-activated protein kinase (MAPK) pathways was effective in blocking the growth of PTEN-null CRPC. Together, these data have revealed the potential adverse effects of antiandrogen chemoprevention in certain genetic contexts (such as PTEN loss) while showing the promise of targeted therapy in the clinical management of this complex and prevalent disease. Significance: Chemoprevention with antiandrogen therapies is attractive for prostate cancer, given its prevalence and established hormonally mediated pathogenesis. However, because PTEN loss has been found in 9% to 45% of HG-PIN in the clinic, the current findings suggest that patients with PTEN-deficient prostate tumors might be better treated with PI3K-targeted therapies. Cancer Discov; 3(1); 44–51. ©2012 AACR. This article is highlighted in the In This Issue feature, p. 1
The role of the peritoneum in the pathogenesis of endometriosis
Authors: Vicky J. Young, Jeremy K. Brown, Philippa T.K. Saunders, Andrew W. Horne
Journal: Human Reproduction Update (2013)

BACKGROUNDEndometriosis affects 6–10% of women of reproductive age and is associated with chronic pelvic pain, dysmenorrhoea, dyspareunia and infertility. Endometriosis is defined by the presence of endometrial tissue outside the uterus, most commonly attached to the pelvic peritoneum. The endometrium in women with endometriosis is reported to be altered and there is increasing evidence that the phenotype of the pelvic peritoneum may also play a role in the establishment and maintenance of the disease. The aim of this review is to discuss the putative role of the pelvic peritoneum in the pathophysiology of peritoneal endometriosis.
Isolation of a 330-kDa glycoprotein from human kidney similar to the Heymann nephritis autoantigen (gp330).
Authors: J J Kanalas, S P Makker
Journal: Journal of the American Society of Nephrology (1990)

Because of the similarities between Heymann nephritis of rat and human membranous glomerulonephritis, we searched for a protein in human kidney similar to that of the putative autoantigen of Heymann nephritis, gp330. Human gp330 was isolated by a purification scheme identical to that used for the isolation of rat gp330. The isolated human gp330 was compared with rat gp330 by peptide mapping and was found to be very similar in structure. Studies of immunologic reactivity of the rat antigen-induced Heymann nephritis nephritogenic autoantibody to human gp330 indicated that some of the rat antigen epitopes were shared with its human counterpart. The human gp330 was capable of eliciting on active Heymann nephritis response in rats when used as an immunogen. The nephritogenic autoantibody eluted from these rat kidney glomeruli showed equal binding to both rat and human antigens. Finally, a polyclonal antibody to human gp330 was able to induce passive Heymann nephritis in rats. These results demonstrate that there is a gp330 protein in human kidney that is very similar to the putative autoantigen of Heymann nephritis.
Transforming Growth Factor-β<sub>1</sub> Gene Polymorphisms Are Associated with Disease Progression in Idiopathic Pulmonary Fibrosis
Authors: Antoni Xaubet, Alejandra Marin-Arguedas, Sergio Lario, Julio Ancochea, Ferran Morell, Juan Ruiz-Manzano, Eulogio Rodriguez-Becerra, Jose M. Rodriguez-Arias, Pablo Iñigo, Sergi Sanz, Josep M. Campistol, Joaquim Mullol, Cesar Picado
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Transforming growth factor-beta1 (TGF-beta1) is a cytokine that plays a key role in the development of idiopathic pulmonary fibrosis. There have been reports on the presence of two genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta1 protein, located in codons 10 and 25. The objective of this study was to investigate the association between TGF-beta1 gene polymorphisms in codons 10 and 25 and the susceptibility to idiopathic pulmonary fibrosis and the progression of the disease. Compared with healthy control subjects (n = 140), patients with idiopathic pulmonary fibrosis (n = 128) showed no significant deviations in genotype or allele frequencies. One hundred and ten patients with idiopathic pulmonary fibrosis were followed up for 30.3 +/- 25 months. The presence of a proline allele at codon 10 was independently associated with a significant increase in alveolar arterial oxygen tension difference during follow-up, after controlling for the effect of treatment (coefficient = 0.59; 95% confidence intervals, 0.23 to 0.96; p = 0.002). These findings suggest that (1) TGF-beta1 gene polymorphisms in codons 10 and 25 do not predispose to the development of idiopathic pulmonary fibrosis; and (2) TGF-beta1 gene polymorphisms may affect disease progression in patients with idiopathic pulmonary fibrosis.
Treatment of community-acquired lower respiratory tract infections in adults
Authors: A Ortqvist
Journal: European Respiratory Journal (2002)

Community-acquired lower respiratory tract infection (LRTI) is a common cause of acute illness in adults. The spectrum of disease ranges from a mild mucosal colonisation or infection, acute bronchitis or acute exacerbation of chronic bronchitis/chronic obstructive pulmonary disease (AE-CB/COPD), to an overwhelming parenchymal infection with the patient presenting with severe community-acquired pneumonia (CAP). Although the great majority of LRTIs are self-limiting viral infections, CAP is most often a bacterial disease with a substantial mortality. Thus, antibiotic treatment is rarely indicated for acute bronchitis and is only indicated for the more severe cases of AE-CB/COPD, but it is nearly always indicated for CAP, for which a delay in treatment may increase the risk of a fatal outcome. It may be difficult to differentiate between a viral and a bacterial LRTI, or between bronchitis/AE-CB/COPD and CAP. This may be one reason why antibiotics are prescribed to more than two-thirds of patients with LRTIs in Europe and the USA. Considering the worldwide development of antibiotic resistance, this is not an acceptable situation. Since an empirical approach is nearly always necessary in the management of LRTI, greater emphasis must be placed on the decision of whether or not to prescribe an antibiotic at all. This decision should be based on an assessment of the severity of the disease, including underlying risk factors, and on markers for bacterial/parenchymal/ invasive LRTI. The choice of empirical therapy must be based on the same data together with epidemiological information. The choice of antibiotic must always cover Streptococcus pneumoniae, which remains the main pathogen of morbidity and mortality in CAP. In hospital, attempts should be made to obtain an aetiological diagnosis in order to be able to switch to a specific treatment or to evaluate a failure of empirical therapy. Several guidelines for the management of community-acquired pneumonia have been published during the last 10 yrs. Some reports indicate that the implementation of such guidelines has resulted in lowered costs, length of stay in hospital and mortality. However, the results from these studies are not consistent and the evidence is still weak.
Mesenchymal-to-Epithelial Transition Facilitates Bladder Cancer Metastasis: Role of Fibroblast Growth Factor Receptor-2
Authors: Christine L. Chaffer, Janelle P. Brennan, John L. Slavin, Tony Blick, Erik W. Thompson, Elizabeth D. Williams
Journal: Cancer Research (2006)

Abstract Epithelial-to-mesenchymal transition (EMT) increases cell migration and invasion, and facilitates metastasis in multiple carcinoma types, but belies epithelial similarities between primary and secondary tumors. This study addresses the importance of mesenchymal-to-epithelial transition (MET) in the formation of clinically significant metastasis. The previously described bladder carcinoma TSU-Pr1 (T24) progression series of cell lines selected in vivo for increasing metastatic ability following systemic seeding was used in this study. It was found that the more metastatic sublines had acquired epithelial characteristics. Epithelial and mesenchymal phenotypes were confirmed in the TSU-Pr1 series by cytoskeletal and morphologic analysis, and by performance in a panel of in vitro assays. Metastatic ability was examined following inoculation at various sites. Epithelial characteristics associated with dramatically increased bone and soft tissue colonization after intracardiac or intratibial injection. In contrast, the more epithelial sublines showed decreased lung metastases following orthotopic inoculation, supporting the concept that EMT is important for the escape of tumor cells from the primary tumor. We confirmed the overexpression of the IIIc subtype of multiple fibroblast growth factor receptors (FGFR) through the TSU-Pr1 series, and targeted abrogation of FGFR2IIIc reversed the MET and associated functionality in this system and increased survival following in vivo inoculation in severe combined immunodeficient mice. This model is the first to specifically model steps of the latter part of the metastatic cascade in isogenic cell lines, and confirms the suspected role of MET in secondary tumor growth. (Cancer Res 2006; 66(23): 11271-8)