tbuckley/cabot-search huggingface dataset:
Efficacy of Oral Sildenafil in Hemodialysis Patients with Erectile Dysfunction
Authors: Ivan Seibel, Carlos Eduardo Poli de Figueiredo, Cla[Combining Acute Accent]udio Telo[Combining Diaeresis]ken, Joa[Combining Tilde]o Feliz Moraes
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The aim of this study was to evaluate the efficacy and safety of oral sildenafil to treat erectile dysfunction (ED) in chronic renal failure in patients on hemodialysis (HD). A double-blind, randomized, placebo-controlled study of oral sildenafil (50 mg) administered as required in HD patients with ED was designed. Patients on HD for at least 6 mo and who had a stable relationship with a female sexual partner were included. Patients older than 70 yr with penile anatomic abnormalities, cirrhosis, diabetes, angina, severe anemia, and those who were on nitrate treatment or with a recent history of stroke or myocardial infarction were not included. The International Index of Erectile Dysfunction (IIEF) was employed to evaluate ED and treatment response. Forty-one patients were evaluated (21 received placebo, and 20 sildenafil). Baseline clinical and demographic parameters were similar in both groups. Sildenafil was associated with improvement in the score of all questions and domains of the IIEF, except those related to sexual desire. Using the erectile function domain to evaluate primary efficacy, improvement was observed in 85% of the sildenafil patients compared with 9.5% of placebo patients. Sildenafil use resulted in normal EF scores in 35% of sildenafil patients. Sildenafil was well tolerated. Headaches and flushing occurred in both groups. Dyspepsia was reported by two patients in the sildenafil group. In conclusion, oral sildenafil seems to be an effective and safe treatment for ED in selected patients with chronic renal failure on hemodialysis.
Hepatosplenic schistosomiasis: a great neglected disease of the liver.
Authors: K S Warren
Journal: Gut (1978)

Schistosomiasis mansoni and japonica, helminth infections involving the livers of 100 million people, are among the 9great neglected diseases of mankind9 on the basis both of their prevalence and the relative lack of interest shown in them by clinicians and biomedical investigators. Schistosomiasis is not only an interesting disease in itself but has the added advantage of providing unique human and animal models of hepatic pathophysiology, immunopathogenesis, and collagen metabolism.
Effects of Exercise Training on Insulin Sensitivity in Adolescents with Type I Diabetes
Authors: Kyle W Landt, Barbara N Campaigne, Frederick W James, Mark A Sperling
Journal: Diabetes Care (1985)

We investigated the influence of a program of exercise training consisting of three weekly sessions, each 45 min long, for 12 wk, on indices of physical fitness, glycemic control, and insulin sensitivity in nine adolescents with type I diabetes; six age-matched adolescents with diabetes of equivalent duration served as nonexercised controls. All subjects were instructed not to change dialy insulin dose or caloric intake. In the exercised group, maximal oxygen uptake during graded cycle ergometry to volitional exhaustion increased by 9 ± 2.7% (P &amp;lt; 0.01) and lean body mass increased by 4 ± 1.8% (P &amp;lt; 0.05). Insulin sensitivity, assessed via the euglycemic clamp technique at insulin infusion rates of 100 mU/M2/min, showed an increase of insulin-mediated glucose disposal from 274 ± 33 to 338 ± 28 mg/M2/min, representing an increase in insulin sensitivity of 23 ± 5% (P &amp;lt; 0.01). None of these indices changed in the control group. Despite increased insulin sensitivity, glycohemoglobin levels remained at 12 ± 1% before and after the 12 wk of exercise training, indicating no improvement in overall glycemic control. No increase in hypoglycemic reactions was reported in either group. We conclude that exercise training may be a valuable adjunct in managing type I diabetes providing there is concomitant attention to diet and insulin. Exercise training alone, however, does not improve glycemic control, although it improves physical fitness and insulin sensitivity.
An Evolved Adeno-associated Viral Variant Enhances Gene Delivery and Gene Targeting in Neural Stem Cells
Authors: Jae-Hyung Jang, James T Koerber, Jung-Suk Kim, Prashanth Asuri, Tandis Vazin, Melissa Bartel, Albert Keung, Inchan Kwon, Kook In Park, David V Schaffer
Journal: Molecular Therapy (2011)

Gene delivery to, and gene targeting in, stem cells would be a highly enabling technology for basic science and biomedical application. Adeno-associated viral (AAV) vectors have demonstrated the capacity for efficient delivery to numerous cells, but their application to stem cells has been limited by low transduction efficiency. Due to their considerable advantages, however, engineering AAV delivery systems to enhance gene delivery to stem cells may have an impact in stem cell biology and therapy. Therefore, using several diverse AAV capsid libraries—including randomly mutagenized, DNA shuffled, and random peptide insertion variants—we applied directed evolution to create a "designer" AAV vector with enhanced delivery efficiency for neural stem cells (NSCs). A novel AAV variant, carrying an insertion of a selected peptide sequence on the surface of the threefold spike within the heparin-binding site, emerged from this evolution. Importantly, this evolved AAV variant mediated efficient gene delivery to rat, mouse, and human NSCs, as well as efficient gene targeting within adult NSCs, and it is thus promising for applications ranging from basic stem cell biology to clinical translation. Gene delivery to, and gene targeting in, stem cells would be a highly enabling technology for basic science and biomedical application. Adeno-associated viral (AAV) vectors have demonstrated the capacity for efficient delivery to numerous cells, but their application to stem cells has been limited by low transduction efficiency. Due to their considerable advantages, however, engineering AAV delivery systems to enhance gene delivery to stem cells may have an impact in stem cell biology and therapy. Therefore, using several diverse AAV capsid libraries—including randomly mutagenized, DNA shuffled, and random peptide insertion variants—we applied directed evolution to create a "designer" AAV vector with enhanced delivery efficiency for neural stem cells (NSCs). A novel AAV variant, carrying an insertion of a selected peptide sequence on the surface of the threefold spike within the heparin-binding site, emerged from this evolution. Importantly, this evolved AAV variant mediated efficient gene delivery to rat, mouse, and human NSCs, as well as efficient gene targeting within adult NSCs, and it is thus promising for applications ranging from basic stem cell biology to clinical translation.
Role of alginate in infection with mucoid Pseudomonas aeruginosa in cystic fibrosis.
Authors: S S Pedersen, N Hoiby, F Espersen, C Koch
Journal: Thorax (1992)

BACKGROUND: Chronic bronchopulmonary infection with mucoid, alginate producing Pseudomonas aeruginosa occurs characteristically in patients with cystic fibrosis. Alginate may be a virulence factor for P aeruginosa infection in such patients. METHODS: Forced vital capacity (FVC), nutritional state and the antibody response to P aeruginosa were determined at regular intervals from three years before chronic P aeruginosa infection to 10 years afterwards in 73 patients with cystic fibrosis. All patients were treated intensively with antipseudomonal chemotherapy during the study period. RESULTS: FVC was reduced in all patients who subsequently developed P aeruginosa infection before they acquired the infection, indicating significant pre-existing lung damage when compared with patients who remained free of P aeruginosa. Lung function and nutritional state remained unchanged after 10 years of infection, except in the patients who died of P aeruginosa lung infection. The FVC and height and weight of patients infected with nonmucoid strains of P aeruginosa were similar to those of uninfected patients. Patients infected with mucoid strains had poorer lung function and nutritional state for the first five years after infection compared with patients with nonmucoid strains. Such infection was also associated with greater IgG and IgA antibody responses to P aeruginosa standard antigen compared with nonmucoid infection. Concentrations of antibody to alginate were similar in patients with non-mucoid and mucoid infection. Noticeably increased concentrations of IgA antibodies to P aeruginosa standard antigen were observed early after the onset of infection in patients who subsequently died. CONCLUSION: Alginate producing P aeruginosa infection is associated with a hyperimmune response and poor clinical condition, suggesting that alginate production is a virulence factor in such infections in patients with cystic fibrosis.
In Situ Nucleic Acid Hybridization of Pyruvate Dehydrogenase Complex–E2 in Primary Biliary Cirrhosis: Pyruvate Dehydrogenase Complex–E2 Messenger Rna Is Expressed in Hepatocytes But Not in Biliary Epithelium
Authors: Kenichi Harada, Jarada Van de Water, Patrick S.C. Leung, Ross L. Coppel, Yasuni Nakanuma, Mevvill Eric Gershwin
Journal: Hepatology (1997)

Pyruvate dehydrogenase–E2, or a cross–reactive molecule, has been shown by a variety of immunohistochemical methods to be present in increased amounts in biliary epithelial cells (BEC) in primary biliary cirrhosis (PBC). In this study, to further understand the nature of the immunoreactive molecule in BEC, we examined the expression of pyruvate dehydrogenase complex–E2 (PDC–E2) messenger RNA (mRNA) and PDC–E2 protein in sections of livers from patients and controls to help identify the molecule found in BEC. We performed in situ hybridization using an antisense probe against the major epitope of PDC–E2. The data were very striking and suggested that there was no increased production of PDC–E2 in BEC. For example, in livers from patients with PBC, PDC–E2 mRNA was found in periportal hepatocytes in 16 of 17 cases (94%). In contrast, interlobular bile ducts and septal bile ducts had detectable levels of PDC–E2 mRNA in only 1 of 17 (6%) and 3 of 8 (38%) cases, respectively. Interestingly, proliferating bile ductules contained detectable levels of mRNA in 12 of 15 cases (80%). In control liver, periportal hepatocytes were positive in 15 of 17 cases (88%). Interlobular bile ducts, septal bile ducts, and proliferating bile ductules expressed mRNA signals in 4 of 17 (24%), 2 of 10 (20%), and 14 of 16 (88%), respectively. When formalin–fixed, paraffin–embedded sections were examined by immunohistochemical staining with anti–PDC–E2 monoclonal antibody (mAb) C355.1, the interlobular bile ducts showed typical aberrant apical staining in all 10 PBC cases, but 0 of 9 liver controls. Periportal hepatocytes, proliferating bile ductules and infiltrating mononuclear cells stained with C355.1 but in a characteristic mitochondrial staining pattern. The presence of a PDC–E2-like molecule recognized by C355.1 is not reflected by the expression levels of PDC–E2 mRNA in the BEC of patients with PBC.
Role of Androgens on MCF-7 Breast Cancer Cell Growth and on the Inhibitory Effect of Letrozole
Authors: Luciana F. Macedo, Zhiyong Guo, Syreeta L. Tilghman, Gauri J. Sabnis, Yun Qiu, Angela Brodie
Journal: Cancer Research (2006)

Abstract Previous work has shown that androgens inhibit breast cancer cells and tumor growth. On the other hand, androgens can be converted to mitogenic estrogens by aromatase in breast cancer cells. Here, we report that androgens, such as the aromatizable androstenedione and the non-aromatizable 5α-dihydrotestosterone, inhibit MCF-7 cell proliferation. This effect is observed only in the absence or at a low concentration of estrogens and is evident in cells with low aromatase activity. Growth of a new aromatase stably transfected MCF-7 cell line (Ac1) was stimulated by conversion of androstenedione into estrogens and was sensitive to aromatase inhibitors. We show that blockade of the androgen receptor (AR) in these cells by the antiandrogen casodex or by the anti-AR small interfering RNA inhibited the antiproliferative effect of dihydrotestosterone and letrozole (aromatase inhibitor). We also show that suppression of the estrogen-induced antiapoptotic protein Bcl-2 may be involved in the antiproliferative effects of androgens and letrozole. These effects can be reversed by casodex. In conclusion, the results suggest that aromatase inhibitors may exert their antiproliferative effect not only by reducing the intracellular production of estrogens but also by unmasking the inhibitory effect of androgens acting via the AR. (Cancer Res 2006; 66(15): 7775-82)
Characterisation of phenotypes based on severity of emphysema in chronic obstructive pulmonary disease
Authors: H. Makita, Y. Nasuhara, K. Nagai, Y. Ito, M. Hasegawa, T. Betsuyaku, Y. Onodera, N. Hizawa, M. Nishimura
Journal: Thorax (2007)

<h3>Background:</h3> Airflow limitation in chronic obstructive pulmonary disease (COPD) is caused by a mixture of small airway disease and emphysema, the relative contributions of which may vary among patients. Phenotypes of COPD classified purely based on severity of emphysema are not well defined and may be different from the classic phenotypes of "pink puffers" and "blue bloaters". <h3>Methods:</h3> To characterise clinical phenotypes based on severity of emphysema, 274 subjects with COPD were recruited, excluding those with physician-diagnosed bronchial asthma. For all subjects a detailed interview of disease history and symptoms, quality of life (QOL) measurement, blood sampling, pulmonary function tests before and after inhalation of salbutamol (0.4 mg) and high-resolution CT scanning were performed. <h3>Results:</h3> Severity of emphysema visually evaluated varied widely even among subjects with the same stage of disease. No significant differences were noted among three groups of subjects classified by severity of emphysema in age, smoking history, chronic bronchitis symptoms, blood eosinophil count, serum IgE level or bronchodilator response. However, subjects with severe emphysema had significantly lower body mass index (BMI) and poorer QOL scores, evaluated using St George's Respiratory Questionnaire (SGRQ), than those with no/mild emphysema (mean (SD) BMI 21.2 (0.5) vs 23.5 (0.3) kg/m<sup>2</sup>, respectively; SGRQ total score 40 (3) vs 28 (2), respectively; p&lt;0.001 for both). These characteristics held true even if subjects with the same degree of airflow limitation were chosen. <h3>Conclusions:</h3> The severity of emphysema varies widely even in patients with the same stage of COPD, and chronic bronchitis symptoms are equally distributed irrespective of emphysema severity. Patients with the phenotype in which emphysema predominates have lower BMI and poorer health-related QOL.
Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases
Authors: Henri Duboc, Sylvie Rajca, Dominique Rainteau, David Benarous, Marie-Anne Maubert, Elodie Quervain, Ginette Thomas, Véronique Barbu, Lydie Humbert, Guillaume Despras, Chantal Bridonneau, Fabien Dumetz, Jean-Pierre Grill, Joëlle Masliah, Laurent Beaugerie, Jacques Cosnes, Olivier Chazouillères, Raoul Poupon, Claude Wolf, Jean-Maurice Mallet, Philippe Langella, Germain Trugnan, Harry Sokol, Philippe Seksik
Journal: Gut (2012)

Gut microbiota metabolises bile acids (BA). As dysbiosis has been reported in inflammatory bowel diseases (IBD), we aim to investigate the impact of IBD-associated dysbiosis on BA metabolism and its influence on the epithelial cell inflammation response.Faecal and serum BA rates, expressed as a proportion of total BA, were assessed by high-performance liquid chromatography tandem mass spectrometry in colonic IBD patients (42) and healthy subjects (29). The faecal microbiota composition was assessed by quantitative real-time PCR. Using BA profiles and microbiota composition, cluster formation between groups was generated by ranking models. The faecal BA profiles in germ-free and conventional mice were compared. Direct enzymatic activities of BA biotransformation were measured in faeces. The impact of BA on the inflammatory response was investigated in vitro using Caco-2 cells stimulated by IL-1β.IBD-associated dysbiosis was characterised by a decrease in the ratio between Faecalibacterium prausntizii and Escherichia coli. Faecal-conjugated BA rates were significantly higher in active IBD, whereas, secondary BA rates were significantly lower. Interestingly, active IBD patients exhibited higher levels of faecal 3-OH-sulphated BA. The deconjugation, transformation and desulphation activities of the microbiota were impaired in IBD patients. In vitro, secondary BA exerted anti-inflammatory effects, but sulphation of secondary BAs abolished their anti-inflammatory properties.Impaired microbiota enzymatic activity observed in IBD-associated dysbiosis leads to modifications in the luminal BA pool composition. Altered BA transformation in the gut lumen can erase the anti-inflammatory effects of some BA species on gut epithelial cells and could participate in the chronic inflammation loop of IBD.
Association between low cortical bone mineral density, soft-tissue calcification, vascular calcification and chondrocalcinosis: a case-control study
Authors: A Abhishek, S Doherty, R Maciewicz, K Muir, W Zhang, M Doherty
Journal: Annals of the Rheumatic Diseases (2013)

To examine the association between bone mineral density (BMD), soft-tissue calcification, vascular calcification and chondrocalcinosis (CC).A case-control study within the Genetics of Osteoarthritis and Lifestyle (GOAL) database (n=3170). All GOAL participants completed a questionnaire self-reporting current and early adult life exposures. Radiographs of knees, hands and pelvis were scored for osteoarthritis (OA), CC, pelvic vascular calcification, peri-articular knee calcification and metacarpal index (MCI-measure of cortical BMD). Calcaneal dual-energy X-ray absorptiometry (DEXA) was performed. Cases had radiographic CC, while controls did not have CC at any radiographed site. OR, 95% CI were used to measure association between risk factors and CC. Logistic regression was used to adjust for confounding and to estimate the adjusted OR (aOR).Low MCI (aOR (95%) for CC in 1st tertile 1.41 (1.06 to 1.89), with 3rd tertile referent), soft-tissue calcification (aOR (95%) for CC 1.81 (1.36 to 2.42)), and vascular calcification (aOR (95%) for CC 1.76 (1.13 to 2.75)) independently associated with CC. There was a negative association between body mass index and CC (aOR (95%) for CC in 2nd and 3rd tertiles 0.68 (0.53 to 0.89), and 0.67 (0.51 to 0.88) respectively with 1st tertile referent). Age and OA associated with CC. However, only age and low MCI independently associated with CC at >1 joint. Self-reported meniscectomy, low cortical BMD, vascular calcification, and soft-tissue calcification independently associated with knee CC.This study identifies several novel associations of CC including low cortical BMD. The association between vascular calcification, soft-tissue calcification, and CC suggests a generalised constitutional predisposition to calcium crystal formation.
Randomized, Double-Blind, Placebo-Controlled Trial of Epoetin Alfa in Men With Castration-Resistant Prostate Cancer and Anemia
Authors: Eric Winquist, Jim A. Julian, Malcolm J. Moore, Abdenour Nabid, Jinka Sathya, Lori Wood, Peter Venner, Mark Levine
Journal: Journal of Clinical Oncology (2008)
Human Leukocyte Antigen Class I Gene Mutations in Cervical Cancer
Authors: L. A. Koopman, A. R. van der Slik, M. J. Giphart, G. J. Fleuren
Journal: JNCI Journal of the National Cancer Institute (1999)

Various mechanisms contribute to the loss of human leukocyte antigen (HLA) class I expression that is frequently observed in cancers. Although some single allele losses have been ascribed to mutations in HLA class I genes, direct evidence for this phenomenon in vivo is still lacking. Thus, we investigated whether HLA class I gene mutations could account for the loss of allele-specific expression in cervical carcinomas.We used polymerase chain reaction-based techniques, including sequencing, oligonucleotide hybridization, and microsatellite analysis, to identify HLA class I gene defects in two tumor-derived cell lines and to confirm the presence of these defects in the original tumors.In one tumor, in exon 2 of the HLA-B15 gene, a four-nucleotide insertion resulted in a stop codon in exon 3. In the other tumor, in two duplicated copies of the HLA-A24 gene, single-point mutations resulted in stop codons in exons 2 and 5.To our knowledge, this is the first report of HLA class I gene mutations identified in primary tumors that lead to loss of allelic expression in tumor cells. Such tumor-specific mutations may permit the cell to escape HLA class I-restricted cytotoxic T-cell responses.
A Within-Patient Analysis for Time-Varying Risk Factors of CKD Progression
Authors: Liang Li, Alexander Chang, Stephen G. Rostand, Lee Hebert, Lawrence J. Appel, Brad C. Astor, Michael S. Lipkowitz, Jackson T. Wright, Cynthia Kendrick, Xuelei Wang, Tom H. Greene
Journal: Journal of the American Society of Nephrology (2013)

Recent data suggest that nonlinear GFR trajectories are common among patients with CKD, but the modifiable risk factors underlying these changes in CKD progression rate are unknown. Analyses relating baseline risk factors to subsequent GFR decline are suboptimal because these relationships often attenuate as follow-up time increases and these analyses do not account for temporal changes in risk factors. We identified 74 participants in the African American Study of Kidney Disease and Hypertension who had both a period of rapid GFR decline and an extended period of stability during a follow-up period of ≥12 years. We performed a within-patient comparison of time-varying risk factors measured during the periods of GFR decline and stability and identified several risk factors associated with faster GFR decline: more hospitalization episodes and hospitalization days per year; higher BP, serum phosphorus, and urine protein-to-creatinine ratio; lower serum albumin and urine sodium-to-potassium ratio; slower rate of decline of serum urea nitrogen, serum creatinine, serum uric acid, and serum phosphorus; and faster rate of decline of serum hematocrit and serum bicarbonate. By allowing each patient to serve as his or her own control, this novel, within-patient analytic approach holds considerable promise as a means to identify time-varying risk factors associated with stabilization of GFR or acceleration of GFR decline.