tbuckley/cabot-search huggingface dataset:
Author response: linking lifestyle and microbes
Authors: Fergus Shanahan, Siobhan F Clarke, Eileen F Murphy, Orla O'Sullivan, Paul Cotter
Journal: Gut (2014)

Marlicz and Loniewski1 offer complementary comments regarding the design and execution of our study of exercise and associated dietary extremes on gut microbial diversity.2 They expand on some of the caveats already raised by us. First, we were careful not …
Response to Letter Regarding Article, “Reoperation of Left Heart Valve Bioprostheses According to Age at Implantation”
Authors: Vincent Chan, Tarek Malas, Harry Lapierre, Munir Boodhwani, B-Khanh Lam, Fraser D. Rubens, Paul J. Hendry, Roy G. Masters, William Goldstein, Thierry G. Mesana, Marc Ruel
Journal: Circulation (2012)

Regarding Article, "Reoperation of Left Heart Valve Bioprostheses According to Age at Implantation"We thank Charitos and colleagues for their interest in this article 1 and also for their comments.The actuarial curves in Figure 2 represent freedom from reoperation adjusted for preoperative atrial fibrillation and concomitant coronary artery bypass grafting, whereas the curves in Figure 1 represent unadjusted data. 1 The adjusted curves in Figure 2 included younger patients with atrial fibrillation and concomitant coronary artery bypass grafting matched to older patients with these comorbidities.Although atrial fibrillation and concomitant coronary bypass grafting are known to negatively impact long-term survival following valve replacement, 2,3 in this study, younger patients were impacted to a greater degree.For example, in patients Ͻ60 years of age who underwent bioprosthetic aortic valve replacement with preoperative atrial fibrillation, 9 of 19 (47%) died within 10 years of surgery in comparison with 21 of 178 (12%) in patients Ͼ60 years of age (PϽ0.001).In patients Ͻ60 years of age who underwent bioprosthetic mitral valve replacement and concomitant coronary artery bypass grafting, 9 of 44 (20%) died within 10 years of surgery in comparison with 26 of 310 (8%) in patients Ͼ60 years of age (Pϭ0.01).Figure 2 therefore displays a greater freedom from reoperation in younger patients compared with Figure 1 because of the competing risk of death.
Rhabdomyolysis in 119 students after repetitive exercise
Authors: A C-M Lin, C-M Lin, T-L Wang, J-G Leu
Journal: British Journal of Sports Medicine (2004)

Exercise induced rhabdomyolysis is well known, but has rarely been reported in high school students. This is the report of 119 cases in high school students who exercised vigorously (120 push ups in five minutes) in cold weather. Most of them developed muscle pain and dark urine within two to four days of the exercise.
Neuroprotective Effect of Mild Hypothermia in Patients Undergoing Coronary Artery Surgery With Cardiopulmonary Bypass
Authors: Howard J. Nathan, George A. Wells, Janet L. Munson, Denise Wozny
Journal: Circulation (2001)

Neuropsychological deficits occur in 30% to 80% of patients undergoing heart surgery and are due in part to ischemic cerebral injury during cardiopulmonary bypass. We tested whether mild hypothermia, the most efficacious neuroprotective strategy found in laboratory studies, improved cognitive outcome in patients undergoing coronary artery surgery.Patients 60 years or older scheduled for coronary artery surgery were enrolled. During cardiopulmonary bypass, patients were initially cooled to 32 degrees C then randomly assigned to rewarming to 37 degrees C (control) or 34 degrees C (hypothermic), with no further intraoperative warming. Testing was scheduled preoperatively and 1 week and 3 months postoperatively. Eleven tests were combined into 3 cognitive domains: memory, attention, and psychomotor speed and dexterity. A patient was classified as having a cognitive deficit if a decrease of >/=0.50 SD was realized in 1 or more domains. The incidence of cognitive deficits 1 week after surgery, which was the primary outcome, was 62% () in the control group and 48% () in the hypothermic group (relative risk 0.77, P=0.048). In the hypothermic group, the magnitude of deterioration in attention and in speed and dexterity was reduced by 55.6% (P=0.038) and 41.3% (P=0.042), respectively. At 3 months, the hypothermic group still performed better on one test of speed and dexterity (grooved pegboard). There was no difference in morbidity or mortality.Our findings support a neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery and should encourage physicians and perfusionists to pay careful attention to brain temperature during cardiopulmonary bypass.
Repeat Imaging for Intracranial Aneurysms in Patients with Autosomal Dominant Polycystic Kidney Disease with Initially Negative Studies
Authors: Robert W. Schrier, Mark M. Belz, Ann M. Johnson, William D. Kaehny, Richard L. Hughes, David Rubinstein, Patricia A. Gabow
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Patients with autosomal dominant polycystic kidney disease (ADPKD) have a higher incidence of intracranial aneurysms (ICA) than the general population. These ICA also rupture at an earlier age in patients with ADPKD and are associated with high morbidity and mortality. In a recent study, 25% of patients with ADPKD with a documented ICA demonstrated a new ICA on follow-up. It is not known, however, whether patients with ADPKD who have had a negative ICA imaging study would demonstrate an ICA on a repeat imaging study. Only 2 (2.6%) of 76 patients with ADPKD with an initially negative study demonstrated an ICA on follow-up, despite the high frequency of risk factors such as hypertension, smoking, and a family history of ruptured ICA. The mean length of follow-up was 9.8 yr (median, 9.7 yr). These findings have important health care and economic implications in following patients with ADPKD.
Survey of Pseudomonas aeruginosa genotypes in colonised cystic fibrosis patients
Authors: S. Van daele
Journal: European Respiratory Journal (2006)

The current authors aimed to examine whether cystic fibrosis (CF) patients in Belgium shared <i>Pseudomonas aeruginosa</i> genotypes and to compare the genotypes of isolates from the same patients during two consecutive years. A Belgian databank of the <i>P. aeruginosa</i> genotypes of all colonised CF patients was created. Sputum samples from a total of 276 <i>P. aeruginosa</i> colonised patients during 2003, and from a subgroup of 95 patients in 2004, were analysed. Patients were asked about any social contact between each other by questionnaire. All <i>P. aeruginosa</i> isolates exhibiting different colonial morphology on McConkey agar were first genotyped using arbitrarily primed PCR, whereafter single representatives of each randomly amplified polymorphic DNA-type were further genotyped by fluorescent amplified fragment length polymorphism analysis. In the 213 patients from whom <i>P. aeruginosa</i> could be cultured (resulting in 910 isolates), a total of 163 genotypes were found. The majority (75%) of patients harboured only one genotype. In most of the limited number of clusters, previous contacts between patients could be suspected. In 80% of the patients studied during both years, <i>P. aeruginosa</i> genotype remained unchanged. In conclusion, most colonised cystic fibrosis patients harbour only one <i>Pseudomonas aeruginosa</i> genotype, despite showing different colonial morphotypes. The number of clusters is limited, and most patients seem to retain the same genotypic strain during both years.
Pulmonary hypertension in COPD
Authors: A. Chaouat, R. Naeije, E. Weitzenblum
Journal: European Respiratory Journal (2008)

Mild-to-moderate pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD); such a complication is associated with increased risks of exacerbation and decreased survival. Pulmonary hypertension usually worsens during exercise, sleep and exacerbation. Pulmonary vascular remodelling in COPD is the main cause of increase in pulmonary artery pressure and is thought to result from the combined effects of hypoxia, inflammation and loss of capillaries in severe emphysema. A small proportion of COPD patients may present with "out-of-proportion" pulmonary hypertension, defined by a mean pulmonary artery pressure >35-40 mmHg (normal is no more than 20 mmHg) and a relatively preserved lung function (with low to normal arterial carbon dioxide tension) that cannot explain prominent dyspnoea and fatigue. The prevalence of out-of-proportion pulmonary hypertension in COPD is estimated to be very close to the prevalence of idiopathic pulmonary arterial hypertension. Cor pulmonale, defined as right ventricular hypertrophy and dilatation secondary to pulmonary hypertension caused by respiratory disorders, is common. More studies are needed to define the contribution of cor pulmonale to decreased exercise capacity in COPD. These studies should include improved imaging techniques and biomarkers, such as the B-type natriuretic peptide and exercise testing protocols with gas exchange measurements. The effects of drugs used in pulmonary arterial hypertension should be tested in chronic obstructive pulmonary disease patients with severe pulmonary hypertension. In the meantime, the treatment of cor pulmonale in chronic obstructive pulmonary disease continues to rest on supplemental oxygen and a variety of measures aimed at the relief of airway obstruction.
Urinary excretion of hydroxylysine and its glycosides as an index of collagen degradation.
Authors: S M Krane, F G Kantrowitz, M Byrne, S R Pinnell, F R Singer
Journal: Journal of Clinical Investigation (1977)

Urimary excretion of hydroxyprolin (Hyp) is one index of total collagen degradation, from all sources. Since some of the Hyp released from collagen may be further metabolized before it is excreted, other markers are necessary to measure collagen breakdown. Excretion of the glycosides of hydroxylysine (Hyl), glucosyl galactosyl hydroxylysine (Hy1[Gl)cGa1]), and galactosyl hydroxylysine (Hyl[Ga)]), more accurately reflects collagen metabolism since these products occur in specificratios in different tissue collagens and are themselves metabolized only to a minor degree. The ratios of total Hy1/Hyp and Hyl(GlcGal)/Hyl(Ga1) were measured in the urine of norma. subjects and of patients with Paget's disease of bone, hyperphosphatasia, and extensive thermal burns. In patients with extensive thermal burns the pattern of urinary Hy1 and its glycosides was consistent with degradation of collagen in dermis and fascia. When bone collagen degradation was dominant, the pattern of urinary metabolites reflected that source. Pagetic bone collagen has an amino acid composition similar to normal bone and Hy1(G1cGa1/Hyl(G1) of 0.396-0.743,vs. normal of 0.474+/-0.088. In untreated patients with severe Paget's disease of bone or hyperphosphatasia (urinary Hyp greater than 2.0 micronmol/mg creatinine) urinary Hyl/Hyp averaged 0.052+/-0.042 (0.042+/-0.009 in normal bone) and Hy1(G1cGa1)/Hy1(Ga1) 0.601+/-0.017 (0.47+/-0.009 in normal bone). When bone resorption was decreased sufficiently with calcitonin or disodium etidronate in these patients, both the urinary ratios of Hy1/Hyp and Hy1(G1cGa1)/Hyl(Gal) rose. In normal subjects treated with calcitonin and excreting relatively little Hyp, the ratio of Hy1/H)P approached 0.7 and Hy1(G1ycGa1)/Hy1(Ga1) approached 3.5. There increased ratios reveal the existence of a source of collagen breakdown other than skin or bone. The first subcompoent of complement, Clq, which has collagen-like sequences, relatively high amounts of Hy1, and most of the glycosylated Hy1 as Hy1(G1cGa1), could be the source of these metabolites.
Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis
Authors: C. Blanchard
Journal: Journal of Clinical Investigation (2006)

Eosinophilic esophagitis (EE) is an emerging disorder with a poorly understood pathogenesis. In order to define disease mechanisms, we took an empirical approach analyzing esophageal tissue by a genome-wide microarray expression analysis. EE patients had a striking transcript signature involving 1% of the human genome that was remarkably conserved across sex, age, and allergic status and was distinct from that associated with non-EE chronic esophagitis. Notably, the gene encoding the eosinophil-specific chemoattractant eotaxin-3 (also known as CCL26) was the most highly induced gene in EE patients compared with its expression level in healthy individuals. Esophageal eotaxin-3 mRNA and protein levels strongly correlated with tissue eosinophilia and mastocytosis. Furthermore, a single-nucleotide polymorphism in the human eotaxin-3 gene was associated with disease susceptibility. Finally, mice deficient in the eotaxin receptor (also known as CCR3) were protected from experimental EE. These results implicate eotaxin-3 as a critical effector molecule for EE and provide insight into disease pathogenesis.
PARP-1 Inhibition as a Targeted Strategy to Treat Ewing's Sarcoma
Authors: J. Chad Brenner, Felix Y. Feng, Sumin Han, Sonam Patel, Siddharth V. Goyal, Laura M. Bou-Maroun, Meilan Liu, Robert Lonigro, John R. Prensner, Scott A. Tomlins, Arul M. Chinnaiyan
Journal: Cancer Research (2012)

Ewing's sarcoma family of tumors (ESFT) refers to aggressive malignancies which frequently harbor characteristic EWS-FLI1 or EWS-ERG genomic fusions. Here, we report that these fusion products interact with the DNA damage response protein and transcriptional coregulator PARP-1. ESFT cells, primary tumor xenografts, and tumor metastases were all highly sensitive to PARP1 inhibition. Addition of a PARP1 inhibitor to the second-line chemotherapeutic agent temozolamide resulted in complete responses of all treated tumors in an EWS-FLI1-driven mouse xenograft model of ESFT. Mechanistic investigations revealed that DNA damage induced by expression of EWS-FLI1 or EWS-ERG fusion genes was potentiated by PARP1 inhibition in ESFT cell lines. Notably, EWS-FLI1 fusion genes acted in a positive feedback loop to maintain the expression of PARP1, which was required for EWS-FLI-mediated transcription, thereby enforcing oncogene-dependent sensitivity to PARP-1 inhibition. Together, our findings offer a strong preclinical rationale to target the EWS-FLI1:PARP1 intersection as a therapeutic strategy to improve the treatment of ESFTs.
Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and D-galactosamine-treated mice.
Authors: V Lehmann, M A Freudenberg, C Galanos
Journal: The Journal of Experimental Medicine (1987)

The toxic properties of human recombinant tumor necrosis factor (TNF) were investigated in mice made hypersensitive to endotoxin by treatment with D-galactosamine. C3H/TifF mice treated with D-galactosamine were rendered sensitive to the lethal effects of submicrogram amounts of TNF. In the absence of D-galactosamine, TNF caused approximately 80% lethality with 500 micrograms. The duration of sensitization to TNF lasted up to 8 h after D-galactosamine administration, that towards LPS, up to 4 h. As with LPS, with TNF sensitization could be inhibited by uridine administered up to 2 h after D-galactosamine/TNF, showing that the early biochemical alterations in the liver known to be necessary for sensitization to LPS are also necessary for sensitization to TNF. In contrast to LPS, the toxicity of TNF was expressed also in D-galactosamine-treated endotoxin-resistant C3H/HeJ mice. The susceptibility of these mice to TNF was identical to that of endotoxin sensitive mice. In the absence of D-galactosamine the toxicity of TNF in C3H/HeJ mice was comparable to that obtained in C3H/TifF mice, being lethal with amounts of the order of 500 micrograms. The present results support the hypothesis that TNF is a mediator of lethal toxicity of endotoxin.
Phenotypic variability and incomplete penetrance of spontaneous fractures in an inbred strain of transgenic mice expressing a mutated collagen gene (COL1A1).
Authors: R Pereira, K Halford, B P Sokolov, J S Khillan, D J Prockop
Journal: Journal of Clinical Investigation (1994)

Phenotype variability and incomplete penetrance are frequently observed in human monogenic diseases such as osteogenesis imperfecta. Here an inbred strain of transgenic mice expressing an internally deleted gene for the pro alpha 1(I) chain of type I procollagen (COL1A1) was bred to wild type mice of the same strain so that the inheritance of a fracture phenotype could be examined in a homogeneous genetic background. To minimize the effects of environmental factors, the phenotype was evaluated in embryos that were removed from impregnated females 1 d before term. Examination of stained skeletons from 51 transgenic embryos from 11 separate litters demonstrated that approximately 22% had a severe phenotype with extensive fractures of both long bones and ribs, approximately 51% had a mild phenotype with fractures of ribs only, and approximately 27% had no fractures. The ratio of steady-state levels of the mRNA from the transgene to the level of mRNA from the endogenous gene was the same in all transgenic embryos. The results demonstrated that the phenotypic variability and incomplete penetrance were not explained by variations in genetic background or levels in gene expression. Instead, they suggested that phenotypic variation is an inherent feature of expression of a mutated collagen gene.
Distress and Depression in Men Who Have Sex With Men: The Urban Men’s Health Study
Authors: Thomas C. Mills, Jay Paul, Ron Stall, Lance Pollack, Jesse Canchola, Y. Jason Chang, Judith T. Moskowitz, Joseph A. Catania
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: This study estimates the prevalence of depression and describes the correlates and independent associations of distress and depression among U.S. men who have sex with men. METHOD: A household-based probability sample of men who have sex with men (N=2,881) was interviewed between 1996 and 1998 in four large American cities. With cutoff points of 15 and 22 for the Center for Epidemiological Studies Depression Scale, individual correlates and predictors of distress and depression were examined, and multinomial logistic regression was performed. RESULTS: The 7-day prevalence of depression in men who have sex with men was 17.2%, higher than in adult U.S. men in general. Both distress and depression were associated with lack of a domestic partner; not identifying as gay, queer, or homosexual; experiencing multiple episodes of antigay violence in the previous 5 years; and very high levels of community alienation. Distress was also associated with being of other than Asian/Pacific Islander ethnicity and experiencing early antigay harassment. Depression was also associated with histories of attempted suicide, child abuse, and recent sexual dysfunction. Being HIV positive was correlated with distress and depression but not significantly when demographic characteristics, developmental history, substance use, sexual behavior, and current social context were controlled by logistic regression. CONCLUSIONS: Rates of distress and depression are high in men who have sex with men. These high rates have important public health ramifications. The predictors of distress and depression suggest prevention efforts that might be effective when aimed at men who have sex with men.
Radiotherapy and Adjuvant Trastuzumab in Operable Breast Cancer: Tolerability and Adverse Event Data From the NCCTG Phase III Trial N9831
Authors: Michele Y. Halyard, Thomas M. Pisansky, Amylou C. Dueck, Vera Suman, Lori Pierce, Larry Solin, Larry Marks, Nancy Davidson, Silvana Martino, Peter Kaufman, Leila Kutteh, Shaker R. Dakhil, Edith A. Perez
Journal: Journal of Clinical Oncology (2009)

To assess whether trastuzumab (H) with radiotherapy (RT) increases adverse events (AEs) after breast-conserving surgery or mastectomy.Patients with early-stage resected human epidermal growth factor receptor 2 (HER-2) -positive breast cancer (BC) were randomly assigned to doxorubicin (A) and cyclophosphamide (C), followed by weekly paclitaxel (T; AC-T-H or AC-TH-H). RT criteria (with or without nodal RT) were postlumpectomy breast or (optional) postmastectomy chest wall. RT of internal mammary nodes was prohibited. RT commenced within 5 weeks after T, concurrently with H. Analysis included 1,503 irradiated patients for RT-associated AEs across treatment arms. Rates of cardiac events (CEs) with and without RT were compared within arms.No significant differences among arms were found in incidence of acute skin reaction, pneumonitis, dyspnea, cough, dysphagia, or neutropenia. A significant difference occurred in incidence of leukopenia, with higher rates for AC-T-H versus AC-T (odds ratio = 1.89; 95% CI, 1.25 to 2.88). At a median follow-up of 3.7 years (range, 0 to 6.5 years), RT with H did not increase relative frequency of CEs regardless of treatment side. The cumulative incidence of CEs with AC-T-H was 2.7% with or without RT. With AC-TH-H, the cumulative incidence was 1.7% v 5.9% with or without RT, respectively.Concurrent adjuvant RT and H for early-stage BC was not associated with increased acute AEs. Further follow-up is required to assess late AEs.
cis-Activation of the Human Telomerase Gene (hTERT) by the Hepatitis B Virus Genome
Authors: I. Horikawa, J. C. Barrett
Journal: JNCI Journal of the National Cancer Institute (2001)

Telomerase catalyzes the elongation of telomeric repeat DNA to maintain telomere length and structure (1). Although telomerase is a complex composed of a catalytic subunit (hTERT) and an RNA component (hTER), it is the expression of hTERT (2,3) that is the major determinant of telomerase activity in human cells (1,4). Maintaining telomere length by telomerase is associated with human cell immortalization and oncogenesis (1); however, no mutations in the hTERT or hTER telomerase genes have been found in human cancers. Hepatocellular carcinoma is often associated with both telomerase activation and viral infection. Here, we show the cisactivation of the hTERT gene by an insertion of viral DNA into the hTERT promoter region. A 66-base-pair (bp) sequence within the promoter region of hTERT gene (positions −372 to −307) (Fig. 1, A) is identical to a cellular sequence at the integration site of the hepatitis B virus (HBV) genome in a telomerase-positive (Fig. 1, B) hepatocellular carcinoma cell line, huH-4 (GenBank X51995) (5,6). This sequence corresponds to the upstream junction of the HBV integration (Fig. 1, A). Southern blot analysis confirmed an huH-4-specific rearrangement within the hTERT promoter and suggested an intact hTERT coding region in this cell line. Genomic polymerase chain reaction (PCR) by use of the primers from HBV (near the enhancer region or at the preS1 region) and hTERT sequences (in exon 1 or intron 2) generated huH-4-specific products (Fig. 1, C) that allowed identification of the downstream integration site of HBV (Fig. 1, A and E). The HBV genome was disrupted within its preS1 region and inserted at position −257 of the hTERT promoter, with an associated 49-bp deletion (positions −306 to −258) of the hTERT promoter. The integrated HBV genome was rearranged so that a HBV enhancer sequence (7) was placed about 1.6 kilobase upstream of the junction. The presence of a full-length hTERT messenger RNA starting from the endogenous transcription initiation site in huH-4 cells has been shown by the ribonuclease protection assay [see (5)] Affiliation of authors: Laboratory of Biosystems and Cancer, Cancer and Aging Section, Division of Basic Sciences, Center for Cancer Research, National Cancer Institute, Bethesda, MD. Correspondence to: Izumi Horikawa, Ph.D., National Institutes of Health, Bldg. 40, Rm. 2609, MSC-3020, Bethesda, MD 20892–3020 (e-mail: horikawi@mail.nih.gov). See “Notes” following “References.”