tbuckley/cabot-search huggingface dataset:
Intergenerational Cardiovascular Disease Risk Factors Involve Both Maternal and Paternal BMI
Authors: Idoia Labayen, Jonatan R. Ruiz, Francisco B. Ortega, Helle-Mai Loit, Jaanus Harro, Toomas Veidebaum, Michael Sjöström
Journal: Diabetes Care (2010)

OBJECTIVE To examine the association between parental BMI and offspring cardiovascular disease (CVD) risk factors. RESEARCH DESIGN AND METHODS The study comprised 940 children (9.5 ± 0.4 years) and 873 adolescents (15.5 ± 0.5 years). Parental weight and height were reported by the mother and the father, and BMI was calculated. CVD risk factors included total (sum of five skinfolds) and central (waist circumference) body fat, blood pressure, cardiorespiratory fitness, insulin sensitivity, total cholesterol, HDL cholesterol, triglycerides, and fibrinogen. RESULTS Maternal and paternal BMI were positively associated with total and central fatness in offspring (P &amp;lt; 0.001). BMIs of both parents were significantly related to fibrinogen levels (P &amp;lt; 0.02), but these associations disappeared when controlling for fatness. There was a positive relationship between maternal and paternal BMI and waist circumference in the offspring regardless of total adiposity and height (P &amp;lt; 0.001). Maternal BMI was negatively associated with offspring cardiorespiratory fitness independently of fatness (P &amp;lt; 0.02). These relationships persisted when overweight descendants were excluded from the analysis. There were no significant associations between parental BMI and the other CVD risk factors. CONCLUSIONS Both maternal and paternal BMI increase CVD risk factors of their offspring, characterized by total and central body fat, and higher maternal BMI was associated with poorer cardiorespiratory fitness. Our findings give further support to the concept that adiposity in parents transmits susceptibility to CVD risk to descendants, which is detectable even in the absence of overweight in offspring.
mRNA expression profiles show differential regulatory effects of microRNAs between estrogen receptor-positive and estrogen receptor-negative breast cancer
Authors: Chao Cheng, Xuping Fu, Pedro Alves, Mark Gerstein
Journal: Genome biology (2009)

Abstract Background Recent studies have shown that the regulatory effect of microRNAs can be investigated by examining expression changes of their target genes. Given this, it is useful to define an overall metric of regulatory effect for a specific microRNA and see how this changes across different conditions. Results Here, we define a regulatory effect score (RE-score) to measure the inhibitory effect of a microRNA in a sample, essentially the average difference in expression of its targets versus non-targets. Then we compare the RE-scores of various microRNAs between two breast cancer subtypes: estrogen receptor positive (ER + ) and negative (ER - ). We applied this approach to five microarray breast cancer datasets and found that the expression of target genes of most microRNAs was more repressed in ER - than ER + ; that is, microRNAs appear to have higher RE-scores in ER - breast cancer. These results are robust to the microRNA target prediction method. To interpret these findings, we analyzed the level of microRNA expression in previous studies and found that higher microRNA expression was not always accompanied by higher inhibitory effects. However, several key microRNA processing genes, especially Ago2 and Dicer , were differentially expressed between ER - and ER + breast cancer, which may explain the different regulatory effects of microRNAs in these two breast cancer subtypes. Conclusions The RE-score is a promising indicator to measure microRNAs' inhibitory effects. Most microRNAs exhibit higher RE-scores in ER - than in ER + samples, suggesting that they have stronger inhibitory effects in ER - breast cancers.
Portal Hypertension and Liver Surgery Following Selective Internal Radiation Therapy With 90Yttrium Microspheres
Authors: Richard S. Stubbs
Journal: Journal of Clinical Oncology (2006)

TO THE EDITOR: I wish to comment on the letter in the November 10, 2005, issue of the Journal of Clinical Oncology by Ayav et al. During the last 7 years, we have treated more than 200 patients with Yttrium microspheres and have published a number of papers on the subject. We and others have previously commented on the development of portal hypertension following this treatment, but have never seen this become a clinical problem. Certainly it adds an additional dimension to any subsequent abdominal surgery, including hepatectomy, but so too does neoadjuvant chemotherapy used for downstaging before liver resection. While we think it useful that Ayav et al have highlighted this feature of selective internal radiation therapy (SIRT), we think their conclusions are rather strong and should not go unchallenged. We have reoperated on many patients after SIRT, including five patients for hepatic cryoablation and four patients for hepatic resection, as have other groups from around the world with large experience of this treatment. Prohibitive problems and complications have not been encountered by us or reported by others, even when this treatment has been given to those with underlying liver disease, as is so often the case in patients with hepatocellular carcinoma. For the authors to conclude on the basis of a single bad experience that, “this therapy should be considered as a treatment option only for unresectable patients without any co-existing portal hypertension, and should not be considered as a downstaging therapy” is simply not justifiable. Liver resection has and can be performed safely after SIRT. Any treatment that can achieve downstaging of nonresectable liver tumors to such a degree as to allow subsequent resection should be considered a triumph. The fact that the subsequent resection presents additional challenges for the surgeon is no reason to not use the treatment in this context. Those groups with a large experience of SIRT can all attest to the high response rate achieved by the treatment and to the fact that occasionally further surgical options become possible. It would be a shame if the use of the modality was curtailed to any extent as a result of a poor experience in one patient.
LONG-TERM OUTCOMES OF CORONARY ARTERY BYPASS GRAFTING OR PERCUTANEOUS CORONARY INTERVENTION WITH DRUG-ELUTING STENT FOR THREE-VESSEL CORONARY ARTERY DISEASE IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Tatsuya Ito, Nobuyoshi Tanaka, Daisuke Yokota, Yoshihiro Ko, Tsuyoshi Itoh, Atsuko Kodama, Souichiro Ebisawa, Maoto Habara, Tairo Kurita, Takahiko Suzuki
Journal: Journal of the American College of Cardiology (2011)
LOCAL SPECIFIC THERAPY OF EXPERIMENTAL PNEUMOCOCCAL MENINGITIS
Authors: Fred W. Stewart
Journal: The Journal of Experimental Medicine (1928)

1. In experimental Type I pneumococcal meningitis of dogs central cord involvement is common after the 2nd day of the disease. 2. These central cord lesions may progress toward extensive suppurative myelitis. 3. Abscesses are infrequent; they arise either as direct perivascular extensions of the meningeal disease or at the site of infected purpuric lesions. 4. In prolonged untreated meningitis of reinfected animals, nothing resembling the disappearance of exudate following crisis in pneumonia occurs. The tendency is toward organization. 5. Late lesions are characterized by the marked development of a perivascular clasmatocytic apparatus, similar to, but more extensive than that hitherto reported in experimental herpetic encephalitis.
Long-term Mortality After Stroke Among Adults Aged 18 to 50 Years
Authors: Loes C. A. Rutten-Jacobs, Renate M. Arntz, Noortje A. M. Maaijwee, Henny C. Schoonderwaldt, Lucille D. Dorresteijn, Ewoud J. van Dijk, Frank-Erik de Leeuw
Journal: JAMA (2013)

LEADINGcausesofmortality,withanannual 6 million fatal events worldwide. 1 Stroke mainly affects elderly people, yet approximately 10% of strokes occur in patients younger than 50 years. 24][5][6][7][8][9] Itisexactlythislong-termprognosis that is particularly important in adults in these ages, given that they have a long life expectancy during a demanding time of life in which they are beginning their families and building their careers.Thetermyoungstrokeisusedherein to refer to a stroke that occurs in adults aged 18 through 50 years.The prognosis of young stroke is generally considered benign, given that short-term mortality is lower compared with that of older patients with stroke.Notably, these older patients have a much higher a priori mortality rate, simply because of their age.A more sensible approach would therefore be to compare mortality in a population of adults with young stroke with mortality in the age-and sex-matched general population to calculate the excess
Oxaliplatin and Axonal Na+ Channel Function <i>In vivo</i>
Authors: Arun V. Krishnan, David Goldstein, Michael Friedlander, Matthew C. Kiernan
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The aim of the study was to investigate the pathophysiology of oxaliplatin-induced neurotoxicity using clinical nerve excitability techniques that provide information about axonal ion channel function. Experimental Design: Excitability studies were combined with standard nerve conduction studies and clinical assessment in 22 patients undergoing treatment with oxaliplatin. Results: Excitability studies recorded before and immediately after oxaliplatin infusion for 89 treatment cycles revealed significant increases in refractoriness and relative refractory period postinfusion in all patients, consistent with an effect of oxaliplatin on axonal Na+ channels. However, those patients that developed chronic neuropathy had significantly greater changes. Following cessation of oxaliplatin treatment, 41% of patients had persistent symptoms and nerve conduction abnormalities consistent with the development of chronic neuropathy. Conclusion: The present study provides evidence that oxaliplatin-induced neurotoxicity is mediated through an effect on axonal Na+ channels. Clinical nerve excitability techniques may prove beneficial in monitoring for early signs of neurotoxicity and in the assessment of future prophylactic therapies.
Inhibition of Oesophageal Squamous Cell Carcinoma Progression by in vivo Targeting of Hyaluronan Synthesis
Authors: Sören Twarock, Till Freudenberger, Eva Poscher, Guang Dai, Katharina Jannasch, Christian Dullin, Frauke Alves, Klaus Prenzel, Wolfram T Knoefel, Nikolas H Stoecklein, Rashmin C Savani, Bernhard Homey, Jens W Fischer
Journal: Molecular Cancer (2011)

Oesophageal cancer is a highly aggressive tumour entity with at present poor prognosis. Therefore, novel treatment options are urgently needed. Hyaluronan (HA) is a polysaccharide present in the matrix of human oesophageal squamous cell carcinoma (ESCC). Importantly, in vitro ESCC cells critically depend on HA synthesis to maintain the proliferative phenotype. The aim of the present study is (1) to study HA-synthase (HAS) expression and regulation in human ESCC, and (2) to translate the in vitro results into a mouse xenograft model of human ESCC to study the effects of systemic versus tumour targeted HAS inhibition on proliferation and distribution of tumour-bound and stromal hyaluronan.mRNA expression was investigated in human ESCC biopsies by semiquantitative real-time RT PCR. Furthermore, human ESCC were xenografted into NMRI nu/nu mice. The effects on tumour progression and morphology of 4-methylumbelliferone (4-MU), an inhibitor of HA-synthesis, and of lentiviral knock down of HA-synthase 3 (HAS3), the main HAS isoform in the human ESCC tissues and the human ESCC cell line used in this study, were determined. Tumour progression was monitored by calliper measurements and by flat-panel detector volume computed tomography (fpVCT). HA content, cellular composition and proliferation (Ki67) were determined histologically.mRNA of HAS isoform 3 (HAS3) was upregulated in human ESCC biopsies and HAS3 mRNA was positively correlated to expression of the epidermal growth factor (EGF) receptor. EGF was also proven to be a strong inductor of HAS3 mRNA expression in vitro. During the course of seven weeks, 4-MU inhibited progression of xenograft tumours. Interestingly, remodelling of the tumour into a more differentiated phenotype and inhibition of cell proliferation were observed. Lentiviral knockdown of HAS3 in human ESCC cells prior to xenografting mimicked all effects of 4-MU treatment suggesting that hyaluronan produced by ESCC is accountable for major changes in tumour environment in vivo.Systemic inhibition of HA-synthesis and knockdown of tumour cell HAS3 cause decreased ESCC progression accompanied by tumour stroma remodelling and may therefore be used in novel approaches to ESCC therapy.
Quality in the technical performance of screening flexible sigmoidoscopy: recommendations of an international multi-society task group
Authors: T R Levin
Journal: Gut (2005)

<b>Background:</b> Flexible sigmoidoscopy (FS) is a complex technical procedure performed in a variety of settings, by examiners with diverse professional backgrounds, training, and experience. Potential variation in technical quality may have a profound impact on the effectiveness of FS on the early detection and prevention of colorectal cancer. <b>Aim:</b> We propose a set of consensus and evidence based recommendations to assist the development of continuous quality improvement programmes around the delivery of FS for colorectal cancer screening. <b>Recommendations:</b> These recommendations address the intervals between FS examinations, documentation of results, training of endoscopists, decision making around referral for colonoscopy, policies for antibiotic prophylaxis and management of anticoagulation, insertion of the FS endoscope, bowel preparation, complications, the use of non-physicians as FS endoscopists, and FS endoscope reprocessing. For each of these areas, continuous quality improvement targets are recommended, and research questions are proposed.
Effects of Once-Weekly Dosing of a Long-Acting Release Formulation of Exenatide on Glucose Control and Body Weight in Subjects With Type 2 Diabetes
Authors: Dennis Kim, Leigh MacConell, Dongliang Zhuang, Prajakti A. Kothare, Michael Trautmann, Mark Fineman, Kristin Taylor
Journal: Diabetes Care (2007)

OBJECTIVE—In patients with type 2 diabetes, exenatide reduces A1C, postprandial and fasting glucose, and weight. In this study we investigated the effects of continuous exenatide administration from a long-acting release (LAR) formulation. RESEARCH DESIGN AND METHODS—In this randomized, placebo-controlled phase 2 study, exenatide LAR (0.8 or 2.0 mg) was administered subcutaneously once weekly for 15 weeks to subjects with type 2 diabetes (n = 45) suboptimally controlled with metformin (60%) and/or diet and exercise (40%): 40% female, A1C (mean ± SD) 8.5 ± 1.2%, fasting plasma glucose 9.9 ± 2.3 mmol/l, weight 106 ± 20 kg, and diabetes duration 5 ± 4 years. RESULTS—From baseline to week 15, exenatide LAR reduced mean ± SE A1C by −1.4 ± 0.3% (0.8 mg) and −1.7 ± 0.3% (2.0 mg), compared with +0.4 ± 0.3% with placebo LAR (P &amp;lt; 0.0001 for both). A1C of ≤7% was achieved by 36 and 86% of subjects receiving 0.8 and 2.0 mg exenatide LAR, respectively, compared with 0% of subjects receiving placebo LAR. Fasting plasma glucose was reduced by −2.4 ± 0.9 mmol/l (0.8 mg) and −2.2 ± 0.5 mmol/l (2.0 mg) compared with +1.0 ± 0.7 mmol/l with placebo LAR (P &amp;lt; 0.001 for both). Exenatide LAR reduced self-monitored postprandial hyperglycemia. Subjects receiving 2.0 mg exenatide LAR had body weight reductions (−3.8 ± 1.4 kg) (P &amp;lt; 0.05), whereas body weight was unchanged with both placebo LAR and the 0.8-mg dose. Mild nausea was the most frequent adverse event. No subjects treated with exenatide LAR withdrew from the study. CONCLUSIONS—Exenatide LAR offers the potential of 24-h glycemic control and weight reduction with a novel once-weekly treatment for type 2 diabetes.
DNA Sequencing of Cancer: What Have We Learned?
Authors: Juliann Chmielecki, Matthew Meyerson
Journal: Annual Review of Medicine (2013)

DNA sequencing has taught us much about the structure of cancer genomes and enabled the discovery of novel genes that drive and maintain tumorigenesis. With the advent and application of next-generation massively parallel sequencing technologies, one can rapidly generate and analyze data from the cellular “-omes”: genomes, exomes, and transcriptomes. This review highlights recent genomic discoveries in signal transduction, metabolism, epigenetic modifications, cell cycle and genome maintenance, RNA processing, and transcription. Additionally, genomic sequencing has revealed the complexity of the cancer genome and has enabled the discovery of functional rearrangements with therapeutic and diagnostic potentials.
Forty-Year Journey of Angiogenesis Translational Research
Authors: Yihai Cao, Jack Arbiser, Robert J. D’Amato, Patricia A. D’Amore, Donald E. Ingber, Robert Kerbel, Michael Klagsbrun, Sharon Lim, Marsha A. Moses, Bruce Zetter, Harold Dvorak, Robert Langer
Journal: Science Translational Medicine (2011)

Antiangiogenic drugs successfully treat retinal vascular diseases, but challenges remain in the realm of cancer therapy.
CN-17 * IMPACT OF AGE AT DIAGNOSIS ON OBESITY IN PEDIATRIC BRAIN TUMOR SURVIVORS
Authors: K. Strobel, P. Simpson, P. Donohoue, S. Firat, S. Jogal
Journal: Neuro-Oncology (2014)

INTRODUCTION: Obesity is a long-term morbidity for children diagnosed with CNS tumors. Body Mass Index (BMI) normally declines until the age of adiposity rebound (AR), after which it increases. Tumor location, radiation therapy, or surgery near the hypothalamus increases risk of obesity. We hypothesized involvement of the hypothalamus would result in greater BMI, and diagnosis/treatment before AR would lead to the greatest BMI. METHODS: Retrospective cohort of brain tumor survivors diagnosed from 2001-2011 at Children's Hospital of Wisconsin: chart review extracted BMI (recorded as BMI z-score) at diagnosis and two-year follow-up. Children were categorized into six groups, based on age at diagnosis and hypothalamic involvement (HI). Consistent with CDC growth curves, ages were classified as "before AR" (0-41.99 months), "during AR" (42-83.99 months) and "after AR" (84.00 - 120 months old). BMI z-scores were compared using Wilcoxon signed ranks tests. RESULTS: 116 children had two-year follow-up. BMI z-score at diagnosis was similar across groups. Children pre-AR and post-AR with HI had higher BMI z-scores at two-year follow up than at diagnosis (before AR 0.466 to 1.589 p = 0.004 N = 12, after AR 0.519 to 1.268 p = 0.001 N = 18). No group without HI had increased BMI z-score at two-year follow up (before AR 0.663 to 0.518 N = 24, during AR 0.279 to 0.278 N = 18, after AR 0.658 to 0.793 N = 24). The before AR and during AR cohort with HI had a higher BMI z-score at two-year follow up then those without HI (p = 0.004 and 0.015). The after AR cohort did not significantly differ from those without HI at two-year follow up. CONCLUSIONS: Children with CNS tumors with HI have increased BMI compared to those without hypothalamic involvement. Diagnosis before adiposity rebound is associated with a greater BMI than diagnosis at later age. Future studies can help elucidate the endocrine causes of changes.
THE EFFECT OF POTASSIUM DEFICIENCY ON THE REABSORPTION OF PROTEIN IN THE RENAL TUBULE OF THE RAT
Authors: Ashton B. Morrison, Kenneth D. Gardner
Journal: The Journal of Experimental Medicine (1963)

Male Wistar rats were made potassium-deficient by feeding a diet low in potassium, while controls were pair-fed the same diet supplemented with potassium. Four weeks later 10 mg of T-1824 was injected into each rat. It was found that the characteristic granules which accumulate in the renal collecting tubule cells as a result of potassium deficiency were colored blue and that a diminished coloration of the convoluted tubule cells of the kidney was present. Quantitative measurements of the renal T-1824 content showed that it was decreased as a result of potassium deficiency. The daily rate of protein excretion was increased by the potassium deficiency. It is concluded that potassium deficiency decreases reabsorption of protein in the convoluted tubules of the kidney and that increased proteinuria thus results. Also, the granules which appear in renal collecting tubule cells as a result of potassium deficiency contain serum protein, which probably enters the cells from the tubular lumen.
SPONTANEOUS AND EXPERIMENTAL LEUKEMIA OF THE FOWL
Authors: Harry C. Schmeisser
Journal: The Journal of Experimental Medicine (1915)

1. The spontaneous occurrence of myeloid leukemia of the fowl is confirmed 2. Myeloid leukemia of the fowl is transmissible by intravenous or intraperitoneal injection of an organic emulsion. The latter is in confirmation of the work of Ellermann and Bang (6, 7), who first successfully transmitted the disease. They were followed by Hirschfeld and Jacoby (13)) whose successful transmissions, however, seem to be limited to a strain which had its origin in a fowl presented to them by Ellermann and Bang. Burckhardt (14, 15) likewise transmitted the disease, but here again the stock animal came from Hirschfeld and Jacoby and therefore indirectly from Ellermann and Bang. The transmission reported above is of special interest, because it originated in an animal absolutely unrelated to that of the previous investigators.
Prognostic factors of mycological cure following treatment of onychomycosis with oral antifungal agents
Authors: B. Sigurgeirsson, C. Paul, D. Curran, E.G.V. Evans
Journal: British Journal of Dermatology (2002)

There is considerable literature on the efficacy and safety of various drugs used in treating onychomycosis; however, little information is available regarding prognostic factors which may be associated with non-response to conventional treatment.To identify parameters influencing mycological cure at 72 weeks following treatment of toenail onychomycosis with oral antifungal agents.Univariate and multivariate logistic regression analysis from a randomized double-blind controlled trial including 496 patients with toenail onychomycosis caused by dermatophytes.Baseline parameters including patient's age, gender, weight, number of toenails involved, percentage of nail involvement, duration of infection, history of previous treatment were not associated with mycological cure. In the multivariate prognostic factor analysis based on factors assessed at week 12, positive mycological culture at 12 weeks [odds ratio (OR): 0.583; 95% confidence interval (CI): 0.370-0.918] was negatively associated with mycological cure at 72 weeks. Similarly, in the multivariate prognostic factor analysis based on factors assessed at week 24, positive direct microscopy at 24 weeks (OR: 0.373; 95% CI: 0.211-0.659) and mycological culture at 24 weeks (OR: 0.293; 95% CI: 0.168-0.513) were negatively associated with mycological cure at 72 weeks.Mycological culture at 12 and 24 weeks and direct microscopic examination at 24 weeks can help in early identification of patients failing to respond to conventional oral antifungal treatment.
Inheritance and influence of histocompatibility (HL-A) antigens in adult coeliac disease
Authors: P. L. Stokes, P. Asquith, G. K. T. Holmes, P. Mackintosh, W. T. Cooke
Journal: Gut (1973)

In a study of histocompatibility antigens in adult coeliac disease the HL-A phenotypes have been determined in 117 patients and 149 of their first-degree relatives, of whom 94 had had a jejunal biopsy performed. There was an increased frequency of the HL-A 8 antigen in the patients and their relatives. Family studies showed no irregularity in the inheritance of both this antigen and the HL-A 1 and 8 haplotype.