tbuckley/cabot-search huggingface dataset:
Consequences of Change in Waist Circumference on Cardiometabolic Risk Factors Over 9 Years
Authors: Beverley Balkau, Pascaline Picard, Sylviane Vol, Leopold Fezeu, Eveline Eschwège
Journal: Diabetes Care (2007)

Obesity and abdominal adiposity have been shown in prospective studies to be risk factors for cardiovascular disease and particularly for diabetes (1–8). In cross-sectional studies, both are related with risk factors for these diseases (9–12), but there are few publications on the effects of changes in abdominal adiposity (13). We characterized men and women who gained and lost abdominal adiposity over 9 years and describe the incidence and the improvement in cardiometabolic risk factors according to changes in waist circumference.

From the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort (9,14,15), 1,868 men and 1,939 women aged 30–64 years at baseline were followed over 9 years. The 73% of the baseline cohort that we studied were older, less frequently abdominally obese, hypertriglyceridemic, hyperinsulinemic, smokers, and fewer had metabolic syndrome. Cardiometabolic abnormalities and the metabolic syndrome were defined according to the National Cholesterol Education Program (NCEP) criteria (16), except high blood pressure, which included antihypertensive treatment (Table 1); hyperinsulinemia was defined by upper quartiles of fasting insulin ≥57.3 pmol/l for men and ≥52.8 pmol/l. The incidence and improvement of cardiometabolic risk factors were studied by age-adjusted logistic regression, according to waist change: ≤ −3.0 cm, −2.9 to +2.9 cm, 3.0–6.9 cm, and ≥7.0 cm. Statistical significance was defined as P < 0.05.

The median increase in waist circumference was 3 cm in men and …
Effect of Age on Breast Cancer Outcomes in Women With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From a Herceptin Adjuvant Trial
Authors: Ann H. Partridge, Shari Gelber, Martine J. Piccart-Gebhart, Florine Focant, Matthew Scullion, Eileen Holmes, Eric P. Winer, Richard D. Gelber
Journal: Journal of Clinical Oncology (2013)

Purpose Previous research has suggested that young age at diagnosis is an independent risk factor for breast cancer recurrence and death. No prior studies have adequately controlled for human epidermal growth factor receptor 2 (HER2) status or anti-HER2 treatment. We sought to evaluate whether age was a prognostic or predictive factor in the HERA trial. Patients and Methods We used 2-year median follow-up data and dichotomized age at 40 years to evaluate its prognostic effect on outcomes for women assigned to trastuzumab for 1 year or observation. Results Of the 1,703 women randomly assigned to 1 year of trastuzumab and 1,698 to observation, 722 (21%) were age ≤ 40 years at study entry. In separate Cox models, controlling for relevant prognostic and predictive factors, disease-free (DFS) and overall survival (OS) hazard ratios (HRs) were consistent for women age ≤ 40 versus &gt; 40 years, regardless of treatment assignment (observation group: DFS HR age ≤ 40 v &gt; 40 years, 1.18; 95% CI, 0.90 to 1.54; OS HR age ≤ 40 v &gt; 40 years, 1.01; 95% CI, 0.60 to 1.69; trastuzumab group: DFS HR age ≤ 40 v &gt; 40 years, 1.11; 95% CI, 0.81 to 1.51; OS HR age ≤ 40 v &gt; 40 years, 1.18; 95% CI, 0.66 to 2.09). Interaction between age group and treatment effect was not statistically significant (DFS P = .89; OS P = .55). Conclusion In a retrospective analysis of a large randomized controlled trial of women with early-stage HER2-positive breast cancer, age was not strongly associated with risk of early recurrence or prediction of benefit from trastuzumab therapy. Future research should investigate whether age is a predictor of later recurrence and evaluate the impact of age within groups with other tumor subtypes.
Disseminated Penicillium marneffei infection presenting as a right upper lobe mass in an HIV positive patient
Authors: H. McShane, C. M Tang, C. P Conlon
Journal: Thorax (1998)

A 35 year old HIV positive patient from Hong Kong presented with a fever, cough and a skin rash in association with a lung mass, all of which were due to disseminated <i>Penicillium marneffei</i>infection. He made a good response to antifungal therapy. The lung mass is a previously undescribed pulmonary manifestation of disseminated <i>Penicillium marneffei </i>infection. Infections with this fungus should be suspected in any patient with HIV and respiratory symptoms who has visited southeast Asia.
Whole-Genome Profiling of Pediatric Diffuse Intrinsic Pontine Gliomas Highlights Platelet-Derived Growth Factor Receptor α and Poly (ADP-ribose) Polymerase As Potential Therapeutic Targets
Authors: Maryam Zarghooni, Ute Bartels, Eric Lee, Pawel Buczkowicz, Andrew Morrison, Annie Huang, Eric Bouffet, Cynthia Hawkins
Journal: Journal of Clinical Oncology (2010)

Diffuse intrinsic pontine glioma (DIPG) is one of the most devastating of pediatric malignancies and one for which no effective therapy exists. A major contributor to the failure of therapeutic trials is the assumption that biologic properties of brainstem tumors in children are identical to cerebral high-grade gliomas of adults. A better understanding of the biology of DIPG itself is needed in order to develop agents targeted more specifically to these children's disease. Herein, we address this lack of knowledge by performing the first high-resolution single nucleotide polymorphism (SNP) -based DNA microarray analysis of a series of DIPGs.Eleven samples (nine postmortem and two pretreatment surgical samples), the largest series thus far examined, were hybridized to SNP arrays (250 k or 6.0). The study was approved by the research ethics board at our institution. All array findings were validated using quantitative polymerase chain reaction, fluorescence in situ hybridization, immunohistochemistry, and/or microsatellite analysis.Analysis of DIPG copy number alterations showed recurrent changes distinct from those of pediatric supratentorial high-grade astrocytomas. Thirty-six percent of DIPGs had gains in platelet-derived growth factor receptor alpha (PDGFRA; 4 to 18 copies) and all showed PDGFR-alpha expression. Low-level gains in poly (ADP-ribose) polymerase (PARP) -1 were identified in three cases. Pathway analysis revealed genes with loss of heterozygosity were enriched for DNA repair pathways.To our knowledge, our data provides the first, comprehensive high-resolution genomic analysis of pediatric DIPG. Our findings of recurrent involvement of the PDGFR pathway as well as defects in DNA repair pathways coupled with gain of PARP-1 highlight two potential, biologically based, therapeutic targets directed specifically at this devastating disease.
An Autoantibody-Mediated Immune Response to Calreticulin Isoforms in Pancreatic Cancer
Authors: Su-Hyung Hong, David E. Misek, Hong Wang, Eric Puravs, Thomas J. Giordano, Joel K. Greenson, Dean E. Brenner, Diane M. Simeone, Craig D. Logsdon, Samir M. Hanash
Journal: Cancer Research (2004)

Abstract The identification of circulating tumor antigens or their related autoantibodies provides a means for early cancer diagnosis as well as leads for therapy. We have used a proteomic approach to identify proteins that commonly induce a humoral response in pancreatic cancer. Aliquots of solubilized proteins from a pancreatic cancer cell line (Panc-1) were subjected to two-dimensional PAGE, followed by Western blot analysis in which sera of individual patients were tested for primary antibodies. Sera from 36 newly diagnosed patients with pancreatic cancer, 18 patients with chronic pancreatitis, 33 patients with other cancers, and 15 healthy subjects were analyzed. Autoantibodies were detected against either one or two calreticulin isoforms identified by mass spectrometry in sera from 21 of 36 patients with pancreatic cancer. One of 18 chronic pancreatitis patients and 1 of 15 healthy controls demonstrated autoantibodies to calreticulin isoform 1; none demonstrated autoantibodies to isoform 2. None of the sera from patients with colon cancer exhibited reactivity against either of these two proteins. One of 14 sera from lung adenocarcinoma patients demonstrated autoantibodies to calreticulin isoform 1; 2 of 14 demonstrated autoantibodies to isoform 2. Immunohistochemical analysis of calreticulin in pancreatic/ampullary tumor tissue arrays using an isoform nonspecific antibody revealed diffuse and consistent cytoplasmic staining in the neoplastic epithelial cells of the pancreatic and ampullary adenocarcinomas. The detection of autoantibodies to calreticulin isoforms may have utility for the early diagnosis of pancreatic cancer.
Relative Efficacy of Monophasic and Biphasic Waveforms for Transthoracic Defibrillation After Short and Long Durations of Ventricular Fibrillation
Authors: Gregory P. Walcott, Sharon B. Melnick, Fred W. Chapman, Janice L. Jones, William M. Smith, Raymond E. Ideker
Journal: Circulation (1998)

Background —Recently, interest has arisen in using biphasic waveforms for external defibrillation. Little work has been done, however, in measuring transthoracic defibrillation efficacy after long periods of ventricular fibrillation. In protocol 1, we compared the efficacy of a quasi-sinusoidal biphasic waveform (QSBW), a truncated exponential biphasic waveform (TEBW), and a critically damped sinusoidal monophasic waveform (CDSMW) after 15 seconds of fibrillation. In protocol 2, we compared the efficacy of the more efficacious biphasic waveform from protocol 1, QSBW, with CDSMW after 15 seconds and 5 minutes of fibrillation. Methods and Results —In protocol 1, 50% success levels, ED 50 , were measured after 15 seconds of fibrillation for the 3 waveforms in 6 dogs. In protocol 2, defibrillation thresholds were measured for QSBW and CDSMW after 15 seconds of fibrillation and after 3 minutes of unsupported fibrillation followed by 2 minutes of fibrillation with femoral-femoral cross-circulation. In protocol 1, QSBW had a lower ED 50 , 16.0±4.9 J, than TEBW, 20.3±4.4 J, or CDSMW, 27.4±6.0 J. In protocol 2, QSBW had a lower defibrillation threshold after 15 seconds, 38±10 J, and after 5 minutes, 41.5±5 J, than CDSMW after 15 seconds, 54±19 J, and 5 minutes, 80±30 J, of fibrillation. The defibrillation threshold remained statistically the same for QSBW for the 2 fibrillation durations but rose significantly for CDSMW. Conclusions —In this animal model of sudden death and resuscitation, these 2 biphasic waveforms are more efficacious than the CDSMW at short durations of fibrillation. Furthermore, the QSBW is even more efficacious than the CDSMW at longer durations of fibrillation.
Repair of protease-damaged elastin in neonatal rat aortic smooth muscle cell cultures.
Authors: P J Stone, S M Morris, B M Martin, M P McMahon, B Faris, C Franzblau
Journal: Journal of Clinical Investigation (1988)

The objective of this study was to investigate the elastin repair process in the rat aortic smooth muscle cell culture after proteolytic injury. Although little studied in vivo, elastin repair is thought to occur through a sequential process involving enzymatic removal (debridement) of damaged fibers followed by synthesis of tropoelastin, its subsequent processing, and eventual incorporation into new insoluble elastin. A second repair mechanism of proteolytically damaged elastin in a culture system is reported here. Repair in this system relates directly to restoration of resistance to elastin solubilization by hot alkali. As expected, severe injuries were observed with porcine pancreatic elastase (PPE). Using PPE, only 6% of the elastin, relative to control, was resistant to hot alkali immediately after elastase treatment. 4 wk later, resistance to hot alkali had increased dramatically to a mean of 90%. Repair took longer after injury with 75 micrograms of PPE as compared with 50 micrograms of PPE. The limited elastic fiber proteolysis induced by either human neutrophil elastase or porcine trypsin was repaired in culture within 2 wk. Elastin that had been radiolabeled with [3H]lysine 4-5 wk before injury was converted from a hot NaOH-susceptible to a NaOH-resistant elastin fraction during recovery from PPE injury. At the same time, the frayed elastic fibers that were seen with the electron microscope immediately after PPE treatment were replaced by continuous bands of elastin that resembled those in control cultures. Restoration of NaOH resistance did not require a net increase in total cell layer elastin, suggesting that relatively little new tropoelastin incorporation into the cell layer was required for this type of repair. These results suggested a salvage repair mechanism for proteolytically damaged elastin.
Modulation of Anthracycline-Induced Cardiotoxicity by Aerobic Exercise in Breast Cancer
Authors: Jessica M. Scott, Aarif Khakoo, John R. Mackey, Mark J. Haykowsky, Pamela S. Douglas, Lee W. Jones
Journal: Circulation (2011)

A nthracycline-containing chemotherapy (eg, doxorubi- cin) is well known to cause dose-dependent, progressive cardiac damage clinically manifest as decreased left ventricular (LV) ejection fraction and, ultimately, heart failure (HF) (Table 1). 1,2Unfortunately, the only clinically accepted method to minimize injury is dose modification and/or therapy discontinuation. 3An important current challenge in breast cancer management is therefore to maximize the benefits of doxorubicin while minimizing cardiac damage.Identification and examination of new interventions to prevent and/or treat doxorubicin-induced cardiotoxicity are urgently required.Aerobic exercise is a nonpharmacological therapy that promises to attenuate doxorubicin-induced cardiotoxicity.Aerobic exercise is well documented to improve systolic and diastolic function and attenuate pathological cardiac remodeling, resulting in improved exercise tolerance and resistance to fatigue during exertion in patients with HF. 4,5 The cardioprotective properties of aerobic exercise in the context of doxorubicin have, in contrast, received scant attention.It is not generally used in cancer patients despite its lack of "side effects" and the paucity of alternative strategies to prevent/ treat doxorubicin-associated cardiac damage.As a first step in the possible use of exercise in cancer patients, we reviewed the mechanisms of doxorubicininduced cardiotoxicity and the available evidence supporting the utility of aerobic exercise to prevent/treat cardiac injury.We also explored the molecular mechanisms that may underlie the cardioprotective properties of aerobic exercise.These findings have implications for future research regarding the application and effectiveness of exercise and doxorubicin treatment in humans.
Prognostic significance of Ki-67 labeling index after short-term presurgical tamoxifen in women with ER-positive breast cancer
Authors: A. DeCensi, A. Guerrieri-Gonzaga, S. Gandini, D. Serrano, M. Cazzaniga, S. Mora, H. Johansson, E.A. Lien, G. Pruneri, G. Viale, B. Bonanni
Journal: Annals of Oncology (2010)
Cardiac Overexpression of Melusin Protects From Dilated Cardiomyopathy Due to Long-Standing Pressure Overload
Authors: Marika De Acetis, Antonella Notte, Federica Accornero, Giulio Selvetella, Mara Brancaccio, Carmine Vecchione, Mauro Sbroggiò, Federica Collino, Beniamina Pacchioni, Gerolamo Lanfranchi, Alessandra Aretini, Roberta Ferretti, Angelo Maffei, Fiorella Altruda, Lorenzo Silengo, Guido Tarone, Giuseppe Lembo
Journal: Circulation Research (2005)

We have previously shown that genetic ablation of melusin, a muscle specific beta 1 integrin interacting protein, accelerates left ventricle (LV) dilation and heart failure in response to pressure overload. Here we show that melusin expression was increased during compensated cardiac hypertrophy in mice subjected to 1 week pressure overload, but returned to basal levels in LV that have undergone dilation after 12 weeks of pressure overload. To better understand the role of melusin in cardiac remodeling, we overexpressed melusin in heart of transgenic mice. Echocardiography analysis indicated that melusin over-expression induced a mild cardiac hypertrophy in basal conditions (30% increase in interventricular septum thickness) with no obvious structural and functional alterations. After prolonged pressure overload (12 weeks), melusin overexpressing hearts underwent further hypertrophy retaining concentric LV remodeling and full contractile function, whereas wild-type LV showed pronounced chamber dilation with an impaired contractility. Analysis of signaling pathways indicated that melusin overexpression induced increased basal phosphorylation of GSK3beta and ERK1/2. Moreover, AKT, GSK3beta and ERK1/2 were hyper-phosphorylated on pressure overload in melusin overexpressing compared with wild-type mice. In addition, after 12 weeks of pressure overload LV of melusin overexpressing mice showed a very low level of cardiomyocyte apoptosis and stromal tissue deposition, as well as increased capillary density compared with wild-type. These results demonstrate that melusin overexpression allows prolonged concentric compensatory hypertrophy and protects against the transition toward cardiac dilation and failure in response to long-standing pressure overload.
A 24‐week pegylated interferon alpha‐2b versus a 12‐week pegylated interferon alpha‐2b alone or with ribavirin for patients with acute hepatitis C
Authors: Chia‐Yen Dai, Wan‐Long Chuang, Ming‐Lung Yu
Journal: Hepatology (2014)

We read with great interest the manuscript by Santantonio et al.1 reporting on the results of the open, randomized, multicenter trial to assess efficacy and safety of a 24-week course of pegylated interferon (Peg-IFN) alpha-2b versus a 12-week course of Peg-IFN alone or with ribavirin (RBV) in acute hepatitis C (AHC) patients. With similar rates of sustained virological response (SVR; 70.5%-72.1% and 81.6% by intent-to-treat and per-protocol analysis, respectively), the researchers concluded that Peg-IFN induces a high SVR rate in AHC patients and treatment regimens do not influence the response rate. For chronic hepatitis C (CHC) patients, we have previously reported, in our randomized, controlled trials, that a rapid virological response (RVR; 87%) only for hepatitis C virus (HCV) genotype 2–infected patients and an RVR (43.5%) with a low viral load for genotype 1–infected patients encourage an abbreviated regimen in Taiwan.2, 3 In the present study, 51.5% (63 of 130) of patients infected with HCV genotype 2 or 3 and a 78.5% (102 of 130) RVR rate were reported. With similar SVR rates between a 12-week course of Peg-IFN monotherapy, RBV combination therapy, and a 24-week course of Peg-IFN monotherapy, it is interesting to know whether the RVR and HCV viral load may recommend a 12-week course of Peg-IFN therapy with or without RBV in AHC patients. Furthermore, we have recently suggested the “rapid stopping rule” after 4 weeks of treatment for genotype 1–infected CHC patients with Peg-IFN/RBV therapy: patients with (1) less than 1 log10 IU/mL decrease, (2) interleukin-28B rs8099917 non-TT genotype and HCV RNA level >10,000 IU/mL or less than 3 log10 IU/mL decrease in Taiwan.5,6 Although the study for AHC patients conducted by Santantonio et al.1 has evaluated the virological responses after 2 weeks of treatment (very RVR), which meets with agreed approval, further analyses for earlier identification of AHC patients who would fail to respond to the 12- or 24-week course therapy are needed. Chia-Yen Dai, M.D., Ph.D.1,2,3 Wan-Long Chuang, M.D., Ph.D.1,2 Ming-Lung Yu, M.D., Ph.D.1,2,3 1Hepatobiliary Division Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung, Taiwan 2Hepatitis Center Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung, Taiwan 3Department of Occupational and Environmental Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung, Taiwan
DY determinants, possibly associated with novel class II molecules, stimulate autoreactive CD4+ T cells with suppressive activity.
Authors: G Pawelec, N Fernandez, T Brocker, E M Schneider, H Festenstein, P Wernet
Journal: The Journal of Experimental Medicine (1988)

A set of T cell clones (TCC) isolated from HLA-DR-, Dw-, DQ-matched allogeneic MLCs was found to proliferate autonomously when stimulated with cells carrying a wide range of class I or II specificities. This apparently unrestricted proliferation was relatively weak, and only low levels of IL-2 were present in the supernatants of stimulated cells. Autologous as well as allogeneic PBMC and B lymphoblastoid cell lines (B-LCL) were capable of stimulating such clones, which were also restimulated by suppressive, but not by helper, TCC. Moreover, such clones displayed the unusual property of autostimulation. mAb inhibition experiments suggested that class II- or class II-restricted antigens were involved in stimulation. Thus, certain "broad" mAbs (TU39, SG520) reacting with multiple locus products inhibited activation of these reagents, but none of those reacting more specifically with DR (TU34, TU37, L243, Q2/70, SG157), DQ (TU22, SPV-L3, Leu 10), or DP (B7/21), or mixtures of these mAbs, were able to do so. Evidence from sequential immunoprecipitation experiments suggested that mAb TU39 bound class II-like molecules other than DR, DQ, and DP on TCC and B-LCL, and it is therefore proposed that such putative novel class II-like molecules may carry the stimulating determinants for these autoreactive clones. DY-reactive clones lacked helper activity for B cells but mediated potent suppressive activity on T cell proliferative responses that was not restricted by the HLA type of the responding cells. Suppressive activity was induced in normal PBMC by such clones, as well as by independent suppressive clones, which was also inhibited only by mAb TU39. These findings lead to the proposal that DY-reactive autostimulatory cells may constitute a self-maintaining suppressive circuit, the level of activity of which would be regulated primarily by the availability of IL-2 in the microenvironment.
Serum HIV-1 RNA Levels and Time to Development of AIDS in the Multicenter Hemophilia Cohort Study
Authors: T R O'Brien, W A Blattner, D Waters, E Eyster, M W Hilgartner, A R Cohen, N Luban, A Hatzakis, L M Aledort, P S Rosenberg, W J Miley, B L Kroner, J J Goedert
Journal: JAMA (1996)

To determine if the long-term incidence of the acquired immunodeficiency syndrome (AIDS) is related to human immunodeficiency virus type 1 (HIV-1) RNA levels measured early in HIV-1 infection.Epidemiologic cohort study.Five hemophilia treatment centers in the United States.A total of 165 subjects with hemophilia and HIV-1 infection (age at HIV-1 seroconversion, 1-66 years) followed from 1979 to 1995.The HIV-1 RNA level was measured by polymerase chain reaction over a range of 200 to 1 million or more HIV-1 RNA copies/mL in archived serum specimens collected 12 to 36 months (median, 27 months) after the estimated date of HIV-1 seroconversion. Kaplan-Meier methods were used to examine the risk of AIDS and proportional hazards models were used to estimate relative hazards.The HIV-1 RNA values were similar in subjects younger than 17 years at seroconversion (median, 5214 copies/mL) and those 18 to 34 years old (median, 4693 copies/mL), but higher in those 35 years or older (median, 12069 copies/mL) (P = .02 compared with each younger group). At 10 years after seroconversion, the proportions of subjects with AIDS were 72% among subjects with 100,000 or more HIV-1 RNA copies/mL measured 12 to 36 months after HIV-1 seroconversion (n = 9), 52% among subjects with 10,000 to 99,999 copies/mL (n = 55), 22% among subjects with 1000 to 9,999 copies/mL (n = 82), and 0% among subjects with fewer than 1000 copies/mL (n = 19) (P < .001). The age-adjusted relative hazard for AIDS for subjects with 10,000 or more copies/mL was 14.3 (95% confidence interval, 1.9-105.6) compared with subjects with fewer than 1000 copies/mL.The HIV-1 RNA level during early chronic HIV-1 infection is a strong, age-independent predictor of clinical outcome; low levels define persons with a high probability of long-term AIDS-free survival.