tbuckley/cabot-search huggingface dataset:
Diversity in Cardiovascular Outcomes Among Chinese and South Asian Patients
Authors: John Z. Ayanian
Journal: Circulation (2010)

W ith a combined population of 2.8 billion people, China and the countries of South Asia, including India, Pakistan, and Bangladesh, comprise 40% of the global population of nearly 7 billion people.Immigration to North America from China and South Asia has increased substantially in recent decades.In 2000, people of Chinese descent represented 1.0% of the US population, and those of South Asian descent represented 0.8%. 1 In 2006, the corresponding proportions of the Canadian population were even higher at 4.3% and 4.2%, respectively. 2With the recent growth of these ethnic groups in North America, their health risks, quality of care, and outcomes have become more important to assess.
The Effect of the PREMIER Interventions on Insulin Sensitivity
Authors: Jamy D. Ard, Steve C. Grambow, Di Liu, Cris A. Slentz, William E. Kraus, Laura P. Svetkey
Journal: Diabetes Care (2004)

OBJECTIVE—This ancillary study of PREMIER sought to determine the effects on insulin sensitivity of a comprehensive behavioral intervention for hypertension with and without the Dietary Approaches to Stop Hypertension (DASH) dietary pattern. RESEARCH DESIGN AND METHODS— Participants were assigned to one of three nonpharmacologic interventions for blood pressure (group A, advice only; group B, established; and group C, established plus DASH). The established intervention included weight loss, reduced sodium intake, increased physical activity, and moderate alcohol intake; the DASH dietary pattern was added to the established intervention for those in group C. The DASH dietary pattern is high in fruits, vegetables, and low-fat dairy products while being lower in total fat, saturated fat, and cholesterol. It is abundant in nutrients such as magnesium, calcium, and protein, which have been associated with improved insulin sensitivity. Insulin sensitivity was measured at baseline and at 6 months using the frequently sampled intravenous glucose tolerance test with minimal model analysis. RESULTS—Both intervention groups decreased total calories, percentage of calories from fat, and sodium intake to similar levels, with similar amounts of energy expenditure and weight loss. Covariate differences seen only in group C included increased intake of protein, potassium, calcium, and magnesium. Compared with control subjects, insulin sensitivity improved significantly only in group C, from 1.96 to 2.95 (P = 0.047). Group B did have a significant decrease in fasting insulin and glucose, but the changes in insulin sensitivity did not reach statistical significance when compared with control subjects. CONCLUSIONS—These results suggest that including the DASH dietary pattern as part of a comprehensive intervention for blood pressure control enhances insulin action beyond the effects of a comprehensive intervention that does not include DASH.
Crk1/2-dependent signaling is necessary for podocyte foot process spreading in mouse models of glomerular disease
Authors: Britta George, Rakesh Verma, Abdulsalam A. Soofi, Puneet Garg, Jidong Zhang, Tae-Ju Park, Laura Giardino, Larisa Ryzhova, Duncan B. Johnstone, Hetty Wong, Deepak Nihalani, David J. Salant, Steven K. Hanks, Tom Curran, Maria Pia Rastaldi, Lawrence B. Holzman
Journal: Journal of Clinical Investigation (2012)

The morphology of healthy podocyte foot processes is necessary for maintaining the characteristics of the kidney filtration barrier. In most forms of glomerular disease, abnormal filter barrier function results when podocytes undergo foot process spreading and retraction by remodeling their cytoskeletal architecture and intercellular junctions during a process known as effacement. The cell adhesion protein nephrin is necessary for establishing the morphology of the kidney podocyte in development by transducing from the specialized podocyte intercellular junction phosphorylation-mediated signals that regulate cytoskeletal dynamics. The present studies extend our understanding of nephrin function by showing that nephrin activation in cultured podocytes induced actin dynamics necessary for lamellipodial protrusion. This process required a PI3K-, Cas-, and Crk1/2-dependent signaling mechanism distinct from the previously described nephrin-Nck1/2 pathway necessary for assembly and polymerization of actin filaments. Our present findings also support the hypothesis that mechanisms governing lamellipodial protrusion in culture are similar to those used in vivo during foot process effacement in a subset of glomerular diseases. In mice, podocyte-specific deletion of Crk1/2 prevented foot process effacement in one model of podocyte injury and attenuated foot process effacement and associated proteinuria in a delayed fashion in a second model. In humans, focal adhesion kinase and Cas phosphorylation - markers of focal adhesion complex-mediated Crk-dependent signaling - was induced in minimal change disease and membranous nephropathy, but not focal segmental glomerulosclerosis. Together, these observations suggest that activation of a Cas-Crk1/2-dependent complex is necessary for foot process effacement observed in distinct subsets of human glomerular diseases.
Voltage-tension relations in single frog atrial cardiac cells.
Authors: M Tarr, J W Trank, K K Goertz
Journal: Circulation Research (1986)

Voltage-clamp experiments were performed on isolated single frog (Rana catesbeiana or Rana pipiens) atrial cells to determine the voltage-contraction relations of the single cardiac cell. The contractile responses of the single cell associated with long duration (3 second) depolarizing steps consisted of a rise to peak (phasic) followed by a decay to a sustained contraction (tonic). These phasic-tonic type contractile responses could be obtained under conditions where membrane potential was well controlled along the entire length of the cell. Thus, the data obtained on the single cell indicate that the phasic-tonic contractile response is the characteristic contractile response of frog atrial tissue. The voltage dependence of the extent of relaxation to the tonic component following the peak of the contraction was affected dramatically by the intracellular sodium concentration. This result indicates that both the relaxation following peak contraction as well as the tonic contraction are related to calcium control via the sodium-calcium exchanger. The data also indicate that calcium entry via the inward calcium current is required for the contractile response to have a phasic component. These data indicate that calcium entry via the inward calcium current followed by the sodium-calcium exchanger first reducing and then maintaining the intracellular calcium level produces the characteristic phasic-tonic contractile response.
The elegance of the gastric mucosal barrier: designed by nature for nature
Authors: Kenneth E L McColl
Journal: Gut (2011)

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.
Familial Felty's syndrome.
Authors: L M Blendis, K L Jones, E B Hamilton, R Williams
Journal: Annals of the Rheumatic Diseases (1976)

A family is described in which the mother and 2 of the 5 children had Felty's syndrome, a pattern of inheritance suggesting a dominant defect and one which has not previously been reported. The family is also of interest in that the other sib had rheumatoid arthritis.
A novel M cell–specific carbohydrate-targeted mucosal vaccine effectively induces antigen-specific immune responses
Authors: Tomonori Nochi, Yoshikazu Yuki, Akiko Matsumura, Mio Mejima, Kazutaka Terahara, Dong-Young Kim, Satoshi Fukuyama, Kiyoko Iwatsuki-Horimoto, Yoshihiro Kawaoka, Tomoko Kohda, Shunji Kozaki, Osamu Igarashi, Hiroshi Kiyono
Journal: The Journal of Experimental Medicine (2007)

Mucosally ingested and inhaled antigens are taken up by membranous or microfold cells (M cells) in the follicle-associated epithelium of Peyer's patches or nasopharynx-associated lymphoid tissue. We established a novel M cell–specific monoclonal antibody (mAb NKM 16–2-4) as a carrier for M cell–targeted mucosal vaccine. mAb NKM 16–2-4 also reacted with the recently discovered villous M cells, but not with epithelial cells or goblet cells. Oral administration of tetanus toxoid (TT)– or botulinum toxoid (BT)–conjugated NKM 16–2-4, together with the mucosal adjuvant cholera toxin, induced high-level, antigen-specific serum immunoglobulin (Ig) G and mucosal IgA responses. In addition, an oral vaccine formulation of BT-conjugated NKM 16–2-4 induced protective immunity against lethal challenge with botulinum toxin. An epitope analysis of NKM 16–2-4 revealed specificity to an α(1,2)-fucose–containing carbohydrate moiety, and reactivity was enhanced under sialic acid–lacking conditions. This suggests that NKM 16–2-4 distinguishes α(1,2)-fucosylated M cells from goblet cells containing abundant sialic acids neighboring the α(1,2) fucose moiety and from non-α(1,2)-fucosylated epithelial cells. The use of NKM 16–2-4 to target vaccine antigens to the M cell–specific carbohydrate moiety is a new strategy for developing highly effective mucosal vaccines.
Prediction of Type 1 Diabetes in the General Population
Authors: Mikael Knip, Sari Korhonen, Petri Kulmala, Riitta Veijola, Antti Reunanen, Olli T. Raitakari, Jorma Viikari, Hans K. Åkerblom
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate the utility of GAD antibodies (GADAs) and islet antigen-2 antibodies (IA-2As) in prediction of type 1 diabetes over 27 years in the general population and to assess the 6-year rates of seroconversion. RESEARCH DESIGN AND METHODS A total of 3,475 nondiabetic subjects aged 3–18 years were sampled in 1980, and 2,375 subjects (68.3%) were resampled in 1986. All subjects were observed for development of diabetes to the end of 2007. GADAs and IA-2As were analyzed in all samples obtained in 1980 and 1986. RESULTS A total of 34 individuals (1.0%; 9 developed diabetes) initially had GADAs and 22 (0.6%; 9 developed diabetes) IA-2As. Seven subjects (0.2%) tested positive for both autoantibodies. The positive seroconversion rate over 6 years was 0.4% for GADAs and 0.2% for IA-2As, while the inverse seroconversion rates were 33 and 57%, respectively. Eighteen subjects (0.5%) developed type 1 diabetes after a median pre-diabetic period of 8.6 years (range 0.9–20.3). Initial positivity for GADAs and/or IA-2As had a sensitivity of 61% (95% CI 36–83) for type 1 diabetes. Combined positivity for GADAs and IA-2As had both a specificity and a positive predictive value of 100% (95% CI 59–100). CONCLUSIONS One-time screening for GADAs and IA-2As in the general childhood population in Finland would identify ∼60% of those individuals who will develop type 1 diabetes over the next 27 years, and those subjects who have both autoantibodies carry an extremely high risk for diabetes. Both positive and inverse seroconversions do occur over time reflecting a dynamic process of β-cell autoimmunity.
Tumor Cells Fail to <b> <i>trans</i> </b>-Induce Telomerase in Human Umbilical Vein Endothelial Cell Cultures
Authors: Esterina Pascale, Graziella Cimino Reale, Ettore D’Ambrosio
Journal: Cancer Research (2004)

Abstract The shortening of the telomeres that occurs in most somatic cells and untransformed cell cultures is considered a hallmark of cellular senescence. Re-activation of telomerase, which is usually present in immortal cells, avoids telomere shortening and considerably extends the culture life span. Normal human endothelial cells are characterized by an accelerated rate of telomere shortening and reach replicative senescence after a limited number of cell divisions. It has recently been reported that human telomerase reverse transcriptase expression may be strongly up-regulated in human endothelial cells cocultivated with tumor cells. Due to the important implications of this finding on tumor progression, we have extensively analyzed for the presence of telomerase in primary human endothelial cells either cocultivated with tumor cells or grown with tumor-conditioned medium. We found modest, but readily detectable, amounts of telomerase in all human endothelial cell cultures analyzed that disappeared as the cultures approached senescence. Quantitative reverse transcription-PCR also showed a direct correlation between human telomerase reverse transcriptase expression and the proliferative index of the cultures. Nevertheless, we did not find any evidence of induction of telomerase activity by tumor cells in any of the tested conditions. All data indicate that telomerase in human endothelial cells follows an activation program that is strictly associated to the culture growth rate.
Circulating miRNAs as Surrogate Markers for Circulating Tumor Cells and Prognostic Markers in Metastatic Breast Cancer
Authors: Dharanija Madhavan, Manuela Zucknick, Markus Wallwiener, Katarina Cuk, Caroline Modugno, Martina Scharpff, Sarah Schott, Jörg Heil, Andrey Turchinovich, Rongxi Yang, Axel Benner, Sabine Riethdorf, Andreas Trumpp, Christof Sohn, Klaus Pantel, Andreas Schneeweiss, Barbara Burwinkel
Journal: Clinical Cancer Research (2012)

The use of circulating tumor cells (CTC) as a prognostic marker in metastatic breast cancer (MBC) has been well established. However, their efficacy and accuracy are still under scrutiny mainly because of methods of their enrichment and identification. We hypothesized that circulating miRNAs can predict the CTC status of patients with MBC, and tested for the same. Furthermore, we aimed at establishing a panel of circulating miRNAs capable of differentiating MBC cases from healthy controls.Circulating miRNAs from plasma of CTC-positive and CTC-negative patients with MBC, and healthy controls, were profiled by TaqMan Human MicroRNA arrays. Candidates from the initial screen were validated in an extended cohort of 269 individuals (61 CTC-positive, 72 CTC-negative, 60 CTC-low MBC cases, and 76 controls).CTC-positive had significantly higher levels of miR-141, miR-200a, miR-200b, miR-200c, miR-203, miR-210, miR-375, and miR-801 than CTC-negative MBC and controls (P < 0.00001), whereas miR-768-3p was present in lower amounts in MBC cases (P < 0.05). miR-200b was singled out as the best marker for distinguishing CTC-positive from CTC-negative patients (AUC 0.88). We identified combinations of miRNAs for differentiating MBC cases from controls (AUC 0.95 for CTC-positive; AUC 0.78 for CTC-negative). Combinations of miRNAs and miR-200b alone were found to be promising prognostic marker for progression-free and overall survival.This is the first study to document the capacity of circulating miRNAs to indicate CTC status and their potential as prognostic markers in patients with MBC.
Assessing CpG island methylator phenotype, 1p/19q codeletion, and MGMT promoter methylation from epigenome-wide data in the biomarker cohort of the NOA-04 trial
Authors: B. Wiestler, D. Capper, V. Hovestadt, M. Sill, D. T. W. Jones, C. Hartmann, J. Felsberg, M. Platten, W. Feiden, K. Keyvani, S. M. Pfister, O. D. Wiestler, R. Meyermann, G. Reifenberger, T. Pietsch, A. von Deimling, M. Weller, W. Wick
Journal: Neuro-Oncology (2014)

Molecular biomarkers including isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation, 1p/19q codeletion, and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation may improve prognostication and guide treatment decisions for patients with World Health Organization (WHO) anaplastic gliomas. At present, each marker is individually tested by distinct assays. Illumina Infinium HumanMethylation450 BeadChip arrays (HM450) enable the determination of large-scale methylation profiles and genome-wide DNA copy number changes. Algorithms have been developed to detect the glioma CpG island methylator phenotype (G-CIMP) associated with IDH1/2 mutation, 1p/19q codeletion, and MGMT promoter methylation using a single assay. Here, we retrospectively investigated the diagnostic and prognostic performance of these algorithms in comparison to individual marker testing and patient outcome in the biomarker cohort (n = 115 patients) of the NOA-04 trial. Concordance for IDH and 1p/19q status was very high: In 92% of samples, the HM450 and reference data agreed. In discordant samples, survival analysis by Kaplan-Meier and Cox regression analyses suggested a more accurate assessment of biological phenotype by the HM450 analysis. The HM450-derived MGMT-STP27 model to calculate MGMT promoter methylation probability revealed this aberration in a significantly higher fraction of samples than conventional methylation-specific PCR, with 87 of 91 G-CIMP tumors predicted as MGMT promoter-methylated. Pyrosequencing of discordant samples confirmed the HM450 assessment in 14 of 17 cases. G-CIMP and 1p/19q codeletion are reliably detectable by HM450 analysis and are associated with prognosis in the NOA-04 trial. For MGMT, HM450 suggests promoter methylation in the vast majority of G-CIMP tumors, which is supported by pyrosequencing.
Tracing the Origin of Glomerular Extracapillary Lesions from Parietal Epithelial Cells
Authors: Bart Smeets, Sandra Uhlig, Astrid Fuss, Fieke Mooren, Jack F.M. Wetzels, Jürgen Floege, Marcus J. Moeller
Journal: Journal of the American Society of Nephrology (2009)

Cellular lesions form in Bowman's space in both crescentic glomerulonephritis and collapsing glomerulopathy. The pathomechanism and origin of the proliferating cells in these lesions are unknown. In this study, we examined proliferating cells by lineage tracing of either podocytes or parietal epithelial cells (PECs) in the nephrotoxic nephritis model of inflammatory crescentic glomerulonephritis. In addition, we traced the fate of genetically labeled PECs in the Thy-1.1 transgenic mouse model of collapsing glomerulopathy. In both models, cellular bridges composed of PECs were observed between Bowman's capsule and the glomerular tuft. Genetically labeled PECs also populated larger, more advanced cellular lesions. In these lesions, we detected de novo expression of CD44 in activated PECs. In contrast, we rarely identified genetically labeled podocytes within the cellular lesions of crescentic glomerulonephritis. In conclusion, PECs constitute the majority of cells that compose early extracapillary proliferative lesions in both crescentic glomerulonephritis and collapsing glomerulopathy, suggesting similar pathomechanisms in both diseases.
Self-Control and External Control of Mechanical Ventilation Give Equal Air Hunger Relief
Authors: ELISABETH BLOCH-SALISBURY, CHRISTINA M. SPENGLER, ROBERT BROWN, ROBERT B. BANZETT
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Elevated end-tidal partial pressure of CO2 (Pet CO2 ) causes air hunger; this sensation becomes intense with a relatively small rise in Pet CO2 if ventilation is held constant. Spontaneously breathing subjects increase ventilation in response to CO2, thereby greatly diminishing air hunger. In healthy subjects and ventilator-dependent patients, experimenter-induced increases in ventilator tidal volume (Vt) relieve air hunger even if Pet CO2 is kept elevated. We addressed two questions: (1) Can paralyzed, ventilator-dependent patients use the sensation of air hunger to effectively control ventilator Vt using nonrespiratory motor pathways; and (2) Do subjects obtain more relief when in control of their own ventilator? Four subjects were trained to increase ventilator Vt using a mouth-operated switch. Subjects' ratings of air hunger intensity in response to elevated Pet CO2 were compared during three conditions: (1) constant Vt; (2) subject-controlled Vt; and (3) experimenter-controlled Vt. When given control of their ventilator, all subjects increased Vt in response to increased Pet CO2 , thereby relieving air hunger. Air hunger relief was similar when the experimenter mimicked these Vt changes. These results suggest that: (1) ventilator-dependent patients can use sensation, conscious decisions, and nonrespiratory motor pathways to achieve an appropriate respiratory response to increased Pco 2 and (2) control of one's own ventilation is unimportant in these circumstances. Bloch-Salisbury E, Spengler CM, Brown R, Banzett RB. Self-control and external control of mechanical ventilation give equal air hunger relief.
Phase I Assessment of New Mechanism-Based Pharmacodynamic Biomarkers for MLN8054, a Small-Molecule Inhibitor of Aurora A Kinase
Authors: Arijit Chakravarty, Vaishali Shinde, Josep Tabernero, Andres Cervantes, Roger B. Cohen, E. Claire Dees, Howard Burris, Jeffrey R. Infante, Teresa Macarulla, Elena Elez, Jordi Andreu, Edith Rodriguez-Braun, Susana Rosello, Margaret von Mehren, Neal J. Meropol, Corey J. Langer, Bert ONeil, Douglas Bowman, Mengkun Zhang, Hadi Danaee, Laura Faron-Yowe, Gary Gray, Hua Liu, Jodi Pappas, Lee Silverman, Chris Simpson, Bradley Stringer, Stephen Tirrell, Ole Petter Veiby, Karthik Venkatakrishnan, Katherine Galvin, Mark Manfredi, Jeffrey A. Ecsedy
Journal: Cancer Research (2010)

The mitotic kinase Aurora A is an important therapeutic target for cancer therapy. This study evaluated new mechanism-based pharmacodynamic biomarkers in cancer patients in two phase I studies of MLN8054, a small-molecule inhibitor of Aurora A kinase. Patients with advanced solid tumors received MLN8054 orally for 7 consecutive days in escalating dose cohorts, with skin and tumor biopsies obtained before and after dosing. Skin biopsies were evaluated for increased mitotic cells within the basal epithelium. Tumor biopsies were assessed for accumulation of mitotic cells within proliferative tumor regions. Several patients in the highest dose cohorts showed marked increases in the skin mitotic index after dosing. Although some tumors exhibited increases in mitotic cells after dosing, others displayed decreases, a variable outcome consistent with dual mechanisms of mitotic arrest and mitotic slippage induced by antimitotics in tumors. To provide a clearer picture, mitotic cell chromosome alignment and spindle bipolarity, new biomarkers of Aurora A inhibition that act independently of mitotic arrest or slippage, were assessed in the tumor biopsies. Several patients, primarily in the highest dose cohorts, had marked decreases in the percentage of mitotic cells with aligned chromosomes and bipolar spindles after dosing. Evidence existed for an exposure-effect relationship for mitotic cells with defects in chromosome alignment and spindle bipolarity that indicated a biologically active dose range. Outcomes of pharmacodynamic assays from skin and tumor biopsies were concordant in several patients. Together, these new pharmacodynamic assays provide evidence for Aurora A inhibition by MLN8054 in patient skin and tumor tissues.
Arterial stenting and balloon angioplasty in ostial atherosclerotic renovascular disease: a randomised trial
Authors: Peter JG van de Ven, Robert Kaatee, Jaap J Beutler, Frederick JA Beek, Arend-Jan J Woittiez, Erik Buskens, Hein A Koomans, Willem P Th Mali
Journal: The Lancet (1999)