tbuckley/cabot-search huggingface dataset:
Loss of TIMP3 Enhances Interstitial Nephritis and Fibrosis
Authors: Zamaneh Kassiri, Gavin Y. Oudit, Vijay Kandalam, Ahmed Awad, Xiuhua Wang, Xiuhua Ziou, Nobuyo Maeda, Andrew M. Herzenberg, James W. Scholey
Journal: Journal of the American Society of Nephrology (2009)

The balance of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) determines the integrity of the extracellular matrix. TIMP3 is the most highly expressed tissue inhibitor of metalloproteinase (TIMP) in the kidney, but its function in renal disease is incompletely understood. In this study, TIMP3-/- mice demonstrated an age-dependent chronic tubulointerstitial fibrosis. After unilateral ureteral obstruction (UUO), young TIMP3-/- mice exhibited increased renal injury (tubular atrophy, cortical and medullary thinning, and vascular damage) compared with wild-type mice. In addition, TIMP3-/- mice had greater interstitial fibrosis; increased synthesis and deposition of type I collagen; increased activation of fibroblasts; enhanced apoptosis; and greater activation of MMP2, but not MMP9, after UUO. TIMP3 deficiency also led to accelerated processing of TNFalpha, demonstrated by significantly higher TACE activity and greater soluble TNFalpha levels by 3 d after UUO. The additional deletion of TNFalpha markedly reduced inflammation, apoptosis, and induction of a number of MMPs. Moreover, inhibition of MMPs in TIMP3-/-/TNFalpha-/- mice further abrogated postobstructive injury and prevented tubulointerestitial fibrosis. In humans, TIMP3 expression increased in the renal arteries and proximal tubules of subjects with diabetic nephropathy or chronic allograft nephropathy. Taken together, these results provide evidence that TIMP3 is an important mediator of kidney injury, and regulating its activity may have therapeutic benefit for patients with kidney disease.
Dominating versus eliminating the competition: Sex differences in human intrasexual aggression
Authors: Joyce F. Benenson
Journal: Behavioral and Brain Sciences (2009)

Abstract Archer presents a traditional view of intrasexual competition. Knowledge of a species' social structure provides a more complete picture. Human males compete against individuals with whom they may cooperate later in inter-group aggression. By contrast, females compete against individuals for a mate's continued support. Females' aggression may aim at eliminating the competition, whereas males simply may attempt to dominate others.
Remarks on a Case of Recurrent Sarcoma of the Mammary Gland Treated by Coley's Fluid with a Fatal Result
Authors: A. M. Sheild
Journal: BMJ (1897)

SARCOMA.JTHEBRISAL specific gravity of only ioo6 or Ioo8, and contained a small proportion of albumen.On another occasion a similar attack was accompanied by slight left hemiplegia, with marked im- pairment of articulation; and, in my absence, two distin- guished colleagues, not aware of the previous history, came to a diagnosis of advanced Bright's disease, and gave a most unfavourable prognosis.On both occasions a dose of calomel put an end to the serious symptoms almost at once-the hemiplegia, of course, excepted, which only disappeared very gradually."8. Gangrene of the extremities and (g) angina pectoris are symptoms which have occurred in other cases of arterial hypermyotrophy, but they were not present in the above.The existence of enlargement of the heart in cases of arte- rial hypermyotrophy renders it necessary to diagnose this condition from the other causes of cardiac hypertrophy; but the presence of vertigo, thickened arteries, and the other symptoms above mentioned, together with the absence of the
Sex Differences in Perceived Stress and Early Recovery in Young and Middle-Aged Patients With Acute Myocardial Infarction
Authors: Xiao Xu, Haikun Bao, Kelly Strait, John A. Spertus, Judith H. Lichtman, Gail D’Onofrio, Erica Spatz, Emily M. Bucholz, Mary Geda, Nancy P. Lorenze, Héctor Bueno, John F. Beltrame, Harlan M. Krumholz
Journal: Circulation (2015)

Background— Younger age and female sex are both associated with greater mental stress in the general population, but limited data exist on the status of perceived stress in young and middle-aged patients presenting with acute myocardial infarction. Methods and Results— We examined sex difference in stress, contributing factors to this difference, and whether this difference helps explain sex-based disparities in 1-month recovery using data from 3572 patients with acute myocardial infarction (2397 women and 1175 men) 18 to 55 years of age. The average score of the 14-item Perceived Stress Scale at baseline was 23.4 for men and 27.0 for women ( P &lt;0.001). Higher stress in women was explained largely by sex differences in comorbidities, physical and mental health status, intrafamily conflict, caregiving demands, and financial hardship. After adjustment for demographic and clinical characteristics, women had worse recovery than men at 1 month after acute myocardial infarction, with mean differences in improvement score between women and men ranging from −0.04 for EuroQol utility index to −3.96 for angina-related quality of life ( P &lt;0.05 for all). Further adjustment for baseline stress reduced these sex-based differences in recovery to −0.03 to −3.63, which, however, remained statistically significant ( P &lt;0.05 for all). High stress at baseline was associated with significantly worse recovery in angina-specific and overall quality of life, as well as mental health status. The effect of baseline stress on recovery did not vary between men and women. Conclusions— Among young and middle-aged patients, higher stress at baseline is associated with worse recovery in multiple health outcomes after acute myocardial infarction. Women perceive greater psychological stress than men at baseline, which partially explains women’s worse recovery.
Targeted nanoparticles for drug delivery through the blood–brain barrier for Alzheimer's disease
Authors: Celeste Roney, Padmakar Kulkarni, Veera Arora, Peter Antich, Frederick Bonte, Aimei Wu, N.N. Mallikarjuana, Sanjeev Manohar, Hsiang-Fa Liang, Anandrao R. Kulkarni, Hsing-Wen Sung, Malladi Sairam, Tejraj M. Aminabhavi
Journal: Journal of Controlled Release (2005)
Acquired attenuation of chemoreceptor function in chronically hypoxic man at high altitude
Authors: John V. Weil, Edward Byrne-Quinn, Ingvar E. Sodal, Giles F. Filley, Robert F. Grover
Journal: Journal of Clinical Investigation (1971)

To determine whether chronic exposure to hypoxia during adulthood produces alterations in the control of ventilation, measurements of the resting ventilatory response to hypoxia and hypercapnia, as well as ventilatory response to hypoxia during exercise, were carried out in a group of 10 long-term (3-39 yr) non-native residents of Leadville, Colo. (elevation 3100 m). A group of 8 subjects native to Leadville was also studied and 10 low altitude subjects of Denver, Colo. (elevation 1600 m) served as controls. Hypoxic ventilatory drive was measured as the shape parameter A of isocapnic VE-PA(o2) curves. In the non-native high altitude resident this parameter averaged 43% of the value for low altitude controls (P<0.05) denoting a diminished ventilatory response to hypoxia. The degree of attenuation was related to the length of time spent at high altitude. In the high altitude natives the parameter A averaged 9.6% of control (P<0.01). Similarly hypercapnic ventilatory drive as measured by the slope of the isoxic VE-PA(co2) lines was reduced in the non-native residents to 65% of control (P<0.05) and in the natives averaged 54% of control (P<0.01). In contrast with these findings at rest induction of hypoxia during exercise produced an increase in ventilation comparable to that in the controls in both groups of highlanders. Hence chronic exposure to hypoxia during adulthood in man results in marked attenuation of the ventilatory response to hypoxia at rest and this is a function of the length of exposure to hypoxia. This attenuation of the ventilatory response to hypoxia was associated with a decrease in hypercapnic ventilatory drive. The fact that hypoxic ventilatory drive was almost completely absent while hypercapnic drive was only partially reduced parallels closely the more important role of the peripheral chemoreceptors in mediating ventilatory responses to hypoxia than to hypercapnia. This suggests that the alterations in ventilatory control at altitude are due to failure of peripheral chemoreceptor function.
C-Reactive Protein and the Future Risk of Thromboembolic Stroke in Healthy Men
Authors: J. David Curb, Robert D. Abbott, Beatriz L. Rodriguez, Pamela Sakkinen, Jordan S. Popper, Katsuhiko Yano, Russell P. Tracy
Journal: Circulation (2003)

Evidence suggests that C-reactive protein (CRP) is related to thromboembolic (TE) stroke. Whether associations are altered in the presence of other risk factors is unclear. The purpose of this study was to additionally assess the relation between CRP and TE stroke.On the basis of 20 years of follow-up after CRP measurement, 259 cases of TE stroke were identified and compared with 1348 controls. Subjects were aged 48 to 70 years when CRP was measured. Levels of CRP were positively associated with TE stroke throughout the 20 years of follow-up. Although associations were modest within 5 years of CRP measurement, the odds of stroke in the top versus bottom CRP quartile increased over time to a 3.8-fold excess by 10 to 15 years into follow-up (P<0.001). For men without hypertension or diabetes, the overall corresponding odds were 1.6 to 1.7 (P<0.05). In men <or=55 years of age, the odds increased to a 3-fold excess (P=0.006), and in nonsmokers, there was a 5.8-fold excess (P<0.001). Associations in past and current smokers, in men >55 years of age, and in those with hypertension or diabetes were not significant.Findings suggest that elevated CRP in middle adulthood and in men with healthier risk factor profiles may be important as a risk factor for TE stroke. Use of CRP levels as a clinical screen to identify an increased risk of cardiovascular disease in otherwise healthy men warrants consideration.
Predicting gene function in a hierarchical context with an ensemble of classifiers
Authors: Yuanfang Guan, Chad L Myers, David C Hess, Zafer Barutcuoglu, Amy A Caudy, Olga G Troyanskaya
Journal: Genome biology (2008)

Abstract Background: The wide availability of genome-scale data for several organisms has stimulated interest in computational approaches to gene function prediction. Diverse machine learning methods have been applied to unicellular organisms with some success, but few have been extensively tested on higher level, multicellular organisms. A recent mouse function prediction project (MouseFunc) brought together nine bioinformatics teams applying a diverse array of methodologies to mount the first large-scale effort to predict gene function in the laboratory mouse. Results: In this paper, we describe our contribution to this project, an ensemble framework based on the support vector machine that integrates diverse datasets in the context of the Gene Ontology hierarchy. We carry out a detailed analysis of the performance of our ensemble and provide insights into which methods work best under a variety of prediction scenarios. In addition, we applied our method to Saccharomyces cerevisiae and have experimentally confirmed functions for a novel mitochondrial protein. Conclusion: Our method consistently performs among the top methods in the MouseFunc evaluation. Furthermore, it exhibits good classification performance across a variety of cellular processes and functions in both a multicellular organism and a unicellular organism, indicating its ability to discover novel biology in diverse settings.
Rigid point feature registration using mutual information
Authors: Anand Rangarajan, Haili Chui, James S. Duncan
Journal: Medical Image Analysis (1999)

We have developed a new mutual information-based registration method for matching unlabeled point features. In contrast to earlier mutual information-based registration methods, which estimate the mutual information using image intensity information, our approach uses the point feature location information. A novel aspect of our approach is the emergence of correspondence (between the two sets of features) as a natural by-product of joint density estimation. We have applied this algorithm to the problem of geometric alignment of primate autoradiographs. We also present preliminary results on three-dimensional robust matching of sulci derived from anatomical magnetic resonance images. Finally, we present an experimental comparison between the mutual information approach and other recent approaches which explicitly parameterize feature correspondence.
939 PRECLINICAL PHARMACOKINETIC AND ADME CHARACTERIZATION OF VCH-222, A NOVEL NON-NUCLEOSIDE HCV NS5B POLYMERASE INHIBITOR
Authors: N. Chauret, C. Chagnon-Labelle, M. Diallo, J. Laquerre, J. Laterreur, S. May, L. Ste-Marie
Journal: Journal of Hepatology (2009)
A Single Factor Underlies the Metabolic Syndrome: A confirmatory factor analysis 
Authors: Manel Pladevall, Bonita Singal, L Keoki Williams, Carlos Brotons, Heidi Guyer, Josep Sadurni, Carles Falces, Manuel Serrano-Rios, Rafael Gabriel, Jonathan Edward Shaw, Paul Z Zimmet, Steven Haffner
Journal: Diabetes Care (2006)

OBJECTIVE—Confirmatory factor analysis (CFA) was used to test the hypothesis that the components of the metabolic syndrome are manifestations of a single common factor.
In vitro bioelectric properties of bronchial epithelium from transplanted lungs in recipients with cystic fibrosis.
Authors: V T Tsang, E W Alton, M E Hodson, M Yacoub
Journal: Thorax (1993)

BACKGROUND--Bronchial epithelial function after heart-lung transplantation (HLT) for cystic fibrosis (CF) may be affected by the original disease as well as other factors such as prolonged organ ischaemic time, the interruption of bronchial arterial and lymphatic supply, infection, rejection, and cyclosporin. In vitro measurement of the bioelectric properties of the bronchial mucosal lining may be an effective means of characterising the mucosal function of the lung allografts in response to pharmacological agents. METHODS--Bronchial mucosal tissues from explanted native lungs of CF and non-CF patients at transplantation were used to assess the possible application of a mini-Ussing chamber. With this technique, the bioelectric responses of bronchial mucosal biopsies from six patients with CF, one patient with congenital heart disease, four with primary pulmonary hypertension, and one with emphysema, all after HLT, were studied. The bioelectric and pharmacological responses of biopsies of bronchial mucosa from patients after HLT were compared with biopsies from non-CF non-HLT subjects. RESULTS--The altered bioelectric properties of CF tissues could be detected by the mini-Ussing chamber technique. The basal bioelectric values and the responses to amiloride and isoprenaline in CF patients were not different from those in non-CF patients two years after HLT. No significant difference in the basal bioelectric properties and responses to amiloride and isoprenaline was found between HLT recipients and non-CF non-HLT subjects. CONCLUSIONS--The mini-Ussing chamber is an effective means of characterising the typical CF bioelectric defect which was not found in the transplanted lungs of CF patients up to two years after HLT. Furthermore, values were unaltered in comparison with non-transplanted lungs, suggesting that bronchial epithelial function is maintained after HLT.
Characterization of the fetal glucose transporter in rabbit kidney. Comparison with the adult brush border electrogenic Na+-glucose symporter.
Authors: J C Beck, M S Lipkowitz, R G Abramson
Journal: Journal of Clinical Investigation (1988)

Glucose transport was characterized in rabbit renal brush border membrane vesicles (BBMV) of the fetus late in gestation. Highly purified, osmotically reactive fetal BBMV contained a glucose transporter that was qualitatively indistinguishable from that in the adult: both are concentrative, Na+ dependent, electrogenic, stereospecific, and sensitive to phlorizin. Although the apparent Km for glucose is similar in the fetus and adult, the Vmax is significantly higher in the adult. When the membrane potential was clamped with a protonophore, this difference diminished; however, Vmax remained significantly higher in adult BBMV. This postnatal increase in Vmax was paralleled by a similar increase in the number of phlorizin binding sites. These findings indicate that the maturational increase in glucose transport is, in part, consequent to a more favorable electrical potential for Na+-dependent glucose transport and, in part, the result of the insertion of new transporters. The homogenate activity of several brush border enzymes also demonstrated significant maturational increases. The magnitude of these changes was variable and enzyme dependent. These combined observations suggest that mature expression of membrane proteins (transporters and enzymes) occurs at different stages of development of renal proximal tubule cells.
Coding potential of the products of alternative splicing in human
Authors: Guido Leoni, Loredana Le Pera, Fabrizio Ferrè, Domenico Raimondo, Anna Tramontano
Journal: Genome biology (2011)

Analysis of the human genome has revealed that as much as an order of magnitude more of the genomic sequence is transcribed than accounted for by the predicted and characterized genes. A number of these transcripts are alternatively spliced forms of known protein coding genes; however, it is becoming clear that many of them do not necessarily correspond to a functional protein. In this study we analyze alternative splicing isoforms of human gene products that are unambiguously identified by mass spectrometry and compare their properties with those of isoforms of the same genes for which no peptide was found in publicly available mass spectrometry datasets. We analyze them in detail for the presence of uninterrupted functional domains, active sites as well as the plausibility of their predicted structure. We report how well each of these strategies and their combination can correctly identify translated isoforms and derive a lower limit for their specificity, that is, their ability to correctly identify non-translated products. The most effective strategy for correctly identifying translated products relies on the conservation of active sites, but it can only be applied to a small fraction of isoforms, while a reasonably high coverage, sensitivity and specificity can be achieved by analyzing the presence of non-truncated functional domains. Combining the latter with an assessment of the plausibility of the modeled structure of the isoform increases both coverage and specificity with a moderate cost in terms of sensitivity.
Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance
Authors: Alexandre Fort, Kosuke Hashimoto, Daisuke Yamada, Md Salimullah, Chaman A Keya, Alka Saxena, Alessandro Bonetti, Irina Voineagu, Nicolas Bertin, Anton Kratz, Yukihiko Noro, Chee-Hong Wong, Michiel de Hoon, Robin Andersson, Albin Sandelin, Harukazu Suzuki, Chia-Lin Wei, Haruhiko Koseki, Yuki Hasegawa, Alistair R R Forrest, Piero Carninci
Journal: Nature Genetics (2014)
MOUSE CD1-SPECIFIC NK1 T CELLS: Development, Specificity, and Function
Authors: Albert Bendelac, Miguel N. Rivera, Se-Ho Park, Jessica H. Roark
Journal: Annual Review of Immunology (1997)

▪ Abstract NK1 T cells are a specialized population of α/β T cells that coexpress receptors of the NK lineage and have the unique potential to very rapidly secrete large amounts of cytokines, providing early help for effector cells and regulating the Th1 or Th2 differentiation of some immune responses. NK1 T cells express a restricted TCR repertoire made of an invariant TCR α chain, Vα14-Jα281, associated with polyclonal Vβ8, Vβ7, and Vβ2 TCR β chains. NK1 T cells recognize the products of the conserved family of MHC class I–like CD1 genes, apparently in the absence of foreign antigens. Thus, this novel regulatory pathway, which straddles the innate and the adaptive immune systems, is unique in that its activation may not require associative recognition of antigen. Here, we review the specificity and function of mouse NK1 T cells, and we discuss the relationship of this lineage to mainstream T cells and NK cells.
Phase I/II Study of G3139 (Bcl-2 Antisense Oligonucleotide) in Combination with Doxorubicin and Docetaxel in Breast Cancer
Authors: Stacy L. Moulder, W. Fraser Symmans, Daniel J. Booser, Timothy L. Madden, Cindy Lipsanen, Linda Yuan, Abenaa M. Brewster, Massimo Cristofanilli, Kelly K. Hunt, Thomas A. Buchholz, James Zwiebel, Vicente Valero, Gabriel N. Hortobagyi, Francisco J. Esteva
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Preclinical data showed enhancement of breast cancer cell death when G3139 was combined with anthracyclines and taxanes. We evaluated the efficacy and safety of a Bcl-2 antisense oligonucleotide, G3139, in combination with doxorubicin (A) and docetaxel (T) in patients with locally advanced breast cancer (LABC). Experimental Design: Following a brief phase I to determine the phase II dose, patients with locally advanced breast cancer received G3139 administered by continuous i.v. infusion for 5 to 7 days with bolus A (50 mg/m2) and T (75 mg/m2) administered on either day 3 or 6 of therapy with G3139. Cycles were repeated every 21 days × 6 in the neoadjuvant setting. Serial plasma samples were obtained for pharmacokinetic analysis. Tissue samples were obtained before and after therapy for pharmacodynamic analysis of Bcl-2 expression. Results: Thirty patients (median age, 49 years; range, 24-71 years) received 160 cycles. During the phase I portion of the trial, the dose of G3139 was escalated from 3 to 7 mg/kg/d (i.v. for 5 days) in combination with AT. During the phase II portion of the trial, several doses and schedules of G3139 were evaluated. There were no pathologic complete responses. Pharmacodynamic studies showed limited Bcl-2 down-regulation in the primary tumors. Conclusions: G3139 in combination with doxorubicin and docetaxel is well tolerated. No pathologic complete response was seen and pharmacodynamic studies showed very little down-regulation of Bcl-2 in primary tumors, perhaps related to issues with insufficient drug delivery to the intact tumor.
Ethnic Differences in Diabetes Management in Patients With and Without Comorbid Medical Conditions
Authors: Riyadh Alshamsan, Azeem Majeed, Eszter Panna Vamos, Kamlesh Khunti, Vasa Curcin, Salman Rawaf, Christopher Millett
Journal: Diabetes Care (2011)

To examine ethnic disparities in diabetes management among patients with and without comorbid medical conditions after a period of sustained investment in quality improvement in the U.K.This cross-sectional study examined associations between ethnicity, comorbidity, and intermediate outcomes for mean A1C, total cholesterol, and blood pressure levels in 6,690 diabetes patients in South West London.The presence of ≥ 2 cardiovascular comorbidities was associated with similar blood pressure control among white and South Asian patients when compared with whites without comorbidity but with worse blood pressure control among black patients, with a mean difference in systolic blood pressure of +1.5, +1.4, and +6.2 mmHg, respectively.Despite major reforms to improve quality, disparities in blood pressure management have persisted in the U.K., particularly among patients with cardiovascular comorbidities. Policy makers should consider the potential impacts of quality initiatives on high-risk groups.