tbuckley/cabot-search huggingface dataset:
Erectile Dysfunction in a Murine Model of Sleep Apnea
Authors: Galia K. Soukhova-O'Hare, Zahoor A. Shah, Zhenmin Lei, Alexander D. Nozdrachev, C. Venkateswara Rao, David Gozal
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Erectile dysfunction (ED) is frequent in obstructive sleep apnea syndrome (OSAS). Chronic intermittent hypoxia (CIH), one of the hallmarks of OSAS, could mediate ED.To determine whether intermittent hypoxia during sleep affects erectile dysfunction in mice.Three groups of C57BL/6 mice were exposed to CIH for 5 or 24 weeks. Sexual function was evaluated by in vivo telemetry of corpus spongiosum pressure. Spontaneous erections, sexual activity during mating, and noncontact tests were assessed after 5 weeks of CIH and after treatment with tadalafil. Plasma testosterone was measured after 8 and 24 weeks of CIH, and the expression of nitric oxide synthase (NOS) isoforms was examined in penile tissue.Noncontact, spontaneous, and contact sexual activity in the mice was suppressed after CIH. Spontaneous erection counts decreased after the first week of CIH by 55% (P < 0.001) and remained unchanged thereafter. Recovery of erectile activity during normoxia for 6 weeks was incomplete. Compared with control mice, latencies for mounts and intromissions increased by 60- and 40-fold, respectively (P < 0.001), and the sexual activity index decreased sixfold. Tadalafil treatment significantly attenuated these effects. Immunoblot analyses of NOS proteins in the erectile tissue showed decreased expression of endothelial NOS after CIH (P < 0.01), with no changes in plasma testosterone levels after 8 and 24 weeks of CIH.CIH during sleep is associated with decreased libido in mice. The decreased expression of endothelial NOS protein in erectile tissue and the favorable response to tadalafil suggest that altered nitric oxide mechanisms underlie CIH-mediated ED. No changes in testosterone emerge after intermittent hypoxia.
Racial Disparity in Cardiac Procedures and Mortality Among Long-Term Survivors of Cardiac Arrest
Authors: Peter W. Groeneveld, Paul A. Heidenreich, Alan M. Garber
Journal: Circulation (2003)

Background— It is unknown whether white and black Medicare beneficiaries have different rates of cardiac procedure utilization or long-term survival after cardiac arrest. Methods and Results— A total of 5948 elderly Medicare beneficiaries (5429 white and 519 black) were identified who survived to hospital discharge between 1990 and 1999 after admission for cardiac arrest. Demographic, socioeconomic, and clinical information about these patients was obtained from Medicare administrative files, the US census, and the American Hospital Association’s annual institutional survey. A Cox proportional hazard model that included demographic and clinical predictors indicated a hazard ratio for mortality of 1.30 (95% CI 1.09 to 1.55) for blacks aged 66 to 74 years compared with whites of the same age. The addition of cardiac procedures to this model lowered the hazard ratio for blacks to 1.23 (95% CI 1.03 to 1.46). In analyses stratified by race, implantable cardioverter-defibrillators (ICDs) had a mortality hazard ratio of 0.53 (95% CI 0.45 to 0.62) for white patients and 0.50 (95% CI 0.27 to 0.91) for black patients. Logistic regression models that compared procedure rates between races indicated odds ratios for blacks aged 66 to 74 years of 0.58 (95% CI 0.36 to 0.94) to receive an ICD and 0.50 (95% CI 0.34 to 0.75) to receive either revascularization or an ICD. Conclusions— There is racial disparity in long-term mortality among elderly cardiac arrest survivors. Both black and white patients benefited from ICD implantation, but blacks were less likely to undergo this potentially life-saving procedure. Lower rates of cardiac procedures may explain in part the lower survival rates among black patients.
The parafibromin tumor suppressor protein interacts with actin-binding proteins actinin-2 and actinin-3
Authors: Sunita K Agarwal, William F Simonds, Stephen J Marx
Journal: Molecular Cancer (2008)

Germline and somatic inactivating mutations in the HRPT2 gene occur in the inherited hyperparathyroidism-jaw tumor syndrome, in some cases of parathyroid cancer and in some cases of familial hyperparathyroidism. HRPT2 encodes parafibromin. To identify parafibromin interacting proteins we used the yeast two-hybrid system for screening a heart cDNA library with parafibromin as the bait. Fourteen parafibromin interaction positive preys representing 10 independent clones encoding actinin-2 were isolated. Parafibromin interacted with muscle alpha-actinins (actinin-2 and actinin-3), but not with non-muscle alpha-actinins (actinin-1 and actinin-4). The parafibromin-actinin interaction was verified by yeast two-hybrid, GST pull-down, and co-immunoprecipitation. Yeast two-hybrid analysis revealed that the N-terminal region of parafibromin interacted with actinins. In actin sedimentation assays parafibromin did not dissociate skeletal muscle actinins from actin filaments, but interestingly, parafibromin could also bundle/cross-link actin filaments. Parafibromin was predominantly nuclear in undifferentiated proliferating myoblasts (C2C12 cells), but in differentiated C2C12 myotubes parafibromin co-localized with actinins in the cytoplasmic compartment. These data support a possible contribution of parafibromin outside the nucleus through its interaction with actinins and actin bundling/cross-linking. These data also suggest that actinins (and actin) participate in sequestering parafibromin in the cytoplasmic compartment.
A high number of transmissions of H7N7 avian influenza A virus to humans
Authors: N Navani
Journal: Thorax (2004)

▴ Koopmans M, Wilbrink B, Conyn M, et al. Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Lancet2004;363:587–93 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] People exposed to chickens on Dutch poultry farms affected by H7N7 avian influenza A virus (A/H7) were asked to report signs of conjunctivitis or influenza-like illness from February to June 2003. Of the estimated 3410 or more at risk, 453 had health … [1]: {openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DKoopmans%26rft.auinit1%253DM.%26rft.volume%253D363%26rft.issue%253D9409%26rft.spage%253D587%26rft.epage%253D593%26rft.atitle%253DTransmission%2Bof%2BH7N7%2Bavian%2Binfluenza%2BA%2Bvirus%2Bto%2Bhuman%2Bbeings%2Bduring%2Ba%2Blarge%2Boutbreak%2Bin%2Bcommercial%2Bpoultry%2Bfarms%2Bin%2Bthe%2BNetherlands.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252804%252915589-X%26rft_id%253Dinfo%253Apmid%252F14987882%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/S0140-6736(04)15589-X&link_type=DOI [3]: /lookup/external-ref?access_num=14987882&link_type=MED&atom=%2Fthoraxjnl%2F59%2F5%2F395.atom [4]: /lookup/external-ref?access_num=000189104900006&link_type=ISI
IMMUNOLOGICAL AND CHEMICAL INVESTIGATIONS OF VACCINE VIRUS
Authors: Robert F. Parker, Thomas M. Rivers
Journal: The Journal of Experimental Medicine (1935)

By means of differential centrifugation in the horizontal and angle centrifuges it is possible to obtain appreciable quantities of relatively pure elementary bodies of vaccinia. Such preparations of elementary bodies exhibit an extremely high titer of vaccine virus. The elementary bodies are specifically agglutinated by serum from rabbits immunized by means of injections of bacteria-free vaccine virus. Virus-free filtrates of dermal vaccine virus and of bacteria-free testicular vaccine virus contain a soluble substance or substances that is precipitated by antivaccinal sera.
Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study
Authors: M.V. Dieci, C. Criscitiello, A. Goubar, G. Viale, P. Conte, V. Guarneri, G. Ficarra, M.C. Mathieu, S. Delaloge, G. Curigliano, F. Andre
Journal: Annals of Oncology (2014)
Mannose-binding lectin deficiency increases mortality risk from pneumococcal infection
Authors: R M Jones
Journal: Thorax (2008)

Low serum levels or genotypic variants of the innate immune molecule mannose-binding lectin (MBL) have been associated with increased susceptibility to infectious diseases. Few studies of MBL have included sufficiently large sample sizes and conclusions drawn have been conflicting. This study set out to reanalyse existing data from studies on MBL in order to define the serum level of MBL deficiency and determine the …
Cytokinesis failure and attenuation: new findings in Fanconi anemia
Authors: Philip J. Mason, Monica Bessler
Journal: Journal of Clinical Investigation (2010)

The hallmarks of the rare inherited disorder Fanconi anemia (FA) are progressive bone marrow failure and susceptibility to cancer. The former is the major cause of death for patients with FA, as it usually occurs earlier in life than cancer development. Despite spectacular advances in unraveling the molecular details of FA, the origin of the bone marrow failure that is central to this condition for most patients has long been puzzling and controversial. Two studies recently published in the JCI, including one in this issue, will add to the debate. They also highlight the fact that studying rare disorders can elucidate important new clinical and biological principles.
Association of Comorbid Conditions and Mortality in Hemodialysis Patients in Europe, Japan, and the United States
Authors: David A. Goodkin, Jennifer L. Bragg-Gresham, Karl G. Koenig, Robert A. Wolfe, Takashi Akiba, Vittorio E. Andreucci, Akira Saito, Hugh C. Rayner, Kiyoshi Kurokawa, Friedrich K. Port, Philip J. Held, Eric W. Young
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Mortality rates among hemodialysis patients vary greatly across regions. Representative databases containing extensive profiles of patient characteristics and outcomes are lacking. The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective, observational study of representative samples of hemodialysis patients in France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States (US) that captures extensive data relating to patient characteristics, prescriptions, laboratory values, practice patterns, and outcomes. This report describes the case-mix features and mortality among 16,720 patients followed up to 5 yr. The crude 1-yr mortality rates were 6.6% in Japan, 15.6% in Europe, and 21.7% in the US. After adjusting for age, gender, race, and 25 comorbid conditions, the relative risk (RR) of mortality was 2.84 (<i>P</i> &lt; 0.0001) for Europe compared with Japan (reference group) and was 3.78 (<i>P</i> &lt; 0.0001) for the US compared with Japan. The adjusted RR of mortality for the US <i>versus</i> Europe was 1.33 (<i>P</i> &lt; 0.0001). For most comorbid diseases, prevalence was highest in the US, where the mean age (60.5 ± 15.5 yr) was also highest. Older age and comorbidities were associated with increased risk of death (except for hypertension, which carried a multivariate RR of mortality of 0.74 [<i>P</i> &lt; 0.0001]). Variability in demographic and comorbid conditions (as identified by dialysis facilities) explains only part of the differences in mortality between dialysis centers, both for comparisons made across continents and within the US. Adjustments for the observed variability will allow study of association between practice patterns and outcomes.
Core Protein of Hepatitis C Virus Induces Cardiomyopathy
Authors: Takashi Omura, Minoru Yoshiyama, Tetsuya Hayashi, Shuhei Nishiguchi, Masahiko Kaito, Shinichiro Horiike, Katsuhiko Fukuda, Sakiko Inamoto, Yasushi Kitaura, Yasuhiro Nakamura, Masakazu Teragaki, Takeshi Tokuhisa, Hiroshi Iwao, Kazuhide Takeuchi, Junichi Yoshikawa
Journal: Circulation Research (2004)

Hepatitis C virus (HCV) has been reported to be associated with cardiomyopathy. However, the mechanism of cardiomyopathy in chronic HCV infection is still unclear. Therefore, we investigate the development of cardiomyopathy in mice transgenic for the HCV-core gene. After the age of 12 months, mice developed cardiomyopathy that appeared as left ventricular dilatation, and systolic and diastolic dysfunction assessed by Doppler echocardiography. Histologically, hypertrophy of cardiomyocytes, cardiac fibrosis, disarray and scarcity of myofibrils, vacuolization and deformity of nuclei, myofibrillar lysis, streaming of Z-bands, and an increased number of bizarre-shaped mitochondria were found in HCV-core transgenic mice. These histological changes are just consistent with cardiomyopathy. In conclusion, the HCV-core protein directly plays an important role in the development of cardiomyopathy.
Injury risk associated with playing actions during competitive soccer
Authors: N Rahnama, T Reilly, A Lees
Journal: British Journal of Sports Medicine (2002)

To assess the exposure of players to injury risk during English Premier League soccer matches in relation to selected factors.Injury risk was assessed by rating the injury potential of playing actions during competition with respect to (a) type of playing action, (b) period of the game, (c) zone of the pitch, and (d) playing either at home or away. In all, 10 games from the English Premier League 1999-2000 were chosen for analysis. A notation system was used whereby 16 soccer specific playing actions were classified into three categories: those inducing actual injury, those with a potential for injury (graded as mild, moderate, or high), and those deemed to have no potential for injury. The pitch was divided into 18 zones, and the position of each event was recorded along with time elapsed in the game, enabling six 15 minute periods to be defined.Close to 18 000 actions were notated. On average (mean (SD)), 1788 (73) events (one every three seconds), 767 (99) events with injury potential (one every six seconds), and 2 (1) injuries (one every 45 minutes) per game were recorded. An overall injury incidence of 53 per 1000 playing hours was calculated. Receiving a tackle, receiving a "charge", and making a tackle were categorised as having a substantial injury risk, and goal catch, goal punch, kicking the ball, shot on goal, set kick, and heading the ball were all categorised as having a significant injury risk. All other actions were deemed low in risk. The first 15 minutes of each half contained the highest number of actions with mild injury potential, the last 15 minutes having the highest number of actions with moderate injury potential (p<0.01). The first and last 15 minutes of the game had the highest number of actions with high injury potential, although not significant. More actions with mild injury potential occurred in the goal area, and more actions with moderate and high injury potential occurred in the zone adjacent to the goal area (p<0.001). There was no significant difference between home and away with regard to injury potential.Playing actions with high injury risk were linked to contesting possession. Injury risk was highest in the first and last 15 minutes of the game, reflecting the intense engagements in the opening period and the possible effect of fatigue in the closing period. Injury risk was concentrated in the areas of the pitch where possession of the ball is most vigorously contested, which were specific attacking and defending zones close to the goal. Injury potential was no greater in away matches than at home.
The pre-eclampsia community guideline (PRECOG): how to screen for and detect onset of pre-eclampsia in the community
Authors: Fiona Milne, Chris Redman, James Walker, Philip Baker, Julian Bradley, Carol Cooper, Michael de Swiet, Gillian Fletcher, Mervi Jokinen, Deirdre Murphy, Catherine Nelson-Piercy, Vicky Osgood, Stephen Robson, Andrew Shennan, Angela Tuffnell, Sara Twaddle, Jason Waugh
Journal: BMJ (2005)

Pre-eclampsia is a major cause of poor outcome in pregnancy: the category “hypertensive diseases of pregnancy” remains a leading cause of direct maternal deaths in the United Kingdom1; pre-eclamptic conditions represent one in three cases of severe obstetric morbidity2; hypertension and/or proteinuria is the leading single identifiable risk factor in pregnancy associated with stillbirth (one in five stillbirths in otherwise viable babies)3; and pre-eclampsia is strongly associated with fetal growth restriction, low birth weight, preterm delivery, respiratory distress syndrome, and admission to neonatal intensive care.4

In 46% of maternal deaths1 and 65% of fetal deaths5 due to pre-eclampsia reported through the Confidential Enquiries into Maternal Deaths and the Confidential Enquiry into Stillbirths and Deaths in Infancy, different management would reasonably have expected to alter the outcome. There was a failure to identify and act on known risk factors at booking and to recognise and respond to signs and symptoms from 20 weeks' gestation.6

No guidelines exist for the screening and early detection of pre-eclampsia in the community, and there is no uniformity in referral thresholds and assessment procedures.

We developed the pre-eclampsia community guideline (PRECOG) under the auspices of the charity Action on Pre-eclampsia, following the National Institute for Clinical Excellence's recommendations for the development of guidelines.7 Our guideline is supported by the Royal College of Obstetricians and Gynaecologists, the Royal College of Midwives, the Royal College of General Practitioners, and the National Childbirth Trust. Box 1 lists the definitions used in the guideline; pre-eclampsia is defined as new hypertension and proteinuria (see bmj.com for definition of levels of evidence).

The pre-eclampsia community guideline provides an evidence based risk assessment, with criteria for early referral for specialist input, a two tiered schedule for monitoring women in the community after …
Molecular Population Genetics of Redundant Floral-Regulatory Genes in Arabidopsis thaliana
Authors: Richard C Moore, Sarah R Grant, Michael D Purugganan
Journal: Molecular Biology and Evolution (2004)

Functional redundancy between duplicated genes is predicted to be transitory, as one gene either loses its function or gains a new function, or both genes accrue degenerative, yet complimentary mutations. Yet there are many examples where functional redundancy has been maintained between gene duplicates. To determine whether selection is acting on functionally redundant gene duplicates, we performed molecular evolution and population genetic analyses between two pairs of functionally redundant MADS-box genes from the model plant Arabidopsis thaliana: SEPALLATA1 (SEP1) and SEPALLATA2 (SEP2), involved in floral organ identity, and SHATTERPROOF1 (SHP1) and SHATTERPROOF2 (SHP2), involved in seed shattering. We found evidence for purifying selection acting to constrain functional divergence between paralogous genes. The protein evolution of both pairs of duplicate genes is functionally constrained, as evidenced by Ka/Ks ratios of 0.16 between paralogs. This functional constraint is stronger in the highly conserved DNA-binding and protein-binding MIK region than in the C-terminal region. We also assayed the evolutionary forces acting between orthologs of the SEP and SHP genes in A. thaliana and the closely related species, Arabidopsis lyrata. Heterogeneity analyses of the polymorphism-to-divergence ratio indicate selective sweeps have occurred within the transcriptional unit of SHP1 and the promoter of SHP2 in the A. thaliana lineage. Similar analyses identified a significant reduction in polymorphism within the SEP1 locus, spanning the 3′ region of intron 1 to exon 3, that may represent an intragenic sweep within the SEP1 locus. We discuss whether the evolutionary forces acting on SEP1 and SEP2 versus SHP1 and SHP2 vary according to their position in the floral developmental pathway, as found with other floral-regulatory genes.
Variation in transcriptional regulation of cyclin dependent kinase inhibitor p21waf1/cip1 among human bronchogenic carcinomas
Authors: Michael W Harr, Timothy G Graves, Erin L Crawford, Kristy A Warner, Cheryl AM Reed, James C Willey
Journal: Molecular Cancer (2005)

Cell proliferation control depends in part on the carefully ordered regulation of transcription factors. The p53 homolog p73, contributes to this control by directly upregulating the cyclin dependent kinase inhibitor, p21waf1/cip1. E2F1, an inducer of cell proliferation, directly upregulates p73 and in some systems upregulates p21 directly. Because of its central role in controlling cell proliferation, upregulation of p21 has been explored as a modality for treating bronchogenic carcinoma (BC). Improved understanding of p21 transcriptional regulation will facilitate identification of BC tissues that are responsive to p21-directed therapies. Toward this goal, we investigated the role that E2F1 and p73 each play in the transcriptional regulation of p21.Among BC samples (N = 21) p21 transcript abundance (TA) levels varied over two orders of magnitude with values ranging from 400 to 120,000 (in units of molecules/106 molecules beta-actin). The p21 values in many BC were high compared to those observed in normal bronchial epithelial cells (BEC) (N = 18). Among all BC samples, there was no correlation between E2F1 and p21 TA but there was positive correlation between E2F1 and p73alpha (p < 0.001) TA. Among BC cell lines with inactivated p53 and wild type p73 (N = 7) there was positive correlation between p73alpha and p21 TA (p < 0.05). Additionally, in a BC cell line in which both p53 and p73 were inactivated (H1155), E2F1 TA level was high (50,000), but p21 TA level was low (470). Transiently expressed exogenous p73alpha in the BC cell line Calu-1, was associated with a significant (p < 0.05) 90% increase in p21 TA and a 20% reduction in E2F1 TA. siRNA mediated reduction of p73 TA in the N417 BC cell line was associated with a significant reduction in p21 TA level (p < 0.01).p21 TA levels vary considerably among BC patients which may be attributable to 1) genetic alterations in Rb and p53 and 2) variation in TA levels of upstream transcription factors E2F1 and p73. Here we provide evidence that p73 upregulates p21 TA in BC tissues and upregulated p21 TA may result from E2F1 upregulation of p73 but not from E2F1 directly.
Estimation of Somatomedin-C Levels in Normals and Patients with Pituitary Disease by Radioimmunoassay
Authors: Richard W. Furlanetto, Louis E. Underwood, Judson J. Van Wyk, A. Joseph D'Ercole
Journal: Journal of Clinical Investigation (1977)

The development of a radioimmunoassay for somatomedin-C has for the first time made it possible to discriminate between serum concentrations of a single peptide or closely related group of peptides and the net somatomedin activity measured by less specific bioassay and radioreceptor techniques. Antibodies to human somatomedin-C were raised in rabbits using a somatomedin-C ovalbumin complex as the antigen. A variety of peptide hormones at concentrations up to 1 μM are not recognized by the antibody. Insulin at concentrations >0.1 μM cross reacts in a non-parallel fashion; purified somatomedin-A is only 3% as active as somatomedin-C; and radiolabeled cloned rat liver multiplication stimulating activity does not bind to the antibody. Immunoreactive somatomedin-C can also be quantitated in the sera of a variety of subhuman species.