tbuckley/cabot-search huggingface dataset:
Roles and regulation of the cardiac sodium channel Nav1.5: Recent insights from experimental studies
Authors: H ABRIEL
Journal: Cardiovascular Research (2007)

During the past decade, Na(v)1.5, the main voltage-gated Na(+) channel in the heart, has been shown to be involved in many cardiac diseases. Genetic variants in the gene SCN5A, encoding Na(v)1.5, have been linked to various cardiac phenotypes, such as the congenital and acquired long QT syndromes, Brugada syndrome, conduction slowing, sick sinus syndrome, atrial fibrillation, and even cases of dilated cardiomyopathy. This unexpected phenotypic diversity may reflect that Na(v)1.5 is not only restricted to the initiation of the action potential and rapid cardiac conduction, but may also be involved in other, not-yet elucidated, functions. Despite the fact that our understanding of the regulation of expression, localization, and function of Na(v)1.5 is deepening, we are still far from a comprehensive view. Much of our current knowledge has been obtained by carrying out experiments using "cellular expression systems", e.g. host cells expressing exogenous Na(v)1.5. Although very informative, these techniques are limited, in that Na(v)1.5 is not expressed in the physiological cellular environment of a cardiac cell. Recently, however, there have been several studies published which used approaches closer to "normal" or pathological physiology. In an attempt to summarize recently published data, this article will review the phenotypes of genetically-modified mouse strains where Na(v)1.5 expression and activity are directly or indirectly modified, as well as the regulation of Na(v)1.5 function using native cardiac myocytes. Despite obvious limitations, the reviewed studies provide an overview of the complex multi-factorial and multi-protein regulation of Na(v)1.5.
TUR and Adjuvant Intravesical Chemotherapy in T1G3 Bladder Tumors: Recurrence, Progression and Survival in 137 Selected Patients Followed Up to 20 Years
Authors: Vincenzo Serretta, Carlo Pavone, Giovan Battista Ingargiola, Giuseppe Daricello, Rosalinda Allegro, Michele Pavone-Macaluso
Journal: European Urology (2003)
Nighttime Intensivist Staffing and Mortality among Critically Ill Patients
Authors: David J. Wallace, Derek C. Angus, Amber E. Barnato, Andrew A. Kramer, Jeremy M. Kahn
Journal: New England Journal of Medicine (2012)

Hospitals are increasingly adopting 24-hour intensivist physician staffing as a strategy to improve intensive care unit (ICU) outcomes. However, the degree to which nighttime intensivists are associated with improvements in the quality of ICU care is unknown.
P98 A Questionnaire Survey Of Parent Experiences And Perspectives In Children Diagnosed With Interstitial Lung Disease (ild)
Authors: C. Gilbert, A. Bush, S. Cunningham
Journal: Thorax (2014)

<h3>Background and objectives</h3> Paediatric ILD is rare, so even clinicians in large centres will see very few cases. We aimed to report the experience of parents of children diagnosed with ILD in order to inform current clinical practice, and future planning of health care. <h3>Methods</h3> Between February 2014 and March 2014, UK based families with children given a diagnosis of ILD completed an anonymous comprehensive web-based survey developed by the chILD Lung Foundation. The survey consisted of mainly closed questions, with some open qualitative questions. <h3>Results</h3> Of the 37 families who completed the questionnaire, 70% of participants reported that they were very happy/happy with the overall management of their child. Diagnoses: unknown 38% (n = 14), neuroendocrine hyperplasia of infancy 16% (n = 6), <i>ABCA3</i> mutations 8% (n = 3), obliterative bronchiolitis (OB) 24% (n = 9), follicular bronchiolitis 3% (n = 1), pulmonary interstitial glycogenosis 3% (n = 1), surfactant protein C mutations (<i>SP-C</i>) 5% (n = 2) and chronic bronchiolitis 3% (n = 1). Median age at diagnosis was 35 weeks (range 1 week to 8 years), with 25 weeks the median time from first symptoms to diagnosis (range 1 week to 8 years). Areas of concern were (a) communication; care plans/treatment strategies were provided by a respiratory consultant in only 19 of 37 cases, (b) written information: &gt;50% families could not recall receiving any written information on ILD or their child’s specific disease after diagnosis or information on their child’s prognosis, (c) psychological support; 91% of respondents reported significant/moderate anxiety, however psychological services were reported as offered to only 7 of 37 families, (d) feeding issues; reported by 77% of families (which is not a feature of ILD described in the literature) and these persisted in 35%, mostly long-term gastrostomy dependency and oral aversion. Qualitative responses included requests for better written communication between hospitals and training for smaller hospitals, and improved specialist nurse support of children with ILD. <h3>Conclusion</h3> These data provide a broader understanding of parent experiences and perspectives, which should be important now for professionals looking after children with ILD as well as for those planning of future services.
Regular exercise reduces fibrinogen levels: a review of longitudinal studies.
Authors: E Ernst
Journal: British Journal of Sports Medicine (1993)

Fibrinogen can be considered as a major cardiovascular risk factor. Therefore there is a growing interest in methods to lower its plasma level. This paper is aimed at reviewing the data investigating the effects of regular exercise on plasma fibrinogen levels. Cross-sectional studies strongly suggest that regular exercise will reduce fibrinogen levels, and longitudinal data confirm this. The average decrease achieved by regular endurance exercise over several months is around 0.4 g/l. It can be extrapolated that this corresponds to a substantial decrease in risk of coronary heart disease. It is concluded that regular exercise is the most practicable approach known to date to lower plasma fibrinogen levels.
The Present Position of the Radical Operations for Chronic Suppurative Otitis
Authors: H. Ed. Jones
Journal: BMJ (1896)

m T cHiLoinmAL 1321 substantiate this proposition.Certainly the earlier cited cases show prolonged taxis to be attended with more serious consequences than prolonged strangulation alone.By way of deduction again from these I should say that if there is any doubt as to a severe hernia being reducible or not, in treatment give the benefit of the doubt to an early surgical operation.And, in the second place, that if from any cause there may be delay in operating, such as for want of instrument or assistance, suspend all attempts at reduction by taxis after one trial.
ENCEPHALOMYELITIS ACCOMPANIED BY MYELIN DESTRUCTION EXPERIMENTALLY PRODUCED IN MONKEYS
Authors: Thomas M. Rivers, Francis F. Schwentker
Journal: The Journal of Experimental Medicine (1935)

The repeated intramuscular injections of aqueous emulsions and alcohol-ether extracts of sterile normal rabbit brains in some manner produced pathological changes accompanied by myelin destruction in the brains of 7 of 8 monkeys (Macacus rhesus). Eight, control monkeys remained well. Cultures from the involved brains remained sterile, and no transmissible agent was demonstrated by means of intracerebral inoculations of emulsions of bits of the brains into monkeys, rabbits, guinea pigs, and white mice.
The long-term impact of early parental death: lessons from a narrative study
Authors: Jackie Ellis, Chris Dowrick, Mari Lloyd-Williams
Journal: Journal of the Royal Society of Medicine (2013)

Summary Objective To explore the individual experiences of those who had experienced the death of a parent(s) before the age of 18, and investigate how such experiences were perceived to impact on adult life. Design An exploratory qualitative design using written (n = 5) and oral (n= 28) narratives and narrative analysis was adopted to explore the experiences 33 adults (7 men and 26 women) who had experienced parental death during childhood. Setting UK Participants Individuals living in the North West of England who had lost a parent(s) before the age of 18. Main outcome measures Views of adults bereaved of a parent before the age of 18 of impact of parental loss in adult life. Results While individual experiences of bereavement in childhood were unique and context bound, the narratives were organized around three common themes: disruptions and continuity, the role of social networks and affiliations and communication and the extent to which these dynamics mediated the bereavement experience and the subsequent impact on adult life. Specifically they illustrate how discontinuity (or continuity that does not meet the child's needs), a lack of appropriate social support for both the child and surviving parent and a failure to provide clear and honest information at appropriate time points relevant to the child's level of understanding was perceived to have a negative impact in adulthood with regards to trust, relationships, self-esteem, feeling of self-worth loneliness and isolation and the ability to express feelings. A model is suggested for identifying and supporting those that may be more vulnerable to less favourable outcomes in adult life. Conclusions The findings suggest that if the negative consequences are to be minimized it is crucial that guidelines for ‘best practice’ that recognize the complex nature of the bereavement experience are followed.
New Strategies in the Treatment of Multiple Myeloma
Authors: Nikhil C. Munshi, Kenneth C. Anderson
Journal: Clinical Cancer Research (2013)

Abstract Multiple myeloma is the second most common hematologic malignancy affecting terminally differentiated plasma cells. Although high-dose chemotherapy and autologous stem cell transplantation have improved survival in younger patients, the natural history of multiple myeloma has been changed with the availability of six new agents approved in the past 10 years (thalidomide, bortezomib, lenalidomide, liposomal doxorubicin, carfilzomib, and pomalidomide). Despite this significant improvement in the overall outcome, multiple myeloma remains incurable in the majority of patients, prompting a continued search for additional therapeutic options. Extensive molecular and genomic characterization of multiple myeloma cells in their bone marrow milieu, which affects myeloma cell growth and survival, has provided a number of novel drugable targets and pathways. Perturbation of protein catabolism at multiple levels has become an important target in multiple myeloma. Similarly, improvements in monoclonal antibody generation and vaccine development, along with identification of a number of cell surface and cellular targets, have led to the development of various strategies, including antibodies and antibody–drug conjugates that are under investigation preclinically and in early clinical studies. We propose that eventually, molecularly informed multiagent combination therapies will be required to eliminate the multiple myeloma cell clone for long-term disease control. Clin Cancer Res; 19(13); 3337–44. ©2013 AACR.
Asthma mortality in Russia between 1980 and 1989
Authors: R.g. Oganov, G.ya. Maslennikova
Journal: European Respiratory Journal (1999)

There is evidence that mortality due to asthma has increased in a number of nations over the last two decades. This study was conducted to assess asthma mortality rates in Russia from 1980 to 1989. Data obtained were compared with figures from other countries. National asthma deaths were obtained from the Ministry of Health of the Russian Federation. Age- and sex-specific rates per 100,000 population per year were adjusted to the European population. Annual changes in mortality rates for the study period were estimated by linear regression analysis. Between 1980 and 1989, asthma mortality rates per 100,000 population per year increased from 3.7 to 5.3 in the total Russian population. Differences according to age and sex were observed. Asthma deaths increased with age and in most cases males showed higher death rates than females. There was a statistically significant annual increase in mortality rates for young males < 5 yrs of age and for adult males aged 35-64 yrs, as well as for females aged > or = 65 yrs. Asthma mortality rates in Russia between 1980 and 1989 may be considered moderate as compared with death rates reported for the same period in other countries.
Control of Cardiovascular Risk Factors in Patients With Diabetes and Hypertension at Urban Academic Medical Centers
Authors: Samy I. McFarlane, Scott J. Jacober, Nathaniel Winer, Jasjeet Kaur, Jonathan P. Castro, MaryLou A. Wui, Agnes Gliwa, Hans Von Gizycki, James R. Sowers
Journal: Diabetes Care (2002)

OBJECTIVE—There are national mandates to reduce blood pressure (BP) to &amp;lt;130/85 mmHg, LDL cholesterol to &amp;lt;100 mg/dl, and HbA1c to &amp;lt;7% and to institute aspirin therapy in patients with diabetes. The objective of this study was to determine the proportion of patients in urban institutions with diabetes and hypertension who meet these treatment goals. RESEARCH DESIGN AND METHODS—Using American Diabetes Association (ADA) guidelines, we evaluated the control of cardiovascular disease (CVD) risk factors in 1,372 patients receiving medical care at two major urban medical centers in Brooklyn and Detroit. Information was extracted from charts of outpatient clinics. RESULTS—Of 1,372 active clinic patients with diabetes and hypertension, 1,247 (90.9%) had type 2 diabetes, and 26.7% met the target blood pressure of 130/85 mmHg. A total of 35.5% met the goal LDL cholesterol level of &amp;lt;100 mg/dl, 26.7% had an HbA1c &amp;lt;7%, and 45.6% were on antiplatelet therapy. Only 3.2% of patients met the combined ADA goal for BP, LDL cholesterol, and HbA1c. CONCLUSIONS—Optimal control of CVD risk factors in adults with diabetes was achieved only in a minority of patients. Results reflect the inherent difficulties in achieving these complex guidelines in our present health care systems.
Tumor Engraftment in Nude Mice and Enrichment in Stroma- Related Gene Pathways Predict Poor Survival and Resistance to Gemcitabine in Patients with Pancreatic Cancer
Authors: Ignacio Garrido-Laguna, Maria Uson, N.V. Rajeshkumar, Aik Choon Tan, Elizabeth de Oliveira, Collins Karikari, Maria C. Villaroel, Ana Salomon, Gretchen Taylor, Rajni Sharma, Ralph H. Hruban, Anirban Maitra, Daniel Laheru, Belén Rubio-Viqueira, Antonio Jimeno, Manuel Hidalgo
Journal: Clinical Cancer Research (2011)

The goal of this study was to evaluate prospectively the engraftment rate, factors influencing engraftment, and predictability of clinical outcome of low-passage xenografts from patients with resectable pancreatic ductal adenocarcinoma (PDA) and to establish a bank of PDA xenografts.Patients with resectable PDA scheduled for resection at the Johns Hopkins Hospital were eligible. Representative pieces of tumor were implanted in nude mice. The status of the SMAD4 gene and content of tumor-generating cells were determined by immunohistochemistry. Gene expression was carried out by using a U133 Plus 2.0 array. Patients were followed for progression and survival.A total of 94 patients with PDA were resected, 69 tumors implanted in nude mice, and 42 (61%) engrafted. Engrafted carcinomas were more often SMAD4 mutant, and had a metastatic gene expression signature and worse prognosis. Tumors from patients resistant to gemcitabine were enriched in stroma-related gene pathways. Tumors sensitive to gemcitabine were enriched in cell cycle and pyrimidine gene pathways. The time to progression for patients who received treatment with gemcitabine for metastatic disease (n = 7) was double in patients with xenografts sensitive to gemcitabine.A successful xenograft was generated in 61% of patients attempted, generating a pool of 42 PDA xenografts with significant biological information and annotated clinical data. Patients with PDA and SMAD4 inactivation have a better engraftment rate. Engraftment is a poor prognosis factor, and engrafted tumors have a metastatic gene expression signature. Tumors from gemcitabine-resistant patients were enriched in stromal pathways.
Characterization of protein kinase C isotype expression in adult rat heart. Protein kinase C-epsilon is a major isotype present, and it is activated by phorbol esters, epinephrine, and endothelin.
Authors: M A Bogoyevitch, P J Parker, P H Sugden
Journal: Circulation Research (1993)

The pattern of protein kinase C (PKC) isotype expression in whole extracts of dispersed, freshly isolated adult rat ventricular myocytes and adult rat heart ventricle was examined by immunoblot analysis using antisera specific for PKC-alpha, -beta 1, -gamma, -delta, -epsilon, -zeta, or -eta isotypes. This analysis revealed significant levels of expression of the Ca(2+)-independent isotype PKC-epsilon, which was detected as band of 97-kd molecular mass. PKC-zeta was detected principally as a 66-kd band that probably represented a proteolytic product of the holoenzyme. PKC-eta was detected only in whole ventricle as a doublet at 75 and 81 kd and was therefore probably present in nonmyocytic cells. PKC-alpha, -beta 1, -gamma, and -delta could not be detected. Because of our inability to detect PKC-alpha, -beta 1, -gamma, and -delta in whole extracts, PKC isotypes were partially purified from whole heart by DEAE Sepharose chromatography. PKC-alpha, -beta 1, -gamma, and -delta could still not be detected in the appropriate fractions. All PKC isotypes were detectable in appropriate positive control extracts (brain or certain cultured cell lines). In unstimulated isolated cardiomyocytes, the majority (80-95%) of the PKC-epsilon immunoreactivity was present in the soluble fraction of the extract. On exposure of the cardiomyocytes to 1 microM phorbol 12-myristate 13-acetate (PMA), PKC-epsilon undergoes a rapid (&lt; 30 seconds), sustained (at least 60 minutes), and virtually complete association with the Triton X-100-soluble membrane fraction. There was an associated loss of PKC-epsilon from the soluble fraction. The EC50 for PMA of the translocation event was 15-37 nM. Exposure of cardiomyocytes to 1 microM 4 beta-phorbol 12,13-didecanoate or 1 microM phorbol 12,13-dibutyrate also resulted in translocation of PKC-epsilon to the membrane fraction, whereas exposure to 1 microM 4 alpha-phorbol 12,13-didecanoate was without effect. PKC-epsilon also translocated on exposure of cardiomyocytes to 50 microM epinephrine or 100 nM endothelin-1. However, in both cases, the extent of translocation was significantly less than that after exposure to PMA. We conclude that interventions that lead to hypertrophy of cardiomyocytes (phorbol esters, epinephrine, and endothelin-1) activate PKC-epsilon.
Selective Estrogen Receptor Alpha Agonist GTx-758 Decreases Testosterone with Reduced Side Effects of Androgen Deprivation Therapy in Men with Advanced Prostate Cancer
Authors: Evan Y. Yu, Robert H. Getzenberg, Christopher C. Coss, Marc M. Gittelman, Thomas Keane, Ronald Tutrone, Laurence Belkoff, Robert Given, Joel Bass, Franklin Chu, Michael Gambla, Franklin Gaylis, James Bailen, Michael L. Hancock, Jordan Smith, James T. Dalton, Mitchell S. Steiner
Journal: European Urology (2014)
<b> <i>Notch1</i> </b> and <b> <i>Notch2</i> </b> Have Opposite Effects on Embryonal Brain Tumor Growth
Authors: Xing Fan, Irina Mikolaenko, Ihab Elhassan, XingZhi Ni, Yunyue Wang, Douglas Ball, Daniel J. Brat, Arie Perry, Charles G. Eberhart
Journal: Cancer Research (2004)

Abstract The role of Notch signaling in tumorigenesis can vary; Notch1 acts as an oncogene in some neoplasms, and a tumor suppressor in others. Here, we show that different Notch receptors can have opposite effects in a single tumor type. Expression of truncated, constitutively active Notch1 or Notch2 in embryonal brain tumor cell lines caused antagonistic effects on tumor growth. Cell proliferation, soft agar colony formation, and xenograft growth were all promoted by Notch2 and inhibited by Notch1. We also found that Notch2 receptor transcripts are highly expressed in progenitor cell-derived brain tumors such as medulloblastomas, whereas Notch1 is scarce or undetectable. This parallels normal cerebellar development, during which Notch2 is predominantly expressed in proliferating progenitors and Notch1 in postmitotic differentiating cells. Given the oncogenic effects of Notch2, we analyzed its gene dosage in 40 embryonal brain tumors, detecting an increased copy number in 15% of cases. Notch2 gene amplification was confirmed by fluorescence in situ hybridization in one case with extremely high Notch2 mRNA levels. In addition, expression of the Notch pathway target gene Hes1 in medulloblastomas was associated with significantly shorter patient survival (P = 0.01). Finally, pharmacological inhibition of Notch signaling suppresses growth of medulloblastoma cells. Our data indicate that Notch1 and Notch2 can have opposite effects on the growth of a single tumor type, and show that Notch2 can be overexpressed after gene amplification in human tumors.
Brain Uptake of Myoinositol after Exogenous Administration
Authors: Stephen M. Silver, Barbara M. Schroeder, Richard H. Sterns
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. An acute increase in plasma tonicity results in an adaptive increase in brain organic osmolyte content, but this process requires several days to occur. Slow reaccumulation of brain organic osmolytes may contribute to osmotic demyelination. It was investigated whether administration of intravenous myoinositol in rats could speed entry of the osmolyte into the brain. Two groups of animals were studied: normonatremic animals and animals with hyponatremia (105 mmol/L) of 3–d duration. Animals were intravenously administered either 1 M NaCl to induce a 25 to 28 mM increase in serum sodium concentration over 200 min or an infusate that maintained serum sodium concentration. In some animals, myoinositol was administered intravenously over the same time period to raise plasma myoinositol levels by 5 to 10 mM. Brain myoinositol, electrolyte, and water contents were determined at the end of the infusions. In both normonatremic and hyponatremic rats, infusion of hypertonic saline without myoinositol or infusion of myoinositol without hypertonic saline did not increase brain myoinositol levels above control levels. In normonatremic animals, concurrent infusion of hypertonic saline and myoinositol increased brain myoinositol levels by about 50% above control levels. Brain myoinositol content in animals with uncorrected hyponatremia was about 50% of that found in normonatremic controls; concurrent infusion of hypertonic saline and myoinositol increased brain myoinositol to levels similar to those found in normonatremic controls. Intravenous infusion of myoinositol did not alter brain water content compared with animals not infused with myoinositol. In conclusion, systemic infusion of myoinositol can rapidly increase brain myoinositol content, but only when plasma tonicity is concomitantly increased.