tbuckley/cabot-search huggingface dataset:
370. Potent In Vivo Inhibition of HIV-1 Infection in Thy/Liv-SCID-Hu Mice after In Vivo Treatment with a Combination of SV40-Derived Vectors Targeting CCR5 Expression
Authors: Mahesh Patel, Pierre Cordelier, David S. Strayer, Harris Goldstein
Journal: Molecular Therapy (2004)

The efficacy of gene therapy using constructs that downregulate the expression of CCR5, the cellular coreceptor necessary for infection by the majority of primary HIV-1 isolates, to protect cells from in vivo HIV-1 infection was examined using an SV40 virus-vector gene delivery system that efficiently tranduces human leukocytes combined with an HIV-1-infectible thy/liv-SCID-hu mouse model. Three different SV40-derived vectors expressing a single chain antibody, (2C7), a ribozyme (VcKA1), or a small interfering RNA (siRNA) duplex (RNAi5) specific for CCR5 were used. After the SV40 vectors were injected into the human thymic grafts of thy/liv-SCID-hu mice, the thymic implants were challenged by injection with HIV-1 JR-CSF. Two weeks later, the number of HIV-1-infected thymocytes in the thymic grafts was determined by limiting dilution coculture to quantify HIV-1 infection in the human thymic grafts. The data combined from three separate experiments performed according to this protocol demonstrated that the number of HIV-1-infected thymocytes in the thymic grafts of thy/liv-SCID-hu mice (n = 10 mice) injected with the combination of SV(2C7), SV(VcKA1), and SV(RNAi5), 81 ± 18 TCID/106 thymocytes, was significantly lower (p = 0.000011) than that of the thymic grafts of thy/liv-SCID-hu mice (n = 10 mice) injected with the control rSV40 vector, SV(HBS), 2,375 ± 382 TCID/106 thymocytes. HIV-1 infection of the human thymic implants was inhibited more effectively by treatment with the combination of the three vectors than by treatment with SV(2C7) or SV(RNAi5) alone. Analysis of thymocytes for populations single or double positive for CD4 and CD8 indicated that thymopoiesis in the human thymic graft was not affected by transduction with the SV(2C7), SV(VcKA1), and SV(RNAi5) vectors. Thus, these findings demonstrate the in vivo efficacy of HIV-1-specific gene therapy delivered by SV40-based vectors targeting expression of CCR5.
Abstract 12606: Autophagy is Required for Mitochondrial Biogenesis in the Heart
Authors: Zhonggang Li, Quanjiang Zhang, Karla Pires, E. Dale Abel
Journal: Circulation (2014)

Autophagy is an essential process that maintains cellular homeostasis via lysosomal degradation pathways. Autophagy has been found to be involved in various pathophysiological conditions in the heart, including myocardial hypertrophy and ischemic heart disease. However, the precise mechanism by which autophagy maintains cardiac function in the non-stressed heart is incompletely understood. We generated cardiac-specific ATG3 deficient mice (cATG3 KO mice) by crossing αMHC-Cre mice with floxed ATG3 mice. Relative to their wild type (WT) littermates, cATG3 KO mice revealed reduced ATG3 expression and inhibited autophagy specifically in the heart. At 4 months of age, cATG3 KO mice showed impaired cardiac contractile function, characterized by a 25% reduction in fractional shortening by echocardiography (p &lt;0.01), Moreover, cATG3 KO mice revealed increased lipid accumulation, reduced fatty acid oxidation and impaired mitochondrial respirations in the heart, without evidence of fibrosis or inflammation. Mitochondrial dysfunction in cATG3 KO mice was accompanied with mitochondrial content loss and reduced expression of mitochondrial biogenesis related genes (PGC1α, NRF1, NRF2 and TFAM). Interestingly, autophagy inhibition, induced mitochondrial biogenesis defects and mitochondrial dysfunction in neonatal cATG3 KO mice (1 week old), prior to the onset of cardiac contractile dysfunction and heart failure, suggesting that cardiac mitochondrial dysfunction may be an early event in the progression of heart failure in the autophagy deficient mice. Finally, in response to exercise training mitochondrial biogenesis (PGC1 alpha induction and increased respiration rates) was completely inhibited in ATG3 deficient mice. In conclusion, autophagy is essential for generating signals that promote mitochondrial biogenesis, and is indispensable for normal heart function under basal conditions.
DEPARTMENTS OF MEDICINE IN 1970. II. TEACHING POLICIES
Authors: R H WILLIAMS
Journal: Annals of Internal Medicine (1959)

Medical Education1 July 1959DEPARTMENTS OF MEDICINE IN 1970. II. TEACHING POLICIESROBERT H. WILLIAMS, M.D., F.A.C.P.ROBERT H. WILLIAMS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-51-1-110 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA questionnaire was submitted to the head of the department of medicine at each medical school in the United States. A similar questionnaire was sent to full-time staff members of departments of medicine between the ages of 38 and 50 who were members of the American Society for Clinical Investigation and/or the Association of American Physicians. In a previous paper1 certain premises and other background factors bearing upon the questions are reported, and opinions relative to many staff policies are presented. This paper deals with teaching policies.PRE-COLLEGE EDUCATIONWith the increase in necessary training following medical school graduation, and...Bibliography1. Williams RH: Departments of medicine in 1970. I. Staff policies, Ann. Int. Med. 50: 1252, 1959. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Seattle, Washington*Received for publication May 12, 1958.From the Symposium on Whither Internal Medicine, presented in summary at the Thirty-ninth Annual Session of The American College of Physicians, Atlantic City, New Jersey, May 1, 1958.From the Department of Medicine, University of Washington School of Medicine, Seattle, Washington.Requests for reprints should be addressed to Robert H. Williams, M.D., Professor and Executive Officer, Department of Medicine, University of Washington School of Medicine, Seattle 5, Washington. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEndocrinology and Metabolism in the University of Washington Teaching Program 1 July 1959Volume 51, Issue 1Page: 110-128KeywordsQuestionnaires ePublished: 1 December 2008 Issue Published: 1 July 1959 PDF downloadLoading ...
UK private health sector wants NHS regulator
Authors: John Warden
Journal: BMJ (1999)

Independent hospitals in Britain, pressing to be brought into the same regulatory system as that being developed for the NHS, took their case last week to the House of Commons health committee, which is investigating the regulation of private health care.

In a paper prepared for the committee the Independent Healthcare Association stated that setting up two parallel regulatory systems for the public and private health sectors would be inefficient. …
Abstract 4388: In-Vivo Pulmonary Vascular Stiffness Obtained from Color M-Mode Tissue Doppler Imaging and Pressure Measurements Predicts Clinical Outcomes Better than Indexed Pulmonary Vascular Resistance in Pediatric Patients with Pulmonary Arterial Hypertension
Authors: Kendall S Hunter, Craig J Lanning, K Scott Kirby, D Dunbar Ivy, Robin Shandas
Journal: Circulation (2008)

Introduction: Pulmonary vascular stiffness (PVS) is increasingly recognized as an important component of right ventricular afterload in patients with pulmonary arterial hypertension (PAH). In adult and pediatric PAH populations, stiffness has also been shown to improve prediction of mortality and outcomes, respectively. Despite these promising findings, methods to determine PVS clinically remain limited. Here we examine the ability of a minimally-invasive method to quantify proximal PVS in a pediatric PAH population, and hypothesize this measurement will offer better disease outcomes prediction over indexed pulmonary vascular resistance (PVRI), the current gold standard. Methods: Color M-mode Tissue Doppler Images of the right pulmonary artery (RPA) were obtained using ultrasound during right-heart catheterization of 36 individuals undergoing reactivity testing (n=86) who ranged in age from 1 month to 19 yrs (mean = 6.5±5.2 yrs, 19 males). These measurements yielded RPA diameter and intravascular pressure, from which an estimate of the circumferential elastic (Young’s) modulus (E), the continuum component of stiffness, was derived. Echo imaging added only 5 minutes to the procedure. Follow up was obtained in 19 patients (mean = 4.9±4.7 yrs, range 1 month to 16 yrs, 9 males) at a median time of 15 months (range 1–26 months). Cumulative logistic regression was used to relate continuous values of E and PVRI to three outcomes categories: improvement; stable (no change); or worsening. These were determined from change in WHO score from initial assessment to follow up. Results: E had better correlation to pulse pressure (PP) (R2=0.61) compared to mean pressure (R2=0.43); this agrees with other findings of PP as a good proxy of stiffness. E displayed substantially better correlation (R2L=0.49) to outcomes compared to PVRI (R2L=0.33). In more practical terms, E wrongly predicted outcome only once (5%), compared to four errors by PVRI (21%), and offered clearer prognosis in an additional 3 individuals; thus 37% of the group would benefit from such improved prediction. Conclusion: We conclude that elastic modulus is a measure of proximal vascular stiffening and most importantly offers superior outcomes prediction compared to pulmonary vascular resistance.
Circadian regulation of GABAA receptor function by CKIε-CKIδ in the rat suprachiasmatic nuclei
Authors: Ke Ning, Lei Li, Mingxia Liao, Baosong Liu, John G Mielke, Yonghong Chen, Ying Duan, Youssef H El-Hayek, Qi Wan
Journal: Nature Neuroscience (2004)
Abstract 2798: Targeting IL13R alpha2 heterogeneity in malignant glioma with engineered T cells
Authors: Sadhak Sengupta, Irina Balyasnikova, Seema Naheed, Maciej S. Lesniak, Richard P. Junghans, Prakash Sampath
Journal: Cancer Research (2014)

Abstract A majority of malignant glioma exclusively expresses Interleukin 13 receptor alpha chain variant 2 (IL13Rα2), making it an ideal candidate for targeted immunotherapy. A number of immunotherapeutic molecules have been developed against IL13Rα2 with varied levels of therapeutic efficacy. However, the importance of IL13Rα2 as a successful immunotherapy candidate is under scrutiny due to its heterogeneous expression on the tumor. We have used an IL13-chimeric antigen receptor (IL13CAR) expressing T cells to target the IL13Rα2 heterogeneity on malignant glioma. IL13Rα2 was over-expressed on U251MG human glioma cell line by stable transfection (IL13Rα2Hi) to evaluate the effects of its increased expression in tumor progression and immunotherapeutic efficacy, compared to the regular U251 cells (IL13Rα2Lo) and IL13Rα2-knocked down U251 cells (IL13Rα2KD). Tumor cells readily formed neurospheres under established culture conditions. Increased expression of IL13Rα2 was observed in IL13Rα2Hi-neurosphere derived tumor cells when compared to those derived from IL13Rα2Lo neurospheres, as well as the parental IL13Rα2Hi cells. IL13Rα2Hi-neurosphere derived tumor cells were also resistant to radiation therapy and temozolomide chemotherapy when compared to those IL13Rα2Lo neurospheres-derived tumor cells, as well as parental cell lines. Higher levels of IFN gamma and TNF alpha in the culture supernatants, increased T cell proliferation, and CAR+ TCR enrichment were observed when IL13CAR T cells were co-cultured with IL13Rα2Hi-neurosphere derived tumor cells, in comparison to co-culture with IL13Rα2Lo -neurosphere derived tumor cells, as well as the parental cells. IL13CAR T cells, upon co-culture with IL13Rα2Hi-neurosphere derived tumor cells exerted highest levels of cytotoxicity. Together, these results predict that IL13Rα2 heterogeneity can be addressed by a combination of established therapeutic regimen and targeted immunotherapy. While those cells expressing lower levels of IL13Rα2 are susceptible to radiation and chemotherapy, the high IL13Rα2-expressing tumor cells that escape these treatments can be candidates for IL13Rα2-targeted immunotherapy. Note: This abstract was not presented at the meeting. Citation Format: Sadhak Sengupta, Irina Balyasnikova, Seema Naheed, Maciej S. Lesniak, Richard P. Junghans, Prakash Sampath. Targeting IL13R alpha2 heterogeneity in malignant glioma with engineered T cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2798. doi:10.1158/1538-7445.AM2014-2798
Psychiatry, stigma, and resistance
Authors: N. Britten
Journal: BMJ (1998)

The Royal College of psychiatrists has just launched a five year campaign aiming to reduce the stigmatisation experienced by people with mental health problems and to close the gap between professional and public assessment of treatment. The campaign is targeted primarily at the general public, whose attitudes differ significantly from those of health professionals. 1 2 The main problem that the campaign seeks to address is the resistance of sufferers to seeking or accepting advice and treatment. It is based on the assumption that this resistance is linked to public attitudes towards treatment of mental problems and the stigma experienced by sufferers.

The campaign literature cites a study by Jorm et al, which shows that the public more often perceives psychiatric medication as harmful than helpful.2 There are several possible explanations for this. For the general public such questions may well …
Continuously Propagating Cells Derived From Normal Mouse Bone Marrow&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Daniel Billen, G. A. Debrunner
Journal: JNCI Journal of the National Cancer Institute (1960)

Serums from various animals were tested as adjuvants to synthetic medium to determine the most effective menstruum for growth of cells from explanted normal mouse bone marrow. Fetal calf serum was particularly effective in bringing about prolonged growth. The technique of tantalum-wire overlay of the explants and the use of fetal calf serum have enabled us to obtain large numbers of continuous cell lines. The histories and description of several of these lines are given. A medium deficient in glucose and high serum levels favored development of monocytic-like cell lines, whereas in the glucose-supplemented medium a large, flat-cell type appeared to have the selective advantage. These lines were shown through cytological studies not to be contaminants from established cell lines. The one heteroploid cell line tested gave negative results for possible protective action in recipient irradiated isologous mice.
Abstract P052: History of High Cholesterol and Incidence of Dementia: The 90+ Study
Authors: Marcella A Evans, Claudia H Kawas, Maria M Corrada
Journal: Circulation (2014)

Background: Hypercholesterolemia at midlife has been associated with increased dementia risk. However, some studies suggest that this relationship may change with age. It is not known if an association between cholesterol and dementia incidence persists in the oldest-old (people aged 90+) [[Unable to Display Character: &amp;#8211;]] the most rapidly growing segment of the population. We examined whether a history of high cholesterol is associated with dementia incidence in The 90+ Study, a longitudinal population-based study of the oldest-old. Methods: We analyzed data from 569 participants who were non-demented at baseline, had one or more follow-up visits, and provided self-reported history of high cholesterol. Participants were evaluated every six months, with dementia diagnosis (DSM-IV criteria) at follow-up determined in a hierarchal manner from: neurological exam, Mini-Mental Status Exam, informant questionnaires, and the Cognitive Abilities Screening Instrument (telephone short form). We used Cox regression to estimate the association between history of high cholesterol and incident dementia, using age as the time scale and adjusting for gender and education. Results: Participants had a mean age of 93.3 years (range 90-103) at baseline and were primarily Caucasian (99%), women (69%), and with at least some college education (77%). 200 participants (35%) reported a history of high cholesterol. After a mean follow-up of 3.3 years (range 0.1-9.0), 224 individuals (39%) were diagnosed with dementia (68% from neurological exam). People who reported a history of high cholesterol at baseline were less likely to develop dementia compared to people without a history of high cholesterol (HR=0.76, 95% CI 0.57[[Unable to Display Character: &amp;#8211;]]1.02, p=0.072). Conclusions: Contrary to findings in younger ages, high cholesterol appears to be associated with lower dementia risk in the oldest-old. A potential mechanism could be that with advanced age a compensatory increase in cholesterol synthesis or uptake occurs in order to preserve function of the aging brain, as the cholesterol molecule has a variety of biological roles related to brain health. Further research is needed to analyze direct measurements of serum cholesterol, as well as to examine the effects of a variety of factors (such as use and duration of cholesterol-lowering medications, low cholesterol as a proxy for poor health and frailty, and duration of hypercholesterolemia) on the observed association. Our results imply that target cholesterol levels in the oldest-old may be different from those recommended in younger populations, at least in regards to cognitive health.
Effects of buspirone and alprazolam on the cognitive performance of normal elderly subjects
Authors: R P Hart, C C Colenda, R M Hamer
Journal: American Journal of Psychiatry (1991)

To increase understanding of the potential in elderly persons for disability related to behavioral side effects of anxiolytic medications, cognitive and psychomotor effects of clinical doses of buspirone and a popular intermediate-acting benzodiazepine, alprazolam, were examined in carefully screened, healthy elderly subjects.Sixty subjects recruited through community organizations and newspaper advertisements and screened on the basis of history, physical examination, and laboratory studies were randomly assigned to one of three drug treatment groups. After 2 days of washout placebo, subjects were given 0.25 mg t.i.d. of alprazolam, 5 mg t.i.d. of buspirone, or placebo three times a day for a total of 14 days in a double-blind design. Behavioral assessments were completed beginning 1 hour after ingestion of medication on the second washout placebo day, day 1 of the treatment period, and day 14 of the treatment period. Tests included the continuous performance test, recall memory for word lists, digit-symbol substitution, retention of pictorial stimuli over 1 hour, the Profile of Mood States, and subjective ratings of mental status.Buspirone did not affect reaction time, vigilance, psychomotor speed, or memory function. Alprazolam had minimal effects on vigilance, psychomotor speed, and memory on the first treatment day and had no effects after repeated doses.Buspirone did not produce behavioral side effects that could lead to disability, and alprazolam had minimal side effects. Because the patients were carefully screened, it is unclear whether these medications in the doses used would have more side effects in less healthy elderly patients.
The natural killer T-cell ligand α-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice
Authors: Seokmann Hong, Michael T. Wilson, Isao Serizawa, Lan Wu, Nagendra Singh, Olga V. Naidenko, Toru Miura, Tomoku Haba, David C. Scherer, Jie Wei, Mitchell Kronenberg, Yasuhiko Koezuka, Luc Van Kaer
Journal: Nature Medicine (2001)
Abstract 13464: Underutilization of Invasive Coronary Angiography Post Out of Hospital Cardiac Arrest: is a Paradigm Shift Needed?
Authors: Krishnan Ramanathan, Christopher Cheung, Brian Grunau, Mona Habibi, Marc W Deyell, Carolyn M Taylor, Dion Stub, Christopher B Fordyce, Kendeep Kaila, Jim Christenson, Graham C Wong, Michael E Farkouh
Journal: Circulation (2014)

BACKGROUND: The immediate post-resuscitation 12-lead electrocardiogram (ECG) aids in the diagnosis of an acute coronary syndrome (ACS) following an out-of-hospital cardiac arrest (OHCA). Guidelines support immediate coronary angiography (CA) for a finding of acute ST-elevation (STE), no such recommendations exist for ST-depression (STD) post-OHCA. We aimed to assess the relationship of STE and STD on the post-resuscitation ECG with diagnostic CA findings. METHODS: A retrospective analysis of consecutive patients admitted to a Vancouver Hospital with CA capability post-OHCA, between November 2009 and December 2011. Patients were identified using the Resuscitation Outcomes Consortium Cardiac Arrest Registry and included if they had an interpretable post-resuscitation ECG. ST-segment changes &gt;0.1mV in 2 contiguous leads were deemed significant. A stenosis ≤70% (or ≤50% for left main) was defined as obstructive coronary artery disease (CAD). RESULTS: Our cohort of n=231 pts had a mean age of 65±17y and 74% were males. The presenting rhythm was ventricular tachycardia/fibrillation (49%), pulseless electrical activity (19%), asystole (17%), and unspecified (15%). The post-resuscitation ECG demonstrated STE in 33%, STD in 27% and no ST abnormality in 40%. The QRS morphology included narrow complex (42%), intraventricular conduction delay (25%), RBBB (27%), and LBBB (6%). The rate of CA was 41% (n=94), with a mean LVEF of 42%. In Table 1 below the odd ratios describe the association of STE and STD with CA findings compared to patients with no ST abnormality. CONCLUSIONS: A high proportion of patients with OHCA demonstrated ST-segment abnormalities on the post-resuscitation ECG. The association with obstructive CAD was greatest with STE, the presence of STD showed a trend towards an association with both, occlusive and obstructive CAD. A randomized clinical trial is needed to assess the utility of diagnostic CA in OHCA patients with STD on the post-resuscitation ECG.
Abstract P233: Estimating Rates of Cardiovascular Death Using Royston-Parmar Survival Models: An Example in a High Risk Patient Population in Sweden
Authors: Julia Sandberg, Leif Jorgensen, Mark Danese, Benjamin Taylor, Ryan Kilpatrick, Patrik Sobocki
Journal: Circulation (2015)

INTRODUCTION: The aim of this retrospective cohort study was to estimate the hazard rates of cardiovascular (CV) death in a high risk population in Sweden as inputs to a cost effectiveness model. We evaluated the use of Royston-Parmar (RP) flexible parametric models to estimate time-varying event risks. HYPOTHESIS: We assessed the hypothesis that due to time-varying risks of patients with acute coronary syndrome, the RP model is a suitable method to estimate the hazard and event rate of CV death. METHODS: De-identified primary care electronic medical records were obtained for a 10% sample of the adult (>18yrs) Swedish population from 2003 – 2011 (N = 49,857). Patients with incident acute coronary syndrome were selected and followed through time. The hazard of CV death was estimated for each cohort overall as well as for the sub-populations of high dose statin users (>40 mg simvastatin or equivalent) and non-statin users. RP flexible (spline-based) parametric survival models were used to estimate the time-...