tbuckley/cabot-search huggingface dataset:
Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet.
Authors: L C Hudgins, M Hellerstein, C Seidman, R Neese, J Diakun, J Hirsch
Journal: Journal of Clinical Investigation (1996)

A new experimental approach was used to determine whether a eucaloric, low fat, high carbohydrate diet increases fatty acid synthesis. Normally volunteers consumed low fat liquid formula diets (10% of calories as fat and 75% as glucose polymers, n = 7) or high fat diets (40% of calories as fat and 45% as glucose polymers, n = 3) for 25 d. The fatty acid composition of each diet was matched to the composition of each subject's adipose tissue and compared with the composition of VLDL triglyceride. By day 10, VLDL triglyceride was markedly enriched in palmitate and deficient in linoleate in all subjects on the low fat diet. Newly synthesized fatty acids accounted for 44 +/- 10% of the VLDL triglyceride. Mass isotopomer distribution analysis of palmitate labeled with intravenously infused 13C-acetate confirmed that increased palmitate synthesis was the likely cause for the accumulation of triglyceride palmitate and "dilution" of linoleate. In contrast, there was minimal fatty acid synthesis on the high diet. Thus, the dietary substitution of carbohydrate for fat stimulated fatty acid synthesis and the plasma accumulation of palmitate-enriched, linoleate-deficient triglyceride. Such changes could have adverse effects on the cardiovascular system.
Innovative Approaches to Understanding and Addressing Health Disparities in Diabetes Care and Research
Authors: William T. Cefalu, Sherita Hill Golden
Journal: Diabetes Care (2015)

With the recent published update on the management of hyperglycemia in patients with type 2 diabetes (T2D) as outlined from the American Diabetes Association and the European Association for the Study of Diabetes 2012 position statement, treatment strategies continue to evolve (1). The update is very timely when one considers the growing number of new agents and, as stated by the authors, the “growing uncertainty regarding their proper selection and sequence” (1). The approach to the patient from the position statement clarified the separation of those factors felt to be “modifiable” (i.e., patient attitude, resources, support system, etc.) as opposed to those that usually are not (i.e., disease duration, life expectancy, comorbidities, etc.). However, as timely and up-to-date as the recommendations seem to be, and that the focus continues to be on personalizing treatment strategies, there are other important factors not considered or addressed by the update that greatly affect our treatment decisions.

Specifically, we recognize that among the world’s population there are observable differences in diabetes prevalence, incidence, mortality, and disease burden that clearly impact our approach to treatment (2). While these factors contribute to disparities in diabetes presentation, diagnosis, and treatment, they are not easily measured, adequately studied, or routinely considered in daily management. Given the importance of the topic of health disparities in diabetes, our editorial team has featured six articles in this issue of Diabetes Care that report on research related to understanding health disparities. The topics range from discussing the impact of interventions led by community health workers (CHWs) to understanding the role of language barriers on diabetes complications, evaluating cerebral structural changes in diabetic kidney disease in African Americans (AAs), and understanding racial differences in underlying biological factors (3–8).

It is reported that minority groups in the U.S. may have less …
FBXW7 regulates glucocorticoid response in T-cell acute lymphoblastic leukaemia by targeting the glucocorticoid receptor for degradation
Authors: A Malyukova, S Brown, R Papa, R O'Brien, J Giles, T N Trahair, L Dalla Pozza, R Sutton, T Liu, M Haber, M D Norris, R B Lock, O Sangfelt, G M Marshall
Journal: Leukemia (2012)
Outreach by Primary-Care Physicians
Authors: Matthew Henk
Journal: JAMA (1975)

Outreach can be accomplished by the primary-care physician if he institutes data systems that permit identification of cohorts of his patients by age, sex, diagnoses, and area of residence. These systems were used by the Rochester Family Medicine Program to identify and invite patients at risk to receive prophylactic influenza immunization, participate in an obesity treatment group, and receive screening tests for lead intoxication. (<i>JAMA</i>233:256-259, 1975)
Acute dehydrating disease caused by Vibrio cholerae serogroups O1 and O139 induce increases in innate cells and inflammatory mediators at the mucosal surface of the gut
Authors: F Qadri
Journal: Gut (2003)

<b>Background and aims:</b> The general concept is that as <i>Vibrio cholerae</i> is not invasive, it mediates a non-inflammatory type of infection. This is being re-evaluated based on available data that natural cholera infection or cholera toxin induces a Th2-type of immune profile and stimulates the humoral immune response, innate cells, and mediators in the host. <b>Methods:</b> To perform a comprehensive analyses of the inflammatory components, we studied mucosal biopsies from patients, both adults and children with acute watery diarrhoea caused by <i>V cholerae</i> O1 and O139. Patients with cholera, adults (n = 30) and children (n = 18), as well as healthy controls (n = 24) were studied. Histochemical, immunohistochemical, and ultrastructural studies were carried out to elucidate the contribution of the different factors using paraffin and frozen duodenal and/or rectal sections as appropriate. Samples were collected during the acute stage and during early and/or late convalescence. <b>Results:</b> Following natural cholera infection, patients responded with increases in neutrophil polymorphs during the acute stage (p&lt;0.001) compared with healthy controls whereas mucosal mast cells (MMC) (p = 0.008) and eosinophils (p = 0.034) increased in the gut during convalescence. Electron microscopic analyses of duodenal biopsies from adult patients showed increased piecemeal degranulation in both MMC and eosinophils and accumulation of lipid bodies in MMC. Duodenal biopsies from <i>V cholerae</i> O1 infected patients showed upregulation of myeloperoxidase, lactoferrin, PGHS-1, SCF, tryptase, tumour necrosis factor α, α-defensin, and eotaxin during the acute stage and chymase, interleukin 3 and major basic protein during convalescence. <b>Conclusion:</b> We have shown that innate cells and their mediators are upregulated in acute watery diarrhoea. These cells and factors of the innate arm may be important in the host’s defence against cholera. Such effects may need to be simulated in a vaccine to achieve long lasting protection from cholera.
Long-term expression of angiostatin suppresses metastatic liver cancer in mice
Authors: Ruian Xu, Xueying Sun, Lai-Yin Tse, Hua Li, Pui-Chung Chan, Sue Xu, Weidong Xiao, Hsiang-Fu Kung, Geoffrey W. Krissansen, Sheung-Tat Fan
Journal: Hepatology (2003)

Metastatic liver cancer has a very poor prognosis and lacks effective therapy. Anti-angiogenic therapies, which starve tumors of blood supply, have proven to be effective in preclinical models because tumor growth is angiogenesis dependent. However, long-term, high-level, and sustained expression of angiogenesis inhibitors, such as angiostatin, is necessary to prevent dormant tumors from becoming active again. To achieve this objective, we engineered a recombinant adeno-associated virus (AAV) vector encoding mouse angiostatin, an endogenous inhibitor of tumor vascularization. After intraportal delivery of this vector, high-level, stable transgene expression of angiostatin lasting for at least 6 months was observed locally in hepatocytes. Gene transfer of AAV-angiostatin via the portal vein led to significant suppression of the growth of both nodular and metastatic EL-4 lymphoma tumors established in the liver and prolonged the survival time of the mice. The growth of neovessels was inhibited significantly, and extensive apoptosis of tumor cells was observed. The anti-angiogenic activity of angiostatin was independent of vascular endothelial growth factor (VEGF). The AAV-angiostatin viruses did not appear to be toxic to mice, and there was no detectable apoptosis of hepatocytes. In conclusion, these encouraging results warrant future investigation of the use of AAV-mediated anti-angiogenic gene therapy for targeting unresectable liver metastases, especially after surgical removal of primary tumors.
Neurodevelopmental outcomes after preterm birth
Authors: Michael Colvin, William McGuire, Peter W Fowlie
Journal: BMJ (2004)

The major clinical outcomes that are important to preterm infants and their families are survival and normal long term neurodevelopment. In developed countries over the past 30 years, better perinatal care has considerably improved these outcomes. This article covers the prevalence of neurodevelopmental problems and their types. For most preterm infants of > 32 weeks' gestation, survival and longer term neurodevelopment are similar to those of infants born at term. Overall, outcomes are also good for infants born after shorter gestations. Most infants survive without substantial neurodevelopmental problems and most go on to attend mainstream schools, ultimately living independent lives. Neonatal death rate for preterm infants in Scotland since 1989 (deaths per 1000 live births by gestational age band). Adapted from Scottish perinatal and infant mortality and morbidity report, 2001 A few preterm babies, however, do develop important and lasting neurodevelopmental problems. The period between 20 and 32 weeks after conception is one of rapid brain growth and development. Illness, undernutrition, and infection during this time may compromise neurodevelopment. The clinical consequences can include serious neuromotor problems (principally cerebral palsy), visual and hearing impairments, learning difficulties, and psychological, behavioural, and social problems. ![][1]</img> Most substantial impairment occurs in the 0.2% of infants born before 28 weeks' gestation, or with birth weights of < 1000 g (extremely low birth weight). The survival rate for extremely preterm infants has improved over the past decade, but the overall prevalence of neurodisability after preterm birth has not fallen. In a recent North American follow … [1]: /embed/graphic-2.gif
Compensation of Chief Executive Officers at Nonprofit US Hospitals
Authors: Karen E. Joynt, Sidney T. Le, E. John Orav, Ashish K. Jha
Journal: JAMA Internal Medicine (2013)

<h3>Importance</h3> Hospital chief executive officers (CEOs) can shape the priorities and performance of their organizations. The degree to which their compensation is based on their hospitals' quality performance is not well known. <h3>Objective</h3> To characterize CEO compensation and examine its relation with quality metrics. <h3>Design, Setting, and Participants</h3> Retrospective observational study. Participants included 1877 CEOs at 2681 private, nonprofit US hospitals. <h3>Main Outcomes and Measures</h3> We used linear regression to identify hospital structural characteristics associated with CEO pay. We then determined the degree to which a hospital's performance on financial metrics, technologic metrics, quality metrics, and community benefit in 2008 was associated with CEO pay in 2009. <h3>Results</h3> The CEOs in our sample had a mean compensation of $595 781 (median, $404 938) in 2009. In multivariate analyses, CEO pay was associated with the number of hospital beds overseen ($550 for each additional bed; 95% CI, 429-671;<i>P</i> &lt; .001), teaching status ($425 078 more at major teaching vs nonteaching hospitals; 95% CI, 315 238-534 918;<i>P</i> &lt; .001), and urban location. Hospitals with high levels of advanced technologic capabilities compensated their CEOs $135 862 more (95% CI, 80 744-190 990;<i>P</i> &lt; .001) than did hospitals with low levels of technology. Hospitals with high performance on patient satisfaction compensated their CEOs $51 706 more than did those with low performance on patient satisfaction (95% CI, 15 166-88 247;<i>P</i> = .006). We found no association between CEO pay and hospitals' margins, liquidity, capitalization, occupancy rates, process quality performance, mortality rates, readmission rates, or measures of community benefit. <h3>Conclusions and Relevance</h3> Compensation of CEOs at nonprofit hospitals was highly variable across the country. Compensation was associated with technology and patient satisfaction but not with processes of care, patient outcomes, or community benefit.
Neural Responses Following Autotransplantation of the Canine Heart
Authors: VALLEE L. WILLMAN, THEODORE COOPER, LOUIS G. CIAN, C. ROLLINS HANLON
Journal: Circulation (1963)

Orthotopic autotransplantation of the canine heart is followed by loss of direct sympathetic and parasympathetic neural regulation. Stimulation of the vagus nerve or stellate ganglion fails to alter cardiac rate. Myocardial catecholamines are depleted and [see figure in the PDF file] hypersensitivity to exogenous l -norepinephrine is present for months. One year after the operation, there is evidence of cardiac reinnervation and return of normal responses to catecholamines.
616 Population pharmacokinetic analysis of ribavirin (COPEGUS®) after single and multiple dose administration in adult chronic hepatitis C (CHC) patients receiving concurrent peginterferon alpha-2a (40KD) (PEGASYS®)
Authors: J.R. Wade, E. Snoeck, M. Lamb, E. Duffe, K. Jorga
Journal: Journal of Hepatology (2006)
Disruption of Lymphocyte Function and Signaling in CD45–associated Protein–null Mice
Authors: Akio Matsuda, Satoshi Motoya, Shioko Kimura, Renee McInnis, Abby L. Maizel, Akiko Takeda
Journal: The Journal of Experimental Medicine (1998)

CD45-AP specifically associates with CD45, a protein tyrosine phosphatase essential for lymphocyte differentiation and antigen receptor–mediated signal transduction. CD45 is thought to mediate antigen receptor signaling by dephosphorylating regulatory tyrosine residues on Src family protein tyrosine kinases such as Lck. However, the mechanism for regulating CD45 protein tyrosine phosphatase activity remains unclear. CD45-AP–null mice were created to examine the role of CD45-AP in CD45-mediated signal transduction. T and B lymphocytes showed reduced proliferation in response to antigen receptor stimulation. Both mixed leukocyte reaction and cytotoxic T lymphocyte functions of T cells were also markedly decreased in CD45-AP–null mice. Interestingly, the interaction between CD45 and Lck was significantly reduced in CD45-AP–null T cells, indicating that CD45-AP directly or indirectly mediates the interaction of CD45 with Lck. Our data indicate that CD45-AP is required for normal antigen receptor signaling and function in lymphocytes.
ST segment response to acute coronary occlusion: coronary hemodynamic and angiographic determinants of direction of ST segment shift.
Authors: R G Macdonald, J A Hill, R L Feldman
Journal: Circulation (1986)

To assess the relationship between the direction of ST segment response to transient coronary occlusion and collateral function, we studied 25 patients with diagnostic ST segment changes during transient occlusion of the proximal left anterior descending artery (LAD). Electrocardiographic leads I, II, V2, and V5; left ventricular filling, aortic, and distal coronary pressures; and great cardiac vein flow were measured during percutaneous transluminal coronary angioplasty (PTCA) of the LAD. During a 1 min LAD balloon occlusion, 16 patients had reversible ST elevation (group I) and nine patients had ST depression (group II). The ST responses in individual patients were consistent during repeated occlusions, and ST depression never preceded ST elevation. Angiography before PTCA showed less severe LAD stenosis in group I (69 +/- 15%) than in group II (88 +/- 10%; p less than .01) and collateral filling of the LAD in no group I patient but in six of nine patients in group II (p less than .01). During LAD occlusion, determinants of myocardial oxygen demand (left ventricular filling pressure, aortic pressure, heart rate, and double product) were similar in both groups. Group I patients, however, had lower distal coronary pressure (25 +/- 8 vs 41 +/- 16 mm Hg) and residual great cardiac vein flow (33 +/- 14 vs 51 +/- 22 ml/min) and higher coronary collateral resistance (3.1 +/- 2.1 vs 1.5 +/- 0.8 mm Hg/ml/min) than group II patients (all p less than .05). In patients with ST elevation during LAD occlusion, stenosis before PTCA was less severe, visible collaterals were not present, and hemodynamic variables during LAD occlusion reflected poorer collateral function.(ABSTRACT TRUNCATED AT 250 WORDS)
Nucleolin-Mediated Cellular Trafficking of DNA Nanoparticle Is Lipid Raft and Microtubule Dependent and Can Be Modulated by Glucocorticoid
Authors: Xuguang Chen, Samuel Shank, Pamela B Davis, Assem G Ziady
Journal: Molecular Therapy (2010)

DNA nanoparticles (DNPs) are nonviral gene transfer vectors with excellent in vivo potential. Previously, we reported that cell surface nucleolin directly binds DNPs, and functions as an important receptor for DNPs. However, the fate of the nucleolin-DNP complex following cellular uptake remains elusive. In this study, we examined the role of lipid rafts in the uptake of DNPs, and found that both nucleolin and DNPs are recovered from the low-density raft fractions of the sucrose gradient. Furthermore, nucleolin colocalizes with, and coimmunoprecipitates with a raft protein, flotillin. Disruption of lipid rafts by depleting membrane cholesterol significantly inhibited DNP transfection, while inhibition of other endocytic pathways had little effect. Following the uptake, the nuclear import of the DNPs required microtubules but not F-actin. By coimmunoprecipitation in conjunction with tandem mass spectrometry, we identified glucocorticoid receptor (GCR) as a nucleolin-associated protein, and confirmed this result by western blot. Cortisone or dexamethasone increased nucleolin's association with GCR, and transfection by DNPs. Finally, we detected the expression of nucleolin on the surface of airway epithelia in vivo. Taken together, our findings shed light on important determinants of DNP trafficking in cells and support the notion that nucleolin is a good target for nonviral gene delivery.
Phenotypic characteristics of Kaposi's sarcoma tumour cells derived from patch-, plaque- and nodular-stage lesions: analysis of cell cultures isolated from AIDS and non-AIDS patients and review of the literature
Authors: T. Simonart, P. Hermans, L. Schandene, J.P. Van Vooren
Journal: British Journal of Dermatology (2000)

Kaposi's sarcoma (KS) is commonly thought to be derived from endothelial cells because of the predominant expression of endothelial markers in KS lesions. However, the heterogeneity of the spindle-cell compartment makes the precise lineage relationship of KS tumour cells unclear. Cultured KS-derived spindle cells constitutively overexpress antiapoptotic proteins and exhibit invasive properties, which suggests that they may adequately represent the tumour cells of KS.We aimed to investigate the expression of a wide variety of immunohistochemical markers by spindle cells derived from patch-, plaque- and nodular-stage lesions from patients with iatrogenic, sporadic and acquired immune deficiency syndrome-related KS, and to review the data reported by other laboratories.Cells from six KS cell cultures derived from four subjects were examined by immunostaining.Comparison of these data indicates that KS-derived spindle cells generally express myofibroblast antigens but lack endothelial and/or leucocyte markers.As the myofibroblast phenotype is not the predominant feature of KS tissues, our findings further substantiate the view that the in vivo dominant endothelial population represents a reactive hyperplasia rather than the true KS tumour process.
Effect of Rotablator Atherectomy and Adjunctive Balloon Angioplasty on Coronary Blood Flow
Authors: Terry R. Bowers, Richard E. Stewart, William W. O'Neill, Venu M. Reddy, Robert D. Safian
Journal: Circulation (1997)

Background The purpose of this study was to assess serial changes in coronary blood flow velocity before and after Rotablator atherectomy and after adjunctive percutaneous transluminal coronary angioplasty (PTCA). Since Rotablator atherectomy results in luminal enlargement by plaque pulverization and distal embolization, improvement in coronary blood flow could be attenuated despite luminal enlargement. Methods and Results Intracoronary Doppler blood flow velocity measurements were obtained with a Doppler Flowire. Basal average peak velocity (bAPV), hyperemic APV (hAPV), diastolic/systolic velocity ratio (DSVR), and coronary flow reserve (CFR) were assessed before intervention, after Rotablator, and after adjunctive PTCA. Complete clinical, angiographic, and Doppler data were obtained in 22 patients. There was a small but significant difference ( P =.02) in resting heart rate and mean arterial pressure before and after Rotablator and after adjunctive PTCA. Minimum lumen diameter increased from 0.8±0.1 to 1.5±0.2 to 2.0±0.1 mm ( P &lt;.001), corresponding to decreases in diameter stenosis from 72±3% to 41±4% to 36±3% ( P &lt;.001). Although bAPV, hAPV, and DSVR increased significantly ( P &lt;.001), CFR remained abnormally low in 19 of 22 patients (despite an increase from baseline to post-PTCA). hAPV &gt;30 cm/s was the best Doppler correlate of angiographic success. Conclusions Rotablator atherectomy and adjunctive PTCA significantly improve distal coronary blood flow velocity and DSVR but not CFR. Failure to normalize CFR could be secondary to parallel increases in bAPV and hAPV, “acquired” microvascular disease due to distal microembolization or spasm, and/or angiographically inapparent dissection or residual stenosis. Adjunctive PTCA contributes significantly to the overall physiological benefit of a combined procedure.
Management of coronary artery disease.
Authors: A. M. Barrett
Journal: BMJ (1969)

ticular form.A number of patients are excluded from these results on the grounds of " advanced diseases or other reason."Those exclusions rise as high as 354 out of 892 patients seen with cancer of the hypo- pharynx (p.33), so that a considerable element of selection appears to be taking place.If in future editions of this useful book figures are also given as described by Mac- donald,' Berkson and Gage,2 or MacComb,' the appropriate corrections can be made when necessary to make these results comparable with other series.-Iam, etc., Hull.