tbuckley/cabot-search huggingface dataset:
Clinic-Based Treatment of Opioid-Dependent HIV-Infected Patients Versus Referral to an Opioid Treatment Program
Authors: Gregory M. Lucas, Amina Chaudhry, Jeffrey Hsu, Tanita Woodson, Bryan Lau, Yngvild Olsen, Jeanne C. Keruly, David A. Fiellin, Ruth Finkelstein, Patricia Barditch-Crovo, Katie Cook, Richard D. Moore
Journal: Annals of Internal Medicine (2010)

Background: Opioid dependence is common in HIV clinics. Buprenorphine–naloxone (BUP) is an effective treatment of opioid dependence that may be used in routine medical settings. Objective: To compare clinic-based treatment with BUP (clinic-based BUP) with case management and referral to an opioid treatment program (referred treatment). Design: Single-center, 12-month randomized trial. Participants and investigators were aware of treatment assignments. (ClinicalTrials.gov registration number: NCT00130819) Setting: HIV clinic in Baltimore, Maryland. Patients: 93 HIV-infected, opioid-dependent participants who were not receiving opioid agonist therapy and were not dependent on alcohol or benzodiazepines. Intervention: Clinic-based BUP included BUP induction and dose titration, urine drug testing, and individual counseling. Referred treatment included case management and referral to an opioid-treatment program. Measurements: Initiation and long-term receipt of opioid agonist therapy, urine drug test results, visit attendance with primary HIV care providers, use of antiretroviral therapy, and changes in HIV RNA levels and CD4 cell counts. Results: The average estimated participation in opioid agonist therapy was 74% (95% CI, 61% to 84%) for clinic-based BUP and 41% (CI, 29% to 53%) for referred treatment (P < 0.001). Positive test results for opioids and cocaine were significantly less frequent in clinic-based BUP than in referred treatment, and study participants receiving clinic-based BUP attended significantly more HIV primary care visits than those receiving referred treatment. Use of antiretroviral therapy and changes in HIV RNA levels and CD4 cell counts did not differ between the 2 groups. Limitation: This was a small single-center study, follow-up was only moderate, and the study groups were unbalanced in terms of recent drug injections at baseline. Conclusion: Management of HIV-infected, opioid-dependent patients with a clinic-based BUP strategy facilitates access to opioid agonist therapy and improves outcomes of substance abuse treatment. Primary Funding Source: Health Resources and Services Administration Special Projects of National Significance program.
Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin.
Authors: W A Bauman, S Shaw, E Jayatilleke, A M Spungen, V Herbert
Journal: Diabetes Care (2000)

OBJECTIVE: Of patients who are prescribed metformin, 10-30% have evidence of reduced vitamin B12 absorption. B12-intrinsic factor complex uptake by ileal cell surface receptors is known to be a process dependent on calcium availability Metformin affects calcium-dependent membrane action. The objective of this study was to determine the magnitude and mechanism of the reduction in serum vitamin B12 after metformin administration. RESEARCH DESIGN AND METHODS: A comparative study design was employed using 2 groups (metformin and control). A total of 21 patients with type 2 diabetes received sulfonylurea therapy; 14 of these 21 patients were switched to metformin. Monthly serum total vitamin B12 measurements and holotranscobalamin (holoTCII) (B12-TCII) were performed. After 3 months of metformin therapy, oral calcium supplementation was administered. RESULTS: Serial serum vitamin B12 determinations revealed a similar decline in vitamin B12 and holoTCII. Oral calcium supplementation reversed the metformin-induced serum holoTCII depression. CONCLUSIONS: Patients receiving metformin have diminished B12 absorption and low serum total vitamin B12 and TCII-B12 levels because of a calcium-dependent ileal membrane antagonism, an effect reversed with supplemental calcium.
The Neural Substrate of Spectral Preference in Drosophila
Authors: Shuying Gao, Shin-ya Takemura, Chun-Yuan Ting, Songling Huang, Zhiyuan Lu, Haojiang Luan, Jens Rister, Andreas S. Thum, Meiluen Yang, Sung-Tae Hong, Jing W. Wang, Ward F. Odenwald, Benjamin H. White, Ian A. Meinertzhagen, Chi-Hon Lee
Journal: Neuron (2008)
Origin of IgA-secreting plasma cells in the mammary gland.
Authors: M E Roux, M McWilliams, J M Phillips-Quagliata, P Weisz-Carrington, M E Lamm
Journal: The Journal of Experimental Medicine (1977)

Lymphoblasts from the mesenteric lymph nodes (MN) of mice home to the mammary glands of syngeneic recipients late in pregnancy and during lactation, and within hours of transfer most can be shown to contain IgA. Homing does not occur in virgins, in early pregnancy, or after weaning. Homing MN lymphoblasts are sensitive to antiserum to IgA plus complement, but not to other class-specific antisera. Thus, lymphoblasts in MN with the potential to home to the mammary gland are already committed to IgA synthesis and bear surface IgA before reaching their destination. These results explain observations, made by others, of specific IgA antibodies and IgA plasma cells in milk and colostrum after oral immunization. Under natural conditions it is likely that IgA precursor cells, after stimulation in the gut-associated lymphoid tissue by intestinal antigens, migrate to the mammary gland where they secrete antibodies which constitute an important defense mechanism of the newborn. In the absence of lactation, these cells probably form part of the normal traffic to the lamina propria of the small intestine.
Comparison of wild-type and subacute sclerosing panencephalitis strains of measles virus. Neurovirulence in ferrets and biological properties in cell cultures.
Authors: H Thormar, P D Mehta, H R Brown
Journal: The Journal of Experimental Medicine (1978)

The neurovirulence of two wild type (wt) and seven Subacute Sclerosing Panencephalitis (SSPE) measles virus strains was tested in young adult ferrets by intracerebral (IC) inoculation of infected Vero cell suspensions. Wt strains Edmonston and Woodfolk and SSPE strains Mantooth, Halle, and LEC-S did not produce a detectable encephalitis in the ferrets, but caused a significant formation of serum antibodies against measles virus. SSPE strains LEC, IP-3, Biken, and D.R., on the other hand, were all neurovirulent in ferrets, particularly strain D.R. which caused an acute encephalitis in all inoculated animals. Strain Biken was of particular interest since it caused a subacute encephalitis in four of seven ferrets. The subacute encephalitis was characterized by a long incubation time, persistence of virus in the brain for at least 8 mo, widespread inflammatory lesions, and production of measles virus specific IgG in the brain. A study of the biological properties of the various measles virus strains showed that wt strains Edmonston and Woodfolk and SSPE strains Mantooth, Halle, and LEC-S produced free virus particles in significant titers both in Vero and ferret brain (FB) cultures. Cytopathic effect (CPE) with cell-fusion was marked in Vero cultures, whereas only minimal CPE and no cell-fusion were observed in the FB cultures. SSPE strains LEC, IP-3, Biken, and D.R., on the other hand, were mostly cell-associated in Vero and FB cultures, although atypical cell-free particles were produced by strains Biken and IP-3. All four strains showed cell-fusing activity in FB cultures, particularly strain D.R., which was the only strain that spread more actively by fusion in FB than in Vero cultures. The results are discussed in relation to the neurovirulence of the various measles virus strains in adult ferrets. Pronounced cell-fusing activity in FB cells and cell-association with minimal or no production of cell-free virus seem to be essential to establish a brain infection in the animals.
Non–High-Density Lipoprotein Cholesterol Levels Predict Five-Year Outcome in the Bypass Angioplasty Revascularization Investigation (BARI)
Authors: Vera Bittner, Regina Hardison, Sheryl F. Kelsey, Bonnie H. Weiner, Alice K. Jacobs, George Sopko
Journal: Circulation (2002)

Background— Current National Cholesterol Education Program guidelines recommend that non–high-density lipoprotein cholesterol (non-HDL-C) be considered a secondary target of therapy among individuals with triglycerides &gt;2.26 mmol/L. It is not known whether non-HDL-C relates to prognosis among patients with coronary heart disease. Methods and Results— Lipid levels were available at baseline among 1514 patients (73% men; mean age, 61 years) enrolled in the Bypass Angioplasty Revascularization Investigation (BARI); all had multivessel coronary artery disease. Patients were followed for 5 years. Outcomes of death, nonfatal myocardial infarction, and death or myocardial infarction were modeled using univariate and multivariate time-dependent proportional hazards methods; angina pectoris at 5 years was modeled using univariate and multivariate logistic regression. Non-HDL-C was a strong and independent predictor of nonfatal myocardial infarction (multivariate relative risk, 1.049 [95% confidence intervals, 1.006 to 1.093] for every 0.26 mmol/L increase) and angina pectoris (multivariate odds ratio, 1.049 [95% confidence intervals, 1.004 to 1.096] for every 0.26 mmol/L increase), but it did not relate to mortality. HDL-C and LDL-C did not predict events during follow-up. Conclusions— Among patients with lipid values in BARI, non-HDL-C is a strong and independent predictor of nonfatal myocardial infarction and angina pectoris at 5 years, even after consideration of powerful clinical variables. Our data suggest that non-HDL-C is an appropriate treatment target among patients with coronary heart disease.
Overexpression of human truncated peroxisome proliferator-activated receptor induces apoptosis in HL-1 cardiomyocytes
Authors: J. Beaumont, T. Arias, S. Ravassa, J. Diez
Journal: Cardiovascular Research (2008)

Our goal was to analyse whether truncated peroxisome proliferator-activated receptor alpha (PPARalpha) overexpression induces apoptosis of cardiomyocytes.We constructed a recombinant vector of human truncated PPARalpha and a mammalian expression vector to transfect PPARalpha into a line of murine cardiomyocytes designated HL-1. Four hallmarks of apoptosis were measured in these transfected cells: depolarization of mitochondrial membrane, activation of caspase-3, phosphatidylserine (PS) externalization, and DNA fragmentation. Co-transfection with human cyclic adenosine monophosphate response element-binding protein (CREB) and human CREB binding protein (CBP) and analysis of apoptosis regulatory proteins, Bcl-2 and Bax, were also performed in truncated PPARalpha-transfected cells to determine the potential mechanisms by which truncated PPARalpha may influence apoptosis. Progressive depolarization of mitochondrial membrane, activation of caspase-3, PS externalization, DNA fragmentation, and cell death were observed in HL-1 cells upon increasing levels of transfected truncated PPARalpha. The expression of the antiapoptotic protein Bcl-2 decreased in transfected HL-1 cardiomyocytes, whereas no changes in the proapoptotic protein Bax were observed in these cells. Overexpression of CREB plus CBP abolished the inhibitory effect of truncated PPARalpha on Bcl-2 protein.These results demonstrate that human truncated PPARalpha overexpression induces apoptosis in HL-1 cardiomyocytes. In addition, our findings suggest that truncated PPARalpha may induce cardiomyocyte apoptosis through the inhibition of the antiapoptotic protein, Bcl-2. It is proposed that competition with CREB for coactivators like CBP could be involved in this inhibitory effect.
Concomitant Cisplatin Significantly Improves Locoregional Control in Advanced Head and Neck Cancers Treated With Hyperfractionated Radiotherapy
Authors: Pia Huguenin, Karl T. Beer, Abdelkarim Allal, Kaspar Rufibach, Corinne Friedli, Jacques Bernard Davis, Bernhard Pestalozzi, Stephan Schmid, Armin Thöni, Mahmut Ozsahin, Jacques Bernier, Michael Töpfer, Roger Kann, Urs Richard Meier, Peter Thum, Sabine Bieri, Markus Notter, Norbert Lombriser, Christoph Glanzmann
Journal: Journal of Clinical Oncology (2004)

Purpose To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. Patients and Methods From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m 2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. Results There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease–free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. Conclusion The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.
After the horror
Authors: B. Raphael, W. Middleton
Journal: BMJ (1988)

Posttraumatic stress disorder is formal terminology for a common condition, the psychological problems that follow exposure to events such as the Bradford football stadium fire, the Zeebrugge ferry disaster, the Vietnam war, or some less well publicised and more private horror such as assault or rape. These psychological problems may be severe, prolonged, and disabling, and they include intrusive memories, flashbacks, anxiety, numbing of feelings, and irritability. The account of a survivor of the Bradford soccer stadium fire illustrates phenomena associated with the condition.
Long term effects of non-invasive mechanical ventilation on pulmonary haemodynamics in patients with chronic respiratory failure
Authors: B Schonhofer
Journal: Thorax (2001)

Background-It is not known whether long term nocturnal mechanical ventilation (NMV) reduces pulmonary hypertension in patients with chronic respiratory failure (CRF).Methods-Pulmonary haemodynamics, spirometric values, and gas exchange were studied in 33 patients requiring NMV due to CRF (20 with thoracic restriction, 13 with chronic obstructive pulmonary disease (COPD)) at baseline and after 1 year of NMV given in the volume cycled mode.Patients with COPD also received supplemental oxygen.Results-Long term NMV improved gas exchange while lung function remained unchanged.Mean pulmonary artery pressure at rest before NMV was higher in patients with thoracic restriction than in those with COPD (33 (10) mm Hg v 25 (6) mm Hg).After 1 year of NMV mean pulmonary artery pressure decreased in patients with thoracic restriction to 25 (6) mm Hg (mean change -8.5 mm Hg (95% CI -12.6 to -4.3), p<0.01) but did not change significantly in patients with COPD (mean change 2.2 mm Hg (95% CI -0.3 to 4.8)).Conclusions-Long term NMV in CRF improves pulmonary haemodynamics in patients with thoracic restriction but not in patients with COPD.
Transient joint effusion: a forgotten side effect of high dose corticosteroid treatment
Authors: F Schiavon
Journal: Annals of the Rheumatic Diseases (2003)

<h3>Objective</h3> Accumulation of mitochondria underlies T-cell dysfunction in systemic lupus erythematosus (SLE). Mitochondrial turnover involves endosomal traffic regulated by HRES-1/Rab4, a small GTPase that is overexpressed in lupus T cells. Therefore, we investigated whether (1) HRES-1/Rab4 impacts mitochondrial homeostasis and (2) Rab geranylgeranyl transferase inhibitor 3-PEHPC blocks mitochondrial accumulation in T cells, autoimmunity and disease development in lupus-prone mice. <h3>Methods</h3> Mitochondria were evaluated in peripheral blood lymphocytes (PBL) of 38 SLE patients and 21 healthy controls and mouse models by flow cytometry, microscopy and western blot. MRL/lpr mice were treated with 125 μg/kg 3-PEHPC or 1 mg/kg rapamycin for 10 weeks, from 4 weeks of age. Disease was monitored by antinuclear antibody (ANA) production, proteinuria, and renal histology. <h3>Results</h3> Overexpression of HRES-1/Rab4 increased the mitochondrial mass of PBL (1.4-fold; p=0.019) and Jurkat cells (2-fold; p=0.000016) and depleted the mitophagy initiator protein Drp1 both in human (−49%; p=0.01) and mouse lymphocytes (−41%; p=0.03). Drp1 protein levels were profoundly diminished in PBL of SLE patients (−86±3%; p=0.012). T cells of 4-week-old MRL/lpr mice exhibited 4.7-fold over-expression of Rab4A (p=0.0002), the murine homologue of HRES-1/Rab4, and depletion of Drp1 that preceded the accumulation of mitochondria, ANA production and nephritis. 3-PEHPC increased Drp1 (p=0.03) and reduced mitochondrial mass in T cells (p=0.02) and diminished ANA production (p=0.021), proteinuria (p=0.00004), and nephritis scores of lupus-prone mice (p&lt;0.001). <h3>Conclusions</h3> These data reveal a pathogenic role for HRES-1/Rab4-mediated Drp1 depletion and identify endocytic control of mitophagy as a treatment target in SLE.
Resistance to the Phosphaturic and Calcemic Actions of Parathyroid Hormone during Phosphate Depletion
Authors: H. J. Gloor, J-P. Bonjour, J. Caverzasio, H. Fleisch
Journal: Journal of Clinical Investigation (1979)

Recent observations indicate that in thyroparathyroidectomized (TPTX) rats fed a low (0.2 g/100 g) phosphorus diet, the tubular phosphaturic response to parathyroid hormone (PTH) remains markedly blunted even when it is assessed at normal or high plasma concentration and filtered load of inorganic phosphate (Pi). Because 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] decreases the tubular capacity to reabsorb Pi when chronically administered to TPTX rats, we have studied whether this vitamin D(3) metabolite could specifically increase the phosphaturic response to PTH in phosphate-deprived animals. The results show that in Vitamin D-replete TPTX rats fed a low (0.2 g/100 g) phosphorus diet, 1,25(OH)(2)D(3) (2 x 13 pmol/d i.p. for 7 d) markedly enhanced the acute tubular phosphaturic response to PTH (2.5 IU/h i.v.) without affecting the action of the peptide hormone on Ca reabsorption and cyclic-3',5'-AMP excretion. The influence of 1,25(OH)(2)D(3) on the phosphaturic response to PTH could not be ascribed to an increased plasma concentration and(or) filtered load of Pi during the administration of the peptide hormone. However, it could be, at least in part, related to the elevation in the basal level of plasma Pi which was observed in the 1,25(OH)(2)D(3)-treated animals. The results also indicate that 1,25(OH)(2)D(3) significantly enhanced the calcemic response to PTH, which was blunted in these conditions of phosphate deprivation. Unlike 1,25-(OH)(2)D(3), 25-hydroxyvitamin D(3) did not unmask the phosphaturic effect of PTH in phosphate-depleted animals, even when given in doses 100 times larger. Thus, 1,25(OH)(2)D(3) displays a selective and powerful activity in preventing the occurrence of tubular resistance to the phosphaturic action of PTH during Pi depletion. This finding suggests the existence of an important interaction between dietary Pi, 1,25(OH)(2)D(3), and PTH in the homeostasis of phosphate.
Cardiovascular Responses to the Isoprostanes iPF <sub>2α</sub> -III and iPE <sub>2</sub> -III Are Mediated via the Thromboxane A <sub>2</sub> Receptor In Vivo
Authors: Laurent P. Audoly, Bianca Rocca, Jean-Etienne Fabre, Beverly H. Koller, Dennis Thomas, Alex L. Loeb, Thomas M. Coffman, Garret A. FitzGerald
Journal: Circulation (2000)

Isoprostanes (iPs) are free radical-catalyzed products of arachidonic acid that reflect lipid peroxidation in vivo. Several iPs exert biological effects in vitro and may contribute to the functional consequences of oxidant stress. For example, iPF(2alpha)-III (8-iso PGF(2alpha)) and iPE(2)-III modulate platelet function and vascular tone. Although these effects are blocked by antagonists of the receptor (TP) for the cyclooxygenase product thromboxane A(2), it has been speculated that the iPs may activate a receptor related to, but distinct from, the TP.Transgenic mice (TPOEs) were generated in which the TP-beta isoform was under the control of the preproendothelin promoter. They overexpressed TP-beta in the vasculature but not in platelets and exhibited an exaggerated pressor response to infused iPF(2alpha)-III compared with wild-type mice. This was blocked by TP antagonism. The platelet response to the iP was unaltered in TPOEs compared with wild-type mice. By contrast, both the pressor response to iPF(2alpha)-III and its effects on platelet function were abolished in mice lacking the TP gene. This was also true of the effects of infused iPE(2)-III on mean arterial pressure and platelet aggregation.Both iPF(2alpha)-III and iPE(2)-III exert their effects on platelet function and vascular tone in vivo by acting as incidental ligands at membrane TPs rather than via a distinct iP receptor. Activation of TPs by iPs may be of importance in syndromes in which cyclooxygenase activation and oxidant stress coincide, such as in atherosclerosis and reperfusion after tissue ischemia.
Blood Pressure and Decline in Kidney Function
Authors: J. Hunter Young, Michael J. Klag, Paul Muntner, Joanna L. Whyte, Marco Pahor, Josef Coresh
Journal: Journal of the American Society of Nephrology (2002)

The association between BP and decline in kidney function in older persons and the BP component most responsible for kidney disease are unknown. This study investigated the relationship between baseline BP and an incident decline in kidney function among 2181 men and women enrolled in the placebo arm of the Systolic Hypertension in the Elderly Program (SHEP). A decline in kidney function was defined as an increase in serum creatinine equal to or greater than 0.4 mg/dl over 5 yr of follow-up. The incidence and relative risk of a decline in kidney function increased at higher levels of BP for all BP components, independent of age, gender, ethnicity, smoking, diabetes, and history of cardiovascular disease. Systolic BP imparted the highest risk of decline in kidney function. The adjusted relative risk (95% confidence interval) associated with the highest compared with the lowest quartile of BP was 2.44 (1.67 to 3.56) for systolic; 1.29 (0.87 to 1.91) for diastolic; 1.80 (1.21 to 2.66) for pulse; and 2.03 (1.39 to 2.94) for mean arterial pressure. The risk associated with systolic BP remained strong in models containing other BP components, while diastolic, pulse, and mean arterial pressure had no significant association with a decline in kidney function in models containing systolic BP. Therefore, systolic BP is a strong, independent predictor of a decline in kidney function among older persons with isolated systolic hypertension.
Remembering the hippocampus
Authors: Stuart M. Zola, Larry R. Squire
Journal: Behavioral and Brain Sciences (1999)

The proposal that the hippocampus is important for the encoding of episodic information, but not familiarity-based recognition, is incompatible with the available data. An alternative way to think about functional specialization within the medial temporal lobe memory system is suggested, based on neuroanatomy.