tbuckley/cabot-search huggingface dataset:
Very low density lipoproteins in intestinal lymph: origin, composition, and role in lipid transport in the fasting state
Authors: Robert K. Ockner, Faith B. Hughes, Kurt J. Isselbacher
Journal: Journal of Clinical Investigation (1969)

The transport of endogenous lipids in the lipoproteins of mesenteric lymph was studied in fasting rats with mesenteric lymph fistulas. The lymph was found to contain, in addition to chylomicrons (Sf >400), a significant amount of another, more dense, triglyceride-rich fraction, the very low density lipoproteins (VLDL), which showed a peak Sf of 102. The VLDL differed from chylomicrons not only in flotation, but also in per cent lipid composition and electrophoretic mobility in agarose gel. The VLDL fraction was found to contain 47% of the triglyceride and 54% of the cholesterol of fasting lymph and, in the fasting state, was the major lipoprotein species present.
Familial, psychiatric, and socioeconomic risk factors for suicide in young people: nested case-control study
Authors: E. Agerbo
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To estimate the risk of suicide in young people related to family and individual psychiatric and socioeconomic factors. <b>Design:</b> Population based nested case-control study. <b>Setting:</b> Data from longitudinal Danish registers. <b>Cases and controls:</b> 496 young people aged 10-21 years who had committed suicide during 1981-97 in Denmark and 24 800 controls matched for sex, age, and time. <b>Main outcome measures:</b> All suicides in Denmark compared with controls; parents and siblings identified from population based registers; inpatient information from discharge registers of national hospitals; and socioeconomic data from administrative registers. <b>Results:</b> Parental factors associated with an increased risk of suicide in young people were suicide or early death, admission to hospital for a mental illness, unemployment, low income, poor schooling, and divorce, as well as mental illness in siblings and mental illness and short duration of schooling in the young people themselves. The strongest risk factor was mental illness in the young people. The effect of the parents9 socioeconomic factors decreased after adjustment for a family history of mental illness and a family history of suicide. <b>Conclusions:</b> Recognising mental illness in young people and dealing with it appropriately could help prevent suicides. The high relative risk associated with a low socioeconomic status of the parents may be confounded and overestimated if not adjusted for mental illness and suicide in the family. <h3>What is already known on this topic</h3> Young people who commit suicide have a history of mental illness or a family history of mental illness or suicidal behaviour Dysfunctional family backgrounds and socioeconomic adversity also contribute to suicide in young people Targets for preventive strategies are controversial, as few population based studies have been conducted and none have included all the risk factors <h3>What this study adds</h3> Suicide is more likely among young people if a parent commits suicide or there is a history of mental illness in the individual and their siblings Socioeconomic risk factors seem to be less important Preventive strategies should be aimed at the early recognition and optimal treatment of mental illnesses
Cardiopulmonary Failure of the Hunchback
Authors: A. Jay Block
Journal: JAMA (1970)

In a middle-aged man with cardiopulmonary failure secondary to severe kyphoscoliosis, skeletal traction produced improvement by roentgenographic, functional, and clinical criteria. Although an attempt to perpetuate this improvement by surgical spine correction was unsuccessful, it is thought that these therapeutic maneuvers should be attempted again in the absence of other definitive therapy.
Role of Nonmyeloablative Allogeneic Stem-Cell Transplantation After Failure of Autologous Transplantation in Patients With Lymphoproliferative Malignancies
Authors: Katharine Branson, Rajesh Chopra, Panagiotis D. Kottaridis, Grant McQuaker, Anne Parker, Stephen Schey, Ronjon K. Chakraverty, Charles Craddock, Donald W. Milligan, Ruth Pettengell, Judith C.W. Marsh, David C. Linch, Anthony H. Goldstone, Catherine D. Williams, Stephen Mackinnon
Journal: Journal of Clinical Oncology (2002)

Conventional allogeneic stem-cell transplantation (SCT) after a prior failed autograft is associated with a transplant-related mortality rate of 50% to 80%. The aim of the current study was to evaluate the safety and efficacy of sibling, HLA-matched, nonmyeloablative allogeneic SCT with donor lymphocyte infusion (DLI) in patients with lymphoid malignancy after failure of autologous SCT.A total of 38 patients with refractory, progressive, or relapsed disease after autologous SCT were entered onto this study. The conditioning regimen consisted of the humanized monoclonal antibody CAMPATH-1H, fludarabine, and melphalan. Fifteen of 35 assessable patients received DLI after SCT.Sustained neutrophil engraftment was achieved in 37 recipients, and platelet engraftment was achieved in 35 patients. The estimated transplant-related mortality was 7.9% at day 100 and 20% at 14 months, the median duration of follow-up. Eight patients experienced grade I/II acute graft-versus-host disease (GVHD) after transplantation, but no grade III/IV GVHD was observed in this setting. However, grade III/IV GVHD occurred in seven patients who received DLI. The actuarial overall survival at 14 months was 53%, with a progression-free survival of 50%. DLI produced a further response in three of 15 recipients.Nonmyeloablative allogeneic SCT after CAMPATH-1H-containing conditioning is a relatively safe option compared with conventional allogeneic transplantation for patients who have failed previous autologous SCT. The low incidence of early GVHD enabled the subsequent administration of DLI to improve further clinical responses in this poor-risk group of lymphoma and myeloma patients.
Predominantly proinflammatory cytokines decrease after B cell depletion therapy in patients with primary Sjögren's syndrome
Authors: R P E Pollard, W H Abdulahad, H Bootsma, P M Meiners, F K L Spijkervet, M G Huitema, J G M Burgerhof, A Vissink, F G M Kroese
Journal: Annals of the Rheumatic Diseases (2013)

Cytokines are critical in initiating and perpetuating the chronic inflammatory response in primary Sjogren's syndrome (pSS).1 Rituximab has beneficial effects on disease activity in pSS patients2 and results in a rise in B cell activating factor (BAFF) levels.3 Whether (elevated) levels of other (proinflammatory) cytokines are affected was addressed in this study. This information is important for understanding of the effect of rituximab in pSS.

Twenty-eight patients with early-onset pSS2 treated with rituximab (n=18) or placebo (n=10), and 10 age-matched and sex-matched healthy controls (HCs) were assessed for presence of cytokines/chemokines in serum, using a multiplex-25 bead array assay (Invitrogen, Breda, The Netherlands). The following cytokines and chemokines were analysed: GM-CSF, IL-1β, IL-1Ra, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p40/p70, IL-13, IL-15, IL-17, IFN-α, IFN-γ, TNF-α, MCP-1/CCL2, MIP-1α/CCL3; MIP-1β/CCL4, RANTES/CCL5, Eotaxin/CCL11, MIG/CXCL9 and IP-10/CXCL10.

At baseline, levels for nearly all cytokines/chemokines were significantly higher in pSS patients than …
Late-breaking abstract: Antitussive effect of a diphenhydramine-containing multicomponent cough syrup in acute viral cough
Authors: Peter Dicpinigaitis, Sean Dhar, Amber Johnson, Yvonne Gayle, John Brew, Wilson Caparros-Wanderley
Journal: European Respiratory Journal (2014)

Background  Cough is among the most common complaints for which patients seek medical attention. Currently available over-the-counter cough remedies historically have been criticized for lack of scientific evidence supporting their efficacy. Although the first-generation antihistamine diphenhydramine is classified as an antitussive by the US Food and Drug Administration (Fed Regist 1994;59:29172-4), to the authors9 knowledge it has never been shown to inhibit cough reflex sensitivity in subjects with pathological cough.  Methods  22 subjects with acute viral respiratory tract infection (common cold) underwent cough reflex sensitivity measurement employing capsaicin challenge on 3 separate days, 2 hours after ingesting a single dose of study drug (to coincide with peak blood levels) that was administered in a randomized, double-blind manner: a multicomponent syrup containing diphenhydramine (25 mg), phenylephrine (10 mg), in a natural cocoa formulation (Dr. Cocoa, Infirst Healthcare, UK); dextromethorphan (30 mg) syrup; and, placebo syrup. The standard endpoint of cough challenge was used: the concentration of capsaicin inducing ≥5 coughs (C5).  Results  Differences in log C5 responses were analyzed by 1-way ANOVA for dependent samples combined with Tukey9s HSD test for pairwise comparisons. A significant difference (p=0.0024) was established among the groups, with pairwise analysis revealing a significant increase in mean log C5 (0.4±0.12(SEM); p  Conclusion  Our results provide the initial evidence of the ability of diphenhydramine to inhibit cough reflex sensitivity in subjects with acute pathological cough.
Bronchoalveolar lymphocytosis correlates with human T lymphotropic virus type I (HTLV-I) proviral DNA load in HTLV-I carriers
Authors: S Mori
Journal: Thorax (2005)

A study was undertaken to investigate the pathogenesis of pulmonary involvement in human T lymphotropic virus type I (HTLV-I) carriers.The bronchoalveolar lavage (BAL) cell profile of 30 HTLV-I carriers (15 asymptomatic HTLV-I carriers (AHCs) and 15 symptomatic HTLV-I carriers (SHCs)) with chronic inflammatory diseases of respiratory tract and eight patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) was investigated. The HTLV-I proviral deoxyribonucleic acid (DNA) load in peripheral blood mononuclear cells (PBMCs) and BAL fluid from HTLV-I carriers was estimated using the quantitative polymerase chain reaction method and the correlation between the lymphocyte number in BAL fluid and the HTLV-I proviral DNA load in PBMCs and BAL fluid was examined.The percentage of lymphocytes in BAL fluid was increased (>18%) in 11 of 30 HTLV-I carriers although there was no significant difference compared with control subjects. In HTLV-I carriers the lymphocyte number in BAL fluid correlated well with the copy number of HTLV-I proviral DNA in PBMCs. In addition, the copy number of HTLV-I proviral DNA in BAL fluid correlated well with the number of lymphocytes (both CD4+ and CD8+ cells) in BAL fluid.These findings suggest that pulmonary lymphocytosis can occur in a subset of HTLV-I carriers without HAM/TSP and that the increased HTLV-I proviral DNA load may be implicated in the pathogenesis of pulmonary involvement in HTLV-I carriers.
The homeoprotein DLX4 controls inducible nitric oxide synthase-mediated angiogenesis in ovarian cancer
Authors: Bon Trinh, Song Yi Ko, Dhwani Haria, Nicolas Barengo, Honami Naora
Journal: Molecular Cancer (2015)

Homeobox genes encode transcription factors that control patterning of virtually all organ systems including the vasculature. Tumor angiogenesis is stimulated by several homeobox genes that are overexpressed in tumor cells, but the mechanisms of these genes are poorly understood. In this study, we investigated the mechanisms by which DLX4, a homeobox gene that is associated with increased tumor microvessel density, stimulates ovarian tumor angiogenesis.Expression of DLX4 and nitric oxide synthases was analyzed in publicly available transcriptional profiles of ovarian cancer clinical specimens. Levels of inducible nitric oxide synthase (iNOS) were evaluated by quantitative RT-PCR, flow cytometry and nitric oxide assays using ovarian cancer cell lines in which DLX4 was overexpressed or knocked down. Signal Transducer and Activator of Transcription 1 (STAT1) expression and activity were evaluated by luciferase reporter assays, immunofluorescence staining, Western blot and immunoprecipitation. Endothelial cell growth and tumor angiogenesis were evaluated in in vitro assays and xenograft models.We identified that DLX4 induces expression of iNOS, an enzyme that stimulates angiogenesis by generating nitric oxide. Analysis of datasets of two independent patient cohorts revealed that high DLX4 expression in ovarian cancer is strongly associated with elevated expression of iNOS but not of other nitric oxide synthases. Studies using STAT1-expressing and STAT1-deficient cells revealed that DLX4 interacts with STAT1 and induces iNOS expression in part by stimulating STAT1 activity. Expression of DLX4 in ovarian cancer cells stimulated endothelial cell growth in vitro and increased microvessel density in xenograft models, and these stimulatory effects of DLX4 were abrogated when its induction of iNOS was inhibited.These findings indicate that DLX4 promotes ovarian tumor angiogenesis in part by stimulating iNOS expression.
Device-Guided Breathing as Treatment for Hypertension in Type 2 Diabetes Mellitus
Authors: Gijs W. D. Landman, Iefke Drion, Kornelis J. J. van Hateren, Peter R. van Dijk, Susan J. J. Logtenberg, Jan Lambert, Klaas H. Groenier, Henk J. G. Bilo, Nanne Kleefstra
Journal: JAMA Internal Medicine (2013)

<h3>Importance</h3> Biofeedback with device-guided lowering of breathing frequency could be an alternate nonpharmacologic treatment option for hypertension. Evidence from trials with high methodologic quality is lacking. <h3>Objective</h3> To evaluate the effects of device-guided lowering of breathing frequency on blood pressure in patients with type 2 diabetes mellitus and hypertension. <h3>Design</h3> Single-center, double-blind, sham-controlled trial. <h3>Setting</h3> A large nonacademic teaching hospital in the Netherlands. <h3>Participants</h3> Patients with type 2 diabetes mellitus and hypertension. <h3>Intervention</h3> Fifteen-minute sessions with either the device that guides breathing through musical tones to a lower breathing frequency (aiming at &lt;10 breaths/min) or a sham device (music without aiming at lowering of breathing frequency) for an 8-week study period. <h3>Main Outcomes and Measures</h3> Systolic and diastolic blood pressure measured in the physician’s office. <h3>Results</h3> Forty-eight patients were randomized; 21 patients (88%) in the intervention group and 24 patients (100%) in the control group completed the study. There were no significant changes in systolic and diastolic blood pressure, with a difference in systolic blood pressure of 2.35 mm Hg (95% CI, –6.50 to 11.20) in favor of the control group and a difference in diastolic blood pressure of 2.25 mm Hg (95% CI, –2.16 to 6.67) in favor of the intervention group. Three patients in the intervention group experienced adverse events. <h3>Conclusions and Relevance</h3> This high methodologic quality study shows no significant effect of device-guided lowering of breathing frequency on office-measured blood pressure in patients with type 2 diabetes. On the basis of this study, together with results from all but one previous trial, device-guided lowering of breathing frequency does not appear to be a viable nonpharmacologic option for hypertension treatment.
Dual role of proapoptotic BAD in insulin secretion and beta cell survival
Authors: Nika N Danial, Loren D Walensky, Chen-Yu Zhang, Cheol Soo Choi, Jill K Fisher, Anthony J A Molina, Sandeep Robert Datta, Kenneth L Pitter, Gregory H Bird, Jakob D Wikstrom, Jude T Deeney, Kirsten Robertson, Joel Morash, Ameya Kulkarni, Susanne Neschen, Sheene Kim, Michael E Greenberg, Barbara E Corkey, Orian S Shirihai, Gerald I Shulman, Bradford B Lowell, Stanley J Korsmeyer
Journal: Nature Medicine (2008)
The Health Effects of Income Inequality: Averages and Disparities
Authors: Beth C. Truesdale, Christopher Jencks
Journal: Annual Review of Public Health (2015)

Much research has investigated the association of income inequality with average life expectancy, usually finding negative correlations that are not very robust. A smaller body of work has investigated socioeconomic disparities in life expectancy, which have widened in many countries since 1980. These two lines of work should be seen as complementary because changes in average life expectancy are unlikely to affect all socioeconomic groups equally. Although most theories imply long and variable lags between changes in income inequality and changes in health, empirical evidence is confined largely to short-term effects. Rising income inequality can affect individuals in two ways. Direct effects change individuals' own income. Indirect effects change other people's income, which can then change a society's politics, customs, and ideals, altering the behavior even of those whose own income remains unchanged. Indirect effects can thus change both average health and the slope of the relationship between individual income and health.
Cyclophilin A participates in the nuclear translocation of apoptosis-inducing factor in neurons after cerebral hypoxia-ischemia
Authors: Changlian Zhu, Xiaoyang Wang, Johanna Deinum, Zhiheng Huang, Jianfeng Gao, Nazanine Modjtahedi, Martha R. Neagu, Michael Nilsson, Peter S. Eriksson, Henrik Hagberg, Jeremy Luban, Guido Kroemer, Klas Blomgren
Journal: The Journal of Experimental Medicine (2007)

Upon cerebral hypoxia-ischemia (HI), apoptosis-inducing factor (AIF) can move from mitochondria to nuclei, participate in chromatinolysis, and contribute to the execution of cell death. Previous work (Cande, C., N. Vahsen, I. Kouranti, E. Schmitt, E. Daugas, C. Spahr, J. Luban, R.T. Kroemer, F. Giordanetto, C. Garrido, et al. 2004. Oncogene. 23:1514–1521) performed in vitro suggests that AIF must interact with cyclophilin A (CypA) to form a proapoptotic DNA degradation complex. We addressed the question as to whether elimination of CypA may afford neuroprotection in vivo. 9-d-old wild-type (WT), CypA+/−, or CypA−/− mice were subjected to unilateral cerebral HI. The infarct volume after HI was reduced by 47% (P = 0.0089) in CypA−/− mice compared with their WT littermates. Importantly, CypA−/− neurons failed to manifest the HI-induced nuclear translocation of AIF that was observed in WT neurons. Conversely, CypA accumulated within the nuclei of damaged neurons after HI, and this nuclear translocation of CypA was suppressed in AIF-deficient harlequin mice. Immunoprecipitation of AIF revealed coprecipitation of CypA, but only in injured, ischemic tissue. Surface plasmon resonance revealed direct molecular interactions between recombinant AIF and CypA. These data indicate that the lethal translocation of AIF to the nucleus requires interaction with CypA, suggesting a model in which two proteins that normally reside in separate cytoplasmic compartments acquire novel properties when moving together to the nucleus.
Hepatic Ketogenesis and Gluconeogenesis in Humans
Authors: A. J. Garber, P. H. Menzel, G. Boden, O. E. Owen
Journal: Journal of Clinical Investigation (1974)

Splanchnic arterio-hepatic venous differences for a variety of substrates associated with carbohydrate and lipid metabolism were determined simultaneously with hepatic blood flow in five patients after 3 days of starvation. Despite the relative predominance of circulating beta-hydroxybutyrate, the splanchnic productions of both beta-hydroxybutyrate and acetoacetate were approximately equal, totaling 115 g/24 h. This rate of hepatic ketogenesis was as great as that noted previously after 5-6 wk of starvation. Since the degree of hyperketonemia was about threefold greater after 5-6 wk of starvation, it seems likely that the rate of ketone-body removal by peripheral tissues is as important in the development of the increased ketone-body concentrations observed after prolonged starvation as increased hepatic ketone-body production rate. Splanchnic glucose release in this study was 123 g/24 h, which was less than that noted previously after an overnight fast, but was considerably more than that noted during prolonged starvation. Hepatic gluconeogenesis was estimated to be 99 g/24 h, calculated as the sum of lactate, pyruvate, glycerol, and amino acid uptake. This was greater than that observed either after an overnight fast or after prolonged starvation. In addition, a direct relationship between the processes of hepatic ketogenesis and gluconeogenesis was observed.
Autologous Transplantation of Bone Marrow Cells Improves Damaged Heart Function
Authors: S Tomita, R K Li, R D Weisel, D A Mickle, E J Kim, T Sakai, Z Q Jia
Journal: Circulation (1999)

Autologous bone marrow cells (BMCs) transplanted into ventricular scar tissue may differentiate into cardiomyocytes and restore myocardial function. This study evaluated cardiomyogenic differentiation of BMCs, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function.BMCs from adult rats were cultured in cell culture medium (control) and medium with 5-azacytidine (5-aza, 10 micromol/L), TGFbeta1 (10 ng/mL), or insulin (1 nmol/L) (n=6, each group). Only BMCs cultured with 5-aza formed myotubules which stained positively for troponin I and myosin heavy chain. In vivo studies: a cryoinjury-derived scar was formed in the left ventricular free wall. At 3 weeks after injury, fresh BMCs (n=9), cultured BMCs (n=9), 5-aza-induced BMCs (n=12), and medium (control, n=12) were autologously transplanted into the scar. Heart function was measured at 8 weeks after myocardial injury. Cardiac-like muscle cells which stained positively for myosin heavy chain and troponin I were observed in the scar tissue of the 3 groups of BMC transplanted hearts. Only the 5-aza-treated BMC transplanted hearts had systolic and developed pressures which were higher (P<0.05) than that of the control hearts. All transplanted BMCs induced angiogenesis in the scar.Transplantation of BMCs induced angiogenesis. BMCs cultured with 5-aza differentiated into cardiac-like muscle cells in culture and in vivo in ventricular scar tissue and improved myocardial function.
Brain Structure and Function in Chronic Obstructive Pulmonary Disease
Authors: James W. Dodd, Ai Wern Chung, Martin D. van den Broek, Thomas R. Barrick, Rebecca A. Charlton, Paul W. Jones
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Brain pathology is a poorly understood systemic manifestation of chronic obstructive pulmonary disease (COPD). Imaging techniques using magnetic resonance (MR) diffusion tensor imaging (DTI) and resting state functional MR imaging (rfMRI) provide measures of white matter microstructure and gray functional activation, respectively.We hypothesized that patients with COPD would have reduced white matter integrity and that functional communication between gray matter resting-state networks would be significantly different to control subjects. In addition, we tested whether observed differences related to disease severity, cerebrovascular comorbidity, and cognitive dysfunction.DTI and rfMRI were acquired in stable nonhypoxemic patients with COPD (n = 25) and compared with age-matched control subjects (n = 25). Demographic, disease severity, stroke risk, and neuropsychologic assessments were made.Patients with COPD (mean age, 68; FEV(1) 53 ± 21% predicted) had widespread reduction in white matter integrity (46% of white matter tracts; P < 0.01). Six of the seven resting-state networks showed increased functional gray matter activation in COPD (P < 0.01). Differences in DTI, but not rfMRI, remained significant after controlling for stroke risk and smoking (P < 0.05). White matter integrity and gray matter activation seemed to account for difference in cognitive performance between patients with COPD and control subjects.In stable nonhypoxemic COPD there is reduced white matter integrity throughout the brain and widespread disturbance in functional activation of gray matter, which may contribute to cognitive dysfunction. White matter microstructural integrity but not gray matter functional activation is independent of smoking and cerebrovascular comorbidity. The mechanisms remain unclear, but may include cerebral small vessel disease caused by COPD.