tbuckley/cabot-search huggingface dataset:
Changes in Insulin Secretion and Action in Adults With Familial Risk for Type 2 Diabetes Who Curtail Their Sleep
Authors: Amy Darukhanavala, John N. Booth, Lindsay Bromley, Harry Whitmore, Jacqueline Imperial, Plamen D. Penev
Journal: Diabetes Care (2011)

OBJECTIVE Experimental sleep deprivation is accompanied by changes in glucose regulation. However, the effects of chronic sleep insufficiency on insulin secretion and action in populations at high risk for type 2 diabetes are not known. This study examined the relationship between objectively documented habitual sleep curtailment and measures of insulin sensitivity, insulin secretion, and oral glucose tolerance in free-living adults with parental history of type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 47 healthy participants with parental history of type 2 diabetes (26 female/21 male, mean [SD] age 26 [4] years and BMI 23.8 [2.5] kg/m2) completed 13 (SD = 2) days of sleep and physical activity monitoring by wrist actigraphy and waist accelerometry while following their usual lifestyle at home. Laboratory polysomnography was used to screen for sleep disorders. Indices of diabetes risk based on oral glucose tolerance tests were compared between participants with habitual short sleep and those with usual sleep duration &amp;gt;6 h/day. RESULTS Consistent with a behavioral pattern of habitual sleep curtailment, short sleepers obtained an average of 1.5 h less sleep per night and showed signs of increased sleep pressure. Participants who habitually curtailed their sleep had considerably higher indices of insulin resistance and increased insulin secretion but maintained normal glucose tolerance similar to that of subjects who slept more. CONCLUSIONS Young lean adults with parental history of type 2 diabetes who habitually curtail their sleep have increased insulin resistance and compensatory hyperinsulinemia—a pattern that has been associated with higher risk of developing diabetes in such susceptible individuals.
Mechanisms of noradrenaline release in the anoxic heart of the rat
Authors: X.-J. Du, A. M Dart
Journal: Cardiovascular Research (1993)

Journal Article Mechanisms of noradrenaline release in the anoxic heart of the rat Get access Xiao-Jun Du, Xiao-Jun Du Baker Medical Research Institute, Commercial Road, Prahran, Victoria 3181, Australia: X-J Du, A M Dart. Correspondence to Dr Du. Search for other works by this author on: Oxford Academic PubMed Google Scholar Anthony M Dart Anthony M Dart Baker Medical Research Institute, Commercial Road, Prahran, Victoria 3181, Australia: X-J Du, A M Dart. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 11, November 1993, Pages 2011–2015, https://doi.org/10.1093/cvr/27.11.2011 Published: 01 November 1993 Article history Received: 23 February 1993 Accepted: 16 June 1993 Published: 01 November 1993
Sympathetic Innervation of the Juxtaglomerular Cells of the Kidney
Authors: JAN WÅGERMARK, URBAN UNGERSTEDT, ARNE LJUNGQVIST
Journal: Circulation Research (1968)

Combination of a histochemical fluorescence method for biogenic monoamines and staining of juxtaglomerular cell granules demonstrated sympathetic nerve terminals in the rat kidney in the walls of the parts of the juxtaglomerular arterioles that contain granulated cells. This forms a morphological basis for a direct influence of sympathetic nervous activity on the liberation of renin. The juxtaglomerular granules were nonfluorescent, an indication that, in the rat, the granulated juxtaglomerular cells are not equivalent to mast cells.
Cytotoxic T lymphocytes specific for I region determinants do not require interactions with H-2K or D gene products
Authors: P Billings, S Burakoff, ME Dorf, B Benacerraf
Journal: The Journal of Experimental Medicine (1977)

Gene products coded for by the major hisocompatibility complex (MHC) can serve as target antigens for cytotoxic T lymphocytes (CTL) (1). A variety of test systems are available which have yielded information consistently reinforcing the importance of this complex of genes in the generation and effector phases of the cytotoxic immune response. Originally, it was shown that allogeneically-induced CTL had specificity primarily for the products of the K and D loci of the mouse H-2 complex (2). More recently this has also been found to be the case for xenogeneic immunizations (3,4). Additional examples of T cell-mediated lysis have been reported involving viral-infected or chemically- modified syngeneic stimulating and target cells in which homology at H-2K or H-2D was required between the responding and target cells for appreciable lysis to occur (5-7). Moreover, CTL specific for minor histocompatability antigens are able to lyse only target cells bearing these membrane antigens and sharing a common H-2K or H2-D gene product with the effector (8,9). Two hypotheses have been proposed to explain the requirement for H-2 identity between effector and targets in these systems. CTL may recognize new antigenic determinants created by the interaction of the modifier with syngeneic K and D gene products. Alternately, a dual recognition system my exist, requiring an antigen-specific receptor as well as a second receptor with specificity for homologous H-2K or H-2D determinants (5). Neither model can be excluded at this time. The I region also contains genes coding for histocompatibility loci since animals differing at the I-A or I-C regions of the H-2 complex reject skin grafts (10-12), though less rapidly than mice differing at the H-2K or H-2D regions, Also CTL can be generated to I region determinants but less efficiently than CTL specific for H-2K or H-2D gene products (12-14). The question can therefore be raised, whether the I region minor histocompatibility loci function independently from the H-2K or H-2D loci or whether I region-specific cytolysis requires the participation of H-2K or H-2D gene products of the target cell. This communication illustrates the generation of CTL showing specificity for I region determinants in primary mixed lymphocyte cultures. Further, we demonstrate by genetic analysis and byt eh use of speficit alloantisera that CTL directed to Ia determinants (a) do not see these antigens as modifications of H-2K or H-2D gene products but as independent gene products coded for by the I region, and (b) they do not require interaction with target cells bearing the same H-2K or H-2D gene product as the effect CTL.
Integrin α9β1 in airway smooth muscle suppresses exaggerated airway narrowing
Authors: Chun Chen, Makoto Kudo, Florentine Rutaganira, Hiromi Takano, Candace Lee, Amha Atakilit, Kathryn S. Robinett, Toshimitsu Uede, Paul J. Wolters, Kevan M. Shokat, Xiaozhu Huang, Dean Sheppard
Journal: Journal of Clinical Investigation (2012)

Exaggerated contraction of airway smooth muscle is the major cause of symptoms in asthma, but the mechanisms that prevent exaggerated contraction are incompletely understood. Here, we showed that integrin α9β1 on airway smooth muscle localizes the polyamine catabolizing enzyme spermidine/spermine N1-acetyltransferase (SSAT) in close proximity to the lipid kinase PIP5K1γ. As PIP5K1γ is the major source of PIP2 in airway smooth muscle and its activity is regulated by higher-order polyamines, this interaction inhibited IP3-dependent airway smooth muscle contraction. Mice lacking integrin α9β1 in smooth muscle had increased airway responsiveness in vivo, and loss or inhibition of integrin α9β1 increased in vitro airway narrowing and airway smooth muscle contraction in murine and human airways. Contraction was enhanced in control airways by the higher-order polyamine spermine or by cell-permeable PIP2, but these interventions had no effect on airways lacking integrin α9β1 or treated with integrin α9β1–blocking antibodies. Enhancement of SSAT activity or knockdown of PIP5K1γ inhibited airway contraction, but only in the presence of functional integrin α9β1. Therefore, integrin α9β1 appears to serve as a brake on airway smooth muscle contraction by recruiting SSAT, which facilitates local catabolism of polyamines and thereby inhibits PIP5K1γ. Targeting key components of this pathway could thus lead to new treatment strategies for asthma.
Topoisomerase-IIα Is Upregulated in Malignant Peripheral Nerve Sheath Tumors and Associated With Clinical Outcome
Authors: Rolf I. Skotheim, Anne Kallioniemi, Bodil Bjerkhagen, Fredrik Mertens, Helge R. Brekke, Outi Monni, Spyro Mousses, Nils Mandahl, Gunnar Sœter, Jahn M. Nesland, Sigbjørn Smeland, Olli-P. Kallioniemi, Ragnhild A. Lothe
Journal: Journal of Clinical Oncology (2003)

To identify target genes of clinical significance for patients with malignant peripheral-nerve sheath tumor (MPNST), an aggressive cancer for which no consensus therapy exists.Biopsies and clinical data from 51 patients with MPNST were included in this study. Based on our previous research implicating chromosome arm 17q amplification in MPNST, we performed gene expression analyses of 14 MPNSTs using chromosome 17-specific cDNA microarrays. Copy numbers of selected gene probes and centromere probes were then determined by interphase fluorescence in situ hybridization in 16 MPNSTs. Finally, we generated a tissue microarray containing 79 samples from 44 MPNSTs, on which in situ protein expressions of candidate genes were examined and related to clinical end points.Among several deregulated genes found by cDNA microarray analyses, topoisomerase II alpha (TOP2A) was the most overexpressed gene in MPNSTs compared with benign neurofibromas. Excess copies of the TOP2A were also seen at the DNA level in 10 of 16 cases, and high expression of the TOP2A protein was seen in 83% of the tumors on the tissue microarray. The TOP2A-expressing tumors were associated with poor cancer-specific survival and presence of metastases.We have identified TOP2A as a target gene in MPNST, using a focused gene expression profiling followed by a DNA copy number evaluation and clinical validation of the encoded protein using a tissue microarray. This study is the first to suggest that TOP2A expression may be a predictive factor for adverse outcome in MPNST.
UK peers call for extra investment in HIV and AIDS services
Authors: A. O'Dowd
Journal: BMJ (2011)

Current UK policies for HIV and AIDS are “woefully inadequate” and greater focus and priority to be given to the disease, say peers in a report published on 1 September.

The government should take radical steps to boost investment in services for people with HIV and AIDS as well as improving prevention and diagnosis of the disease, it says.

The report from the House of Lords Select Committee on HIV and AIDS in the UK is the result of an eight month investigation and marks the 25th anniversary of the Don’t Die of Ignorance public health campaign in 1986.

New drug treatments since 1986, including antiretrovirals, have helped cut the death rate from AIDS, but there is still neither vaccine nor cure. …
Randomized comparison of pegfilgrastim day 4 versus day 2 for the prevention of chemotherapy-induced leukocytopenia
Authors: C. Zwick, F. Hartmann, S. Zeynalova, V. Pöschel, C. Nickenig, M. Reiser, E. Lengfelder, N. Peter, G. Schlimok, J. Schubert, N. Schmitz, M. Loeffler, M. Pfreundschuh
Journal: Annals of Oncology (2011)

BackgroundTo study the effects of deferring pegfilgrastim until day 4 on the reduction of chemotherapy-induced leukocytopenia.Patients and methodsPatients of age 61–80 years with aggressive lymphoma were randomly assigned to receive 6 mg pegfilgrastim on day 2 or 4 of a 2-week chemotherapy regimen (R-CHOP-14).ResultsTwo hundred and ninety-two and 313 chemotherapy cycles were evaluable in 103 patients. Post-nadir pegfilgrastim serum levels were higher after day 4 than after day 2 application. This was associated with an attenuated leukocyte nadir after day 4 pegfilgrastim and there were fewer days with leukocytes <2 × 103/mm3 compared with day 2 pegfilgrastim. Grade 3 and 4 leukocytopenias (70% versus 43.3%; P < 0.001) and grade 4-only leukocytopenias (47% versus 20.5%;P < 0.001) were more frequent after day 2 pegfilgrastim. There were more chemotherapy cycles with grade 3 and 4 infections after day 2 than day 4 pegfilgrastim (9.4% versus 6.0%; P = 0.118). Interventional antibiotics were given more often after day 2 than after day 4 pegfilgrastim (30.7% versus 21.9% of cycles; P = 0.008). There were five deaths during leukocytopenia after day 2 and none after day 4 pegfilgrastim (P = 0.027).ConclusionsAdministration of pegfilgrastim on day 4 was more effective in reducing severe leukocytopenias and resulted in fewer deaths during leukocytopenia. Pegfilgrastim should be given on day 4 to better exploit its myeloprotective potential.
Country experience with strengthening of health systems and deployment of midwives in countries with high maternal mortality
Authors: Wim Van Lerberghe, Zoe Matthews, Endang Achadi, Chiara Ancona, James Campbell, Amos Channon, Luc de Bernis, Vincent De Brouwere, Vincent Fauveau, Helga Fogstad, Marge Koblinsky, Jerker Liljestrand, Abdelhay Mechbal, Susan F Murray, Tung Rathavay, Helen Rehr, Fabienne Richard, Petra ten Hoope-Bender, Sabera Turkmani
Journal: The Lancet (2014)
Epidemiology—Found in Translation
Authors: Margaret R. Spitz, Neil E. Caporaso, Andrew N. Freedman
Journal: Cancer Discovery (2011)

We highlight the value of carefully designed observational epidemiologic analyses in translating basic science discoveries to clinical application and in providing the impetus for exploring underlying mechanisms for observed associations. Coupling epidemiologic data with an in vitro screen of commonly used therapeutic agents may identify novel applications for further clinical testing.
Biologic and Prognostic Significance of Dermal Ki67 Expression, Mitoses, and Tumorigenicity in Thin Invasive Cutaneous Melanoma
Authors: Phyllis A. Gimotty, Patricia Van Belle, David E. Elder, Todd Murry, Kathleen T. Montone, Xiaowei Xu, Susan Hotz, Shane Raines, Michael E. Ming, Peter Wahl, DuPont Guerry
Journal: Journal of Clinical Oncology (2005)

Tumor cell proliferation is a central feature of melanoma progression. In this study, we characterized three biomarkers of proliferation (Ki67 expression, dermal mitotic rate [MR], and tumorigenicity) in thin (< or = 1.00 mm) primary cutaneous melanomas and examined their association with prognosis.We used immunohistochemistry to determine Ki67 expression using the monoclonal antibody MIB-1 in lesions from a prospective cohort that included 396 patients with thin invasive primary melanomas seen between 1972 and 1991. A multivariate Cox proportional hazards model was used to define independent prognostic factors, and recursive partitioning was used to develop a prognostic tree identifying risk groups.Dermal Ki67 expression was lower than epidermal Ki67 expression in radial growth phase (RGP) melanomas (n = 171), and dermal Ki67 expression and MR were higher in tumorigenic vertical growth phase (VGP) melanomas (n = 193) compared with RGP and nontumorigenic VGP melanomas (n = 42). Dermal Ki67 expression, MR greater than 0, growth phase, thickness, ulceration, tumor-infiltrating lymphocytes, and sex were associated with metastasis at 10 years, however, only dermal Ki67 expression, MR greater than 0, and sex were independent prognostic factors. Two high-risk groups were identified: men and women with dermal MR greater than 0 and dermal Ki67 expression > or = 20% in tumor cells and men with MR greater than 0 and Ki67 expression less than 20%, with 10-year metastasis rates of 39% and 20%, respectively.Proliferation slows as melanoma cells enter the dermis and then increases with the onset of tumorigenic VGP. Ki67 expression and dermal MR provide independent prognostic information that can potentially be used in risk-based management of patients.
Primary human hepatocytes – a valuable tool for investigation of apoptosis and hepatitis B virus infection
Authors: Henning Schulze-Bergkamen, Andreas Untergasser, Andreas Dax, Heiko Vogel, Peter Büchler, Ernst Klar, Thomas Lehnert, Helmut Friess, Markus W Büchler, Michael Kirschfink, Wolfgang Stremmel, Peter H Krammer, Martina Müller, Ulrike Protzer
Journal: Journal of Hepatology (2003)
Remarks ON THE CAUSES AND TREATMENT OF OEDEMA
Authors: J. D. Mann
Journal: BMJ (1905)

OEDEMA due to failure of cardiac or of renal compensation, -or of the two conjointly, is a common clinical phenomenon the pathology and treatment of which demands renewed -consideration in the light of recent investigations on the subject.In gimple cardiac oedema the causal factor is essentially hydrodynamic its action being mediate.The oedema is not the direct result of back pressure, or, at any rate, only to a limited extent; it is chiefly due to changes in the vascular endothelium caused by the imperfect supply of oxygen and of nutrient material to which the partial stagnation of the blood gives rise.The'lack of oxygen and of nutrition impairs the vitality of the vascular walls and makes them unduly 'permeable; the ensuing transudation Is augmented by the -low pressure of the blood supply to the kidneys and the coinci- dent retention in the tissues of sodium chloride.Oedema due to kidney disease is less readily explained.Amongst other causes are changes in the vascular endothelium produced by the toxic action of waste products present in the blood, which, under normal conditions, are removed by the kidneys; the defective elimination of water by the kidneys, and, probably, the occurrence of hydraemic plethora exercise no little influence.During the last few years many sug- gestive experimental and clinical investigations have been made in relation to the part played by sodium chloride in the development of oedema.Within the normal tissues a fluctuating percentage of water is retained, the intake and output of which, to some extent, isregulated by the amount of sodium chloride they contain.
Sputum chemotactic activity in chronic obstructive pulmonary disease: effect of alpha1-antitrypsin deficiency and the role of leukotriene B4 and interleukin 8
Authors: I S Woolhouse
Journal: Thorax (2002)

Neutrophil recruitment to the airway is thought to be an important component of continuing inflammation and progression of chronic obstructive pulmonary disease (COPD), particularly in the presence of severe alpha(1)-antitrypsin (alpha(1)-AT) deficiency. However, the chemoattractant nature of secretions from these patients has yet to be clarified.The chemotactic activity of spontaneous sputum from patients with stable COPD, with (n=11) and without (n=11) alpha(1)-AT deficiency (PiZ), was assessed using the under-agarose assay. The contribution of leukotriene B(4) (LTB(4)) and interleukin 8 (IL-8) to the chemotactic activity was examined using an LTB(4) receptor antagonist (BIIL 315 ZW) and an IL-8 monoclonal antibody, respectively.Sputum neutrophil chemotactic activity (expressed as % n-formylmethionyl leucylphenylalanine (fMLP) control) was significantly higher in patients with alpha(1)-AT deficiency (mean (SE) 63.4 (8.9)% v 36.7 (5.5)%; mean difference 26.7% (95% CI 4.9 to 48.4), p<0.05). The mean (SE) contribution of both LTB(4) and IL-8 (expressed as % fMLP control) was also significantly higher in alpha(1)-AT deficient patients than in patients with COPD with normal levels of alpha(1)-AT (LTB(4): 31.9 (6.3)% v 18.0 (3.7)%; mean difference 13.9% (95% CI -1.4 to 29.1), p<0.05; IL-8: 24.1 (5.2)% v 8.1 (1.2)%; mean difference 15.9% (95% CI 4.7 to 27.2), p<0.05). When all the subjects were considered together the mean (SE) contribution of LTB(4) (expressed as % total chemotactic activity) was significantly higher than IL-8 (46.8 (3.5)% v 30.8 (4.6)%; mean difference 16.0% (95% CI 2.9 to 29.2), p<0.05). This difference was not significantly influenced by alpha(1)-AT phenotype (p=0.606).These results suggest that the bronchial secretions of COPD patients with alpha(1)-AT deficiency have increased neutrophil chemotactic activity. This relates to the increased levels of IL-8 and, in particular LTB(4), which accounted most of the sputum chemotactic activity in the patients with COPD as a whole. Increased chemotactic activity, together with inhibitor deficiency, may contribute to the more rapid disease progression seen in alpha(1)-AT deficiency via increased neutrophil recruitment and release of neutrophil elastase.
Disrupted ciliated epithelium shows slower ciliary beat frequency and increased dyskinesia
Authors: B. Thomas, A. Rutman, C. O'Callaghan
Journal: European Respiratory Journal (2009)

Ciliary function studies for the diagnosis of primary ciliary dyskinesia (PCD) are usually performed on nasal brush biopsy samples. It is not uncommon to find disrupted epithelial strips of tissue in these samples, and occasionally throughout a sample. The aim of the present study was to determine if cilia on disrupted ciliated epithelial edges beat with a normal pattern and frequency similar to that of cilia on undisrupted edges. Nasal brush biopsy samples from 42 children in whom the diagnosis of PCD was excluded were assessed. The epithelial strips were categorised into five groups: intact undisrupted ciliated epithelial edge, ciliated epithelial edge with minor projections, ciliated epithelial edge with major projections, an isolated ciliated cell on an epithelial edge and single unattached ciliated cells. Ciliary beat frequency and beat pattern of 50 samples from each group were determined using high speed digital video microscopy. The cilia on epithelial edges with varying degrees of disruption showed significantly reduced beat frequency and significantly increased dyskinesia compared with those on intact, undisrupted ciliated epithelial edges. Ideally, the assessment of ciliary beat pattern and frequency for PCD diagnosis should only be performed on undisrupted ciliated edges.
Sensitivity to sensitins and tuberculin in Swedish children. IV. The influence of BCG-vaccination
Authors: LO Larsson, M Magnusson, BE Skoogh, A Lind
Journal: European Respiratory Journal (1992)

BCG-vaccinated schoolchildren, 8-9 yrs of age, were simultaneously tested on separate arms with tuberculin and a sensitin. Using the 6 mm cut-off they reacted in 49% to two tuberculin units purified protein derivative (PPD RT23), in 67% to 0.1 micrograms Mycobacterium avium sensitin RS10, and in 58% to 0.1 micrograms M. scrofulaceum sensitin RS95. The corresponding figures for non-BCG-vaccinated schoolchildren of the same age tested at the same time were 3, 25 and 32%, respectively. The results indicate a stimulating influence of BCG-vaccination on tuberculin and sensitin reactivity. Since the sensitin reactions were the larger ones, these reactions were not only due to the vaccination. The BCG-vaccinated schoolchildren seem to have acquired infections by atypical mycobacteria despite vaccination.