tbuckley/cabot-search huggingface dataset:
Microcirculation of the area postrema. Permeability and vascular responses.
Authors: F M Faraci, J Choi, G L Baumbach, W G Mayhan, D D Heistad
Journal: Circulation Research (1989)

The area postrema is a circumventricular organ that plays an important role in neurohumoral regulation of the circulation. We have developed a method to examine permeability and vascular responses of the microcirculation of the area postrema in vivo. A craniotomy was performed over the dorsal brain stem in anesthetized rats, and blood vessels to the area postrema were visualized with fluorescein microscopy. Extravasation of sodium fluorescein (MW, 386), but not 150 kDa (MW) fluorescein isothiocyanate-dextran, occurred in the area postrema under control conditions. There was no extravasation of fluorescein or dextran in the brain stem under control conditions. Acute hypertension produced marked disruption of the barrier to 150 kDa dextran in the area postrema, compared with minimal disruption in the brain stem. We tested the hypothesis that the area postrema has greater permeability to small molecules than the brain stem and that this permeability might be accompanied by distinctive vascular responses. Topical suffusion of adenosine and ADP produced similar dose-related dilation of arterioles to area postrema and dorsal brain stem. Topical and intravenous vasopressin produced similar dose-related constriction of vessels to area postrema and brain stem. Electron microscopy in rats demonstrated that a barrier to horseradish peroxidase, which is absent in capillaries in the area postrema, is present in arterioles that supply the area postrema.(ABSTRACT TRUNCATED AT 250 WORDS)
Decreased Flow-Dependent Dilation in Carotid Arteries of Tissue Kallikrein–Knockout Mice
Authors: Sonia Bergaya, Pierre Meneton, May Bloch-Faure, Eric Mathieu, François Alhenc-Gelas, Bernard I. Lévy, Chantal M. Boulanger
Journal: Circulation Research (2001)

- Flow-dependent dilation is a fundamental mechanism by which large arteries ensure appropriate blood supply to tissues. We investigated whether or not the vascular kallikrein-kinin system, especially tissue kallikrein (TK), contributes to flow-dependent dilation by comparing wild-type and TK-knockout mice in which the presence or absence of TK expression was verified. We examined in vitro changes in the outer diameter of perfused carotid arteries from TK(+/+) and TK(-/-) mice. In both groups, exogenous bradykinin caused a similar dilation that was abolished by the B(2) receptor antagonist HOE-140, as well as by the NO synthase inhibitor N:(omega)-nitro-L-arginine methyl ester. However, purified kininogen dilated only TK(+/+) arteries, demonstrating the essential role of TK in the vascular formation of kinins. In TK(+/+) arteries, increasing intraluminal flow caused a larger endothelium-dependent dilation than that seen in TK(-/-). In both strains the flow response was mediated by NO and by endothelium-derived hyperpolarizing factor, whereas in TK(-/-) vasoconstrictor prostanoids participated as well. HOE-140 impaired flow-dependent dilation in TK(+/+) arteries while showing no effect in TK(-/-). This compound reduced the flow response in TK(+/+) arteries to a level similar to that in TK(-/-). After NO synthase inhibition, HOE-140 no longer affected the response of TK(+/+). Impaired flow-dependent dilation was also observed in arteries from knockout mice lacking bradykinin B(2) receptors as compared with wild-type animals. This study demonstrates the active contribution of the vascular kallikrein-kinin system to one-third of the flow-dependent dilation response via activation of B(2) receptors coupled to endothelial NO release.
Uterine Inversion Associated with Bicornuate Uterus
Authors: C. E. R. Winer
Journal: BMJ (1966)

Vaginal cytology has been studied in 107 selected patients complaining of amenorrhoea.The collection of cells from the lateral wall of the upper third of the vagina and the Shorr staining technique are best for hormonal studies.Different types of cytological curves and the various cytology patterns encountered in certain conditions associated with amenorrhoea are described.A close correlation can exist between the trophic state of the vaginal epithelium and urinary oestrogen excretion.Vaginal cytology is a very valuable test not only for ruling in and ruling out certain causes of amenorrhoea but also as a guide to further hormonal studies.Hormonal cytology should be routine in the investigation of patients with amenorrhoea, and smears taken at weekly intervals for five weeks appear to be quite adequate for the determination of oestrogen secretion.
Mutation of the Circadian Clock Gene <i>Per2</i> Alters Vascular Endothelial Function
Authors: Hema Viswambharan, João M. Carvas, Vladan Antic, Ana Marecic, Corinne Jud, Christian E. Zaugg, Xiu-Fen Ming, Jean-Pierre Montani, Urs Albrecht, Zhihong Yang
Journal: Circulation (2007)

Background— The circadian clock regulates biological processes including cardiovascular function and metabolism. In the present study, we investigated the role of the circadian clock gene Period2 ( Per2 ) in endothelial function in a mouse model. Methods and Results— Compared with the wild-type littermates, mice with Per2 mutation exhibited impaired endothelium-dependent relaxations to acetylcholine in aortic rings suspended in organ chambers. During transition from the inactive to active phase, this response was further increased in the wild-type mice but further decreased in the Per2 mutants. The endothelial dysfunction in the Per2 mutants was also observed with ionomycin, which was improved by the cyclooxygenase inhibitor indomethacin. No changes in the expression of endothelial acetylcholine-M 3 receptor or endothelial nitric oxide synthase protein but increased cyclooxygenase-1 (not cyclooxygenase-2) protein levels were observed in the aortas of the Per2 mutants. Compared with Per2 mutants, a greater endothelium-dependent relaxation to ATP was observed in the wild-type mice, which was reduced by indomethacin. In quiescent aortic rings, ATP caused greater endothelium-dependent contractions in the Per2 mutants than in the wild-type mice, contractions that were abolished by indomethacin. The endothelial dysfunction in the Per2 mutant mice is not associated with hypertension or dyslipidemia. Conclusions— Mutation in the Per2 gene in mice is associated with aortic endothelial dysfunction involving decreased production of NO and vasodilatory prostaglandin(s) and increased release of cyclooxygenase-1–derived vasoconstrictor(s). The results suggest an important role of the Per2 gene in maintenance of normal cardiovascular functions.
Projections of COPD in males in the Netherlands
Authors: N. B. Pride
Journal: European Respiratory Journal (2005)

the initial invasive staging modality after bronchoscopy plus TBNA.Since the publication of our editorial comment, two further prospective studies have investigated the addition of EUS-FNA to a standard work-up for unselected LC patients [3,4].In one of these studies, the results of EUS-FNA were blinded [3].The conclusions were clear; EUS-FNA, when added to MS (and TBNA), improves the pre-operative staging of LC, resulting in a reduced rate of futile thoracotomies.How much additional proof do we need?Should we ask for more evidence from new less invasive methods that exists for the standard methods?When is the right time to change or add to standards?We believe, based on the current literature, that the time has come for EUS-FNA.However, the aim of our editorial comment was not to claim the superiority of one method above the other, but to inform thoracic specialists that, according to the available evidence, the addition of endoscopic ultrasound-guided fine-needle aspiration to a standard work-up improves selection of surgically curable patients with lung cancer.
The reliability and reproducibility of the Schilling test in primary malabsorptive disease and after partial gastrectomy
Authors: J. F. Adams, E. J. Cartwright
Journal: Gut (1963)

A study of the reproducibility and reliability of the Schilling test in patients with primary malabsorptive disease and after partial gastrectomy is reported. The value of the test was assessed by repeated tests in each patient. Consistently normal or abnormal results were obtained in only one of the seven patients with primary malabsorptive disease and in only two of the eight patients who had undergone partial gastrectomy. From these results it is concluded that the result of a single test may be of little clinical value. Assessment of the results suggests that the mean value for a series of Schilling tests may give some indication of value clinically about the capacity to absorb radioactive vitamin B<sub>12</sub> at the time of the tests at least in patients who have undergone partial gastrectomy. The significance of the findings is discussed, particularly in relation to the aetiology of post-gastrectomy megaloblastic anaemia.
Aggressive Fibromatosis (Desmoid Tumor) Is Derived from Mesenchymal Progenitor Cells
Authors: Colleen Wu, Saied Nik-Amini, Puviindran Nadesan, William L. Stanford, Benjamin A. Alman
Journal: Cancer Research (2010)

The cellular origins from which most tumors arise are poorly defined, especially in mesenchymal neoplasms. Aggressive fibromatosis, also known as desmoid tumor, is a locally invasive soft tissue tumor that has mesenchymal characteristics. We found that aggressive fibromatosis tumors express genes and cell surface markers characteristic of mesenchymal stem cells (MSC). In mice that are genetically predisposed to develop aggressive fibromatosis tumors (Apc(wt/1638N)), we found that the number of tumors formed was proportional to the number of MSCs present. Sca-1(-/-) mice, which develop fewer MSCs, were crossed with Apc(wt/1638N) mice. Doubly mutant mice deficient in Sca-1 developed substantially fewer aggressive fibromatosis tumors than wild-type (WT) littermates, but Sca-1 deficiency had no effect on the formation of epithelial-derived intestinal polyps. MSCs isolated from Apc(wt/1638N) mice (or mice expressing a stabilized form of β-catenin) induced aberrant cellular growth reminiscent of aggressive fibromatosis tumors after engraftment to immunocompromised mice, but WT cells and mature fibroblasts from the same animals did not. Taken together, our findings indicate that aggressive fibromatosis is derived from MSCs, and that β-catenin supports tumorigenesis by maintaining mesenchymal progenitor cells in a less differentiated state. Protecting this progenitor cell population might prevent tumor formation in patients harboring a germline APC mutation, where fibromatosis is currently the leading cause of mortality.
B cell stimulatory factor 1 (BSF-1) prepares resting B cells to enter S phase in response to anti-IgM and lipopolysaccharide.
Authors: E M Rabin, J J Mond, J Ohara, W E Paul
Journal: The Journal of Experimental Medicine (1986)

BSF-1 prepares resting BALB/c, DBA/2, and BDF1 B cells to enter S phase more promptly in response to subsequent culture with anti-IgM-based stimulants. It prepares DBA/2 and BDF1 B cells to respond to LPS, but its preparative effect for LPS responses of BALB/c B cells is both inconstant and meager. Preparation mediated by BSF-1 requires extended contact of B cells with the stimulant for full effect. Half-maximal preparation requires approximately 12 h of contact, as judged by delayed addition of BSF-1 or by inhibition of BSF-1 action with anti-BSF-1 mAbs. BSF-1 preparative action on resting DBA/2 B cells is mimicked by anti-Lyb-2.1 antibody. B cell blasts prepared by culture with BSF-1 and anti-IgM show modest responses to high concentrations of BSF-1; large B cells directly isolated from the spleen are not stimulated to enter S phase by BSF-1. These results lead us to conclude that BSF-1 functions principally as an activation factor for resting B cells.
Collagen synthesis in atherosclerosis: too much and not enough
Authors: M Rekhter
Journal: Cardiovascular Research (1999)

Fibrillar collagen is a critical component of atherosclerotic lesions. Uncontrolled collagen accumulation leads to arterial stenosis, while excessive collagen breakdown combined with inadequate synthesis weakens plaques thereby making them prone to rupture. This review discusses cellular sources of collagen synthesis in atherosclerosis, local and systemic factors modulating collagen gene expression, as well as temporal and spatial patterns of collagen production in human and experimental atherosclerotic lesions.
CpG ODN Nanorings Induce IFNα from Plasmacytoid Dendritic Cells and Demonstrate Potent Vaccine Adjuvant Activity
Authors: Bilgi Gungor, Fuat Cem Yagci, Gizem Tincer, Banu Bayyurt, Esin Alpdundar, Soner Yildiz, Mine Ozcan, Ihsan Gursel, Mayda Gursel
Journal: Science Translational Medicine (2014)

Nanorings act as CpG oligodeoxynucleotide surrogates that may function as vaccine adjuvants and anticancer and antiviral agents.
Transient elastography as a screening tool for liver fibrosis and cirrhosis in a community-based population aged over 45 years
Authors: D. Roulot, J.-L. Costes, J.-F. Buyck, U. Warzocha, N. Gambier, S. Czernichow, H. Le Clesiau, M. Beaugrand
Journal: Gut (2010)

<h3>Background</h3> Liver stiffness measurement (LSM) has been used to measure fibrosis in patients with various types of chronic liver diseases. However, its usefulness as a screening procedure in apparently healthy people had not been evaluated to date. <h3>Methods</h3> 1358 subjects &gt;45 years old from a general population attending for a medical check-up were consecutively enrolled in the study. All subjects were submitted to medical examination and laboratory tests in addition to LSM, performed on the same day by a single operator. Subjects with LSM values &gt;8 kPa were referred to a liver unit for further investigations. <h3>Results</h3> 168 subjects were not considered for analysis due to missing data (n=23), LSM failure (n=51) or unreliable LSM values (n=94). Among the 1190 remaining subjects, 89 (7.5%) had LSM &gt;8 kPa including nine patients with LSM &gt;13 kPa. Despite the fact that normal liver tests were observed in 43% of them (38 out of 89), a specific cause of chronic liver disease was found in all cases. Non-alcoholic fatty liver disease (NAFLD) was the likely cause of chronic liver disease in 52 patients, alcoholic liver disease (ALD) in 20, and both causes were associated in seven additional patients. Hepatitis C virus and hepatitis B virus chronic hepatitis was documented in five and four cases, respectively, and primary biliary cirrhosis in one. Liver biopsy was obtained for 27 patients, including the nine patients with LSM &gt;13 kPa, who were diagnosed with liver cirrhosis due to ALD (n=5), chronic hepatitis C (n=3) or chronic hepatitis B (n=1). The 18 remaining biopsies showed liver fibrosis in all cases except one (isolated steatosis), with ALD and NAFLD being present in six and eight cases, respectively. <h3>Conclusion</h3> LSM proved to be a useful and specific procedure to screen for cirrhosis in the general population and to detect undiagnosed chronic liver disease in apparently healthy subjects.
Obesity and the Metabolic Syndrome in Children and Adolescents
Authors: Ram Weiss, James Dziura, Tania S. Burgert, William V. Tamborlane, Sara E. Taksali, Catherine W. Yeckel, Karin Allen, Melinda Lopes, Mary Savoye, John Morrison, Robert S. Sherwin, Sonia Caprio
Journal: New England Journal of Medicine (2004)

The prevalence and magnitude of childhood obesity are increasing dramatically. We examined the effect of varying degrees of obesity on the prevalence of the metabolic syndrome and its relation to insulin resistance and to C-reactive protein and adiponectin levels in a large, multiethnic, multiracial cohort of children and adolescents.We administered a standard glucose-tolerance test to 439 obese, 31 overweight, and 20 nonobese children and adolescents. Baseline measurements included blood pressure and plasma lipid, C-reactive protein, and adiponectin levels. Levels of triglycerides, high-density lipoprotein cholesterol, and blood pressure were adjusted for age and sex. Because the body-mass index varies according to age, we standardized the value for age and sex with the use of conversion to a z score.The prevalence of the metabolic syndrome increased with the severity of obesity and reached 50 percent in severely obese youngsters. Each half-unit increase in the body-mass index, converted to a z score, was associated with an increase in the risk of the metabolic syndrome among overweight and obese subjects (odds ratio, 1.55; 95 percent confidence interval, 1.16 to 2.08), as was each unit of increase in insulin resistance as assessed with the homeostatic model (odds ratio, 1.12; 95 percent confidence interval, 1.07 to 1.18 for each additional unit of insulin resistance). The prevalence of the metabolic syndrome increased significantly with increasing insulin resistance (P for trend, <0.001) after adjustment for race or ethnic group and the degree of obesity. C-reactive protein levels increased and adiponectin levels decreased with increasing obesity.The prevalence of the metabolic syndrome is high among obese children and adolescents, and it increases with worsening obesity. Biomarkers of an increased risk of adverse cardiovascular outcomes are already present in these youngsters.
Enzyme linked immunosorbent assay (ELISA) and immunoprecipitation studies on anti-goblet cell antibody using a mucin producing cell line in patients with inflammatory bowel disease.
Authors: T Hibi, M Ohara, K Kobayashi, W R Brown, K Toda, H Takaishi, Y Hosoda, A Hayashi, Y Iwao, M Watanabe
Journal: Gut (1994)

Circulating anti-goblet cell antibody and its corresponding antigen in patients with inflammatory bowel disease were investigated. Anti-goblet cell antibody in the serum was examined by immunocytochemistry and enzyme linked immunosorbent assay (ELISA), using a colonic cancer cell line, HT29-18-N2, which differentiates into intestinal goblet cells. The frequencies of anti-goblet cell antibody detected by immunocytochemistry were 14 in 48 patients with ulcerative colitis (29%) and five in 15 patients with Crohn's disease (33%). By ELISA, the frequencies of anti-goblet cell antibody were 38% in ulcerative colitis and 33% in Crohn's disease. This antibody did not relate directly to anti-neutrophil cytoplasmic antibodies (ANCA), although the serum samples positive for anti-goblet cell antibody were commonly positive for ANCA in ulcerative colitis. Immunoprecipitation and SDS polyacrylamide gel electrophoresis (PAGE) study showed that the antibody in the ELISA positive serum samples recognised a > 200 kD goblet cell antigen, which remained unchanged after reduction, indicating that it consists of single chain polypeptides. These results suggest that there is a subgroup of inflammatory bowel disease that has circulating anti-goblet cell antibody reactive with a > 200 kD antigen. The antibody detected by newly established ELISA will be a disease marker for this group and the identification of the corresponding antigens may be important for the understanding of the underlying immune abnormalities.
SPONTANEOUS LYMPHOCYTE PROLIFERATION IN SYMPTOM-FREE HTLV-I POSITIVE JAMAICANS
Authors: Alexander Krämer, Steven Jacobson, JayneF. Reuben, EdwardL. Murphy, StefanZ. Wiktor, Beverly Cranston, J.Peter Figueroa, Barrie Hanchard, Dale Mcfarlin, WilliamA. Blattner
Journal: The Lancet (1989)
Gaseous Formaldehyde and Hydrogen Chloride Induction of Nasal Cancer in the Rat&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: R E Albert, A R Sellakumar, S Laskin, M Kuschner, N Nelson, C A Snyder
Journal: JNCI Journal of the National Cancer Institute (1982)

The carcinogenic response to the combined and separate exposures to formaldehyde (HCHO) and hydrochloric acid (HCl) was investigated in male inbred SD rats. The rats were exposed to gaseous HCHO, 14 ppm, and HCl, 10 ppm, in two experiments. In one experiment the gases were premixed at high concentrations before being diluted in the exposure chamber air to maximize the formation of the carcinogen bis(chloromethyl)ether (BCME). In the second experiment exposure was repeated to HCl and HCHO premixed at high concentrations, and not premixed (to minimize BCME formation), as well as to HCHO alone and HCl alone. The second experiment is being reported on at an interim stage. HCHO alone induced squamous carcinomas of the nasal cavity as did the combined exposures to HCHO and HCl. No carcinogenic response was observed with HCl alone. HCHO accounted for most, if not all, of the carcinogenic activity of the mixture of HCHO-HCl.
The Development of Phase I Cancer Trial Methodologies: the Use of Pharmacokinetic and Pharmacodynamic End Points Sets the Scene for Phase 0 Cancer Clinical Trials
Authors: A. Hilary Calvert, Ruth Plummer
Journal: Clinical Cancer Research (2008)

Abstract Although the concept of a phase 0 trial is a relatively new one, there has been a slowly increasing trend toward basing early clinical trial designs on pharmacokinetic and pharmacodynamic end points that has been developing over many years. This article will review the early cancer trial methodologies and the various techniques that have been used to refine them. Several illustrative examples will be presented showing their relevance to trial designs using pharmacodynamic end points and targeted agents. Some criteria for characterizing suitable phase 0 end points are suggested. Four trial designs that are essentially developed for cytotoxic agents using the maximal tolerated dose as an end point are described. Although these trials were not designed with the use of more sophisticated pharmacodynamic end points (such as the measurement of the effect of a targeted agent on its target), they have been developed to optimize the speed with which a dose needed to achieve a particular effect can be determined and are, to this extent, relevant to the design of studies with pharmacodynamic end points.
IS LOW-RENIN HYPERTENSION A STAGE IN THE DEVELOPMENT OF ESSENTIAL HYPERTENSION OR A DIAGNOSTIC ENTITY ?
Authors: P.L. Padfield, J.J. Brown, A.F. Lever, M.A.D. Schalekamp, D.G. Beevers, D.L. Davies, J.I.S. Robertson, M. Tree, M. Titterington
Journal: The Lancet (1975)
Nano-Carbons as Theranostics
Authors: Zhuang Liu, Xing-Jie Liang
Journal: Theranostics (2012)

Nano-carbons, including fullerenes, carbon nanoparticles, carbon nanotubes, graphene, and nano-diamonds, are an important class of nanostructures attracting tremendous interests in the past two decades. In this special issue, seven review articles and research reports are collected, to summarize and present the latest progress in the exploration of various nano-carbons for theranostic applications.