tbuckley/cabot-search huggingface dataset:
Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Modulates the Human In Vivo Metabolism of Bradykinin
Authors: Laine J. Murphey, James V. Gainer, Douglas E. Vaughan, Nancy J. Brown
Journal: Circulation (2000)

Background —Bradykinin is a cardioprotective peptide metabolized by the angiotensin-converting enzyme (ACE). An insertion/deletion (I/D) polymorphism in the ACE gene determines plasma ACE levels. The D allele is associated with cardiovascular disease, which may relate to enhanced angiotensin II production or to increased bradykinin degradation to the inactive metabolite bradykinin 1–5 (BK1–5). Therefore, we determined the effect of the ACE I/D polymorphism on human bradykinin metabolism in vivo. Methods and Results —Bradykinin (400 ng/min) was infused into the brachial artery of volunteers with ACE I/I, I/D, or D/D genotypes (n=9 each). The bradykinin and BK1–5 levels in forearm venous return were quantified by liquid chromatography–mass spectroscopy. Plasma ACE activity was highest in those with the D/D genotype (36.8±6.2 U/mL), intermediate in those with the I/D genotype (25.3±3.3 U/mL), and lowest in those with the I/I genotype (20.3±2.3 U/mL; P =0.017 for effect of number of D alleles). Bradykinin concentrations were 726±242, 469±50, and 545±104 fmol/mL in I/I, I/D, and D/D subjects, respectively ( P &gt;0.10). Significant correlations existed between the number of D alleles and BK1–5 concentrations (1113±290, 1520±318, and 1887±388 fmol/mL in the I/I, I/D, and D/D groups, respectively; P =0.027) and the ratio of BK1–5 to bradykinin (1.87±0.35, 3.09±0.40, and 4.31±0.97 in the I/I, I/D, and D/D volunteers, respectively; P =0.010). The venous blood BK1–5:bradykinin ratio correlated with plasma ACE activity ( r 2 =0.16, P =0.039), and total kinin concentration correlated with net tissue plasminogen activator release across the forearm ( r 2 =0.20, P =0.027). Conclusions —The ACE D allele has a significant effect on the in vivo degradation of bradykinin in humans. The ratio of BK1–5:bradykinin may serve as a marker for tissue ACE activity.
Higher Expression of Serotonin 5-HT<sub>2A</sub> Receptors in the Postmortem Brains of Teenage Suicide Victims
Authors: Ghanshyam N. Pandey, Yogesh Dwivedi, Hooriyah S. Rizavi, Xinguo Ren, Subhash C. Pandey, Christine Pesold, Rosalinda C. Roberts, Robert R. Conley, Carol A. Tamminga
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Abnormalities of serotonin (5-HT) receptor subtypes have been observed in the postmortem brains of adult suicide victims; however, their role in teenage suicide is unexplored. The authors examined whether 5-HT2A receptor subtypes are altered in the postmortem brains of teenage suicide victims. METHOD: Levels of 5-HT2A receptors were determined through examination of [125I] LSD binding, protein expression (by use of Western blotting with a specific 5-HT2A receptor antibody), and mRNA (by means of quantitative reverse transcription polymerase chain reaction) in the prefrontal cortex, hippocampus, and nucleus accumbens of 15 teenage suicide victims and 15 normal matched teenage subjects. The cellular localization of the 5-HT2A receptors was determined by means of gold immunolabeling. RESULTS: The authors observed significantly higher [125I]LSD binding in the prefrontal cortex and greater protein expression and mRNA levels in the prefrontal cortex and hippocampus but not in the nucleus accumbens of suicide victims, compared with normal subjects. Greater protein expression was localized on pyramidal cells in cortical layer V but not in other cortical layers or in the surrounding neuropil of the prefrontal cortex of teenage suicide victims. CONCLUSIONS: The evidence indicates higher levels of 5-HT2A receptor, protein, and mRNA expression in the prefrontal cortex and hippocampus, which have been implicated in emotion, stress, and cognition. There was no higher level in the nucleus accumbens, which has been implicated in drug dependence and craving. Our findings suggest that a higher level of 5-HT2A receptors may be one of the neurobiological abnormalities associated with teenage suicide.
Ferritin Levels and Their Association With Regional Brain Volumes in Tourette's Syndrome
Authors: D. A. Gorman, H. Zhu, G. M. Anderson, M. Davies, B. S. Peterson
Journal: American Journal of Psychiatry (2006)

Objective: A previous small study showed lower serum ferritin levels in subjects with Tourette's syndrome than in healthy subjects. The authors measured peripheral iron indices in a large group of Tourette's syndrome and comparison subjects and explored associations of ferritin levels with regional brain volumes. Method: Ferritin was measured in 107 children and adults (63 Tourette's syndrome, 44 comparison); serum iron was measured in 73 (41 Tourette's syndrome, 32 comparison). Magnetic resonance imaging scans were used to measure volumes of the basal ganglia and cortical gray matter. Results: Ferritin and serum iron were significantly lower in the Tourette's syndrome subjects, although still within the normal range. No association was found between tic severity and either iron index. In the Tourette's syndrome subjects, ferritin did not correlate significantly with caudate volume but did correlate positively with putamen volume. In the comparison subjects, ferritin correlated inversely with caudate volume but did not correlate significantly with putamen volume. Irrespective of diagnosis, ferritin correlated positively with volumes of the sensorimotor, midtemporal, and subgenual cortices. Conclusions: The lower peripheral ferritin and iron levels in persons with Tourette's syndrome are consistent with findings in other movement disorders and suggest that lower iron availability may have a causal role in the pathophysiology of tic disorders. Lower iron stores may contribute to hypoplasia of the caudate and putamen, increasing vulnerability to developing tics or to having more severe tics. Lower iron stores may also contribute to smaller cortical volumes and consequently to reduced inhibitory control of tics.
Airway dimensions measured from micro-computed tomography and high-resolution computed tomography
Authors: J. R. Dame Carroll
Journal: European Respiratory Journal (2006)

Volume averaging results in both over- and underestimation of airway dimensions when they are measured by high-resolution computed tomography (HRCT). The current authors calibrated computerised measurements of airway dimensions from HRCT against a novel three-dimensional micro-computed tomography (CT) standard, which has a 50-fold greater resolution, as well as against traditional morphometry. Inflation-fixed porcine lung cubes were scanned by HRCT and micro-CT. A total of 59 lumen area (Ai), 30 wall area (A(aw)) and 11 lumen volume (Vi) measurements were made. Ai was measured from the cut surface of 11 airways by morphometry. Airways in scanned images were matched using branching points. After calibration, the errors of Ai, A(aw) and Vi HRCT measurements were determined. The current authors found a systematic, size-dependent underestimation of Ai and overestimation of A(aw) from HRCT measurements. This was used to calibrate an HRCT measurement algorithm. The 95% limits of agreement of subsequent measurements were +/-3.2 mm2 for Ai, +/-4.3 mm2 for A(aw), and +/-11.2 mm3 for Vi with no systematic error. Morphometric measurements agreed with micro-CT (+/-2.5 mm2) without systematic error. In conclusion, micro-computed tomography image data from inflation-fixed airways can be used as calibration standards for three-dimensional lumen volume measurements from high-resolution computed tomography, while morphometry is acceptable for two-dimensional measurements. The image dataset could be used to validate other developmental three-dimensional segmentation algorithms.
Amylase creatinine clearance ratio after biliary surgery.
Authors: L A Donaldson, W McIntosh, S N Joffe
Journal: Gut (1977)

The amylase creatinine clearance ratio (ACCR) is considered to be a more sensitive index of acute pancreatitis than the serum amylase level. Serial ACCR estimations were undertaken in 25 patients undergoing an elective cholecystectomy. Using accepted criteria, 28% of these patients developed, in the postoperative period, biochemical evidence of pancreatic gland damage, although the serum amylase level remained normal. This raised ACCR was particularly noted in patients who had undergone an exploration of the common bile duct. The ACCR would appear to be a more sensitive index of pancreatic gland disruption secondary to biliary surgery than the serum amylase level.
Total protein output during rapid reduction of bile salt secretion rates in man.
Authors: P R Harvey, J L Toth, G A Upadhya, R G Ilson, S M Strasberg
Journal: Gut (1989)

An investigation was undertaken to study the effect of bile salt secretion on total biliary protein secretion in man. Bile was collected in eight patients from a tube in the bile duct. Collection was started after a meal and continued for six hours, in order to obtain bile salt secretion rates over the entire physiological range. Total protein secretion rates did not vary with change in bile salt secretion or bile flow. The protein pattern assessed by SDS-PAGE did not vary with bile salt secretion. The results indicate that bile salt secretion has little influence on biliary protein secretion under these conditions in man. Changes in bile salt secretion were associated with linear change in bile flow, but there was no relationship between bile flow and protein secretion rates. This argues against convective sieving of plasma proteins into bile.
Novel Adenovirus Component System That Transfects Cultured Cardiac Cells With High Efficiency
Authors: Trudy A. Kohout, Jeffrey J. O’Brian, Shirley T. Gaa, W. Jonathan Lederer, Terry B. Rogers
Journal: Circulation Research (1996)

Abstract Although it is clear that gene transfection is a potentially valuable approach in the study of cardiac cell function and differentiation, classic transfection methods are limited by their poor efficiencies in cardiac cells. Recent studies show that recombinant replication-defective human adenovirus can transfect primary cardiac cultures with near 100% efficiency. Since such recombinants are time consuming to prepare, the goal of this study was to develop a plasmid/viral transfection system that would capitalize on the advantages of adenovirus. We have found that a “component system” formed by preincubation of Ad5dl312 adenovirus, poly- l -lysine, and an expression plasmid ( lac Z reporter gene under control of the human cytomegalovirus (HCMV) major immediate early promoter) can transfect cultured cardiac cells. Optimal conditions were determined by quantifying β-galactosidase expression. Histochemical analysis of cultures revealed that the component system transfected 70% of the cells under these conditions. Lac Z-positive myocytes could be identified in intact myocytes with the fluorescent substrate C 12 -fluorescein di-β-galactopyranoside. Functional studies with such cells indicated that contractile behavior was maintained in transfected cardiocytes. Furthermore, the component system was used to transfect a DNA vector expressing a physiologically relevant protein, protein kinase Cδ. In summary, this powerful and simple approach can promote the expression of heterologous genes that can be studied at the biochemical and cellular level in cardiac cells.
Evidence for Active Maintenance of Phylotranscriptomic Hourglass Patterns in Animal and Plant Embryogenesis
Authors: Hajk-Georg Drost, Alexander Gabel, Ivo Grosse, Marcel Quint
Journal: Molecular Biology and Evolution (2015)

The developmental hourglass model has been used to describe the morphological transitions of related species throughout embryogenesis. Recently, quantifiable approaches combining transcriptomic and evolutionary information provided novel evidence for the presence of a phylotranscriptomic hourglass pattern across kingdoms. As its biological function is unknown it remains speculative whether this pattern is functional or merely represents a nonfunctional evolutionary relic. The latter would seriously hamper future experimental approaches designed to test hypotheses regarding its function. Here, we address this question by generating transcriptome divergence index (TDI) profiles across embryogenesis of Danio rerio, Drosophila melanogaster, and Arabidopsis thaliana. To enable meaningful evaluation of the resulting patterns, we develop a statistical test that specifically assesses potential hourglass patterns. Based on this objective measure we find that two of these profiles follow a statistically significant hourglass pattern with the most conserved transcriptomes in the phylotypic periods. As the TDI considers only recent evolutionary signals, this indicates that the phylotranscriptomic hourglass pattern is not a rudiment but possibly actively maintained, implicating the existence of some linked biological function associated with embryogenesis in extant species.
A role for asymmetric dimethylarginine in the pathophysiology of portal hypertension in rats with biliary cirrhosis†‡
Authors: Wim Laleman, Anita Omasta, Marc Van de Casteele, Marcel Zeegers, Ingrid Vander Elst, Lien Van Landeghem, Tamara Severi, Jos van Pelt, Tania Roskams, Johan Fevery, Frederik Nevens
Journal: Hepatology (2005)

Reduced intrahepatic endothelial nitric oxide synthase (eNOS) activity contributes to the pathogenesis of portal hypertension (PHT) associated with cirrhosis. We evaluated whether asymmetric dimethylarginine (ADMA), a putative endogenous NOS inhibitor, may be involved in PHT associated with cirrhosis. Two rat models of cirrhosis (thioacetamide [TAA]-induced and bile duct excision [BDE]-induced, n = 10 each), one rat model of PHT without cirrhosis (partial portal vein–ligated [PPVL], n = 10), and sham-operated control rats (n = 10) were studied. We assessed hepatic NOS activity, eNOS protein expression, plasma ADMA levels, and intrahepatic endothelial function. To evaluate intrahepatic endothelial function, concentration–effect curves of acetylcholine were determined in situ in perfused normal rat livers and livers of rats with TAA- or BDE-induced cirrhosis (n = 10) that had been preincubated with either vehicle or ADMA; in addition, measurements of nitrite/nitrate (NOx) and ADMA were made in perfusates. Both models of cirrhosis exhibited decreased hepatic NOS activity. In rats with TAA-induced cirrhosis, this decrease was associated with reduced hepatic eNOS protein levels and immunoreactivity. Rats with BDE-induced cirrhosis had eNOS protein levels comparable to those in control rats but exhibited significantly higher plasma ADMA levels than those in all other groups. In normal perfused liver, ADMA induced impaired endothelium-dependent vasorelaxation and reduced NOx perfusate levels, phenomena that were mimicked by NG-nitro-L-arginine-methyl ester. In contrast to perfused livers with cirrhosis induced by TAA, impaired endothelial cell-mediated relaxation in perfused livers with cirrhosis induced by BDE was exacerbated by ADMA and was associated with a decreased rate of removal of ADMA (34.3% ± 6.0% vs. 70.9% ± 3.2%). In conclusion, in rats with TAA-induced cirrhosis, decreased eNOS enzyme levels seem to be responsible for impaired NOS activity; in rats with biliary cirrhosis, an endogenous NOS inhibitor, ADMA, may mediate decreased NOS activity. (HEPATOLOGY 2005;42:1382–1390.)
Expression of FoxM1 Is Required for the Proliferation of Medulloblastoma Cells and Indicates Worse Survival of Patients
Authors: Markus Priller, Julia Pöschl, Leticia Abrão, André O. von Bueren, Yoon-Jae Cho, Stefan Rutkowski, Hans A. Kretzschmar, Ulrich Schüller
Journal: Clinical Cancer Research (2011)

The transcription factor Forkhead box M1 (FoxM1) is a key regulator of cell-cycle progression. It is involved in the development of multiple organs, and we have previously reported on its important role for the mitotic entry of cerebellar granule neuron precursors. Constitutive expression of FoxM1 is required for the growth of multiple cancer types. This study aimed to determine its role in medulloblastoma, the most frequent malignant brain tumor in childhood that can derive from cerebellar granule neuron precursors.We evaluated the expression of FoxM1 together with its prognostic value in two independent series of human medulloblastoma samples using immunohistochemistry (n = 43) and gene expression arrays (n = 193). The functional impact of FoxM1 expression was characterized by knockdown experiments in four human medulloblastoma cell lines, and the thiazole antibiotic siomycin A was tested to downregulate FoxM1 and inhibit tumor cell growth.FoxM1 was highly expressed in all subtypes of medulloblastoma. Importantly, expression levels of FoxM1 significantly correlated with unfavorable clinical outcome in univariate analysis (P = 0.0005), and FoxM1 was identified as an independent prognostic marker by multivariate analysis (P = 0.037). Knockdown of FoxM1 in medulloblastoma cell lines resulted in a significant decrease of cell viability which was caused by a failure in mitotic spindle formation and caspase-dependent mitotic catastrophe. Siomycin A significantly inhibited the expression of FoxM1 and the growth of medulloblastoma cells.FoxM1 may be used as an additional prognostic marker and may represent a potential novel target to treat patients suffering from medulloblastoma.
Validity of using Hospital Episode Statistics data on monitoring disease trends
Authors: M. A. Elemraid, K. Pollard, M. F. Thomas, A. R. Gennery, K. M. Eastham, S. P. Rushton, F. Hampton, P. Singleton, R. Gorton, D. A. Spencer, J. E. Clark
Journal: Thorax (2010)

We read with interest the article by Koshy et al .1 The findings are important in documenting changes in admission rates of childhood pneumonia and empyema since the introduction of heptavalent pneumococcal conjugate vaccine (PCV7). We are concerned that undue emphasis has been placed on Hospital Episode Statistics (HES) data to define the aetiology of childhood pneumonia, particularly ‘bacterial pneumonia’.2

Given the magnitude of the case numbers reported, it would appear that the analyses are based on all pneumonia …
Familial Aggregation and Segregation Analysis of Eosinophil Levels
Authors: CATHARINE J. HOLBERG, MARILYN HALONEN, ANNE L. WRIGHT, FERNANDO D. MARTINEZ
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The number of circulating eosinophils is associated with the risk of asthma in population samples. Therefore, eosinophil levels may be an intermediate phenotype for asthma amenable to genetic analysis. We examined familial aggregation of the number of eosinophils × 106 L− 1 and the percentage of eosinophils based on a 300 count differential in 644 Hispanic and non-Hispanic white families, with 2,097 subjects, enrolled in the Tucson Children's Respiratory Study. Both measures were adjusted for age, season and year at the time blood was drawn, sex, and ethnicity. Segregation analysis was conducted in the 458 non-Hispanic white families, as there were no significant familial correlations in the Hispanic families, and there was significant heterogeneity by ethnic group. Familial correlations ( ρ ) in the non-Hispanic white families were as follows: mother–father, 0.05; mother–child, 0.18 (p < 0.001); father–child, 0.07; sibling–sibling, 0.31 (p < 0.001). Without covariates analyses indicated a polygenic/multifactorial mode of inheritance. After adjusting for current and past asthma an oligogenic mode of inheritance was suggested, plus additional residual familial components that were mainly maternally mediated. This study supports the notion of multiple, relatively common genes interacting to determine genetic susceptibility to asthma. Holberg CJ, Halonen M, Wright AL, Martinez FD. Familial aggregation and segregation analysis of eosinophil levels.
Voluntary cough suppression as an indication of symptom severity in upper respiratory tract infections
Authors: HA Hutchings, R Eccles, AP Smith, MS Jawad
Journal: European Respiratory Journal (1993)

The aim of the present study was to determine whether the ability to suppress cough voluntarily is an index of cough severity in upper respiratory tract infection. Cough was measured by means of a microphone linked to a pen recorder and subjects were instructed to voluntarily suppress cough in order to determine cough suppression time. Subjective scores of symptom severity, mood and psychological parameters were made prior to cough measurements. The baseline frequency of cough showed a distribution towards the higher frequencies, with a median of 2.1 (lower quartile 1.2, upper quartile 3.2) coughs.min-1. The results for cough suppression fell into two distinct groups, one group reaching a breaking point within 12.6 min; and another group which did not cough during the 20 min cough suppression period. In the group of subjects which broke from the cough suppression, there was an inverse relationship between the cough suppression time and the baseline frequency of cough. The median frequency of cough following cough suppression was significantly greater than the baseline median frequency of cough. The subjects who reached a breaking point had a greater baseline frequency of cough and a greater symptom severity score, and they also felt more feeble, clumsy, sad and antagonistic than the group which did not reach a breaking point. The subjects who reached a breaking point had significantly greater scores for the psychology parameter of obsessional symptoms than the group which did not reach a breaking point.(ABSTRACT TRUNCATED AT 250 WORDS)
ANTIGENIC AND ENZYME SYSTEM CHANGES IN BETA HEMOLYTIC STREPTOCOCCI RESISTANT TO PENICILLIN, STREPTOMYCIN, BACITRACIN AND AUREOMYCIN 1234
Authors: Horace M. Gezon, Dorcas M. Fasan
Journal: Journal of Clinical Investigation (1949)

Previous reports from this laboratory (1, 2) have presented preliminary data, suggesting that there are antigenic and enzyme system changes in beta hemolytic streptococci resistant to penicillin and streptomycin.These data were all qualita- tive and were unconfirmed by quantitative meth- ods.The present study is a continuation of this work.The same strains of group A and C streptococci were made resistant separately to bacitracin and aureomycin.Representative members of each group, resistant to all four antibiotics, were stud- ied for alterations in: 1) streptolysin S; 2) strep- tokinase; 3) proteinase; 4) ribonuclease activity.That such variations might be expected was first suggested by the observation that reversible changes in the hemolytic behavior of streptococci from beta to alpha or gamma type of hemolysis occurred when the organisms were growing on maximal concentrations of either penicillin or streptomycin. MATERIALS AND METHODS Strains of StreptococciSeven group A strains and three group C strains iso- lated in 1946-1947 from throats of patients with acute upper respiratory infections were employed throughout the study.The strain designations for the group A or- 1Presented at the Second National Symposium on Recent Advances in Antibiotics Research held in Wash- ington, D. C.,