tbuckley/cabot-search huggingface dataset:
Striatal Dopamine Transporters and Cognitive Functioning in Healthy Men and Women
Authors: Lyn Harper Mozley, Ruben C. Gur, P. David Mozley, Raquel E. Gur
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: There is growing interest in distinguishing the biological bases of sex differences in behavior from environmental influences. Sex hormone levels seem to be related to some cognitive abilities, particularly memory, and the dopaminergic system participates in the mediation of memory. The dopamine transporter is the primary indicator of dopaminergic tone. This study investigated the relationship between cognition and dopamine transporter availability in healthy men and women. METHOD: Dopamine transporter levels were measured with a technetium-99m radiolabeled analog of cocaine, TRODAT-1, in 66 healthy volunteers (30 men and 36 women). A neuropsychological battery designed to target functions associated with dopaminergic activity was administered during the uptake interval between the radiopharmaceutical injection and image acquisition. RESULTS: Women and younger participants had higher dopamine availability in the caudate nucleus, and these groups also performed better on verbal learning tasks. Furthermore, dopamine transporter availability was correlated with learning performance within groups. Relationships between dopamine availability in the caudate and putamen and executive and motor functioning were observed in women, but not in men. CONCLUSIONS: The results provide further evidence for age effects and sex differences in the neuromodulatory influences of dopamine on behavior in humans.
Impairment of Collateral Formation in Lipoprotein(a) Transgenic Mice
Authors: Ryuichi Morishita, Minako Sakaki, Kei Yamamoto, Sota Iguchi, Motokuni Aoki, Keita Yamasaki, Kunio Matsumoto, Toshikazu Nakamura, Richard Lawn, Toshio Ogihara, Yasufumi Kaneda
Journal: Circulation (2002)

Background— Although lipoprotein(a) (Lp[a]) is a risk factor for atherosclerosis, no study has documented the effects of Lp(a) on angiogenesis. In this study, we examined collateral formation in peripheral arterial disease (PAD) model in Lp(a) transgenic mice. In addition, we examined the feasibility of gene therapy by using an angiogenic growth factor, hepatocyte growth factor (HGF), to treat PAD in the presence of high Lp(a). Methods and Results— In Lp(a) transgenic mice, the degree of natural recovery of blood flow after operation was significantly lower than that in nontransgenic mice. Of importance, there was a significant negative correlation between serum Lp(a) concentration and the degree of natural recovery of blood flow ( P &lt;0.05). In addition, Lp(a) significantly stimulated the growth of vascular smooth muscle, accompanied by the phosphorylation of ERK. These data demonstrated the association of impairment of collateral formation with serum Lp(a) concentration. Thus, we examined the feasibility of therapeutic angiogenesis by using HGF, with the goal of progression to human gene therapy. Intramuscular injection of HGF plasmid resulted in a significant increase in blood flow even in Lp(a) transgenic mice, accompanied by the detection of human HGF protein. A significant increase in capillary density also was detected in Lp(a) transgenic mice transfected with human HGF compared with control ( P &lt;0.01). Conclusions— Overall, a high serum Lp(a) concentration impaired collateral formation. Although the delay of angiogenesis in high serum Lp(a) might diminish angiogenesis, intramuscular injection of HGF plasmid induced therapeutic angiogenesis in the Lp(a) transgenic ischemic hindlimb mouse model as potential therapy for PAD.
Effect of endurance training on lung function: a one year study
Authors: P Kippelen, C Caillaud, E Robert, P Connes, P Godard, C Prefaut
Journal: British Journal of Sports Medicine (2005)

To identify in a follow up study airway changes occurring during the course of a sport season in healthy endurance athletes training in a Mediterranean region.Respiratory pattern and function were analysed in 13 healthy endurance trained athletes, either during a maximal exercise test, or at rest and during recovery through respiratory manoeuvres (spirometry and closing volume tests). The exercise test was conducted on three different occasions: during basic endurance training and then during the precompetition and competitive periods.During the competitive period, a slight but non-clinically significant decrease was found in forced vital capacity (-3.5%, p = 0.0001) and an increase in slope of phase III (+25%, p = 0.0029), both at rest and after exercise. No concomitant reduction in expiratory flow rates was noticed. During maximal exercise there was a tachypnoeic shift over the course of the year (mean (SEM) breathing frequency and tidal volume were respectively 50 (2) cycles/min and 3.13 (0.09) litres during basic endurance training v 55 (3) cycles/min and 2.98 (0.10) litres during the competitive period; p < 0.05).This study does not provide significant evidence of lung function impairment in healthy Mediterranean athletes after one year of endurance training.
Hyperlipidemia in Coronary Heart Disease II. GENETIC ANALYSIS OF LIPID LEVELS IN 176 FAMILIES AND DELINEATION OF A NEW INHERITED DISORDER, COMBINED HYPERLIPIDEMIA
Authors: Joseph L. Goldstein, Helmut G. Schrott, William R. Hazzard, Edwin L. Bierman, Arno G. Motulsky
Journal: Journal of Clinical Investigation (1973)

To assess the genetics of hyperlipidemia in coronary heart disease, family studies were carried out in 2520 relatives and spouses of 176 survivors of myocardial infarction, including 149 hyperlipidemic and 27 normolipidemic individuals. The distribution of fasting plasma cholesterol and triglyceride values in relatives, together with segregation analyses, suggested the presence of five distinct lipid disorders. Three of these—familial hypercholesterolemia, familial hypertriglyceridemia, and familial combined hyperlipidemia—appeared to represent dominant expression of three different autosomal genes, occurring in about 20% of survivors below 60 yr of age and 7% of all older survivors. Two other disorders—polygenic hypercholesterolemia and sporadic hypertriglyceridemia—each affected about 6% of survivors in both age groups.
Discriminating gene expression profiles of memory B cell subpopulations
Authors: Götz R.A. Ehrhardt, Atsushi Hijikata, Hiroshi Kitamura, Osamu Ohara, Ji-Yang Wang, Max D. Cooper
Journal: The Journal of Experimental Medicine (2008)

Morphologically and functionally distinct subpopulations of human memory B (B(Mem)) cells are identifiable by either their expression of CD27 or Fc receptor-like 4 (FCRL4), an immunoglobulin domain containing a receptor with strong inhibitory potential. We have conducted comparative transcriptome and proteome analyses of FCRL4(+) and FCRL4(-) B(Mem) cells and found that these two subsets have very distinctive expression profiles for genes encoding transcription factors, cell-surface proteins, intracellular signaling molecules, and modifiers of the cell-cycle status. Among the differentially expressed transcription factors, runt-related transcription factor 1 (RUNX1) transcript levels were up-regulated in FCRL4(-) cells, whereas RUNX2 transcripts were preferentially detected in FCRL4(+) cells. In vitro evidence for FCRL4 promoter responsiveness and in vivo promoter occupancy suggested that RUNX transcription factors are involved in the generation of these B(Mem) cell subpopulations. A distinctive signature profile was defined for the FCRL4(+) B(Mem) cells by their expression of CD11c, receptor activator for nuclear factor kappaB ligand, and FAS cell-surface proteins, in combination with increased levels of SOX5, RUNX2, DLL1, and AICDA expression. We conclude that this recently identified subpopulation of B(Mem) cells, which normally resides in epithelial tissue-based niches, may serve a unique role in mucosal defense and, conversely, as a target for neoplastic transformation events.
18F-FDG PET scan as follow-up tool for sarcoidosis with symptomatic cardiac conduction disturbances requiring a pacemaker
Authors: S Gyorik, L Ceriani, A Menafoglio, A Gallino, R Wyttenbach
Journal: Thorax (2007)

A 45-year-old man presented to the emergency room after three syncopes. ECG showed sinus rhythm with complete right bundle branch block and left anterior fascicle block. Echocardiography and 24 h ECG monitoring were normal. Chest radiography showed small patchy infiltrations and spiro-ergometry tests showed normal carbon monoxide transfer factor but a reduction in physical capacity (maximum oxygen consumption 70%) associated with an effort-related grade II atrioventricular block. An MRI scan …
Effect of Acute Blood Loss on Glycosylated Hemoglobin Determinations in Normal Subjects
Authors: Harold S Starkman, Marilyn Wacks, J Stuart Soeldner, Agnes Kim
Journal: Diabetes Care (1983)

Nondiabetic adult subjects (N = 12) were studied to determine the effect of an approximately 450-ml acute blood loss upon glycosylated hemoglobin measurements. After blood loss, the hematocrit significantly decreased by week 1 (P &amp;lt; 0.001) and the reticulocyte count peaked by week 2. All glycosylated hemoglobins measured showed significant decreases post blood loss. The nadir was at week 4 for total A1, A1c, and irreversible A1c by high-pressure liquid chromatography (HPLC), and at week 6 for irreversible A1 by HPLC and A1 by electrophoresis. The mean percent decrease in glycosylated hemoglobins ranged from 4.6% (irreversible A1 by HPLC) to 8.6% (total A1c by HPLC).
Asthma deaths in children--a continuing problem.
Authors: C M Mellis, P D Phelan
Journal: Thorax (1977)

The clinical and pathological features of five children who died of asthma over a recent 12-month period are reported. All had severe, chronic asthma requiring maintenance corticosteroid therapy. Three had been receiving beclomethasone dipropionate by inhalation and these had acute inflammation of the tracheobronchial tree at necropsy. Adrenal atrophy was found in all four cases examined histologically, despite normal short tetracosactrin tests in three of these shortly before they died. The need for high-dose corticosteroid by mouth for exacerbations of asthma in those weaned from oral steroids is emphasized by these deaths. The introduction of beclomethasone dipropionate by inhalation has led to an increase in the number of children in this high-risk group.
The ancestral hemochromatosis haplotype is associated with a severe phenotype expression in Italian patients
Authors: A Piperno
Journal: Hepatology (1996)

We evaluate the relation between genotype and phenotype in 47 Italian male patients with homozygous genetic hemochromatosis (GH). Phenotype evaluation was based on the ratio of amount of iron removed (IR) by phlebotomy and age (IR/age). Patients were divided in two classes of phenotype expression: class I included 26 patients with less severe iron overload (IR/age <0.33) and class II included 21 patients with a more marked one (IR/age >0.33). Genetic variability was assessed by haplotype analysis combining alleles at HLA-B, D6S265, HLA-A, and D6S105 loci. A common ancestral haplotype carrying D6S265-1, HLA-A3, and D6S105-8 alleles was present in 13 of 52 (25%) chromosomes in class I and in 24 of 42 (57%) chromosomes in class II (P = .0027). Homozygotes and heterozygotes for the ancestral haplotype had higher iron indices than patients carrying two haplotypes other than the ancestral one. Seven of the eight patients homozygous for the ancestral haplotype were in class II, heterozygotes were equally distributed between the two classes, whereas 14 of 18 carriers of other haplotype combinations were in class I. Our results suggests that the gene defect linked to the ancestral haplotype is the result of a single, severe mutation. The high variability of phenotype expression in heterozygotes for the ancestral haplotype could be accounted for the contribution of the mutation carried by the second haplotype. Combination of different mutations could be responsible for the variable degrees of iron overload found in patients with GH.
Comprehensive Analysis of the Beta-Myosin Heavy Chain Gene in 389 Unrelated Patients With Hypertrophic Cardiomyopathy
Authors: Sara L. Van Driest, Michele A. Jaeger, Steve R. Ommen, Melissa L. Will, Bernard J. Gersh, A. Jamil Tajik, Michael J. Ackerman
Journal: Journal of the American College of Cardiology (2004)
Attenuation of the Ventilatory and Heart Rate Responses to Hypoxia and Hypercapnia with Aging in Normal Men
Authors: Richard S. Kronenberg, Charles W. Drage
Journal: Journal of Clinical Investigation (1973)

The response of ventilation and of heart rate to hypoxia and hypercapnia was determined in eight young normal men age 22-30 yr and eight elderly men age 64-73. The elderly men were selected and carefully screened to eliminate the possibility of cardiopulmonary disease. All the subjects were born at low altitude and had no significant prior exposure to hypoxia. The ventilatory response to hypoxia was measured as the exponential slope constant. k, of regression lines relating the logarithm of incremental ventilation to PAo(2) during isocapnic progressive hypoxia. The heart rate response to hypoxia was measured as the percentage change in heart rate between PAo(2) = 100 and PAo(2) = 40 mm Hg. The ventilatory response to hypercapnia was measured as the slope of regression lines relating ventilation to PAco(2) during rebreathing with PAo(2) > 200 mm Hg. The heart rate response to hypercapnia was measured as the percentage change in heart rate between control values at the start of the rebreathing test and PACO(2) = 55 mm Hg. The ventilatory and heart rate responses to both hypoxia and hypercapnia were significantly decreased in the elderly men as compared to the young men. Hypoxic ventilatory drive was decreased by 51+/-6% (mean +/-SEM: P < 0.001) and hypercapnic drive by 41+/-7% (P < 0.025). The percentage change in heart rate produced by hypoxia was 34+/-5% (mean +/-SEM) in the young normals and 12+/-2% in the old normals (P < 0.005). Similar figures for heart rate in response to hypercapnia were 15+/-3% and -1+/-1% for the young and old normal groups (P < 0.001). We conclude that ventilatory and heart rate responses to hypoxia and hypercapnia diminish with age. These alterations in both ventilatory and circulatory controls could make older individuals more vulnerable to hypoxic disease states.
Headaches and Neuroimaging—Reply
Authors: Brian C. Callaghan, Kevin A. Kerber, James F. Burke
Journal: JAMA Internal Medicine (2015)

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A METHOD FOR THE PHYSIOLOGICAL STUDY OF TISSUES IN VITRO
Authors: Alexis Carrel
Journal: The Journal of Experimental Medicine (1923)

1. A method has been developed which allows the continuous growth of pure strains of fibroblasts, epithelium, and leucocytes in a medium which undergoes but slight spontaneous deterioration. 2. The principle of the method is to leave the tissues undisturbed while the medium is changed. This was realized by special containers allowing the change of the medium without bacterial contamination and by the simultaneous use of a solid and a fluid medium. 3. The curve of growth of pure cultures of fibroblasts and epithelial cells in a nutrient medium is a parabola; in a non-nutrient medium, it is S-shaped and expresses the residual activity of the tissues. Leucocytes invade the culture medium progressively, as do bacteria, but never aggregate in a tissue. 4. The method is used for the study of the morphological and dynamic changes occurring in tissues under the influence of chemical and physical factors.
Evidence that bradykinin stimulates renal prostaglandin synthesis by a mechanism distinct from that of other vasoactive substances.
Authors: C L Cooper, K U Malik
Journal: Circulation Research (1987)

Arginine-vasopressin (AVP), angiotensin II (AII), and norepinephrine (NE) are known to stimulate prostaglandin (PG) synthesis in the intact rat kidney perfused with Tyrode's solution by a mechanism that requires intracellular Ca2+, while PG synthesis elicited by bradykinin (BK) is independent of Ca2+. To elucidate further the differences in the mechanism of action of BK and other vasoactive agents, in this preparation we have investigated the effect of caffeine, an agent known to interfere with the uptake and storage of Ca2+ in intracellular sites, on renal output of PGE2 and 6-keto-PGF1 alpha elicited by AVP, AII, NE, and BK; various combinations of the maximal doses of BK, AII, AVP, and NE on renal PG synthesis; and RHC 80267, an inhibitor of diglyceride and monoglyceride lipase, on the output of PGs produced by these vasoactive agents. Infusion of 1 mM caffeine inhibited PG output elicited by AVP, AII, and NE but not that caused by BK in the absence of extracellular Ca2+. Combined administration of maximal doses of BK (2.8 nmol) with that of AII (0.28 nmol), AVP (0.27 nmol), or NE (3.2 nmol) but not AVP and AII, NE and AVP, or NE and AII produced an additive effect on renal PG output in the presence or absence of Ca2+. The renal vasoconstrictor effect of AVP, AII, and NE produced in the presence of Ca2+ was not additive and remained unaltered when given together with BK.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of anti-GBM antibodies in sera with or without ANCA.
Authors: T Hellmark, J L Niles, A B Collins, R T McCluskey, C Brunmark
Journal: Journal of the American Society of Nephrology (1997)

An appreciable percentage of patients with serum anti-glomerular basement membrane (anti-GBM) antibodies also have antineutrophil cytoplasmic antibodies (ANCA), against either myeloperoxidase (MPO-ANCA), or proteinase 3 (PR3-ANCA). In sera without ANCA, the anti-GBM antibodies have been shown to react mainly with the noncollagenous domain (NC1) of Type IV collagen, and especially with its alpha 3 chain, alpha 3(IV)NC1. In most sera, the antibodies can be partially blocked by a monoclonal antibody (Mab17) against alpha 3(IV)NC1, suggesting that a limited region is recognized. Although there is evidence that some anti-GBM antibodies that coexist with ANCA react with alpha 3(IV)NC1, extensive analysis of the specificity of such anti-GBM antibodies has not been reported. In the study presented here, sera were analyzed from 332 patients tested both for anti-GBM antibodies and ANCA (MPO or PR3-ANCA) and found to have one or more positive tests. Of the 100 sera with anti-GBM antibodies, 38 also had ANCA-25 with MPO-ANCA (66%), 12 with PR3-ANCA (32%), and one with both (2%). Of the 232 sera with ANCA only, 153 had MPO-ANCA (66%), 75 had PR3-ANCA (32%), and four had both (2%). Sera was also analyzed from 259 other patients who had positive ANCA tests and were not tested for anti-GBM antibodies: 138 had MPO-ANCA (54%), and 121 had PR3-ANCA (46%). The relative frequencies of MPO or PR3-ANCA in patients with coexisting anti-GBM antibodies did not differ significantly from those in all patients with ANCA (P = 0.35). Seventeen sera with anti-GBM antibodies only and 16 sera with anti-GBM antibodies plus ANCA were selected for further studies to compare the specificity of anti-GBM antibodies in sera with or without ANCA. Using enzyme-linked immunosorbent assays (ELISA), all sera in both groups were found to react with the NC1 domain (as a hexamer) of bovine Type IV collagen and with alpha 3 (IV)NC1 monomers. Furthermore, all but six sera also reacted with one or more of the alpha 1, 2, and 4 (IV)NC1 monomers, generally with considerably lower titers. Reactivity to alpha 3(IV)NC1 was partially blocked by Mab17, with comparable degrees of inhibition in both groups. Western blot analysis with the human NC1 domains revealed no differences in reactivity between the two groups. Thus, differences in antigen specificities of anti-GBM antibodies in sera with or without ANCA were not detected. The anti-GBM response in both situations is hypothesized to be driven by the same immunogen, which is probably derived from NC1 domains of endogenous Type IV collagen.
Adenosine A2A receptors are expressed in human atrial myocytes and modulate spontaneous sarcoplasmic reticulum calcium release
Authors: L HOVEMADSEN, C PRATVIDAL, A LLACH, F CIRUELA, V CASADO, C LLUIS, A BAYESGENIS, J CINCA, R FRANCO
Journal: Cardiovascular Research (2006)

Alterations in the cyclic AMP-dependent regulation of the cardiac ryanodine receptor (RyR2) have been proposed to account for increased spontaneous calcium release from the sarcoplasmic reticulum (SR) in patients with heart failure, ventricular tachyarrhythmias and atrial fibrillation. While the adenosine A(2A) receptor (A(2A)R) is known to regulate cyclic AMP levels, expression and function of this receptor in human cardiac myocytes has not been investigated.PCR, western blotting and immunofluorescence were used to identify the A(2A)R, and functional effects of A(2A)R stimulation were measured with confocal calcium imaging and patch-clamp technique.The A(2A)R is expressed in the human right atrium and distributed in a banded pattern along the Z-lines, overlapping with the ryanodine receptor. A(2A)R stimulation caused a protein kinase A dependent increase in spontaneous SR calcium release in isolated human atrial myocytes. The A(2A)R agonist CGS21680 increased the frequency of calcium sparks from 0.12+/-0.03 to 0.31+/-0.08 sparks.mum min(-1) (p<0.05) and calcium waves from 0.65+/-0.31 to 5.11+/-1.84 waves.min(-1) (p<0.03). Moreover, spontaneous Na-Ca exchange currents (I(NCX)) increased from 1.19+/-0.17 to 2.50+/-0.42 min(-1) (p<0.001). In contrast, CGS21680 did not alter caffeine inducible calcium release (6.98+/-0.52 vs. 6.82+/-0.57 amol pF(-1), p=0.6) or the spontaneous I(NCX) amplitude (0.32+/-0.05 vs. 0.29+/-0.04 pA pF(-1), p=0.2). Current-voltage relationship and amplitude of the L-type calcium current (1.62+/-0.18 vs. 1.80+/-0.18 pA pF(-1)) were not altered, but calcium release dependent inactivation was faster with CGS21680 (13.4+/-0.7 vs. 15.8+/-1.0 ms, p<0.001).Adenosine A(2A) receptors are expressed in the human atrial myocardium and modulate the frequency of spontaneous calcium release from the SR.