bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Major Phosphoproteins in the cGMP-Mediated Protein Phosphorylation System of Vascular Smooth Muscle Membranes
Authors: Fujita Satoru , Yoshida Yutaka , Islam Omedul , Ma Xin , Fujioka Masaki , Ito Masaaki , Nakano Takeshi , Aizawa Yoshifusa , Imai Shoichi , Higuchi Hiroshi 
Published: April 2003

G&#8320; (215–250 kD) and G<sub>1</sub> (120–140 kD), the unidentified major phosphoproteins in the cGMP-mediated protein phosphorylation system of vascular smooth muscle membranes, were compared for biochemical and immunological properties with the type 1 inositol 1,4,5-trisphosphate receptor (InsP<sub>3</sub>R, 240 kD) and the myosin-binding subunit (MBS, 138 kD) of myosin phosphatase, both of them substrates for cGMP-dependent protein kinase. Two microsomal proteins that were immunoreactive with antibodies to InsP<sub>3</sub>R and MBS were detected, and comigrated with G&#8320; and G<sub>1</sub>, respectively, on SDS-PAGE. When thiophosphorylated G&#8320; and G<sub>1</sub> were subjected to immunoprecipitation, MBS antibody induced the precipitation of a 138-kD phosphoprotein, but did not significantly affect the amount of G<sub>1</sub> remaining in the supernatant, while InsP<sub>3</sub>R antibody precipitated G&#8320; almost completely. Unexpectedly, InsP<sub>3</sub>R antibody coprecipitated a large portion of G<sub>1</sub>, which did not cross-react with either antibody to MBS or InsP<sub>3</sub>R. Just like InsP<sub>3</sub>R, G&#8320; bound to the calmodulin column in a Ca<sup>2+</sup>-dependent manner, and, again, a large portion of G<sub>1</sub> was copurified with G&#8320;. These results suggest that G&#8320; is identical to InsP<sub>3</sub>R, while G<sub>1</sub> consists of several phosphoproteins, including the 138-kD protein associated with InsP<sub>3</sub>R as a major component. MBS is not G<sub>1</sub> or may represent only a minor component of it.
Human Vascular Reactivity and Polymorphisms of the Angiotensin-Converting Enzyme and the Angiotensin Type 1 Receptor Genes
Authors: Steeds R.P. , Toole L.O. , Channer K.S. , Morice A.H. 
Published: April 2003

The D allele of the insertion (I)/deletion (D) polymorphism in the angiotensin-converting enzyme (ACE) gene and the C allele of the A1166-C polymorphism in the angiotensin II type 1 receptor (AGT1R) gene have been associated with altered vascular structure and with an increased risk of myocardial infarction. The aim of this study was to determine whether differences in vascular function could be demonstrated to link the previously described changes in structure and the disease outcome. 70 subjects were recruited at random from patients undergoing colonic resection, resistance arteries were excised and were mounted in a small vessel wire myograph. Vasomotor responses to potassium chloride, noradrenaline, prostaglandin F<sub>2α</sub>, angiotensin I, angiotensin II, acetylcholine and substance P were performed in 30 subjects. Genotype was established in a blinded fashion after completion of myography. To exclude the possibility of masking of genetic influence by non-ACE conversion of angiotensin I, vasomotor responses were then performed to proline<sup>10</sup>-angiotensin I in a further 30 subjects and to angiotensin I in the presence of chymostatin in a further 10 subjects. No significant effect of the I/D polymorphism of the ACE gene was seen on vasomotor function. The C allele of the AGT1R gene was associated with an increase in sensitivity to prostaglandin F<sub>2α</sub> but not with alteration to the other vasoactive agents studied. The I/D ACE and A1166-C AGT1 receptor polymorphism do not appear to result in differences in vasomotor function in isolated human mesenteric resistance arterioles in subjects without evidence of underlying hypertensive or cardiovascular disease.
Sensitive Superoxide Detection in Vascular Cells by the New Chemiluminescence Dye L-012
Authors: Sohn Hae-Young , Gloe Torsten , Keller Matthias , Schoenafinger Karl , Pohl Ulrich 
Published: April 2003

The detection superoxide production in vascular cells is usually limited by a low sensitivity of available assays. We tested the applicability of the luminol derivate L-012 [8-amino-5-chloro-7-phenylpyridol[3,4-d]pyridazine-1,4(2H,3H)dione] to measure superoxide production in cultured endothelial cells (human umbilical vein endothelial cells) and rat aortic segments. Following stimulation with the protein kinase stimulator phorbol 12-myristate 13-acetate (PMA, 1 μ<i>M</i>) there was an 2.8-fold increase of L-012 chemiluminescence, whereas incubation with angiotensin II (100 n<i>M</i>) did not result in a measurable increase. Addition of vanadate (100 μ<i>M</i>) considerably increased the chemiluminescence (up to 17-fold) after PMA and made possible the detection of an enhanced superoxide production after stimulation with angiotensin II (by 1.7-fold). This was due to a ∼9-fold increase in signal intensity of L-012 in the presence of vanadate. Prolonged incubation with vanadate also led to a tyrosine phosphorylation-dependent increase in superoxide formation which was predominantly produced by an NAD(P)H oxidase. Short-term vanadate-enhanced L-012 chemiluminescence represents a highly sensitive assay making it possible to detect small changes of superoxide formation in intact vascular cells.
The Mitogenic Effect of 17β-Estradiol on in vitro Endothelial Cell Proliferation and on in vivo Reendothelialization Are Both Dependent on Vascular Endothelial Growth Factor
Authors: Concina P. , Sordello S. , Barbacanne M.A. , Elhage R. , Pieraggi M.T. , Fournial G. , Plouet J. , Bayard F. , Arnal J.F. 
Published: April 2003

In addition to their actions on reproductive function, estrogens have important effects on endothelial cells. The present study was designed to evaluate the mechanism(s) by which 17β-estradiol (E2) promotes endothelial cell proliferation. The potential involvement of vascular endothelial growth factor (VEGF) was investigated by the coadministration of polyclonal anti-VEGF antibody. First, the effect of E2 on the proliferation of cultured foetal bovine aortic endothelial cells (FBAEC) was studied. E2 stimulated this proliferation with an EC50 between 10<sup>–11</sup> and 10<sup>–10</sup> <i>M</i> and this effect was inhibited by the anti-VEGF antibody. The effect of a physiological dose of E2 was then studied in the rat model of carotid injury. After deendothelializing balloon injury, reendothelialization of the denuded surface may influence the growth of the underlying smooth muscle cells. Male Sprague-Dawley rats were castrated and then received E2 from subcutaneously implanted pellets that released 3.2 μg/kg/day. Endothelial regrowth (Evans blue staining) and neointimal thickening were evaluated 2 weeks after the carotid injury. In comparison to the placebo group, E2 increased the extent of reendothelialization (p = 0.0002) and reduced neointimal thickening (p = 0.0007). Anti-VEGF antibody abolished the effect of E2 on reendothelialization as well as on neointimal thickening. Thoracic aorta VEGF content was increased in E2-treated rats compared to control rats. In conclusion, the present study demonstrates that E2 increases endothelial cell proliferation in vitro and reendothelialization in vivo by means of a mechanism dependent on endogenous VEGF. This effect could contribute to the antiatherogenic effect of a physiological dose of E2.
Mg<sup>2+</sup>-Induced Vasodilation in Human Forearm Vasculature Is Inhibited by N<sup>G</sup>-Monomethyl- <i>L</i>-Arginine but Not by Indometacin
Authors: Dawes Matthew , Ritter James M. 
Published: April 2003

We have investigated the mechanism of the vasodilator action of Mg<sup>2+</sup> in human forearm resistance vasculature. Venous occlusion plethysmography was used to measure vasodilator responses to Mg<sup>2+</sup> infused via the brachial artery in healthy men, and to determine effects on Mg<sup>2+</sup> responses of indometacin (an inhibitor of cyclo-oxygenase) and of N<sup>G</sup>-monomethyl-<i>L</i>-arginine (<i>L</i>-NMMA, an inhibitor of the <i>L</i>-arginine/nitric oxide, <i>L</i>-arg/NO, pathway). Magnesium sulphate infusion (0.05, 0.1, 0.2 mmol·min<sup>–1</sup>) increased plasma Mg<sup>2+</sup> concentration to 1.57 ± 0.16 mmol·l<sup>–1</sup> in venous blood from the infused arm at the highest dose. There was a dose-related increase in forearm blood flow in the infused arm to a maximum of 6.37 ± 1.37 ml·min<sup>–1</sup>·dl forearm<sup>–1</sup> at the highest dose corresponding to an increase of 159 ± 25% in blood flow relative to the non-infused arm. There was no tachyphylaxis during a second infusion following a 21-min recovery period. Indometacin had no effect on vasodilator responses to Mg<sup>2+</sup>, whereas <i>L</i>-NMMA inhibited Mg<sup>2+</sup> responses (area under the dose-response curve) by 43 ± 6% (p = 0.0003 by repeated-measures ANOVA). Therefore the <i>L</i>-arg/NO pathway is responsible, in part, for the vasodilator action of Mg<sup>2+</sup> in human forearm resistance vasculature.
Systemic and Portal Hemodynamic Response to Propranolol in Patients with Portal Hypertension Due to Hepatitis C Virus
Authors: Koshy Abraham , Al-Nakib Basil , Al-Mufti Siham , Hasan Fuad 
Published: April 2003

<b>Objective:</b> Propranolol, a β-adrenergic blocker, has been reported to reduce portal pressure in patients with alcoholic cirrhosis and thereby might be useful in the prophylaxis of variceal bleeding. Since it is not known if the response of patients with portal hypertension due to hepatitis C virus is similar, systemic and portal hemodynamic response to propranolol was evaluated in 10 patients with portal hypertension and hepatitis C virus infection. <b>Methods:</b> Patients were studied before the intravenous infusion of 0.15 mg/kg propranolol, and 30 min after the infusion. <b>Results:</b> Propranolol induced highly significant systemic hemodynamic effects, reducing heart rate from 65 ± 6 to 57 ± 5 (p < 0.0001) and cardiac output from 6.7 ± 1.6 to 5.0 ± 1.1 (liters/min, p < 0.0005). The effect on the pulmonary circulation was a mild increase in diastolic pulmonary artery pressure. Propranolol induced a mild and insignificant decrease in wedged hepatic vein pressure (WHVP), from 32 ± 6 to 29 ± 5 mm Hg, and hepatic venous pressure gradient from 18 ± 3 to 16 ± 5 mm Hg (p > 0.05). Decrease of WHVP of more than 5 mm Hg occurred only in 3 out of 10 patients. <b>Conclusion:</b> It is suggested that propranolol may be useful only in some patients with portal hypertension associated with hepatitis C virus infection.
Comparative Study of Meloxicam and Indomethacin on Ovine Ureteral Motility
Authors: Yousif Mariam H. , Thulesius Olav 
Published: April 2003

<b>Objective:</b> To test the potentially toxic urinary tract effects of indomethacin in comparison with a novel COX-2 inhibitor, meloxicam. <b>Method:</b> In vitro experiments were performed using isolated ring segments of sheep ureter mounted in organ-baths. Changes in isometric tension and frequency of rhythmic contractions were assessed in control and lipopolysaccharide (LPS)-treated preparations prior to and after administration of the tested drugs. <b>Results:</b> Sheep ureteral rings displayed reproducible spontaneous rhythmic contractions which were abolished by indomethacin (10<sup>–6</sup> <i>M</i>) and not by meloxicam (10<sup>–6</sup> <i>M</i>) under control conditions. However, in LPS-treated preparations, to induce COX-2, meloxicam produced a slight inhibitory action. <b>Conclusion:</b> Indomethacin blocks normal motility through inhibition of COX-1, while meloxicam does not interfere with ureteral peristalsis. Meloxicam only exerts a slight inhibition in inflammation-induced preparations due to the specific action as an inhibitor of COX-2. Further studies are needed to evaluate and compare the effects of meloxicam and indomethacin from other measures of effects of COX-1 and COX-2.
Role of Human Lymphocytes Bearing αβ and γδ T-Cell Receptor in Malaria Infection
Authors: Iqbal Jamshaid , Robina J. 
Published: April 2003

<i>Objective:</i> To investigate the role of γδ T cells in the regulation of immune response in Plasmodium falciparum infection. <i>Methods:</i> γδ and αβ T cells were purified from peripheral mononuclear blood cells (PMBC) by positive selection method using monoclonal antibodies. The PMBC were obtained from normal healthy donors. The role of various T cell subsets was investigated by observing their capacity to inhibit the growth of P. falciparum parasites. <i>Results:</i> By positive selection using monoclonal antibodies we were able to obtain a relatively pure fraction (>95%) of γδ T cells from PMBC. The parasite growth inhibitory capacity of activated γδ T cells ranged between 6 and 55%, however, activated αβ T cells failed to inhibit the growth. It was also observed that the inhibitory capacity of γδ T cells was dose-dependent and required physical contact with the organism. <i>Conclusion:</i> Activated γδ T cells have the capacity to inhibit the growth of P. falciparum parasites and thus may act as a first line of defense in controlling the blood stage infection. The significance of γδ T cells in influencing various bacterial infections is discussed.
Rate of and Risk Factors Associated with Retinopathy of Prematurity: A Prospective Study from Kuwait
Authors: Al-Essa Mazen , Azad R.V. , Rashwan Nabil 
Published: April 2003

<i>Objective:</i> To determine the rate of retinopathy of prematurity (ROP) among a population of preterm infants in Kuwait, and to review the risk factors associated with the disease. <i>Methodology:</i> A prospective cohort study of all preterm infants of less than 2,000 g birth weight and/or 36 weeks gestational age who were screened for ROP during 1995 at the neonatal unit of the Maternity Hospital in Kuwait. The rate of and some of the possible risk factors associated with the disease were determined. <i>Results:</i> A total of 130 babies were screened of which 59 (45.4%) developed some stage of ROP. The frequency of blindness was 3 (2.3%). Low birth weight, oxygen therapy, patent ductus arteriosus, intraventricular hemorrhage and blood transfusion were the risk factors found to be associated with the disease. However, with logistic regression analysis, only low birth weight and oxygen were independently associated with ROP. <i>Conclusion:</i> The rate of ROP in our unit is not different from that of the other centers, and low birth weight and oxygen therapy are the main risk factors associated with the disease.
The Introduction of Laparoscopic Appendectomy in a Teaching Hospital
Authors: Khoursheed M. , Sobhi W. , Al-Sharaf K. , Aman S. , Behbehani A. , Dashti H. 
Published: April 2003

<i>Objectives:</i> A retrospective study of laparoscopic appendectomy (LA) versus open appendectomy (OA) was performed on patients with suspected acute appendicitis. Patients were selected for OA or LA according to the clinical evaluation, and preference of the surgeon. <i>Methods:</i> Over a 2-year period 180 patients were included, of whom 94 patients underwent OA, and 86 patients underwent LA. <i>Results:</i> LA was successfully completed in 76 patients (88.3%). The mean hospital stay in OA was 3.2 days versus 2.7 days in LA. The mean operative time was shorter in OA than in LA (51.6 versus 59.8 min). There was no significant difference in convalescence between both the groups, however, there was a tendency towards less narcotic requirement among the LA group. Postoperative complications in patients who underwent OA included: chest infection (3 patients), wound infection (4 patients), thrombophlebitis (1 patient). Complications after LA included: pelvic collection (1 patient), chest infection (1 patient), ileus (1 patient). There was no wound infection in the LA group. There was no death in either groups. <i>Conclusion:</i> LA is a safe procedure comparable to OA, however, it requires skills in laparoscopy and prospective randomized trials are needed to confirm its advantages over conventional appendectomy.
Changes in Acidic Amino Acid Efflux from Rat Brain with Maturation
Authors: Al-Sarraf Hameed 
Published: April 2003

<i>Objective:</i> Our previous studies have shown a greater uptake of acidic amino acids from the blood into the brain of neonatal when compared to that of adult rats. The aim of this study is to investigate whether a developmental change exists in the brain to blood efflux of this group of amino acids. <i>Methods:</i> The whole brain was perfused in situ with Ringer’s solution containing <sup>14</sup>C-aspartate or <sup>14</sup>C-glutamate for 10 min. The perfusion was then continued with <sup>14</sup>C-free perfusate for a further 20 min and samples of jugular venous outflow were taken at 30-second intervals. The amount of radioactivity (in ln dpm) in each sample was then plotted against the sampling time, and the half-time (t<sub>½</sub>) for <sup>14</sup>C-efflux was calculated. <i>Results:</i> Paper chromatography of the outflow samples revealed that more than 91% of the <sup>14</sup>C-labelled acidic amino acid present in the effluent samples for up to 30 min of perfusion was chemically intact. The t<sub>½</sub> for aspartate efflux in neonatal rats was 16.16 ± 0.76 min which was significantly slower (p < 0.05) than that for the adults, 10.06 ± 0.46 min (means ± SEM, n = 3 and 4). The t<sub>½</sub> for glutamate efflux was also small in the adult brain where it was 50% the value seen in the neonates. <i>Conclusion:</i> The above results indicate that the systems involved in the efflux of acidic amino acids out of the brain favour retention and increased levels of this group of amino acids in the developing brain.
Attitudes of General Practitioners and Pediatricians to Management of Acute Pyelonephritis in Children
Authors: Al-Eisa A. , Al-Mosawi M. , Gupta R. , D’Souza T.M. , Sharma P.N. 
Published: April 2003

<i>Objective:</i> To study the attitudes of different groups of physicians toward management of acute pyelonephritis in children and the impact of such attitudes on the long-term sequelae of this problem. <i>Materials and Methods:</i> A questionnaire, describing a case history of a child with acute pyelonephritis, was distributed to general practitioners working in 12 primary health care centers and pediatricians working in the pediatric departments of the 6 main hospitals in Kuwait. The responses of the two groups were analyzed regarding their views toward hospitalization of the child, investigations requested, the choice of antibiotics, its route of administration, duration of treatment and the need for long-term follow-up. <i>Results:</i> A total of 83 general practitioners (group A) and 65 hospital pediatricians (group B) responded to the questionnaire. Hospitalization of the child was thought to be essential by 19% of group A compared to 89% of group B (p < 0.0001). Only 25% of group A decided to fully investigate the child compared to 58% of group B (p < 0.0001). Treatment with a single antibiotic was preferred by 72% of group A compared to 80% of group B. Only 6% of group A, compared to 74% of group B favored parenteral antibiotics (p < 0.0001). A 7-day course of treatment was considered by 70% of group A and 52% of group B (p < 0.02). Long-term follow-up was thought to be necessary by 63% of group A and 75% of group B. <i>Conclusion:</i> A marked discrepancy existed in the management of acute pyelonephritis between the two groups, indicating the need of a unified policy. Children presenting with such a problem can be managed by general practitioners on an outpatient basis provided that proper antibiotics are used, compliance is ensured and appropriate investigations and follow-up are provided.
Cytokines and Cognitive Behavior
Authors: Gibertini Michael 
Published: April 2003

Proinflammatory cytokines help orchestrate host responses to infection and are a major communication link between peripheral immunity and the CNS. These cytokines initiate a number of CNS events that culminate in both physiological and behavioral changes. Peripheral IL-1β also affects information processing. A series of experiments examining the effect of learning intensity, motivation, and cytokine dose are reported. Using a well-established Morris water maze (MWM) system with female C57BL/6 mice, we report that (1) IL-1 (100 ng/mouse, i.p.) has no effect on MWM learning when mice are subjected to a spaced as opposed to a massed learning protocol; (2) water temperature is critical to the IL-1 effect on learning insofar as IL-1 interferes with learning in a warm-water but not a cold-water maze, and (3) higher doses (1,000 ng/mouse, i.p.) of IL-1 in experimental systems known to produce the IL-1-induced learning deficit with lower doses (100 ng/mouse, i.p.) show consistent facilitation, not impairment, of learning.
Urocortin and Inflammation: Confounding Effects of Hypotension on Measures of Inflammation
Authors: Torpy David J. , Webster Elizabeth L. , Zachman E. Keith , Aguilera Greti , Chrousos George P. 
Published: April 2003

Urocortin, a newly isolated 40-amino-acid mammalian peptide homologous to corticotropin-releasing hormone (CRH), activates both CRH type 1 and 2 receptors, but may be an endogenous ligand for CRH receptor type 2. Urocortin given systemically inhibited heat-induced paw edema in the rat, and was therefore ascribed anti-inflammatory properties. We examined the effects of urocortin in the carrageenin-induced subcutaneous inflammation model. Rats were treated with urocortin 200 (n = 6) or 20 nmol/kg (n = 6); inflammatory exudates were reduced by approximately 30% compared to controls (n = 7) at both doses. However, since subcutaneous urocortin has been shown to reduce arterial blood pressure, we tested the hypothesis that its antiedema and antiextravasatory effects were secondary to arterial hypotension. Therefore, we examined the parallel effects of urocortin- and hydralazine-induced hypotension on acute inflammation induced by carrageenin in the rat. Rats were treated with subcutaneous carrageenin and control injections (n = 8), carrageenin and urocortin (20 nmol/kg, n = 9), or carrageenin and intraperitoneal hydralazine (10 mg/kg, n = 8). Mean arterial blood pressure was measured hourly for 7 h in 12 animals, and after 2 h, the nadir of treatment, in a further 13 animals. Rats were then sacrificed, and the inflammatory exudate volume and leukocyte count were measured. Mean exudate volumes were reduced from 4.8 ± 0.5 ml (controls) to 2.4 ± 0.3 ml (p = 0.004) and 2.9 ± 0.6 ml (p = 0.007) in urocortin- and hydralazine-treated animals, respectively. Urocortin and hydralazine both produced a significant fall in blood pressure compared to controls, with mean arterial pressure 2 h after carrageenin injection falling to 51.0 ± 4.1 (p < 0.001) and 34.6 ± 4.6 (p < 0.001) vs. 92.9 ± 3.7 mm Hg in controls, respectively. A significant positive correlation was noted between blood pressure and inflammatory exudate volume (r = 0.52, p = 0.007). As both hydralazine and urocortin lowered blood pressure and inflammatory exudate volume, we suggest that the anti-inflammatory effects of urocortin and related neuropeptides may be nonspecific, acting through hypotension rather than through direct anti-inflammatory mechanisms. The use of inflammatory models which rely on extravasation may be inappropriate for the study of substances that produce hypotension.