bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary pulmonary hypertension in families with hereditary haemorrhagic telangiectasia
Authors: Abdalla S.A. , Gallione C.J. , Barst R.J. , Horn E.M. , Knowles J.A. , Marchuk D.A. , Letarte M. , Morse J.H. 
Published: February 2004

Primary pulmonary hypertension (PPH) is a rare but severe and progressive disease characterised by obstructive lesions of small pulmonary arteries. Patients with PPH often have mutations in the bone morphogenetic protein receptor type II (BMPR2) gene, whereas some carry mutations in the activin receptor-like kinase 1 (ALK‐1) gene, generally associated with hereditary haemorrhagic telangiectasia (HHT) type 2, a vascular dysplasia affecting multiple organs. The aim of this study was to determine whether members of families with PPH and confirmed or probable HHT hadALK‐1mutations.ALK‐1andBMPR2mutation analysis was performed on deoxyribonucleic acid from affected members of four families with PPH and confirmed or suspected HHT.ALK‐1mutations were identified in all four families and three novel mutations found in exon 10, leading to truncated proteins. In the fourth family, a missense mutation, previously reported in four independent HHT families, was detected in exon 8. Analysis of theBMPR2gene revealed no exonic mutations in the probands with both PPH and HHT.The present data bring to 10 the number of reported families with primary pulmonary hypertension and hereditary haemorrhagic telangiectasia type 2, representing 16% of the 61 families with known activin receptor-like kinase 1 mutations. Such mutations might predispose to primary pulmonary hypertension, and specialists should be aware of the potential link between these two disorders.
Response of pulmonary tuberculomas to anti-tuberculous treatment
Authors: Lee H.S. , Oh J.Y. , Lee J.H. , Yoo C.G. , Lee C‐T. , Kim Y.W. , Han S.K. , Shim Y‐S. , Yim J-J. 
Published: February 2004

Pulmonary tuberculomas are well-circumscribed masses caused byMycobacterium tuberculosis. However, the response of tuberculomas to anti-tuberculous (TB) treatment has not been well defined as yet.The response of pulmonary tuberculomas to anti‐TB treatment was retrospectively reviewed in 45 patients diagnosed between January 1997 and December 2001. The areas of pulmonary tuberculomas were estimated by calculating products of the longest and their perpendicular short diameters on chest radiographs. The response to anti‐TB treatment was categorised as “decreased” (>25% reduction in areaversusits initial area), “increased” (>25% increase) and “no change” (the remainder).The mean of treatment duration was 11.5±3.6 months. Three months after treatment, 18 patients (40.0%) were categorised as decreased, 25 (55.6%) as no change and two (4.4%) as increased. Twelve months after treatment, out of 42 patients available for chest radiographs, 32 patients (76.2%) were categorised as decreased, nine (21.4%) as no change and one patient (2.4%) as increased. At the last follow-up (mean follow-up 27.0±10.2 months), 37 patients (82.2%) were categorised as decreased.The majority of pulmonary tuberculomas were decreased by anti-tuberculosis treatment during and even after treatment, although a transient enlargement during the early period of treatment was observed infrequently.
Strategies to increase limited donor resources
Authors: de Perrot M. , Weder W. , Patterson G.A. , Keshavjee S. 
Published: February 2004

A number of strategies have been advocated to increase the number of lung donors including: 1) improvement in donor resuscitation; 2) better methods of lung preservation; 3) extension of the lung donor selection criteria; 4) development of a living-related lung donor programme; and 5) utilisation of nonheart beating donors.Other strategies such as the split-lung technique and techniques of lung reduction to accommodate large lungs into a small-size recipient have also been used successfully. In this article, each of these strategies have been reviewed and some recommendations are suggested based on the authors' own experience and that of the literature.
Effects of obesity upon genioglossus structure and function in obstructive sleep apnoea
Authors: Carrera M. , Barbé F. , Sauleda J. , Tomás M. , Gómez C. , Santos C. , Agustí A.G.N. 
Published: February 2004

Obesity is a common feature of the obstructive sleep apnoea syndrome. It can influence the structure and function of skeletal muscles. However, its effects upon the upper airway muscles have not been explored directly.This study assessed the structure and function of the genioglossus in patients with obstructive sleep apnoea syndrome and in healthy subjects (with and without obesity, defined by a body mass index >30 kg·m−2). Further, to investigate the effects of continuous positive airway pressure (CPAP) treatment, patients with obstructive sleep apnoea syndrome after at least 1 yr under CPAP were also studied.The study found that obese and nonobese patients showed differentin vitrogeniglossus endurance properties. In obese patients, geniglossus endurance was indistinguishable from normal while, nonobese patients, at diagnosis, showed increased genioglossus fatigability; this was not observed in patients treated with CPAP. By contrast, patients with obstructive sleep apnoea syndrome showed at diagnosis a higher percentage of type II fibres than controls and patients under CPAP treatment independently of obesity. This difference is mainly due to a predominance of subtype IIb fibre. This difference was not observed in the group of patients treated with CPAP. Genioglossus twitch force was normal in all patients.These results suggest that different pathogenic mechanisms may underlie the development of obstructive sleep apnoea syndrome in obese and nonobese patients. This observation may have potential clinical implications.
Interactive effects of the ACE DD polymorphism with the NOS III homozygous G849T (Glu298→Asp) variant in determining endothelial function in coronary artery disease
Authors: Schmidt Michael A , Chakrabarti Anjan K , Kehrer Chris , Pfeninnger Dana , Brook Robert D , Kaciroti Niko , Duvernoy Claire , Killeen Anthony A , Rajagopalan Sanjay 
Published: February 2004

The products of nitric oxide synthase (NOS) and angiotensin-converting enzyme (ACE) play a critical role in determining vessel wall structure and function. Polymorphisms in both genes have been independently demonstrated to influence propensity to cardiovascular events. The purpose of this study was to determine the influence of the homozygous G849T(Glu298 Asp) polymorphism in NOS III on peripheral conduit artery endothelial function and to elucidate the modifier role, if any, of a common ACE polymorphism. Three hundred and ninety-seven consecutive subjects presenting to the cardiac catheterization laboratory of the University of Michigan over a period of 18 months were recruited. DNA was extracted and polymerase chain reaction (PCR) analysis for ACE and NOS polymorphisms performed. Patients with homozygosity for G849T at both loci (TT) who belong to DD and II ACE genotype (groups 1 and 2) and those who are negative for this polymorphism (GG) and belong to either DD or II genotype (groups 3 and 4) were identified. The four groups then underwent determination of conduit endothelial function. Heterozygosity of Glu298-Asp or the ID variant of the ACE were not studied. Median FMD value in the TT-DD group was 0.20 (-3.17, 2.01) compared with 2.23% (-0.29, 4.17) in the GG-II group. Median values in the TT-II and the GG-DD groups were 3.04 (-1.16, 6.61) and 2.46% (-1.83, 6.52) respectively. These values were not statistically significant (p > 0.05 by one-way ANOVA). Median nitroglycerin-mediated dilation in the four groups did not differ between the four groups (p = NS by ANOVA). Atherosclerosis burdens as assessed by angiography were not different across the groups. In conclusion, the homozygous NOS III variant (GG) status does not seem to interact additively with the ACE homozygous DD genotype in determining flow-mediated vasodilation in individuals with established atherosclerosis and pre-existent endothelial dysfunction.
Neovascularization in intimal hyperplasia is associated with vein graft failure after coronary artery bypass surgery
Authors: Baklanov Dmitri V , Peters Kevin G , Seidel Amy L , Taylor Doris A , Annex Brian H 
Published: February 2004

Vein graft atherosclerosis is the major limitation of arterial bypass surgery. This study was carried out to determine if the number of microvessels per area of intimal hyperplasia correlated with vein graft disease. Vein grafts (n=24, graft age range 2-19 years) were taken from 22 patients undergoing redo-coronary artery bypass surgery. Mean age of the patients was 68 6 9 years; 92% were males. Samples were divided into three groups (n=8 per group): in group I segments were from grafts without angiographic or histologic disease, in groups II and III segments were from grafts with significant angiographic stenosis, without (group II) and with (group III) atheroma. Intimal hyperplasia was identified by Masson staining, morphometric analysis was performed with NIH image analysis software. Microvessels in the intimal hyper-plasia were identified using immunohistochemical techniques. significance was determined by single-factor ANOVA p, 0.05. The mean area of intimal hyperplasia was similar in groups I and II at 1.06 6 0.25mm2 and 0.97 6 0.37mm2, respectively. The extent of intimal hyperplasia was significantly greater in group III, 1.70 6 0.62mm2 (p < 0.01). In group I, the microvessel count in the intimal hyperplasia was 5.62 6 3.89 vessels/mm2, while in group III it was 15.26 6 3.66/mm2 (p < 0.01 versus group I). Interestingly the number of microvessels per area of intimal hyperplasia in group II was similar to that in group III). In this study, the extent of neovascularization in intimal hyperplasia correlated with stenoses in human vein grafts. Strategies designed to limit neovascularization in intimal hyperplasia may lead to novel therapies to prevent vein graft failure.
Effect of MX-68 on airway inflammation and hyperresponsiveness in mice and guinea-pigs
Authors: Nagao Koichi , Akabane Hirotomo , Masuda Taisei , Komal Masato , Tanaka Hiroyuki , Nagai Hiroichi 
Published: February 2004

Abstract
MX-68 is a newly synthesized antifolate, which is a derivative of methotrexate (MTX). In this paper, the effect of MX-68 on allergic airway responses in mice and guinea-pigs was studied. In the first experiment, antigen-induced airway inflammation and airway hyperresponsiveness (AHR) to acetylcholine in mice were examined and compared with the effects of classical antifolate methotrexate and prednisolone. Mice were sensitized with ovalbumin as an antigen and challenged with ovalbumin inhalation three times. After the last inhalation, AHR and airway inflammation were observed. An increase in Th2 cytokines (IL-4 and IL-5) and a decrease in a Th1 cytokine (IFN-γ) in the bronchoalveolar lavage fluid (BALF), as well as an elevation of the immunoglobulin level in serum, were observed in sensitized mice. Oral administration of MX-68 had no effect on changes of body weight, but prednisolone reduced body weight during the experiment. The antigen-induced AHR and increases in the number of eosinophils and lymphocytes in BALF were significantly inhibited by MX-68. MX-68 interfered with the elevation of IL-4 and IL-5 levels in BALF, but had no effect on the decrease in IFN-γ. Moreover, MX-68 significantly inhibited the elevation of serum IgE and IgG levels. In the guinea-pig model for bronchial asthma, biphasic increases in airway resistance (immediate asthmatic response, IAR, and late asthmatic response, LAR), as well as accumulated inflammatory cells in BALF, were observed after repeated antigen challenge. These asthmatic responses and inflammatory signs were significantly decreased by administration of MX-68. These results suggest that MX-68 obviously has an anti-inflammatory effect in an animal model of asthma and would be useful clinically for the treatment of bronchial asthma.
Pharmacological characterization and identification of EP3 prostanoid receptor binding sites in hamster uterus homogenates
Authors: Sharif N A , Xu S X 
Published: February 2004

Abstract
The pharmacological properties of [3H]-prostaglandin E2 ([3H]-PGE2) binding to washed homogenates of hamster uterus were determined. Scatchard analysis of competition data yielded dissociation constants (Kds) of 30.9 + 5.6 nm (n = 3) and apparent receptor density (Bmax) of 25.25 + 1.89 pmol g−1 wet weight tissue (74 + 8% specific binding). Competition studies yielded the following affinity parameters (Ki) for various prostanoids: GR63799X = 13 + 4 nm; PGE2 = 17 + 3 nm; sulprostone = 64 + 5 nm; enprostil = 67 + 3 nm; misoprostol = 124 + 15 nm; cloprostenol = 187 + 33 nm; carba-prostacyclin = 260 + 167 nm; iloprost = 555 + 162 nm; PGF2α = 767 + 73 nm; PGD2 &gt; 3560 nm; fluprostenol = 11790 + 2776 nm; RS93520 = 21 558 + 14228 nm. These data closely matched the pharmacological profile of previously described EP3 receptors such as in bovine corpus luteum (BCLM) and the cloned mammalian EP3 receptors. The high correlation between the current hamster uterus pharmacology data vs the EP3 receptor binding in BCLM (r = 0.94; P &lt; 0.0001), vs cloned human EP3 receptor (r = 0.94, P &lt; 0.0001), vs the cloned mouse EP3 receptor binding (r = 0.78; P &lt; 0.002), vs cloned rat EP3 receptor (r = 0.9, P &lt; 0.0004), and vs EP3 receptor-mediated functional responses (r = 0.72, P &lt; 0.02) substantiated the conclusion that the hamster uterus contains EP3 receptor binding sites.
The effect of repeat dosing with cimetidine on the pharmacokinetics of intravenous granisetron in healthy volunteers
Authors: Youlten Lawrence 
Published: February 2004

Abstract
The primary route of elimination of granisetron is by oxidative hepatic metabolism, thus its pharmacokinetic profile may be altered by co-administration of other drugs that inhibit or induce hepatic drug metabolizing enzymes. This open-label study investigated the effect of inhibition of cimetidine, a potent inhibitor of CYP1A2, CYP2D6 and CYP3A4, on the pharmacokinetic profile of intravenous granisetron in healthy male volunteers. Subjects (n = 12; 18–60 years) received granisetron (40 μg kg−1) infused over 3 min, six days before and on the eighth day of dosing with cimetidine (200 mg, four times a day). Blood samples were taken for pharmacokinetic analysis at intervals over 48 h following the administration of each dose of granisetron. Clinical chemistry, haematology and urinalysis were performed before, and 24 h after, each infusion. Electrocardiogram (ECG), resting blood pressure (BP) and pulse were monitored. There were no significant changes in the ECG, lead II trace or ECG time intervals, pulse or blood pressure on each study day. Minor falls in pulse rate and BP (likely to be related to recumbent posture) were seen during both granisetron dosing days, lasting 2 h after each infusion. No significant changes were apparent in the clinical chemistry, haematology or urinalysis measurements following granisetron dosing. No pharmacokinetic parameters measured after cimetidine administration were significantly different from those taken before. Adverse events were mild-to-moderate in severity and were similar to those reported in other studies with granisetron. The pharmacokinetics of granisetron, when administered as a single dose, appeared to be unaltered by cimetidine, an inhibitor of multiple hepatic enzymes (CYP1A2, CYP2D6 and CYP3A4). Granisetron was equally well tolerated before and after repeated dosing with cimetidine.
Studies on 1-arylpiperazine derivatives with affinity for rat 5-HT7 and 5-HT1A receptors
Authors: Leopoldo Marcello , Berardi Francesco , Colabufo Nicola A , Contino Marialessandra , Lacivita Enza , Perrone Roberto , Tortorella Vincenzo 
Published: February 2004

Abstract
Several 1-aryl-4-(2-arylethyl)piperazine derivatives were synthesized and tested in-vitro for their binding affinity for 5-HT7 and 5-HT1A receptors. These compounds displayed 5-HT7 receptor affinity ranging between Ki = 474 nm and Ki = 8.2 nm, besides high affinity for the 5-HT1A receptor. Intrinsic activity of the most potent compounds was assessed. 4-[2-(3-Methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine (16) and 1-(1,2-benzisoxazol-3-yl)-4-[2-(3-methoxyphenyl)ethyl]piperazine (20) (Ki = 24.5 and 8.2 nm, respectively) behaved as partial agonist and full agonist, respectively, when tested for 5-HT7 receptor-mediated relaxation of substance P-induced guinea-pig ileum contraction.
Biodistribution and safety studies of hDel-1 plasmid-based gene therapy in mouse and rabbit models
Authors: Quezada A , French M , Perrard J , Durland R , Coleman M , Larson J , Ponce R 
Published: February 2004

Abstract
A plasmid encoding the human developmentally regulated endothelial locus-1 (hDel-1) protein formulated with poloxamer 188 is a potential gene therapy for peripheral arterial disease in man. As a prelude to clinical trials, the biodistribution and safety of this therapy were evaluated after intramuscular and intravenous administration in mice and rabbits. In mice, plasmid DNA persisted at the intramuscular injection site for at least 28 days, but was barely detectable in distal tissues by 24 h and essentially cleared by 28 days. By 24 h after intravenous administration, plasmid DNA was readily detected in blood, muscle, and lungs but sporadically and at low levels in other tissues. At 28 days, plasmid DNA was readily detectable only at the intravenous injection site (tail) after low- and high-dose administration, and sporadically in blood and muscle after high-dose administration. In rabbits, the highest intramuscular (4.2 mg kg−1) or intravenous (3.7 mg kg−1) dose caused no deaths; no treatment-related clinical signs; no changes in body weight, clinical pathology parameters, ophthalmology, ECG, or histopathology; and no detectable increase in antinuclear antibodies by 28 days. The results supported testing of hDel-1 plasmid-based gene therapy in phase I clinical trials.
The effects of imidazoline agents on the aggregation of human platelets
Authors: Pinthong Darawan , Songsermsakul Piyada , Rattanachamnong Piyanee , Kendall David A 
Published: February 2004

Abstract
Clonidine (2-[(2, 6-dichlorophenyl)amino]-2-imidazoline), an imidazoline α2-adrenoceptor agonist, is known to exert complex effects on human platelet aggregation distinct from those of the catecholamines, which are non-imidazoline α-adrenoceptor agonists. This study has investigated the aggregatory/anti-aggregatory effects of various imidazolines on human platelets. Blood samples were taken from normal volunteers and platelet aggregation was assessed by a turbidimetric method using a Chronolog aggregometer. Noradrenaline (2 μm) and adenosine diphosphate (1 μm) were used as aggregating agents. The results showed that, with the exception of moxonidine, all of the imidazoline agents used (with or without α2-adrenoceptor activity) were able to inhibit noradrenaline-induced platelet aggregation. Compared with the non-imidazoline α2-adrenergic antagonist, yohimbine, the rank order of potency was: efaroxan (IC50 = 3.07 times 10−8 m) &gt; idazoxan (IC50 = 1.74 times 10−7 m) &gt; tolazoline (IC50 = 3.90 times 10−7 m) &gt; clonidine (IC50 = 1.49 times 10−6 m) ≅ antazoline (IC50 = 1.77 times 10−6 m) &gt; yohimbine (IC50 = 3.19 times 10−6 m) &gt; rilmenidine (IC50 = 1.27 times 10−5 m) &gt; moxonidine (IC50 &gt; 10−4 m). Clonidine-displacing substance (CDS), a putative endogenous ligand at imidazoline receptors, was found to inhibit noradrenaline-induced platelet aggregation. Harmane, norharmane and agmatine, putative candidates for the active principle of CDS, had no effect on noradrenaline-induced platelet aggregation. In contrast to noradrenaline-induced aggregation, ADP-induced platelet aggregation was neither potentiated nor inhibited by the imidazoline agents, with the exceptions of clonidine and moxonidine. In conclusion, most imidazoline agents effectively inhibit noradrenaline-induced human platelet aggregation. The lack of effect of moxonidine and the proposed endogenous ligands suggested this effect was mediated by an ‘atypical’ non-adrenoceptor imidazoline-binding site. The results indicated an anti-aggregatory role of imidazoline compounds on noradrenaline-induced human platelet aggregation. In addition, CDS might be an endogenous modulator that prevented platelet hyper-reactivity to catecholamine stimulation.
(–)-Epicatechin 3-O-gallate ameliorates the damages related to peroxynitrite production by mechanisms distinct from those of other free radical inhibitors
Authors: Yokozawa Takako , Rhyu Dong Young , Cho Eun Ju 
Published: February 2004

Abstract
This study was carried out to elucidate whether the protective activity of (–)-epicatechin 3-O-gallate (ECg) against excessive peroxynitrite (ONOO−) production, is distinct from the activity of several well-known free radical inhibitors, the ONOO− inhibitors ebselen and uric acid, the superoxide anion (O2−) scavenger copper zinc superoxide dismutase (CuZnSOD) and the selective inducible nitric oxide synthase inhibitor l-N6-(1-iminoethyl)lysine hydrochloride (l-NIL). To generate ONOO−, male Wistar rats (n = 6/group) were subjected to ischaemia–reperfusion process together with lipopolysaccharide (LPS) injection. Although ECg did not scavenge the ONOO− precursors nitric oxide (NO) and O2−, it reduced the 3-nitrotyrosine level, a property similar to that of uric acid, but distinct from l-NIL. In addition, the elevation in myeloperoxidase activity was reversed by the administration of ECg, uric acid and SOD, but not by that of l-NIL. Furthermore, ECg was the more potent scavenger of the ONOO− decomposition product, the hydroxyl radical (·OH), than any other free radical inhibitor tested. The LPS plus ischaemia–reperfusion process resulted in renal dysfunction, estimated by measuring the parameters of renal function – serum urea nitrogen and creatinine levels. However, administration of ECg ameliorated renal dysfunction more than that of the other free radical inhibitors. Moreover, ECg reduced the excessive uric acid level, while the others did not, suggesting a property of ECg distinct from the others. Furthermore, proteinuria, which was demonstrated by the low- and high-molecular weight (LMW and HMW) protein bands of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis pattern, caused by LPS plus ischaemia–reperfusion, was attenuated by administration of ECg and l-NIL, after which the HMW band intensities decreased and LMW protein bands were absent. This study indicates that, in an in-vivo model of ONOO− generation, ECg, l-NIL and uric acid exert stronger protective activity against ONOO−-induced oxidative damage than SOD and ebselen, and that the mechanism whereby ECg protects against ONOO− is distinct from that of l-NIL or uric acid.