[KK and KK-Ay strains of mice].
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Animals↗
Biomedical subjects
M Nishimura
Publications and source records attributed to M Nishimura.
[Sleep apnea syndrome in Japan: analysis of pathophysiology and nasal continuous positive airway pressure effectiveness].
Forty eight Japanese sleep apnea syndrome (SAS) patients, whose apnea-hypopnea index (AHI) was more than 30 times/hr. from 5 university hospitals (46 males, 2 females) were enrolled in this study to analyze the characteristics of the disorder and the effectiveness of nasal continuous positive airway pressure (nCPAP) effectiveness. Although the severity of excessive daytime sleepiness (EDS), depressive state, and ventricular premature beats caused by SAS seemed milder in Japanese than reported Caucasian patients, the prevalences of hypertension and glucose intolerance were quite high: 50 and 30% respectively. Treatment with nCPAP for 3 months was completed in 41 of 48 enrollees, a compliance rate of 85.4%, which was substantially higher than studies from Western countries. nCPAP treatment normalized about 50% of hypertensive patients and more than half of glucose intolerant patients. Moreover, EDS, driving ability, the severity of arrhythmia, and so forth were all improved with nCPAP. We, therefore, conclude that 1) SAS could differ between Japanese Caucasians in terms of clinical features resulting from SAS and 2) treatment with nCPAP is effective and should be considered as first-line treatment for patients with moderate to severe SAS, as reported in Western countries.
Adult↗
Immunohistochemical study of human advanced glycation end-products (AGE) and growth factors in cardiac tissues of patients on maintenance dialysis and with kidney transplantation.
Cardiovascular disease is one of the most common complications of dialysis and renal transplant patients, and high levels of AGE are present in end-stage renal failure. To address the potential involvement of AGE and growth factors in the pathophysiology of cardiovascular complications, we performed immunostaining using cardiac tissues from autopsy cases of patients on maintenance dialysis (10 cases), long-term surviving renal transplant patients with functioning grafts (8 cases), control subjects with normal renal function (7 cases) and non diabetic subjects with mild renal insufficiency (8 cases). We used two types of AGE-antibodies, 6D12 [monoclonal anti-AGE antibody, recognizing N epsilon-(carboxymethyl) lysine(CML)-modified AGE] (oxidative AGE) and non-CML-PA [polyclonal, not recognizing CML], and antibodies against PDGFs, PDGF receptors and TGF beta. Positive 6D12 staining was observed in the coronary arterial walls and in macrophages. The accumulation of 6D12-reactive AGE in the coronary arterial walls of maintenance dialysis patients was significantly greater than that of control subjects (p < 0.05). Renal transplantation significantly reduced this accumulation (p < 0.05). On the other hand non-CML-PA mainly detected AGE in intracardiac arterioles and neural tissues. There was little difference in the accumulation of non-CML-AGE among the four groups. PDGFs and PDGF receptors were mainly detected in vascular endothelial cells and infiltrating cells of cardiac tissues of renal transplant patients, but not of maintenance dialysis patients. TGF beta was not detected in cardiovascular tissue of transplant patients. Our results indicated that the accumulation of oxidative AGE (CML-AGE) in the cardiac vascular tissue is one of the factors for cardiovascular complications of maintenance dialysis patients, and also that renal transplantation has a reducing effect on CML-AGE accumulation. PDGFs may be involved in the cardiovascular complications after renal transplantation.
Adult↗
Differential effect of azidothymidine on resting and activated cells: potentiality of this drug for treatment of post-transfusion graft-versus-host disease.
The key factor for the treatment of post-transfusion graft-versus-host disease (PT-GVHD) is the successful eradication of donor-derived cytotoxic T cells (CTLs) which are thought to be a main cause of the disease, with no effects on either peripheral blood mononuclear cells (PBMCs) or tissues of the recipient. In this study, we examined the effect of azidothymidine (AZT: Zidovudine) on resting PBMCs and cultured fibroblast cells which are assumed to be patient cells, and alloreactive CD8(+)-CTL clones which are imagined to be donor-derived activated CTLs, in vitro. We show here that AZT has no effect on resting PBMCs and cultured fibroblast cells, but greatly inhibited the growth of CTL clones.
Anti-HIV Agents↗
[Vascular endothelium-related factors and atherosclerosis/arteriosclerosis: serum hepatocyte growth factor as a possible indicator of vascular lesions].
To investigate the possible involvement of hepatocyte growth factor (HGF) with vascular lesions, we studied the relationship between serum HGF concentrations and the grades of retinal arteriosclerosis, coronary atherosclerosis proliferative changes in the retina of diabetic subjects, and activities of systemic vasculitis. Individuals with more advanced grades of retinal arteriosclerotic change showed higher serum HGF values (grade 0, 0.053 +/- 0.005 ng/ml ; grade 1, 0.144 +/- 0.022 ng/ml ; grade 2, 0.338 +/- 0.36 ng/ml ; grade 3, 0.526 +/- 0.051 ng/ml). The serum HGF concentration was increased in subjects with single- (0.200 +/- 0.012 ng/ml, double- (0.334 +/- 0.018 ng/ml) or triple- (0.379 +/- 0.022 ng/ml) vessel coronary heart diseases, compared with that in subjects with intact coronary arteries (0.112 +/- 0.008 ng/ml). Serum HGF in diabetes without retinopathy was lower than that in nondiabetic subjects (0.041 +/- 0.003 ng/ml vs 0.080 +/- 0.010 ng/ml, p < 0.05), but did not differ from that in other diabetic subjects with background retinopathy (0.058 +/- 0.007 ng/ml) or preproliferative retinopathy (0.048 +/- 0.010 ng/ml). Serum HGF was increased in patients with proliferative retinopathy without photocoagulation (0.213 +/- 0.025 ng/ml, p < 0.01), but not in those with photocoagulation (0.040 +/- 0.008 ng/ml). Serum HGF concentration was increased (p < 0.01) during the acute phase of Schönlein-Henoch purpura (0.31 +/- 0.15 ng/ml), a systemic vasculitis, but it returned to control levels during the remission phase (0.11 +/- 0.10 ng/ml). Increased serum HGF may be involved in the pathogenesis of arteriosclerosis/atherosclerosis, retinal neovascularization, or vasculitis, and measurement of serum HGF may be a useful test for predicting these vascular lesions.
Aged↗
Roles of brain angiotensin II and C-type natriuretic peptide in deoxycorticosterone acetate-salt hypertension in rats.
OBJECTIVE: To investigate the roles of brain angiotensin II and C-type natriuretic peptide (CNP) in the hypertensive mechanism of deoxycorticosterone acetate (DOCA)-salt hypertension. METHODS: We injected 50 microg/kg CV-11 974, an angiotensin II type-1 receptors antagonist, 30 nmol/kg CNP-22, or the vehicle (artificial cerebrospinal fluid) into the cerebral ventricle or intravenously 5 min before the intracerebroventricular infusion of 1.5 mol/I NaCl solution for 30 min into either male normotensive Wistar rats or DOCA-salt hypertensive rats anesthetized with urethane, and their arterial pressures and heart rates were continuously recorded. Blood (2 ml) was collected at the end of the infusion for the measurement of plasma concentration of arginine vasopressin. We infused 10 or 50 microg/kg per day CV-11 974, 10 or 50 nmol/kg per day CNP-22, or the vehicle (1 microl/h) into the cerebral ventricles of DOCA-salt hypertensive rats for 7 days by using osmotic minipumps, and measured their systolic arterial pressures, pulse rates, and urinary excretions of vasopressin. RESULTS: Intracerebroventricular pre-administrations of CV-11 974 and of CNP-22 inhibited increases in mean arterial pressure, heart rate, and plasma vasopressin concentration induced by intracerebroventricular infusion of 1.5 mol/l NaCl into normotensive rats; increases in hemodynamics and plasma level of vasopressin induced by intracerebroventricular infusion of 1.5 mol/l NaCl were suppressed by intracerebroventricular pre-injections of CV-11 974, but not of CNP-22, into DOCA-salt hypertensive rats. Continuous intracerebroventricular infusions of 50 microg/kg per day CV-11 974 attenuated hypertension in DOCA-salt treated rats, accompanied by a reduction in urinary excretion of vasopressin. Continuous intracerebroventricular infusions of 50 nmol/kg per day CNP-22, however, affected neither hypertension nor urinary excretion of vasopressin in DOCA-salt hypertensive rats. CONCLUSION: Brain angiotensin II could play a role in the pressor mechanism of DOCA-salt hypertension by increasing release of vasopressin via type 1 receptors. That brain CNP has an inhibitory effect on release of vasopressin in acute experiments indicates that the impairment of this inhibitory effect of brain CNP on secretion of vasopressin could be involved in the pathogenesis of DOCA-salt hypertension in rats.
Angiotensin II↗
[Usefulness of heart rate variability for evaluating cardiac autonomic nervous function].
To investigate the effect of gastric ulceration on cardiac autonomic nervous function, 24-hour ambulatory electrocardiograms were recorded in patients with artificial gastric ulcers caused by endoscopic treatment of gastric tumors. Their cardiac autonomic nervous activity was assessed by both time- and frequency-domain analyses of heart rate variability obtained from electrocardiogram recordings. The results were compared with those from patients who had undergone endoscopic treatment of esophageal varices or colorectal tumors, or gastrointestinal endoscopy alone. Parameters of time-domain analysis decreased significantly with the formation of gastric ulcers. Because parameters of frequency-domain analysis did not change in the group with gastric ulcers, this decrease in parameter of time-domain analysis suggests increased activity of cardiac sympathetic nervous system. There were no changes in the parameters of either time- or frequency-domain analysis in other groups. These results suggest that artificial gastric ulceration modifies cardiac sympathovagal balance, favoring cardiac sympathetic activity, while artificial esophageal and colon ulcers have no effect on cardiac autonomic nervous activity. Heart rate variability analysis is a useful method of evaluating possible implications between gastric ulceration and cardiac autonomic nervous function.
Aged↗
[Neovascularization and HGF: neovascularization in proliferative diabetic retinopathy and intraocular HGF].
Human hepatocyte growth factor (hHGF) has a strong angioneogenetic action. The present study was designed to investigate the possible involvement of hHGF in neovascularization in proliferative diabetic retinopathy by measuring vitreous hHGF concentration, and to examine the gene expression of hHGF in retinal Müller cells, which are presumed to play a role in proliferative diabetic retinopathy. Patients who had undergone pars plana vitrectomy were studied (33 diabetic patients with proliferative retinopathy and 20 nondiabetic subjects). The mean vitreous hHGF concentration was higher (p < 0.0001) in diabetic subjects with proliferative retinopathy (5.7 +/- 0.7 ng/ml) than in nondiabetic subjects (1.6 +/- 0.2 ng/ml). Furthermore, diabetic subjects with iris neovascularization, which is suggestive of advanced retinal ischemia, showed higher values of mean vitreous hHGF concentration than those without iris neovascularization (7.3 +/- 1.2 ng/ml [n = 14] vs. 4.5 +/- 0.7 ng/ml [n = 19], p < 0.01). Expression of hHGF gene was detected in cultured human Müller cells. Our results indicate that hHGF may be produced in the eye by retinal cells such as Müller cells and may play a role in neovascularization of proliferative diabetic retinopathy.
Diabetic Retinopathy↗
Potential usefulness of photochemotherapy using 8-methoxypsoralen in the treatment of posttransfusion graft-versus-host disease.
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Graft vs Host Disease↗
Sodium sensitivity and cardiovascular events in patients with essential hypertension.
BACKGROUND: In patients with sodium-sensitive hypertension, glomerular pressure is increased and microalbuminuria, a marker of glomerular hypertension, is a predictor of cardiovascular events. Similarly, the lack of a nocturnal decrease in blood pressure in these patients is also associated with an increased risk of cardiovascular events. We hypothesised that sodium sensitivity may be the common factor and carried out a retrospective study of cardiovascular events in patients with essential hypertension who had had sodium sensitivity measured in our clinic. METHODS: Sodium sensitivity was assessed in about 350 patients with essential hypertension during the initial investigation of their disorder. The definition of sodium sensitivity was a 10% or greater difference in blood pressure on low-sodium or high-sodium diets. By alphabetical order, the records of 201 patients were obtained and 156 patients without pre-existing disorders were followed up. The records of patients who had a cardiovascular event or died were reviewed without knowledge of the patient's sodium-sensitivity status. FINDINGS: 62 patients were deemed sodium sensitive and 94 non-sodium sensitive. Left-ventricular hypertrophy was found more frequently in the sodium-sensitive group than in the non-sodium-sensitive group (38 vs 16%; p < 0.01), whereas significantly fewer patients in this group smoked (23 vs 42%; p < 0.05). There were 17 cardiovascular events in the sodium-sensitive group and 14 in the non-sodium-sensitive group. The rate of total, non-fatal and fatal cardiovascular events, was 2.0 per 100 patient-years in the non-sodium-sensitive group and 4.3 per 100 patient-years in the sodium-sensitive group. Cox's proportional-hazards model identified sodium sensitivity (p < 0.01), mean arterial pressure (p < 0.01), and smoking (p < 0.01) as independent cardiovascular risk factors. INTERPRETATION: Cardiovascular events occurred more frequently in patients with sodium-sensitive hypertension. Sodium sensitivity is an independent cardiovascular risk factor in Japanese patients with essential hypertension.
Adult↗
Characterization of Campylobacter jejuni isolates from patients with Guillain-Barré syndrome.
Campylobacter jejuni is a major pathogen preceding Guillain-Barré syndrome (GBS), and most C. jejuni isolates from GBS patients belong to Penner serotype 19 (heat-stable; HS-19). We analyzed sixteen independent clinical isolates from GBS patients, twelve of which belonged to HS-19, three to HS-2, and one to HS-4, using PCR-based RFLP analysis of a flagellin-A (flaA) gene. Two isolates from patients with Miller Fisher syndrome (MFS), and 27 from patients with uncomplicated enteritis were also examined. All HS-19 isolates, regardless of GBS, showed an identical pattern (Cj-1) by RFLP typing and were distinguishable from those of the other Penner serogroups. In contrast, HS-2 and HS-4 isolates were divided into several different RFLP groups, suggesting HS-19 strains are genetically distinctive among C. jejuni isolates. A DNA fingerprinting method also failed to detect any specific band pattern for GBS-related C. jejuni isolates. We examined relationships among anti-GM1 antibody titres in the sera of GBS patients, clinical forms of GBS, serotype of C. jejuni, and the presence of GM1-like structures in lipopolysaccharide (LPS) components from C. jejuni isolates by immunoblotting. HS-19 related GBS was significantly associated with elevated anti-GM1 antibody titers in the sera of the patients, but not associated with any clinical pattern of GBS. No significant correlations were found between anti-GM1 antibody and the pattern of disease, or between GBS-related C. jejuni strains and the presence of GM1-like structures. HS-19 strains seem to be unique among C. jejuni isolates, and HS-19-related GBS may provide an excellent model for clarification of the pathogenesis of GBS.
Blotting, Western↗
CAG repeat length and disease duration in Machado-Joseph disease: a new clinical classification.
To evaluate the clinical characteristics of Machado-Joseph disease (MJD) with reference to CAG repeat length and disease duration, we analyzed neurologic findings in 108 patients from 84 families. The majority of MJD patients presented with an ataxic gait as the initial symptom. Dysarthria and nystagmus were observed from an early stage. Bulging eyes, muscle atrophy and bradykinesia developed later. Patients with a shorter CAG repeat length or later onset had more frequent involvement of proprioceptive sensory deficit. Incidence of abnormal reflexes, tones, and proprioceptive sensation was not associated with disease duration, but with CAG repeat length. Based on these results, we propose a new clinical classification: type A (juvenile type), with hyperreflexia and dystonia, but without a proprioceptive sensory deficit; type C (adult type), with hyporeflexia and a proprioceptive sensory deficit, but without dystonia; and type B (intermediate type), the remaining patients with a mixed presentation.
Adult↗
Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion.
Leukocyte trafficking at the endothelium requires both cellular adhesion molecules and chemotactic factors. Fractalkine, a novel transmembrane molecule with a CX3C-motif chemokine domain atop a mucin stalk, induces both adhesion and migration of leukocytes. Here we identify a seven-transmembrane high-affinity receptor for fractalkine and show that it mediates both the adhesive and migratory functions of fractalkine. The receptor, now termed CX3CR1, requires pertussis toxin-sensitive G protein signaling to induce migration but not to support adhesion, which also occurs without other adhesion molecules but requires the architecture of a chemokine domain atop the mucin stalk. Natural killer cells predominantly express CX3CR1 and respond to fractalkine in both migration and adhesion. Thus, fractalkine and CX3CR1 represent new types of leukocyte trafficking regulators, performing both adhesive and chemotactic functions.
Antigens, CD↗
The AtVAM3 encodes a syntaxin-related molecule implicated in the vacuolar assembly in Arabidopsis thaliana.
The vacuole constitutes a large compartment in plant and fungal cells. The VAM3 gene of Saccharomyces cerevisiae encodes a syntaxin-related protein required for vacuolar assembly. An Arabidopsis thaliana cDNA library, designed for expression in S. cerevisiae, was screened for cDNAs able to complement defective vacuolar assembly of the Deltavam3 mutation. One cDNA, encoding a 33-kDa protein with structural similarities to the other syntaxins, was identified. The product of AtVAM3 (AtVam3p) was expressed in various tissues including roots, leaves, inflorescence stems, flower buds, and young siliques. The AtVAM3 transcripts were abundant in undifferentiated cells in the meristematic region. AtVam3p fractionated predominantly to an 8,000 x g pellet fraction where a vacuolar membrane protein H+-translocating inorganic pyrophosphatase (H+-PPase) also fractionated. Immunoelectron microscopy showed that AtVam3p was localized to restricted regions on the vacuolar membranes. We propose that AtVam3p provides the t-SNARE function in the vacuolar assembly in A. thaliana.
Amino Acid Sequence↗
Stromal and thylakoid-bound ascorbate peroxidases are produced by alternative splicing in pumpkin.
A cDNA encoding stromal ascorbate peroxidase (sAPX) was isolated using poly(A)+ RNA of pumpkin cotyledons by RT-PCR. The cDNA encodes a polypeptide with 372 amino acids and shares complete sequence identity with pumpkin thylakoid-bound ascorbate peroxidase (tAPX), except for the deletion of a putative membrane spanning region located in the carboxy domain of tAPX. Southern blot hybridization and analysis of intron structure indicated that mRNAs for sAPX and tAPX, whose suborganellar localizations in chloroplasts are different, are produced by alternative splicing. Immunoblot analysis showed that the accumulation of sAPX and tAPX was differently regulated during germination and subsequent greening of pumpkin cotyledons.
Alternative Splicing↗
Molecular cloning of a novel human CC chemokine secondary lymphoid-tissue chemokine that is a potent chemoattractant for lymphocytes and mapped to chromosome 9p13.
By searching the Expressed Sequence Tag (EST) data base, we identified partial cDNA sequences potentially encoding a novel human CC chemokine. We determined the entire cDNA sequence which encodes a highly basic polypeptide of 134 amino acids total with a putative signal peptide of 23 amino acids. The predicted mature protein of 111 amino acids has the four canonical cysteine residues and shows 21-33% identity to other human CC chemokines, but has a unique carboxyl-terminal extension of about 30 amino acids which contains two extra cysteine residues. The mRNA was expressed strongly in tissues such as the lymph nodes, Appendix, and spleen. The recombinant protein, which was produced by the baculovirus system and purified to homogeneity, was a highly efficient chemoattractant for certain human T cell lines and a highly potent one for freshly isolated peripheral blood lymphocytes and cultured normal T cells expanded by phytohemagglutinin and interleukin 2. Unlike most other CC chemokines, however, this novel chemokine was not chemotactic for monocytes or neutrophils, suggesting that it is specific for lymphocytes. From these results, we designated this novel CC chemokine as SLC from secondary lymphoid-tissue chemokine. SLC fused with the secreted form of alkaline phosphatase (SLC-SEAP) was used to characterize the SLC receptor. Binding of SLC-SEAP to freshly isolated lymphocytes was blocked by SLC (IC50, 0.12 nM) but not by any other CC chemokine so far tested, suggesting that resting lymphocytes express a class of receptors highly specific for SLC. By using somatic cell hybrids, radiation hybrids, and selected yeast and bacterial artificial chromosome clones, we mapped the SLC gene (SCYA21) at chromosome 9p13 and between chromosomal markers, D9S1978(WI-8765) and AFM326vd1, where the gene for another novel CC chemokine termed ELC from EBI1-ligand chemokine (SCYA19) also exists. Collectively, SLC is a novel CC chemokine specific for lymphocytes and, together with ELC, constitutes a new group of chemokines localized at chromosome 9p13.
Amino Acid Sequence↗
Genetic resistance to urethan-induced pulmonary adenomas in SMXA recombinant inbred mouse strains.
Development of pulmonary adenomas (PAs) in mice is under the genetic control of multiple host genes. We have established a new set of SMXA recombinant inbred strains from PA-susceptible A/J and PA-resistant SM/J mice. The number of urethan-induced PAs was variable among substrains of the SMXA recombinant inbred strains, indicating the involvement of multiple genes. SMXA24 mice were highly resistant to PA, although they had susceptible alleles at all four known susceptibility genes, including kras2 and MHC. To identify the resistance gene in SMXA24, progeny of reciprocal F1 crosses and progeny of backcrosses to A/J were given urethan at 4 weeks of age and examined for induced PA at the age of 5 months. In reciprocal F1 cross progeny, the incidence of PA was very low, indicating that the resistance was a semidominant trait. Quantitative trait analysis of the backcross generation revealed significant linkages to loci on chromosome 12 (logarithm of odds score, 6.47) and chromosome 11 (logarithm of odds score, 4.35). To date, two PA resistance (PAR) genes, Par1 (located on chromosome 11) and Par2 (located on chromosome 18), have been reported. From the map position, one of the resistance genes on chromosome 11 was indistinguishable from Par1. However, another resistance gene on chromosome 12 was new, and we named this gene Par3. A likely candidate gene for Par3 is nPKCn, which is expressed exclusively in skin and lung and is down-regulated in PA. Par1 and Par3 seemed to act synergistically.
Adenoma↗
Heart rate during obstructive sleep apnea depends on individual hypoxic chemosensitivity of the carotid body.
BACKGROUND: In patients with obstructive sleep apnea syndrome (OSAS), there are cyclic fluctuations in heart rate (HR), that is, bradycardia during apnea followed by abrupt tachycardia on resumption of ventilation. Although a previous study suggested that the degree of bradycardia observed during central apnea at high altitude was determined by individual hypoxic chemosensitivity of the carotid body, it is not known whether this is true for subjects with obstructive sleep apnea syndrome. METHODS AND RESULTS: First, we examined apnea-associated HR changes in II subjects with OSAS and analyzed the relationship of the HR change during apnea (delta HR, defined as the difference between the values at the beginning and the end of apnea) and apnea-induced nadir SaO2 in each subject. Second, we conducted an apnea-simulation study in 7 subjects to examine whether the individual pattern of delta HR could be simulated while they held their breath under different levels of arterial oxygenation. The delta HR was highly variable among subjects: 2 showed an increase in HR during apnea, 6 a decrease, and the other 3 a borderline-type response. The slope factor of the nadir of the SaO2-delta HR line obtained from each subject had a significant correlation with the HR change during breath-holding conducted under normoxia (Spearman's rank correlation coefficient, rs = 69, P < .05) or hypoxia (rs = .81, P < .05) but not under hyperoxia. Finally, we evaluated hypoxic chemosensitivity of the carotid body by measuring the ventilatory response to isocapnic progressive hypoxia in all subjects. The magnitude of the ventilatory response ranged from 0.05 to 1.89 L.min-1.%SaO2 fall-1 and showed a significant correlation with the slope factor of the nadir of the SaO2-delta HR line (rs = -.64, P < .05). CONCLUSIONS: The intersubject variation of the HR changes during sleep apnea can be explained in large part by individual hypoxic chemosensitivity of the carotid body regardless of the type of apnea.
Adult↗