Search PubMed⌕ Search

Biomedical subjects

S Mukai

Publications and source records attributed to S Mukai.

At least 55 records · Page 3Linked to original sources
PubMed1999

Critical role of CD11a (LFA-1) in therapeutic efficacy of systemically transferred antitumor effector T cells.

The systemic adoptive transfer of activated T cells, derived from tumor-draining lymph nodes (LNs), mediates the regression of established tumors. In this study, the requirement of cell adhesion molecules, CD11a/CD18 (LFA-1), CD54 (ICAM-1), CD49d/CD29 (VLA-4), and CD106 (VCAM-1), for T cell infiltration into tumors and antitumor function was investigated. Administration of anti-CD11a mAb completely abrogated the efficacy of adoptive immunotherapy for both intracranial and pulmonary metastatic MCA 205 fibrosarcomas. In contrast, adoptive immunotherapy was effective in animals treated with anti-CD49d mAb, anti-CD106 mAb, anti-CD54 mAb, or in CD54 knockout recipients. Trafficking of transferred cells to the intracranial tumor was not affected by any of the mAb. However, the tumor-specific secretion of IFN-gamma by activated LN T cells was suppressed by anti-CD11a mAb or anti-CD54 mAb. To account for the different effects of CD11a and CD54 blockade in vivo, an additional CD11a/CD18 ligand, CD102 (ICAM-2), was demonstrated on tumor-associated macrophages but not on tumor cells. These results show that CD11a mediates a critical function in interactions between effector T cells, tumor cells, and host accessory cells in situ leading to tumor regression.

Animals↗
PubMed1999

Rat retinal ganglion cells culture enriched with the magnetic cell sorter.

The magnetic cell sorter (MACS) technique was applied to isolate retinal ganglion cells (RGCs) for culture. RGCs were labeled retrogradely with 1.1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil). Subsequently retinal cell suspensions were incubated with biotinylated anti-rat Thy-1 antibody and MACS Streptavidin MicroBeads, and then applied onto the column in the magnetic fields. Cells attached on the column were flashed out without magnetism and plated on glass cover slips. RGCs were enriched to 31.0% of all cells with MACS from 0.55% before applying onto the magnetic column. Mean diameters of Dil-labeled cells were significantly larger than those of unlabeled cells. All cells with soma diameter over 11 microm were labeled. The number of viable RGCs were counted in the 10 fields of six cultures at a magnification of x200; the mean numbers on the 2nd, 7th and 14th culture-day were 53+/-3, 24+/-2 and 21+/-3, respectively (mean +/- SEM, n = 6). Thus, the MACS technique was confirmed to be useful for enrichment of RGCs and long-term study of cultured RGCs.

Animals↗
PubMed1999

Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes.

Stickler and Marshall syndromes are dominantly inherited chondrodysplasias characterized by midfacial hypoplasia, high myopia, and sensorineural-hearing deficit. Since the characteristics of these syndromes overlap, it has been argued whether they are distinct entities or different manifestations of a single syndrome. Several mutations causing Stickler syndrome have been found in the COL2A1 gene, and one mutation causing Stickler syndrome and one causing Marshall syndrome have been detected in the COL11A1 gene. We characterize here the genomic structure of the COL11A1 gene. Screening of patients with Stickler, Stickler-like, or Marshall syndrome pointed to 23 novel mutations. Genotypic-phenotypic comparison revealed an association between the Marshall syndrome phenotype and splicing mutations of 54-bp exons in the C-terminal region of the COL11A1 gene. Null-allele mutations in the COL2A1 gene led to a typical phenotype of Stickler syndrome. Some patients, however, presented with phenotypes of both Marshall and Stickler syndromes.

Abnormalities, Multiple↗
PubMed1999

Nonsense and temperature-sensitive mutations in PEX13 are the cause of complementation group H of peroxisome biogenesis disorders.

Peroxisome biogenesis disorders, including Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease, are lethal hereditary diseases caused by abnormalities in peroxisomal assembly. To date, 12 genotypes have been identified. We now have evidence that the complete human cDNA encoding Pex13p, an SH3 protein of a docking factor for the peroxisome targeting signal 1 receptor (Pex5p), rescues peroxisomal matrix protein import and its assembly in fibroblasts from PBD patients of complementation group H. In addition, we detected mutations on the human PEX13 cDNA in two patients of group H. A severe phenotype of a ZS patient (H-02) was homozygous for a nonsense mutation, W234ter, which results in the loss of not only the SH3 domain but also the putative transmembrane domain of Pex13p. A more mildly affected NALD patient (H-01), whose fibroblasts showed the temperature-sensitive (TS) phenotype, was homozygous for a missense mutation in the SH3 domain of Pex13p, I326T. This mutant PEX13 cDNA expression in a PEX13-defective CHO mutant showed I326T to be a TS mutation and thus suggested that Pex13p with the I326T mutation in the SH3 domain is stable at 30 degrees C but is somewhat unstable at 37 degrees C.

Amino Acid Sequence↗
PubMed1999

Isolation, characterization and mutation analysis of PEX13-defective Chinese hamster ovary cell mutants.

We isolated peroxisome biogenesis mutants ZP128 and ZP150 from rat PEX2 -transformed Chinese hamster ovary (CHO) cells, by the 9-(1'-pyrene)nonanol/ultraviolet method. The mutants lacked morphologically recognizable peroxisomes and showed a typical peroxisome assembly-defective phenotype such as a high sensitivity to 12-(1'-pyrene)dodecanoic acid/UV treatment. By means of PEX cDNA transfection and cell fusion, ZP128 and ZP150 were found to belong to a recently identified complementation group H. Expression of human PEX13 cDNA restored peroxisome assembly in ZP128 and ZP150. CHO cell PEX13 was isolated; its deduced sequence comprises 405 amino acids with 93% identity to human Pex13p. Mutation in PEX13 of mutant ZP150 was determined by RT-PCR: G to A transition resulted in one amino acid substitution, Ser319Asn, in one allele and truncation of a 42 amino acid sequence from Asp265 to Lys306 in another allele. Therefore, ZP128 and ZP150 are CHO cell lines with a phenotype of impaired PEX13.

Amino Acid Sequence↗
PubMed1999

Prognostic value of heart rate variability during long-term follow-up in chronic haemodialysis patients with end-stage renal disease.

BACKGROUND: Mortality is high in chronic haemodialysis patients with cardiovascular disease, and many of them die suddenly. Reduced heart rate variability (HRV) is an increased risk for death in various populations, but its prognostic value in haemodialysis patients remains uninvestigated. METHODS: We analysed the associations between 24-h HRV measures and long-term mortality through a prospective follow-up of 31 chronic haemodialysis patients who underwent diagnostic coronary angiography. RESULTS: Of the 31 patients, at baseline, seven had a previous myocardial infarction, five had a history of congestive heart failure and 14 had significant (> or =75%) coronary stenosis (four had multi-vessel stenosis). During follow-up for 60+/-5 months, 14 patients died, 11 of them suddenly. A left ventricular ejection fraction of <0.45, multi-vessel coronary stenosis, ventricular tachycardia on 24-h ECG and decreased/abnormal 24-h HRV (triangular index <22 and abnormal Poincaré plot) carried a univariate risk of all-cause death, while the risk of sudden death was only correlated with decreased HRV (standard deviation of normal-normal R-R interval <50 ms, triangular index <22 and ultra-low frequency power <8.7 ln(ms2)). Multivariate analysis revealed that a triangular index <22 was the best predictor of increased risk for both all-cause and sudden death (hazards ratio (95% CI); 8.1 (1.3-48.6) and 12.6 (1.3-126.4), respectively) and that the association was independent of cardiac function, macrovascular diseases, ventricular arrhythmias and cardiovascular risk factors. The 5-year mortality when the triangular index was > or =22 or <22 was 33 or 88% for patients with coronary artery disease and 0 or 50% for those without. CONCLUSIONS: These results indicate that HRV has an independent prognostic value in chronic haemodialysis patients and identifies an increased risk for all-cause and sudden death.

Adult↗
PubMed1999

Aging and spectral characteristics of the nonharmonic component of 24-h heart rate variability.

To examine whether heart rate variability (HRV) during daily life shows power law behavior independently of age and interindividual difference in the total power, log-log scaled coarse-graining spectra of the nonharmonic component of 24-h HRV were studied in 62 healthy men (age 21-79 yr). The spectra declined with increasing frequency in all subjects, but they appeared as broken lines slightly bending downward, particularly in young subjects with a large total power. Regression of the spectrum by a broken line with a single break point revealed that the spectral exponent (beta) was greater in the region below than above the break point (1.63 +/- 0. 23 vs. 0.96 +/- 0.21, P < 0.001). The break point frequency increased with age (r = 0.51, P < 0.001) and beta correlated with age negatively below the break point (r = 0.39) and positively above the break point (r = 0.70). The contribution to interindividual difference in total power was greater from the differences in the power spectral density at frequencies closer to both ends of the frequency axis and minimal from that at -3.25 log(Hz), suggesting hingelike movement of the spectral shape at this frequency with the difference in total power. These characteristics of the 24-h HRV spectrum were simulated by an artificial signal generated by adding two noises with different beta values. Given that the power law assumption is fundamental to the analysis of dynamics through the log-log scaled spectrum, our observations are substantial for physiological and clinical studies of the heartbeat dynamic during daily life and suggest that the nonharmonic component of HRV in normal subjects during daily life may include at least two 1/fbeta fluctuations that differ in dynamics and age dependency.

Adult↗
PubMed1999

Effects of complement suppression on xenograft survival in hyperacute rejection.

To examine the significance of complement in discordant cardiac xenograft rejection, morphological changes in the rejection reaction were investigated following administration of FUT-175 (FUT), an anticomplement reagent. Guinea pigs were the cardiac donors, and Wistar rats were the recipients. Four groups of rats were constituted as follows: Group 0 was the control group. FUT of 40 mg/kg was injected intraperitoneally in group I. It was followed by continuous intravenous infusion (20 and 40 mg/kg/hr) in groups II and III. In one series, the effects of FUT on complement suppression was examined. In the FUT groups of rats (groups I to III), the serum levels of CH50 and ACH50 were measured at 0, 1, 2 and 4 hr following injection of FUT. In the second series of rats with identical treatments, the graft heart beating time following cardiac transplantation was measured. Cardiac transplantation into untreated rats was also performed as a control (group 0). In another series, the graft hearts in the FUT groups were extracted after 15, 30, 60 and 90 min of coronary reperfusion for morphological examination with scanning electron microscopy. The complement levels decreased significantly in the FUT-treated rats in a dose-dependent manner. Although the graft heart beating times in the FUT-treated groups were significantly longer than in group 0 (103, 106, and 112 min versus 14.7 min, p < 0.01), there was no significant difference in the graft heart beating time or in the morphological changes among the three FUT groups. Our results suggest the presence of factors other than complements contribute to the cardiac xenograft rejection.

Animals↗
PubMed1999

[Emergency coronary artery bypass grafting for ischemic heart disease].

Between June, 1988 and May 1998, 524 patients underwent isolated coronary artery bypass grafting (CABG) utilizing cardiopulmonary bypass in our institution. The 74 patients who underwent CABG on emergency surgery were subjected in this study. Age was ranged 33 to 89 years (mean 65 +/- 1.1; 50 male, 24 female). Of 74 cases, 52 cases underwent emergency CABG due to UAP, and 22 cases were AMI. The hospital mortality rate in 74 cases was 19% (15/74) and 2.4% (11/450) in patients who had scheduled CABG (p < 0.0001). Mortality rate in AMI group was 41% (9/22) and 9.6% (5/52) in UAP (p < 0.005). Number of patients aged 75 years or elder was 14 (19%) in emergency CABG, and 43 (8.9%) in scheduled CABG (p < 0.05). To improve the operative results of emergency CABG, it is important to reduce the number of emergency CABG in elderly, by the careful diagnosis and aggressive surgical treatment as same as in younger patient.

Adult↗
PubMed1998

[A rare case of 2 free thrombi in left atrium with mitral stenosis].

A 64-year-old female was admitted with general fatigue and orthopnea. Preoperative echocardiography showed a free ball thrombus in the left atrium, mitral stenosis and severe tricuspid regurgitation. To avoid a herniation of thrombus to the mitral orifice, an emergency operation was performed. Two free and small mural thrombi were found in the left atrium. Thrombectomy, mitral valve replacement and tricuspid annuloplasty were performed successfully. Postoperative course was uneventful, and she was discharged in good condition on the 21st postoperative day.

Female↗
PubMed1998

[A case of cardiac lipoma in the ventricular septum].

Lipoma in the ventricular septum is very rare. Our review of the English literature revealed that our case is the sixth of removal of lipoma in the ventricular septum. A 60-year-old male was admitted because a mass in the ventricular septum was found incidentally in abdominal CT taken following type B hepatitis. CT scanning of the heart showed 2 cm diameter of tumor in the ventricular septum. The tumor had very low radiodensity, so it was thought to be identical to fat tissue. The tumor was more clearly visualized by MR imaging and the signal intensity was high on the T1-weighted image. The tumor was suspected to be lipoma. The intraoperative histological diagnosis showed the tumor was lipoma. The tumor adhered strictly on the myocardium of the septum, and it was located near the left anterior descending coronary artery. It could not completely resected, in these reasons. Postoperative course was uneventful, and echocardiogram taken 9 months after the operation showed no evidence of enlargement of the residual tumor. It is necessary to follow-up rigidly for the potential of enlargement of the residual tumor.

Heart Neoplasms↗
PubMed1998

Circadian rhythms of atrioventricular conduction properties in chronic atrial fibrillation with and without heart failure.

OBJECTIVES: We examined the circadian variations in atrioventricular (AV) conduction properties during atrial fibrillation (AF) by a technique based on the Lorenz plot of successive ventricular response (VR) intervals and analyzed their relations with clinical features. BACKGROUND: The VR interval in chronic AF shows circadian variation, which is attenuated in patients with an increased risk of death. Although the VR interval is determined by the dynamic processes in the AV node randomly stimulated by rapid atrial activity, the circadian variations of the AV conduction properties related to this mechanism are unknown. METHODS: In 48 patients with chronic AF, Lorenz plots were generated on overlapping sequential segments of 512 VR intervals in 24-h ambulatory electrocardiograms. For each scatter plot, the 1.0-s intercept of the lower envelope (LE1.0) of the plot and the degree of scatter above the envelope (root mean square difference from the envelope [scattering index]) were measured for estimating AV node refractoriness and concealed AV conduction, respectively. RESULTS: In all patients, a significant circadian rhythm was observed for the average VR interval, LE1.0 and scattering index, with an acrophase occurring at night. The mesor, amplitude and acrophase of LE1.0 and the scattering index closely and independently correlated with the corresponding rhythm variables of the average VR interval (partial r2 0.98, 0.86 and 0.68 for LE1.0 and 0.98, 0.92 and 0.92 for scattering index). The amplitudes of these measures were lower in patients with congestive heart failure (CHF) even after adjustment for the effects of age, duration of AF, medications, left atrial diameter and blood pressure (p < 0.01 for all). CONCLUSIONS: These results suggest that 1) both AV node refractoriness and the degree of concealed AV conduction during AF may show a circadian rhythm; 2) the circadian rhythms of these properties may independently contribute to the circadian variation of the VR interval; and 3) these circadian rhythms may be attenuated in patients with CHF.

Aged↗
PubMed1998

Moderately hypothermic cardiopulmonary bypass and selective cerebral perfusion in ascending aorta and aortic arch surgery. Preliminary experience in twenty-two patients.

Deep hypothermic cardiocirculatory arrest is the commonest method of brain protection during transverse aortic arch surgery. Its principle drawbacks consist in the limited safe ischemic period and in the coagulative, renal and pulmonary complications related to low body temperatures and prolonged cardiopulmonary bypass time. Different selective cerebral perfusion techniques have recently raised the interest of some surgical teams in an effort to obviate these problems. The authors' initial experiences with 22 patients, ranging in age from 19 to 78 years (mean, 55 +/- 15 years), who underwent ascending aorta and/or aortic arch replacement using selective cerebral perfusion and moderately hypothermic cardiopulmonary bypass are reported here. Acute aortic dissection and atherosclerotic aneurysm were the commonest lesions observed: ascending aorta associated with partial or complete arch replacement was the most widely performed procedure. With regard to the perfusion technique, after regular cardiopulmonary bypass had been established through the iliac vessels, selective cerebral perfusion was started after aortic arch vessels cannulation (innominate artery, bilateral common carotid artery, innominate artery and left common carotid artery, or right common carotid artery) using a single roller pump separately from the systemic circulation, and brain perfusion was achieved by blood cooled at 30 degrees C, at a flow rate that ranged from 300 ml/min to 1500 ml/min, at a perfusion pressure of approximately 65 mmHg, with the patient maintained at moderate hypothermia (30 degrees C rectal). To perform distal aortic repair, if transverse aortic arch or proximal descending aorta cross-clamping was not feasible, cardiopulmonary bypass flow was lowered to 300-350 ml/min and an open anastomosis was performed, while independently assuring cerebral perfusion (six patients). There were three hospital deaths (mortality rate of 13.6%; s.d. 6.0-25.5%; 70% confidence limit), but none because of cerebral accident. No paraplegia occurred. One patient suffered from right hemiparesis, neither renal nor pulmonary complications were observed. Two chest reexplorations were necessary for bleeding, which were partially related to hemocoagulative disorders. In our experience, the technique of moderately hypothermic cardiopulmonary bypass and selective cerebral perfusion in aortic surgery has provided good results with regard to cerebral protection and organ function preservation. Therefore, allowing a prolonged distal aortic reconstruction period, it may be considered as a safe alternative to profound hypothermia associated with cardiocirculatory arrest in aortic arch surgery.

Acute Disease↗