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Biomedical subjects

M Osawa

Publications and source records attributed to M Osawa.

At least 145 records · Page 8Linked to original sources
PubMed1997

Platelet endothelial cell adhesion molecule-1 is a major SH-PTP2 binding protein in vascular endothelial cells.

Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is rapidly tyrosine phosphorylated in mechanically stimulated vascular endothelial cells (ECs). A 65-kDa protein from ECs specifically bound to the c-Src phosphorylated PECAM-1 cytoplasmic domain and was identified as a protein tyrosine phosphatase SH-PTP2 (SHP2, Syp). PECAM-1 was coimmunoprecipitated by anti-SH-PTP2 from EC extracts as a major binding protein, and the level of association increased when PECAM-1 was tyrosine phosphorylated. This association was mediated by SH2 domains of SH-PTP2. A rapid translocation of SH-PTP2 into cell-cell adhesion sites, where PECAM-1 was localized, occurred in mechanically stimulated cells. Our results suggest that PECAM-1 is a component of a mechanosensing machinery acting upstream of SH-PTP2.

Animals↗
PubMed1997

Acute effect of c-fos antisense oligodeoxynucleotide on hippocampal partial seizures elicited by electrical stimulation in rats.

We examined the effects of antisense oligodeoxynucleotides (ODNs) to c-fos mRNA on hippocampal partial seizures in rats. As control, sense and scrambled control ODNs were also tested. Each ODN (10 nmol/10 microliters) was injected into the lateral ventricles for 2 consecutive days. Fifteen hours after the last injection, electrical stimulation was delivered to assess the effects on after discharge threshold and afterdischarge duration (ADD). One hour after seizures, c-Fos and Jun-B immunocytochemistries were performed. Antisense ODNs significantly decreased ADD and control ODNs failed to change any parameters. In the antisense ODNs group, c-Fos expression occurred ipsilateral to the stimulation site in dentate granule cells, while Jun-B expression was seen bilaterally. In the majority of control ODNs animals, c-Fos and Jun-B expression in dentate granule cells occurred bilaterally. These findings suggest that the injection of antisense ODNs selectively inhibit contralateral c-Fos expression and that c-fos plays a key role in hippocampal excitability and seizure expression during hippocampal partial seizures.

Animals↗
PubMed1997

Studies on the mechanism for Cai-transients in sea urchin zygotes caused by refertilization and external application of sperm extract.

Sea urchin zygotes can be refertilized when they are deprived of the fertilization membrane and the hyaline layer. We have earlier reported that a transient increase of the intracellular Ca2+ concentration (Cai-transient) is induced in zygotes refertilized by sperm or treated with a sperm extract (spex) (M. Osawa et al., 1994, Dev. Biol. 166, 268-276). We investigated quantitative characteristics of the Cai-transient induced by sperm and spex, using a Ca2+ indicator, Indo-1. When sperm or spex was applied to zygotes, the peak value of the Cai-transient was 1.16 or 0.69 microM, respectively. Although these values were lower than the peak value of 1.95 microM measured during normal fertilization, the entire time courses of the three types of Cai-transients were similar. The Cai-transients during fertilization is known to be caused both by the IP3-induced Ca2+ release (IICR) and by a mechanism independent of IICR. The Cai-transients during refertilization and fertilization were not inhibited by an IP3 receptor inhibitor, heparin or by a G-protein inhibitor, GDPbetaS. However, heparin delayed the time courses of both Cai-transients. These results suggest that there may be two signal transduction pathways operating during refertilization, one dependent and the other independent of IICR. By contrast, both heparin and GDPbetaS inhibited the spex-induced Cai-transient. The IP3 content in spex-treated zygotes increased, and the spex-induced Cai-transient occurred even in the absence of external Ca2+. Cai-transient was not observed when spex was injected into zygotes. These data suggest that spex induces IICR in zygotes by activating certain cell surface receptors coupled to G-proteins.

Animals↗
PubMed1997

Pattern reversal visual evoked potentials in classic and common migraine.

Pattern reversal visual evoked potentials (PVEPs) to transient checkerboard were recorded in 19 patients with migraine with visual aura (i.e., classic migraine), 14 patients with migraine without aura (i.e., common migraine) in the interictal period and 43 normal subjects. Latencies and amplitudes of PVEPs in each group were analyzed. In classic migraine patients, P100 amplitude was significantly higher than in normal subjects (p < 0.01), whereas latencies of PVEPs did not significantly differ. There were no significant differences between the common migraine and normal subjects, nor within the classic and common migraine groups in latencies and amplitudes of PVEP. Four patients with classic migraine underwent PVEPs during or 1-2 h immediately after their migraine attacks. Two of these patients who underwent PVEPs 1.5-2 h after their attacks showed abnormally increased PVEP amplitudes. These results suggest that there are different pathophysiologies in the visual pathway between classic and common migraine and furthermore, classic migraine patients in interictal periods may have hyperexcitability in the visual pathway and that the increased amplitude of PVEPs after attacks may be due to cortical spreading depression.

Adolescent↗
PubMed1997

Localization of laminin subunits in the central nervous system in Fukuyama congenital muscular dystrophy: an immunohistochemical investigation.

We have undertaken an immunohistochemical study of laminin subunits in the central nervous system (CNS) of fetuses and patients with Fukuyama congenital muscular dystrophy (FCMD) and of controls including five fetuses. Immunoreaction product deposits with antibodies to laminin alpha 1, alpha 2, beta 1 and gamma 1, and beta-dystroglycan were detected on the surface and vessels of the CNS of controls. No staining with anti-alpha-sarcoglycan antibody was detected in the CNS. Neurons and glia did not react with any of the antibodies used. In utero expression of laminin subunits and beta-dystroglycan seemed to be lower in the cerebrum than in the spinal cord. Moreover, immunostaining for laminin alpha 2 and beta 1 tended to be weak on the fetal spinal cord surface. Expression of laminin subunits and dystrophin-associated proteins in the CNS may be modulated during development, as in the skeletal muscle. The distribution of immunoreaction product deposits was basically the same in FCMD and controls, although laminin alpha 2 and beta-dystroglycan expression appeared to be decreased in the CNS of the FCMD cases. Defects of the pial-glial barrier of the fetal brain surface have been considered the main cause of micropolygyria in FCMD, and these observations suggest that the co-localization and secondary loss of these proteins in association with the unknown product(s) of the FCMD gene might be involved in the CNS lesions of this disorder.

Adult↗
PubMed1997

The possible role of remnant-like particles as a risk factor for sudden cardiac death.

Postmortem plasma lipid and lipoprotein levels were analyzed in two groups of Japanese subjects who died suddenly and unexpectedly due to cardiac (n = 93) or non-cardiac (n = 26) causes. No individuals in either group had a significant medical or cardiac history. In this study, we measured plasma total cholesterol, triglycerides, VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol, and especially triglyceride-rich lipoprotein remnants. Triglyceride and apo E-rich remnant-like particles (RLP) were studied as a possible risk factor for sudden cardiac death in relation to the progression of coronary atherosclerosis. The receiver-operating characteristic curve (ROC) analysis showed that RLP-TG was the most significant risk factor for sudden cardiac death among the lipids and lipoproteins and RLP-C was the best predictor for coronary atherosclerosis. HDL-C and LDL-C levels were within normal limits in the majority of the cases and did not appear to relate to the sudden cardiac death. Apo E phenotyping was performed for the detection of the genetic background in the lipid metabolism. The frequency of the Apo E3/3 (wild type) phenotype, which closely relates with the remnant metabolism, was significantly reduced in the sudden cardiac death group. Our study on the postmortem plasma lipid analysis suggested that RLP-C and RLP-TG are the best risk predictor for coronary atherosclerosis and sudden cardiac death, respectively.

Adult↗
PubMed1997

Molecular evidence for human alpha 2-HS glycoprotein (AHSG) polymorphism.

Alpha 2-HS glycoprotein (AHSG) is a human plasma glycoprotein that exhibits genetic polymorphism on isoelectric focusing (IEF). To identify the origin of two common alleles, AHSG*1 and *2, we examined nucleotide exchanges in the gene. AHSG cDNA was obtained by RT-PCR from poly(A) RNA of seven liver tissue samples and subcloned into a plasmid vector. After sequencing, we found six single nucleotide differences in comparison with the originally reported sequence. In particular, the nucleotide substitutions of C to T at amino acid position 230 and C to G at position 238 were common among the samples exhibiting phenotype 2-1 or 2. Since these substitutions might give rise to a NlaIII site and a SacI site, respectively, for the potential AHSG*2, we analyzed these substitutions by PCR-RFLP using genomic DNA of 68 individuals. The result was consistent with the IEF analysis of the corresponding serum, indicating that AHSG*1 was characterized by ACG (Thr) at position 230 in exon 6 and ACC (Thr) at position 238 in exon 7, and that AHSG*2 was characterized by ATG (Met) at position 230 and AGC (Ser) at position 238.

Amino Acid Sequence↗
PubMed1997

Molecular genetic evidence of clinical heterogeneity in Fukuyama-type congenital muscular dystrophy.

Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive severe muscular dystrophy associated with brain malformation. The gene responsible for FCMD was mapped to chromosome 9q31, a region in which convincing evidence of strong linkage disequilibrium between FCMD and mfd220 (D9S306) was recently found. FCMD is also characterized clinically by a peak motor function which, at best, allows patients to sit unassisted or slide on the buttocks. However, a small fraction of patients acquire the capacity to walk unassisted. Whether such ambulant cases belong to the FCMD spectrum or to a different disease entity has been a topic of considerable debate. We performed linkage analysis for ten families with ambulant cases using DNA markers flanking the FCMD locus. The mfd220 locus yielded a significant lod score of 3.09 for ambulant FCMD. We also found evidence for linkage disequilibrium between ambulant FCMD and mfd220. We further conducted haplotype analysis in FCMD siblings with different phenotypes, one of whom was ambulant while the other was not. The results indicate that the FCMD siblings share exactly the same haplotype at nine marker loci spanning 23.3 cM surrounding the FCMD locus. On the basis of these results, we conclude that, genetically, ambulant cases are, in fact, part of the FCMD spectrum.

Adolescent↗
PubMed1997

Pial-glial barrier abnormalities in fetuses with Fukuyama congenital muscular dystrophy.

This report concerns light and electron microscopic studies on the central nervous system of a 20-week and an 18-week fetus with Fukuyama congenital muscular dystrophy (FCMD). The diagnosis of FCMD was established by prenatal molecular genetic analysis. Cerebral lesions containing neurites, subpial granular cells and glias, accompanied by cortical dysplasia were found in both cases. Small irregular defects, readily detectable by periodic acid-methenamine-silver staining or by immunohistochemical staining for S-100 protein, were observed in the cerebral surface. More severe dysplasia was evident at the areas with the larger defects. Surface defects were also observed in the cerebellum and brain stem, with brain tissue extruding into the leptomeninges. The pyramidal tract was aberrant in the pons and medulla oblongata. The spinal cord appeared normal by light microscopy. Electron microscopic examination revealed an abnormal configuration of the basement membrane and glial cytoplasmic membrane of the brain and spinal cord surfaces, including areas with no detectable defects by light microscopy. These findings suggest that abnormalities of the pial-glial barrier, especially the basement membrane and/or basement membrane-related structures, are involved in the genesis of cortical dysplasia.

Blood-Brain Barrier↗
PubMed1997

Polymorphism analysis of Fukuyama type congenital muscular dystrophy (FCMD) siblings with different phenotypes.

Peak motor function in Fukuyama type congenital muscular dystrophy (FCMD) is generally considered to be no better than sitting without help or sliding on the buttocks. There are a few patients who acquire the ability to stand and a small fraction of our total congenital muscular dystrophy (CMD) population are able to walk at some point. These ambulant cases may reflect a broad spectrum of motor disabilities in the category of FCMD, or may represent another CMD entity, which closely resembles but is distinct from FCMD. Since the localization of the FCMD gene to chromosome 9q3 1 by Toda et al. in 1993 and 1994, polymorphism analysis of this disease has become possible. We describe correlations between clinical features and genetic analysis using microsatellite markers flanking the FCMD locus in two FCMD families each having two affected children with distinctly different motor abilities. The results demonstrate that two sets of FCMD siblings share exactly the same haplotype at nine marker loci spanning 23.3 cM, surrounding the FCMD locus. Our results provide genetic confirmation that some FCMD cases may acquire the ability to walk.

Adolescent↗
PubMed1997

Electrophysiological study of myoclonic seizures in children.

To investigate the neurophysiological mechanisms underlying myoclonic seizures in childhood, we measured the latency between the onset of electromyogram (EMG) potentials and that of corresponding spikes obtained by the back-averaging method. The subjects were nine patients, with various epileptic syndromes, ranging in age from 2 months to 15 years, 11 months. The numbers of seizure events obtained by averaging ranged from five to 51 with a mean of 25. The latencies between averaged spike-and-wave complexes and deltoid EMG potentials ranged from 21 to 80, with a mean of 38 ms. Comparing these results with reported age-matched physiological conduction times, these latencies appeared to be slightly prolonged in all of our patients. Our results support the hypothesis that myoclonic seizures are produced through either a cortical or a subcortical generator, via a polysynaptic mechanism acting on muscles, rather than a monosynaptic corticospinal pathway.

Adolescent↗
PubMed1997

Boron neutron capture therapy: preliminary study of BNCT with sodium borocaptate (Na2B1 2H1 1SH) on glioblastoma.

To plan the optimal BNCT using BSH for glioblastoma patients, the 10B concentration in tumor and blood was investigated in 11 newly diagnosed glioblastoma patients. All patients received 20 mg BSH/kg body weight 2.5-16 hrs prior to tumor removal. The quantitative distribution of 10B was determined by prompt gamma ray spectrometry and/or alpha-track autoradiography. 10B distribution in tumors was heterogeneous, +/- 25% of scattering at the microscopic level, and the distribution was also heterogeneous at the tissue level. 10B concentration in blood decreased in bi-exponential decay as a function of the time after the end of the administration. The T/B ratio showed non-exponential increase with large variation. The maximum T/B ratio would be around 1. The tumor/normal brain (T/N) ratio of 10B concentration was 11.0 +/- 3.2. The 10B content in normal brain is originated in vascular 10B in parenchyma, since the 10B content in normal brain to blood (N/B ratio) being compatible with the blood content in parenchyma. These values allow for BNCT, using thermal neutrons, on brain tumors located less than approximately 3.3 cm in depth from the brain surface of neutron incidence, providing that the dose on the normal endothelium is controlled to less than the tolerance limit. In our preliminary study of BNCT, a 31% 3-year survival was achieved over all for 16 glioblastoma patients and a 50% 2-year survival was achieved on 8 glioblastoma patients in our recent dose escalation study based on these data.

Borohydrides↗
PubMed1997

Simultaneous recording of pattern reversal electroretinograms and visual evoked potentials in migraine.

We recorded full-field pattern reversal electroretinograms (PERGs) and visual evoked potentials (PVEPs) simultaneously in 15 migraine with aura, 14 migraine without aura patients during the interictal period, and in 23 sex- and age-matched normal subjects. All subjects had normal visual fields. The visual aura in all patients was hemianopsia or fortification spectra. Neither migraine group showed significant differences from normal in latency and amplitude of PERGs. In migraine with aura, the amplitudes of PVEPs in classic migraine at the mid-occipital electrode were significantly (p < 0.01) higher than normal. PVEP amplitudes were significantly (p < 0.01) higher on the contralateral side of the aura than the ipsilateral side in both visual aura and normal subjects, but there was no significant difference in latency. This high amplitude and asymmetry of PVEPs may contribute to defective inhibition between interhemispheric visual occipital areas or striate and peristriate areas.

Adult↗
PubMed1997

Bispecific rabbit Fab'-bovine serum albumin conjugate used in hemagglutination immunoassay for beta-microseminoprotein.

A polyclonal bispecific (bifunctional) antibody was prepared to develop a hemagglutination immunoassay for beta-microseminoprotein (beta-MSP), a predominant seminal protein. Three types of F(ab')2 fragments of rabbit IgG, affinity-purified anti-human red blood cell (RBC) F(ab')2 nonaffinity-purified anti-beta-MSP F(ab')2 and nonspecific (nonimmunized) F(ab')2, were mixed to obtain a F(ab')2 mixture containing 10% anti-RBC molecules and 10% anti-beta-MSP molecules. Fab' was obtained from the F(ab')2 mixture, and then reacted with maleimide-activated bovine serum albumin (BSA) at a molar ratio of 10:1. As estimated by the decrease in the maleimide content, approximately 7 Fab' molecules were introduced per one BSA molecule. The bispecific (anti-beta-MSP and anti-RBC) Fab'-BSA conjugate thus prepared was incubated successively with a human RBC suspension and with samples. In the presence of beta-MSP, RBCs become agglutinated, providing a test simple for forensic semen identification.

ABO Blood-Group System↗
PubMed1997

Aneurysm size: a prognostic factor for rupture.

For effective management of patients with unruptured intracranial aneurysms, prognostic criteria for rupture are needed, of which aneurysm size is a key factor. However, the critical size at which an aneurysm becomes hazardous is not known. During the last 5 years, 1558 aneurysm patients have been operated on in our centre. Of these 1248 presented with a subarachnoid haemorrhage (ruptured aneurysms) and 310 without a subarachnoid haemorrhage (unruptured aneurysms). Of the ruptured aneurysms 475 (38%) were small in size with a maximum diameter < 6 mm. Most of these small ruptured aneurysms were located on the anterior communicating artery. Of the 310 patients with unruptured aneurysms 253 (81.6%) had single aneurysms; 113 (44.7%) of those were small in size. Most of these small unruptured aneurysms were located on the middle cerebral artery. The remaining 57 patients with unruptured aneurysms harboured multiple aneurysms totalling 116 aneurysms; 50% of them were small in size. Our of 160 patients with multiple aneurysms presenting with subarachnoid haemorrhage, 34 patients had small aneurysm(s) accompanied with medium or large sized aneurysm(s); in nine (26.5%) of these 34 patients the small aneurysm was the ruptured one. These data suggest that small aneurysms < 6 mm in diameter are not innocuous and hazardous, and surgical treatment should be considered for small unruptured aneurysms even if they are less than 6 mm in diameter.

Adolescent↗
PubMed1997

Atonic epileptic drop attacks associated with generalized spike-and-slow wave complexes: video-polygraphic study in two patients.

PURPOSE: We studied falling manifestations of atonic epileptic drop attacks (AEDA) in 2 patients with cryptogenic epilepsy with myoclonic-astatic seizures. METHODS: Using video-polygraphic examinations. For analysis, we recorded 51 seizures in 1 patient and 18 seizures in the other. The extent of AEDA ranged from collapsing and landing on the buttocks to head nodding only without falling. RESULTS: Detailed video analysis of the drop attacks, with the patient in standing position, demonstrated the first manifestations to be flexion at the waist and knees, followed by further knee flexion, leading to falling straight down and landing on the buttocks. Ictal polygraphs demonstrated diffuse interruptions of ongoing EMG discharges corresponding to the falls, indicating that these attacks are true atonic seizures. CONCLUSIONS: The falling manifestations of AEDA appeared to be characteristic and different from those of tonic drop seizures, which have been described as falling forward with tonic flexion of the hips, upper trunk, and head, as well as abduction or elevation of the arms.

Cerebral Cortex↗
PubMed1997

Experimental studies of methemoglobinemia due to percutaneous absorption of sodium nitrite.

OBJECTIVE: Methemoglobin formation caused by a liniment solution containing sodium nitrite (30 g/L and 140 g/L) was studied in rats with normal or abraded skin, by measuring the methemoglobin concentration before and after application of liniment solutions with differing nitrite concentration. METHODS: Each liniment solution (120 microL) was applied. Methemoglobin was measured for 180 minutes using a hemoximeter. Simultaneously, arterial blood pressure and cutaneous blood flow was measured by laser Doppler flowmetry and a pressure transducer. RESULTS: After the application of each liniment solution to normal skin, the methemoglobin concentration was not significantly modified depending on the time after application. Application of liniment solution to abraded skin (140 g/L) resulted in a marked increase in methemoglobin concentration. A remarkable decrease in arterial blood pressure and subcutaneous blood flow were observed after application of liniment solution to abraded skin (140 g/L). CONCLUSIONS: Each of these findings are characteristic of nitrite and they imply the percutaneous absorption of nitrite. Regardless of the nitrite concentration, the methemoglobin concentration was consistently higher in abraded skin than in normal skin.

Administration, Cutaneous↗