Search PubMed⌕ Search

Biomedical subjects

M Ochiai

Publications and source records attributed to M Ochiai.

At least 55 records · Page 3Linked to original sources

Age of onset anticipation in anxiety disorders.

Anticipation, an increase in severity or a decrease in the age of onset inherent in the transmission of a disease gene from an affected parent to a child, is being increasingly described in human diseases. In this study we searched for possible anticipation in anxiety disorders. Seventeen unilineal families who had anxiety disorders were compared across two successive generations as to age at the onset of anxiety disorders. Life table analyses revealed a significant decrease in the onset of anxiety disorders from older to younger generations. No evidence of a difference in the type of anxiety disorder was found. Anticipation was thus found in families with anxiety disorders and, if it is confirmed by other studies, trinucleotide repeat sequences may be considered to account for the familial aggregation of anxiety disorders.

Adult↗

Proton magnetic resonance spectroscopy of lenticular nuclei in obsessive-compulsive disorder.

Magnetic resonance spectroscopy (MRS) is a safe and non-invasive technique for the in vivo study of brain chemistry and metabolism. As such, it is highly applicable to the study of living brain tissue in psychiatric diseases. Several neuropathological and neuroimaging studies have suggested that abnormalities of the basal ganglia nuclei might be implicated in patients with obsessive-compulsive disorder (OCD). In the present study, we performed proton [1H]MRS of the lenticular nuclei in 12 patients with OCD and 12 healthy normal comparison subjects. The peaks of N-acetyl-aspartate (NAA), creatine (Cr), and choline-containing compounds (Cho) were measured. No differences between OCD patients and normal subjects were found in the NAA/Cr, Cho/Cr and NAA/Cho ratios. Our results suggest the normal viability of neuronal cells, as indicated by the quantification of NAA, Cr and Cho in the lenticular nuclei of patients with OCD.

Adult↗

Impact of cilostazol on clinical and angiographic outcome after primary stenting for acute myocardial infarction.

Cilostazol, an antiplatelet drug that also may inhibit smooth muscle proliferation, was given together with aspirin after primary stenting to treat patients with acute myocardial infarction. In a randomized controlled trials of 50 patients, clinical and angiographic outcome at 6 months was significantly improved with cilostazol, depicting a significantly smaller late loss and/or loss index.

Adult↗

Improved human islet isolation by a tube method for collagenase infusion.

BACKGROUND: Collagenase infusion into the pancreatic duct is an essential step in human islet isolation. We developed a new method for ductal canulation and collagenese infusion. METHODS: A total of 53 pancreata were divided into two groups: group 1 (n=23), the new tube method, and group 2 (n=30), the standard angiocatheter method. In group 1, a polyethylene tube was inserted into the duct and pushed to the tail. The tail was first expanded, followed by expansion of the body and then the head, by pulling out the tube. RESULTS: Total islet number and number/g pancreas (mean+/-SE) were significantly higher in group 1 (481,123+/-43,218 and 8,010+/-722) (mean+/-SE) than in group 2 (300,974+/-35,122 and 5,090+/-515, P<0.01). Total islet equivalent number and islet equivalent number per gram pancreas were also significantly higher in group 1 (319,176+/-39,354 and 5,455+/-652) than in group 2 (202,022+/-23,331 and 3,722+/-468, P<0.04). Islet purity and fragmentation showed no differences between the groups. CONCLUSIONS: The tube method improved islet yields. We recommended this method for human islet isolation.

Catheterization↗

Genetic analysis of the susceptibility in rats to aberrant crypt foci formation by 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine, PhIP.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant heterocyclic amine produced while cooking fish and meat, induces aberrant crypt foci (ACF) and colon cancers in rats. We previously reported that F344 rats were sensitive and ACI rats resistant to ACF formation by PhIP, and that the genetic susceptibility in F344 rats to ACF formation by PhIP was autosomally dominant over ACI rats. To identify candidate susceptibility genes in F344 rats, a preliminary genome-wide linkage analysis was employed using a subset of 170 progeny of (F344 x ACI)F1 x ACI backcross rats with either high or low sensitivity to ACF formation by PhIP. Three chromosomes, 1, 6 and 16, demonstrated the presence of loci with a logarithm of the odds (lod) scores of more than 1.0, and a susceptible gene for ACF formation by PhIP was suggested to reside on chromosomes 16.

Animals↗

A pattern recognition protein for peptidoglycan. Cloning the cDNA and the gene of the silkworm, Bombyx mori.

Peptidoglycan recognition protein (PGRP) specifically binds to peptidoglycan and is considered to be one of the pattern recognition proteins in the innate immunity of insect. The PGRP is an essential component for peptidoglycan to trigger the prophenoloxidase cascade that is now recognized to be an important insect defense mechanism. We cloned cDNA encoding PGRP from the silkworm fat body cDNA library. Northern blot analysis showed that the PGRP gene is constitutively expressed in the fat body, epithelial cell, and hemocytes of naive silkworms. Furthermore, a bacterial challenge intensified the gene expression, with the maximal period being from 6 to 36 h after infection. The upstream sequence of the cloned PGRP gene was shown to contain putative cis-regulatory elements similar to the NF-kappaB-like element, interferon-response half-element, and GATA motif element, which have been found in the promoters of the acute phase protein genes of mammals and insects. A homology search revealed that the homologs of silkworm PGRP are present in mice, nematodes, and bacteriophages. This suggests that the recognition of peptidoglycan as foreign is effected in both vertebrates and invertebrates by PGRP homologs with an evolutionally common origin.

Amino Acid Sequence↗

Efficacy of transradial primary stenting in patients with acute myocardial infarction.

We conducted a prospective observational study to assess the effectiveness of "transradial primary stenting" in 33 patients with acute myocardial infarction, along with acute risk stratification and accelerated patient care. With use of adequate inclusion and exclusion criteria, the radial artery can be used as an access site for catheterization, and transradial primary stenting can be performed rapidly and successfully by trained coronary interventionalists.

Aged↗

Prophenoloxidase-activating enzyme of the silkworm, Bombyx mori. Purification, characterization, and cDNA cloning.

Prophenoloxidase-activating enzyme (PPAE) was purified to homogeneity as judged by SDS-polyacrylamide gel electrophoresis from larval cuticles of the silkworm, Bombyx mori. The purified PPAE preparation was shown to be a mixture of the isozymes of PPAE (PPAE-I and PPAE-II), which were eluted at different retention times in reversed-phase high performance liquid chromatography. PPAE-I and PPAE-II seemed to be post translationally modified isozymes and/or allelic variants. Both PPAE isozymes were proteins composed of two polypeptides (heavy and light chains) that are linked by disulfide linkage(s) and glycosylated serine proteases. The results of cDNA cloning, peptide mapping, and amino acid sequencing of PPAE revealed that PPAE is synthesized as prepro-PPAE with 441 amino acid residues and is activated from pro-PPAE by cleavage of a peptide bond between Lys152 and Ile153. The homology search showed 36.9% identity of PPAE to easter, which is a serine protease involved in dorso-ventral pattern formation in the Drosophila embryo, and indicated the presence of two consecutive clip-like domains in the light chain. A single copy of the PPAE gene was suggested to be present in the silkworm genome. In the fifth instar larvae, PPAE transcripts were detected in the integument, hemocytes, and salivary glands but not in the fat body or mid gut. A polypeptide cross-reactive to mono-specific anti-PPAE/IgG was transiently detected in the extract of eggs between 1 and 3 h after they were laid.

Amino Acid Sequence↗

p53 gene mutations and overexpression of p53 product in cancerous and noncancerous biliary epithelium in patients with pancreaticobiliary maljunction.

To investigate the molecular mechanisms of the high incidence of carcinogenesis in the biliary epithelium of patients with pancreaticobiliary maljunction, we examined p53 gene mutations, loss of heterozygosity of p53, and overexpression of p53 gene product in the cancerous and noncancerous biliary epithelium of 27 patients with pancreaticobiliary maljunction. Mutations of the p53 gene were examined by polymerase chain reaction-single strand conformation polymorphism and a direct sequencing method. Loss of heterozygosity of the p53 gene was determined using a double-targeted fluorescence in situ hybridization method. Expression of p53 gene product was examined using immunohistochemical staining. Mutations of the p53 gene were found in 4 of 5 biliary carcinomas (80%) and in 10 of 26 noncancerous biliary lesions (38.5%). Point mutations of the p53 gene were detected at codons 207, 212, and 217 on exons 5 through 8. The incidence of p53 gene mutations on exons 5, 6, 7, and 8 was 12. 9%, 36.4%, 0.0%, and 13.8%, respectively. Loss of heterozygosity of p53 was shown in 72% of the cells obtained from the cancerous lesion, and in an average of 14% obtained from the noncancerous lesions. Overexpression of p53 protein was found in 57.1% of carcinoma, and in 31.3% of the noncancerous lesions. These results suggest that p53 gene mutations are involved in the carcinogenesis of biliary epithelium in patients with pancreaticobiliary maljunction.

Adult↗

A variable-number-tandem-repeat of the serotonin transporter gene and anxiety disorders.

1. A polymorphism of the variable-number-tandem-repeat (VNTR) in the second intron of the serotonin transporter (ST) gene, which has been reported to be associated with major depression, was studied in anxiety disorders. 2. The VNTR of the human ST gene was compared between 103 patients with anxiety and 106 controls. 3. The frequency of the allele containing 12 copies of the VNTR element (STin2.12) was significantly higher in the combined patient group (p = 0.027), and among patients with OCD (p = 0.0326), and GAD (p = 0.0123), in comparison with in controls. 4. The presence of the STin2.12 allele was significantly associated with the risk of combined anxiety disorders (odds ratio = 2.06, 95% CI 1.09-3.90), OCD (10.2, 1.34-77.4), and GAD (3.61, 1.23-10.6).

Adolescent↗

Transcranial magnetic stimulation of the central and peripheral motor pathways to the lingual muscles in cats.

OBJECTIVE: We have assessed a technique to stimulate the intracranial hypoglossal nerve with ease and reproducibility by using magnetic coils (MCs) and to detect a reliable site of excitation in animal experiments in order to establish a method to evaluate the motor pathway to lingual muscles. METHODS: We recorded the motor responses from the lingual muscles of 5 adult cats under general anesthesia by magnetic and electrical stimulation of the intracranial hypoglossal nerves. Figure of 8 and round MCs were used to investigate the optimal position and direction to evoke the motor responses. RESULTS: The round MC was useful for cortical stimulation. The figure of 8 coil, positioned in the back of the head of the examined side, parallel to the cervical spine, was essential for stimulation of the intracranial hypoglossal nerve. Analysis of the latencies, and the observation that the motor responses disappeared after transection of the nerves at the exit of the hypoglossal canal, demonstrated that the site of the excitation is at the exit of the hypoglossal canal. CONCLUSION: Magnetic stimulation using a figure of 8 coil can elicit tongue motor responses with ease and reliable reproducibility, stimulating the hypoglossal nerve at the exit of the hypoglossal canal.

Animals↗

The excitation site of the accessory nerve to the magnetic stimulation--the relationship between the orientation of the magnetic field and the excitation site.

OBJECTIVE: The relationship between the accessory nerve excitation site and the magnetic field direction was investigated to prove whether the cranial nerve excitation site to the transcranial magnetic stimulation is constant or not. METHODS: Compound muscle action potentials (CMAPs) elicited by the transcranial magnetic stimulation were recorded from the trapezius muscles of 7 adult cats. The waveforms of CMAPs were detected before craniectomy, after craniectomy, and after cutting the accessory nerve at the C1, at the jugular tubercle, and at the jugular foramen. The optimal orientation was determined by rotating the coil clockwise in increments of 22.5 degrees from the rostral direction. RESULTS: The accessory nerve was stimulated by the magnetic stimulation at the C1, at the jugular tubercle or at the jubular foramen, and these excitation sites varied with coil orientation. The average angles of the optimal orientation of the magnetic coil were 77.1 degrees for C1, 122.1-263.6 degrees for the jugular tubercle, and 308.6-32.1 degrees for the jugular foramen. CONCLUSIONS: The accessory nerve excitation site varied with the orientation of the magnetic coil. This study suggested the possibility of a variety of the cranial nerve excitation sites to the transcranial magnetic stimulation.

Accessory Nerve↗

Strain differences of rats in the susceptibility to aberrant crypt foci formation by 2-amino-1-methyl-6-phenylimidazo- [4,5-b]pyridine: no implication of Apc and Pla2g2a genetic polymorphisms in differential susceptibility.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant mutagenic heterocyclic amine contained in cooked food, induces colon tumors in F344 male rats when administered orally. In the present study, PhIP was introduced to various rat strains, and susceptibility to the induction of aberrant crypt foci (ACFs) was analyzed as a biomarker for colon carcinogenesis. BUF/Nac rats were highly susceptible, giving rise to 12.2 +/- 1.7 ACFs per rat. F344 rats were intermediate and ACI/N rats were resistant, giving 3.5 +/- 1.8 and 0.9 +/- 0.7 ACFs per rat, respectively. In spite of this, the extent of DNA damage by PhIP in F344, in terms of the level of PhIP-DNA adducts, was significantly lower than that in ACI/N. The differences in formation of ACFs could be, in some part, implicated in the differential susceptibility to colon carcinogenesis induced by PhIP, especially in a step later than adduct formation. In an attempt to determine the genetic factors implicated in the susceptibility to formation of ACFs, a possible involvement of the adenomatous polyposis gene (Apc) and its modifier secretory phospholipase A2 (Pla2g2a) was analyzed. No genetic polymorphisms in either Apc or Pla2g2a showed a significant correlation to susceptibility to formation of ACFs among rat strains.

Animals↗

A new modification of the 32P-post-labeling method to recover IQ-DNA adducts as mononucleotides.

To obtain accurate estimates of DNA adduct levels yielded by genotoxic compounds, it is essential to completely digest adducted nucleotides to mononucleotides. We previously developed a suitable method, called modified method I, to obtain DNA adducts of heterocyclic amines as 32P-labeled-mononucleoside adduct 5'-phosphate forms, by use of nuclease P1 (NP1) and phosphodiesterase I (PDEI) to digest adducted oligonucleotides. In this study, we applied method I to 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA adduct analysis and found that one of the IQ-DNA adducts, 5-(deoxyguanosin-N2-yI)-2-amino-3-methylimidazo[4,5-f]quinoline 3',5'-diphosphate (pdGp-N2-IQ), was resistant to the 3'-phosphatase activity of NP1, but sensitive to that of T4 polynucleotide kinase (PNK). DNA obtained from the liver of rats fed IQ was 32P-labeled by the standard method and the 32P-labeled nucleotides obtained were incubated with PNK and NP1 to remove 3'-phosphate groups and then digested with PDEI. Three spots were obtained. One major spot was identified as N-(deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline 5'-phosphate (pdG-C8-IQ) and a second abundant adduct as pdG-N2-IQ. The third spot, of which the structure is unknown, was minor. The new method is called modified method II. Modified method II could be applicable to a wide variety of chemicals.

Animals↗

Difference in target organs in carcinogenesis with a heterocyclic amine, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, in different strains of mice.

2-Amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) induces cancers in the forestomach and liver, but not in the colon, of CDF1 male and female mice, which are thought to be resistant to induction of colon cancer by 1,2-dimethylhydrazine. In this study, we examined the carcinogenicity of MeIQ in C57BL/6N female mice, which are susceptible to 1,2-dimethylhydrazine. This strain of mice developed carcinomas of the cecum, colon and liver, but not the forestomach, when given a diet containing 300 ppm of MeIQ. This fact indicates that the target organs of a chemical carcinogen change depending on the strain of a given animal species.

1,2-Dimethylhydrazine↗

Cyclooxygenase-2 (COX-2) mRNA expression levels in normal lung tissues and non-small cell lung cancers.

One of the cyclooxygenase (COX) isoforms, COX-2, is overexpressed in various human cancers. In this study, we examined the gene expression levels of COX-2 in primary non-small cell lung cancers (NSCLC), metastatic lymph nodes, and normal lung tissues. The expression levels of the COX-2 gene were assessed by means of the reverse transcription polymerase chain reaction in 76 autopsy samples (29 primary NSCLC, 29 corresponding normal lung tissues, and 9 metastatic lymph nodes). The expression levels in NSCLC (both adenocarcinomas and squamous cell carcinomas) were significantly higher than in normal lung tissues and were significantly higher in adenocarcinomas than in squamous cell carcinomas. Differences between the levels of expression of COX-2 in primary tumors and their corresponding metastatic lymph nodes in 9 adenocarcinoma patients were not significant. Our results indicate that COX-2 may be associated with carcinogenesis of NSCLC, and that it may be a target for the treatment of NSCLC.

Adenocarcinoma↗

AJvW-2, an anti-vWF monoclonal antibody, inhibits enhanced platelet aggregation induced by high shear stress in platelet-rich plasma from patients with acute coronary syndromes.

The platelet aggregation that is dependent on von Willebrand factor (vWF) is important in the thrombogenesis that occurs under conditions of high shear stress, eg, during acute coronary syndromes (ACSs). A monoclonal antibody, AJvW-2, directed against the A1 domain of human vWF specifically blocks the interaction between plasma vWF and platelet glycoprotein (GP) Ib. To evaluate the association between the vWF-GPIb interaction and the enhanced shear-induced platelet aggregation (SIPA) observed in ACSs, we tested the effect of this antibody on platelet aggregation. Platelet-rich plasma was prepared from the citrated blood of 12 patients with unstable angina (UAP) and 20 patients with acute myocardial infarction (AMI) who were admitted within 3 hours of the onset of cardiac symptoms and from 18 controls. We observed the following: (1) 1.7-fold higher plasma levels of vWF and ristocetin cofactor activity in UAP patients and (2) 2.8-fold higher levels in the AMI group than in controls. Using a cone-and-plate viscometer, we measured the mean value of SIPA under high-shear conditions (108 dyne/cm2) and found them to be 1.3-fold higher in the UAP group and 2.0-fold higher in the AMI group than in controls. The high SIPA in all groups was completely inhibited by 10 microgram/mL AJvW-2. Under low-shear conditions (12 dyne/cm2), platelet aggregation was increased only in the AMI group, but this was unaffected by AJvW-2. We observed a significant correlation in both ACS groups between high SIPA and the plasma vWF level or vWF larger multimers. These findings suggest that the vWF-GPIb interaction is important in coronary occlusion and that inhibition of this interaction (with the use of AJvW-2) may prevent further events in the coronary arteries.

Acute Disease↗

[The application of the endotoxin test for globulin and other blood products].

The application of the endotoxin test for globulin and other blood products were investigated by two different limulus amebocyte lysate (LAL) test methods, colorimetric and kinetic turbidimetric methods, using two endotoxin-specific reagents. By the dilution of the blood products in 40 times or more, spiked endotoxin in the products was recovered accurately showing neither inhibition nor enhancement. The definite difference was not shown between the results obtained by the two LAL test methods. According to the method of the endotoxin test described under General Tests of The Japanese Pharmacopeia (thirteenth edition), JPXIII, the maximum valid dilution (MVD) for these products will be calculated to be 40 or more, so it is capable to measure the endotoxin limit for each product. This study indicates that the endotoxin test is applicable to measure the endotoxin content in globulin and other blood products as an alternative method for the rabbit pyrogen test.

Colorimetry↗