Biomedical subjects

T Arai

Publications and source records attributed to T Arai.

At least 235 records · Page 13Linked to original sources

PubMed1999

Microsatellite instability and K-ras mutations in gastric adenomas, with reference to associated gastric cancers.

Gastric adenomas are often detected in the stomach resected for gastric cancer. Previous investigation have revealed that the prevalence of their malignant transformation is generally low, but the frequent coexistence with carcinoma suggests that they may share some common processes with gastric cancer in tumorigenesis. In contrast to the cumulative information about genetic alterations in gastric cancer, inquiries into the genetic changes of adenoma and coexisting carcinoma in the same individual's stomach are still few. We investigated microsatellite instability (MSI) and K-ras point mutations in codons 12 and 13 in 50 lesions of gastric adenomas in 43 cases, and 31 lesions of gastric cancers that coexisted with these adenomas. In gastric adenomas, we found seven lesions (14.0%) to have microsatellite instability (MSI) at one or more loci, and most of them (six cases) had MSI at only one locus and were not associated with alterations in presumable target molecules. MSI was detected more frequently (11/31, 35.5%) and more extensively (five lesions at multiple loci) in accompanying gastric carcinomas. The prevalence of MSI in adenomas was more frequently found in those with synchronous gastric cancer (6/37, 16.2%, vs. 1/13, 7.6%) than without, and gastric adenoma accompanied by gastric cancer with multiple MSI tended to have MSI more frequently than that accompanied by cancer without MSI (4/5, 80%, vs. 1/24, 4.2%; p = 0. 01). In at least some individuals, MSI appears to represent one step in the pathway of gastric tumorigenesis, shared by adenoma and carcinoma. We found K-ras gene alteration in 8 lesions (16.0%) out of 50 gastric flat adenomas and no difference in its prevalence between adenoma with or without cancer. Only one gastric cancer, which had adenoma without K-ras mutation, had K-ras codon 12 mutation. Adenomas with a higher grade of atypia (p < 0.05) more frequently carried K-ras point mutation, which is consistent with the situation in colorectal adenoma. We conclude that MSI, not K-ras mutation, is a shared genetic alteration in adenoma and carcinoma of the individual stomach.

Adenoma↗

PubMed1999

Comparison of the activities of enzymes related to glycolysis and gluconeogenesis in the liver of dogs and cats.

Activities of enzymes related to glucose metabolism were measured in canine and feline liver. There were no significant differences in plasma glucose and immunoreactive insulin concentrations between dogs and cats. Glucokinase activities were absent in feline liver, however, activities of other glycolytic enzymes such as hexokinase, phosphofructokinase and pyruvate kinase, were significantly higher than those in canine livers. Activities of rate limiting enzymes of gluconeogenesis such as pyruvate carboxylase, fructose-1, 6-bisphosphatase and glucose-6-phosphatase in feline livers were significantly higher than those in canine livers.

Animals↗

PubMed1999

Pre-ischaemic administration of procaine suppresses ischaemic glutamate release and reduces neuronal damage in the gerbil hippocampus.

The effects of intracerebroventricular administration of procaine 2 mumol on ischaemic release of neurotransmitter amino acids in the gerbil hippocampal CAI region were investigated using a microdialysis-high-performance liquid chromatography procedure. Histological outcome was examined by comparing delayed neuronal death between animals treated with procaine before ischaemia and animals treated after ischaemia. Transient forebrain ischaemia for 3 min produced increases in dialysate amino acid concentrations. Aspartate, glutamate and glycine reached 331%, 394% and 233% of pre-ischaemic values. Basal concentrations were restored immediately by reperfusion. Pre-ischaemic administration of procaine suppressed peak release and improved histological outcome. However, post-ischaemic administration did not protect against ischaemic neuronal death. Improvement in ischaemic neuronal damage by pre-ischaemic administration of procaine may be related to suppression of excitatory amino acid release.

Amino Acids↗

PubMed1999

Requirement for a different hydrophobic moiety and reliable chromogenic substrate for endo-type glycosylceramidases.

A series of synthetic lactosides with aglycones that differed in length and structure were used to determine the substrate specificity of endo-type glycosylceramidases. Endoglycoceramidases (EGCase) from bacteria preferred lactosides with an acylamide structure over simple n-alkyl lactosides. While ceramide glycanase (CGase) from leech did not show preference. N -Acylaminoethyl beta-lactosides and n -alkyl lactosides were substrates for both EGCase and CGase, but N-acylaminobutyl beta-lactosides, whose acylamide residue differs from that in ceramide, were not hydrolyzed by EGCases. Thus, EGCases, but not CGase, appear to require an N-acyl group at the same position as that of intact glycosphingolipid for substrate recognition. A p-nitrophenyl lactoside derivative possessing an N-acyl chain was degraded by both EGCases and CGase and this chromogenic substrate may be an alternative substrate for endo-type glycosylceramidase activity. Km of the chromogenic lactoside for CGase and Rhodococcus EGCase were 28 microM and 2.9 mM, respectively.

Chromogenic Compounds↗

PubMed1999

Preliminary results of pelvic autonomic nerve-preserving surgery combined with intraoperative and postoperative radiation therapy for patients with low rectal cancer.

BACKGROUND: In Japan, lateral lymphadenectomy was widely performed for patients with stage II-III rectal tumors because it was thought to contribute to good local control, but the pelvic autonomic nerves were thus sacrificed. Although autonomic nerve-sparing surgery with lateral lymph node dissection has been tried from around 1987, the type of nerve sparing varied and the indications were not established. To examine the possibility of expanding the indications for total pelvic autonomic nerve preservation for patients with low rectal cancer, we conducted a pilot study. METHODS: Between 1993 and 1997, a total of 50 patients with low rectal cancer underwent pelvic autonomic nerve preservation with lateral lymphadenectomy of both sides and intraoperative radiation therapy followed by postoperative radiation therapy. RESULTS: The median follow-up period for surviving patients was 41 months. The 3-year local control rates for all patients, with stage I-II and stage III tumors were 88% (95% confidence interval, 78-97%), 97% (90-100%) and 73% (52-94%), respectively. The site of local recurrences was not near or within the preserved plexus. CONCLUSIONS: The preliminary results showed good local control rate for patients with stage I-II tumors. For patients with stage III tumors, the local control rate was unsatisfactory, but nerve sparing was not the cause of local recurrence. Further investigation of function-preserving surgery without decreasing curability is needed.

Adult↗

PubMed1999

Dexamethasone changes brain monoamine metabolism and aggravates ischemic neuronal damage in rats.

BACKGROUND: Glucocorticoids have been reported to aggravate ischemic brain damage. Because changes in the activities of various neuronal systems are closely related to the outcome of ischemic damage, the authors evaluated the effects of dexamethasone on the monoaminergic systems and ischemic neuronal damage. METHODS: The right middle cerebral artery was occluded for 2 h, and the tissue concentrations of monoamines and their metabolites were determined in the cerebral cortex and the striatum of rats. The turnover of 5-hydroxytryptamine was compared in animals injected with saline and those injected with dexamethasone twice (2 mg/kg in each injection) by evaluating the probenecid-induced accumulation of 5-hydroxyindoleacetic acid. The turnovers of norepinephrine and dopamine were estimated from the alpha-methyl-p-tyrosine-induced depletion of norepinephrine and dopamine, respectively. The effect of dexamethasone on the infarct volume was evaluated by triphenyltetrazolium chloride stain in rats subjected to 2 h of occlusion. RESULTS: Dexamethasone did not affect the cortical 5-hydroxytryptamine or 5-hydroxyindoleacetic acid contents. However, it suppressed the turnover of the cortical 5-hydroxytryptamine on both sides. Dexamethasone reduced the turnover of the striatal 5-hydroxytryptamine and facilitated the dopamine turnover. In rats subjected to 2 h of occlusion and 2 h of reperfusion, the infarct volume was 10.5 times greater in the group that received dexamethasone than in the animals that received saline. CONCLUSIONS: Dexamethasone suppresses the inhibitory serotonergic system and facilitates the excitatory dopaminergic system in the rat telencephalon. This may be a mechanism by which dexamethasone aggravates ischemic neuronal injury.

Animals↗

PubMed1999

Ovarian mucinous cystadenocarcinoma with yolk sac tumor in a 71-year-old woman.

An ovarian mucinous cystadenocarcinoma admixed with a component of yolk sac tumor was encountered in a 71-year-old woman, the first such tumor to be reported. The preoperative serum level of alpha-fetoprotein was elevated (55.6 ng/mL). A right ovarian cystic tumor, 8 cm in maximal dimension, was removed and found to have a solid component. Microscopically, the cystic lesion was a mucinous cystadenocarcinoma, whereas the solid portion was typical yolk sac tumor with microcystic, reticular, and labyrinthine patterns, Schiller-Duval bodies, scattered giant cells with bizarre nuclei, and intracellular and extracellular hyaline globules. There was no evidence of other germ cell tumor components. Yolk sac tumor showed positive reactions for alpha-fetoprotein, carcinoembryonic antigen, and alpha-1-antitrypsin but was negative for CA125, CA19-9, and human chorionic gonadotrophin. The patient died of recurrent tumor 6 months postoperatively without response to combination chemotherapy.

Aged↗

PubMed1999

Dynamic SPET parameters of 123I-MIBG cardiac imaging.

Early dynamic and late 123I-MIBG SPET studies were performed to investigate several parameters used to distinguish the characteristics of various cardiac disorders. Forty-six individuals (34 non-diabetic, 12 diabetic) with or without heart disease were included in the study. Early dynamic and late static SPET images were acquired using a triple-headed gamma camera. After selecting mid-sections from vertical (VLA) and horizontal (HLA) long-axis images, regions of interest were created over the apex, whole heart and anterior, inferior, septal and lateral walls of the heart. Various uptake ratios at 3, 11 and 19 min and 4 h after injection (HU3, HU11, HU19, DUP) and clearances (Kse: between HU3 and HU11; Ke: between HU11 and HU19; Kd: between HU19 and DUP) were calculated. There were significant differences among various cardiac pathologies on the delayed images. Cardiomyopathy patients showed the lowest uptake on the delayed images. When all segments in normal patients and all involved segments in myocardial infarcted patients were compared, there was significantly lower uptake of MIBG in infarcted segments at all time points. Kd showed the lowest value compared with Kse and Ke. In cardiomyopathy patients, Kse, Ke and Kd were significantly different from each other. Both Kse and Ke were significantly higher in cardiomyopathy patients than in normal patients. In conclusion, the results of this study are in line with published data and precise measurement of uptake and clearance was possible when excluding background and blood pool activity.

3-Iodobenzylguanidine↗

PubMed1999

Growing-and-decaying mode solution to the Davey-Stewartson equation.

The growing-and-decaying mode solution to the Davey-Stewartson equation are presented, which describe the long time evolution of the Benjamin-Feir unstable mode in two dimensions. A solution consisting of a line soliton and a growing-and-decaying mode shows that the Benjamin-Feir unstable mode does not destroy the structure of the line soliton. The breather solution and rational growing-and-decaying mode solution are also presented.

Journal Article↗

PubMed1999

Frequent allelic imbalance on chromosome 18q21 in early superficial colorectal cancers.

Genetic alterations in early superficial colorectal cancers have rarely been reported. In the present study, we searched for alterations in the APC and p53 genes in 27 superficial (20 depressed and 7 elevated) and 21 protruding colorectal cancers with submucosal invasion by means of PCR-single strand conformation polymorphism. Allelic imbalance (AI) on five loci, i.e., 1p34-36, 8p21-22, 14q32, 18q21 and 22q12-13, was also analyzed. Since a high incidence of 18q21 AI was detected in the superficial depressed cases, we further screened for alterations in Smad2, Smad4 and DCC. APC alterations were observed in three superficial depressed, one superficial elevated, and 11 protruding colorectal cancers, indicating that the frequency of APC alterations in superficial depressed cases was significantly lower than that in the protruding ones. There was no significant association between p53 alterations and macroscopic types. AI on 18q21 (13/20, 65%) was much higher than those on the other four loci in the superficial depressed cases. Moreover, the frequency of 18q21 AI in the superficial depressed cases was significantly higher than that in the protruding ones. Smad4 alterations were only detected in 1 of the 13 superficial depressed and 3 of the 17 protruding cases, while Smad2 and DCC alterations were not detected in any case examined. These data suggest that the carcinogenetic pathways of protruding and superficial depressed colorectal cancers are different, and that alterations of tumor suppressor gene(s) located on 18q21 other than Smad2, Smad4 and DCC might be associated with most superficial depressed colorectal cancers.

Adult↗

PubMed1999

Antitumor effect on human gastric cancer and induction of apoptosis by vascular endothelial growth factor neutralizing antibody.

Induction of apoptosis by antiangiogenic therapy has been suggested as a new anticancer strategy. To clarify the mechanism of the antitumor effect achieved by inhibition of vascular endothelial growth factor (VEGF), which is a major mediator of angiogenesis, we used an orthotopic transplantation model of human gastric carcinoma line (MT2) treated with a monoclonal VEGF neutralizing antibody (VEGF Ab). We histologically examined the microvessel density (MVD) and the apoptotic index (AI) in this model. Transplanted tumor growth was significantly inhibited by the VEGF Ab (P = 0.03), and there was a significant decrease in the number of mice with liver metastasis (P = 0.004). The MVD detected by immunohistochemical staining with ER-MP12 antibody was 33.6 +/- 8.0 in the control group and 21.1 +/- 5.4 in the treated group, and the difference was significant (P < 0.0001). The AI values of the control and treated groups were 4.73 +/- 1.11 and 7.26 +/- 1.62, respectively, and this difference is also significant (P < 0.0001). However, the expression of VEGF mRNA in transplanted tumors did not show a significant difference between the control and treated groups. These results suggest that the antitumor effect of the VEGF Ab on human gastric carcinoma is exerted by inducing mild hypoxia followed by apoptosis, which does not influence VEGF mRNA expression in the carcinoma.

Adenocarcinoma↗

PubMed1999

Persistent infection of hepatitis C virus in the elderly: a clinical and quantitative pathological study of autopsy cases.

AIMS/BACKGROUND: The entire spectrum of persistent infection by hepatitis C virus (HCV) is still unknown. METHODS: A total of 37 autopsy cases, positive with second generation anti-HCV ELISA, were analyzed. The cases comprised 15 males and 22 females, the average ages being 76.5 in males and 81.1 in females. Twenty-one cases were found to be asymptomatic, while 16 were symptomatic. RESULTS: Based on two pathological parameters of hepatic fibrosis and inflammation, the cases were divided into five groups; group A (non-inflammatory group without significant fibrosis; 11 cases), group B (inflammatory group without significant fibrosis; 9 cases), group C (non-inflammatory group with significant fibrosis; 1 case), group D (inflammatory group with significant fibrosis; 11 cases) and group E (undetermined inflammatory index; 5 cases). All cases in group A and seven cases in group B were asymptomatic. Group A included 6 cases with normal liver. All cases in groups C and D were symptomatic. All examined cases of the inflammatory groups were positive for serum HCV-RNA. CONCLUSION: Anti-HCV-positive elderly autopsy patients include many asymptomatic cases. The two pathological parameters of hepatic fibrosis and inflammation can be used to divide the cases into five groups with each group being well correlated with clinical and virological features.

Adult↗

PubMed1999

Syllable intelligibility for temporally filtered LPC cepstral trajectories.

The intelligibility of syllables whose cepstral trajectories were temporally filtered was measured. The speech signals were transformed to their LPC cepstral coefficients, and these coefficients were passed through different filters. These filtered trajectories were recombined with the residuals and the speech signal reconstructed. The intelligibility of the reconstructed speech segments was then measured in two perceptual experiments for Japanese syllables. The effect of various low-pass, high-pass, and bandpass filtering is reported, and the results summarized using a theoretical approach based on the independence of the contributions in different modulation bands. The overall results suggest that speech intelligibility is not severely impaired as long as the filtered spectral components have a rate of change between 1 and 16 Hz.

Adult↗

PubMed1999

Pure apraxic agraphia with abnormal writing stroke sequences: report of a Japanese patient with a left superior parietal haemorrhage.

A 67 year old Japanese male patient had pure agraphia after a haemorrhage in the left superior parietal lobule. He developed difficulty in letter formation but showed no linguistic errors, consistent with the criteria of apraxic agraphia. He manifested a selective disorder of sequencing writing strokes, although he was able to orally state the correct sequences. The patient's complete recovery after 1 month, without new learning, showed that he had manifested a selective disorder of writing stroke sequences. These findings indicate that the final stage of the execution of writing according to acquired sequential memory shown as a stroke sequence can be selectively disturbed, and should be considered to be distinct from the ability of character imagery and the knowledge of the writing stroke sequence itself. This case also indicates that the left superior parietal lobule plays an important part in the execution of writing.

Aged↗

PubMed1999

Abdominal fat: standardized technique for measurement at CT.

The authors estimated abdominal fat distribution on the basis of measurements at computed tomography (CT). The attenuation range for fat tissue was defined as the interval within the mean plus or minus 2 SDs considered to be individual variation. Fat areas found with this method were closely correlated with those obtained by means of the computed planimetric method or with a fixed attenuation range from -190 to -30 HU as the standard of reference. Although the average CT numbers obtained with different scanners were distributed widely, the calculated fat areas were almost identical. This method might be a practical and standardized method at CT.

Adipose Tissue↗

PubMed1999

Nitric oxide production in the CA1 field of the gerbil hippocampus after transient forebrain ischemia : effects of 7-nitroindazole and NG-nitro-L-arginine methyl ester.

BACKGROUND AND PURPOSE: The present study was designed to examine the time course of nitric oxide (NO) production and the source of NO in the CA1 field of the gerbil hippocampus after transient forebrain ischemia. METHODS: The production of NO in the CA1 field of the hippocampus after transient ischemia was monitored consecutively by measuring total NO metabolites (NOx-, NO2- plus NO3-) with the use of brain microdialysis. 7-Nitroindazole (7-NI) and NG-nitro-L-arginine methyl ester were used to dissect the relative contributions of neuronal NO synthase and endothelial NO synthase to the NO production. The histological outcomes of 7-NI in 5- and 10-minute global ischemia were also evaluated. RESULTS: The production of NO in the CA1 field of the hippocampus after ischemia was dependent on the severity of ischemia. Ischemia for 2 or 5 minutes did not induce a significant increase in NOx- levels in the CA1 field of the hippocampus after reperfusion, whereas the 10- and 15-minute ischemias produced significant and persistent increases in NOx- levels. 7-NI did not inhibit the basal NOx- levels and showed no effects on NOx- levels after 5 minutes of ischemia. However, it completely inhibited the increased NOx- levels after 10 or 15 minutes of ischemia. 7-NI provided minor neuroprotection in 5 minutes but not in 10 minutes of global ischemia. CONCLUSIONS: The increased NO level in the CA1 field of the hippocampus after ischemia is produced mostly by neuronal NO synthase, whereas the basal NO level mainly originates from endothelial NO synthase. The observed neuroprotective effect of 7-NI in 5-minute global ischemia in gerbils may not be due to neuronal NO synthase inhibition by this drug.

Animals↗

PubMed1999

Sensitivity of real time viral detection by an optical biosensor system using a crude home-made antiserum against measles virus as a ligand.

Virus identification in clinical materials during acute phase infections could give necessary information for the treatment of infections by human immunoglobulin (hIg) or interferon (IF). But because of a lack of information, most virus infections have not been treated. We have tried to develop a real time detection system for viruses in general using an optical biosensor and a model virus, Herpes simplex virus Type 1 (HSV-1), and have proved that the HSV-1 virus propagated in Vero cells and diluted in minimum essential medium (MEM) with 10% fetal bovine serum (FBS) could be detected in high sensitivity close to 10 infectious units (50% tissue culture infective dose [TCID50] units) using purified cellular receptor molecules as the ligand because the receptor could be the most specific ligand. However, because ligands available for this system to identify various viral infections in general are limited, we also tested this system using a purified polyclonal antibody which contained many other antigens as the ligand, and produced sensitivity comparable to that using the receptor as a ligand. In this paper, we tested the sensitivity by this system under the worst condition. That is, we used a crude home-made rabbit antiserum against measles virus with host cell debris as a ligand. It was found that less than 500 infectious (TCID50) units of virus were required for detection in a 100 microl solution, and that the efficacy of the commercially available hIg was also estimated by this system. This result suggested that this real time viral detection and titration system was applicable for the diagnosis of all viral infections even under difficult conditions without requiring any complex skills, with high enough sensitivity for clinical purposes. The efficacy of hIg preparations could also be evaluated by this system at the same time of the clinical material sampling.

Animals↗

PubMed1999

Topology effect for DNA structure of cisplatin: topological transformation of cisplatin-closed circular DNA adducts by DNA topoisomerase I.

The reaction of cis-Pt(NH3)2Cl2(cis-DDP)-closed circular DNA adducts with DNA topoisomerse I(topo I) were studied by electron microscopy. We identified unique topoisomers such as a singly-linked catenane (2(1)2), trefoil (3(1), and dimetric catenane (2(1)2), etc., by analysis with electron micrographs. These unique recombination products resulted from cis-DDP-intra-twisting looped DNA adducts by DNA topo I, and the products could be explained a new mechanism based on an odd-even number rule. Our results suggest a new model on the working mechanisms for DNA topology of cis-DDP which enhances the recombination of DNA. Based on our results, we propose the topological idea that the yields of a mini closed circular DNA and pseudo trefoil DNA, etc., can be expected by reaction of cis-DDP-DNA-histone complexes with DNA topo I in the body.

Antineoplastic Agents↗