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Biomedical subjects

M Itoh

Publications and source records attributed to M Itoh.

At least 685 records · Page 38Linked to original sources
PubMed1994

[Evaluation of the mechanism of endothelin-induced rat gastric mucosal lesion formation].

There are several reports on the gastric mucotoxic effect of endothelin (ET). The mechanism of this effect, however, remains largely unknown. To evaluate this, we assessed the gastric injury and changes in gastric mucosal blood flow induced by ET using ONO-1078, a sulfide peptide leukotriene (LT) antagonist, CV-3988, a platelet-activating factor (PAF) antagonist, and diltiazem, a Ca2+ channel blocker. In fasted and anesthetized rats, 2 nmol/kg of ET was infused for 30 min into splenic artery to deliver the drug as much as selectively to the stomach. Ninety minutes after beginning the drug infusion rats were killed and gastric mucosal damage in the removed stomachs was assessed. Gastric mucosal blood flow (GMBF) was measured for 90 min with a 30 min-interval by the laser Doppler flowmetry method. ET induced severe gastric mucosal damage, which was characterized by congestion of mucosal capillary and accompanied by significant reduction of GMBF, as compared with control. However, these mucotoxic effect of ET was significantly inhibited by 20 mg/kg of ONO-1078 given i. g. 60 min before ET infusion and i. v. administration of 10 mg/kg of CV-3988 and 1 mg/kg of diltiazem 30 min prior to ET. From these results, we conclude that PAF, LT and Ca2+ may play important pathogenetic roles as chemical mediators in the mechanism of the formation of ET-induced gastric mucosal lesions.

Animals↗
PubMed1993

Changes of regional cerebral blood flow during listening to an unfamiliar spoken language.

The regional cerebral blood flow (rCBF) was measured with positron emission tomography in eight normal volunteers with the purpose of measuring rCBF changes related to the comprehension of an unfamiliar spoken languages. When attempting to comprehend the meaning of words, the left hemisphere showed dominant increases in rCBF, however, when subjects attempted to evaluate the emotional tone of the same spoken passage, relatively large increases in rCBF more found in the right hemisphere. The results indicate that there may be several different auditory representations of language which involve both left and right hemispheres, both of which may contribute to the overall comprehension of spoken language.

Adolescent↗
PubMed1993

Substrate specificities of catalytic fragments of protein tyrosine phosphatases (HPTP beta, LAR, and CD45) toward phosphotyrosylpeptide substrates and thiophosphotyrosylated peptides as inhibitors.

The transmembrane PTPase HPTP beta differs from its related family members in having a single rather than a tandemly duplicated cytosolic catalytic domain. We have expressed the 354-amino acid, 41-kDa human PTP beta catalytic fragment in Escherichia coli, purified it, and assessed catalytic specificity with a series of pY peptides. HPTP beta shows distinctions from the related LAR PTPase and T cell CD45 PTPase domains: it recognizes phosphotyrosyl peptides of 9-11 residues from lck, src, and PLC gamma with Km values of 2, 4, and 1 microM, some 40-200-fold lower than the other two PTPases. With kcat values of 30-205 s-1, the catalytic efficiency, kcat/Km, of the HPTP beta 41-kDa catalytic domain is very high, up to 5.7 x 10(7) M-1 s-1. The peptides corresponding to PLC gamma (766-776) and EGFR (1,167-1,177) phosphorylation sites were used for structural variation to assess pY sequence context recognition by HPTP beta catalytic domain. While exchange of the alanine residue at the +2 position of the PLC gamma (Km of 1 microM) peptide to lysine or aspartic acid showed little or no effect on substrate affinity, replacement by arginine increased the Km 35-fold. Similarly, the high Km value of the EGFR pY peptide (Km of 104 microM) derives largely from the arginine residue at the +2 position of the peptide, since arginine to alanine single mutation at the -2 position of the EGFR peptide decreased the Km value 34-fold to 3 microM. Three thiophosphotyrosyl peptides have been prepared and act as substrates and competitive inhibitors of these PTPase catalytic domains.

Amino Acid Sequence↗
PubMed1993

Partial purification and characterization of a polyketide biosynthetic enzyme, 6-hydroxymellein synthase, in elicitor-treated carrot cell extracts.

6-Hydroxymellein synthase, an induced polyketide biosynthetic enzyme in carrot cell extracts, was purified about 240-fold and its properties were compared with those of fatty acid synthetases. Synthetic activity of 6-hydroxymellein was inhibited in the presence of sulfhydryl reagents; however, cerulenin, a well-known inhibitor of fatty acid synthetases, showed no inhibitory activity to the enzyme. Biosynthesis of 6-hydroxymellein includes an NADPH-dependent ketoreduction, and, in this reaction, the 4-pro-S-hydrogen of NADPH was specifically transferred to the compound. On the basis of stereochemical analyses of the biosynthetic process, it was concluded that the product of the ketoreduction is an optically active alcohol of R configuration. These stereo-specificities of the reduction process are identical to those of beta-ketoacyl reductase in fatty acid biosynthesis which are considered to be conserved in all organisms. The synthetic rate of 6-hydroxymellein was markedly reduced when the assay was carried out with deuterium-labeled NADPH. The observed isotope effect on the catalytic rate (kH/kD) was 5.20, suggesting that this ketoreduction is one of the rate-limiting processes in 6-hydroxymellein synthesis. More than 85% of the synthetic activity was found in the soluble fraction of carrot cells, and, unlike in fatty acid synthetases in higher plants, organelle-localizing activity was not observed.

Acyltransferases↗
PubMed1993

Genetic susceptibility to the induction of murine experimental autoimmune orchitis (EAO) without adjuvant. I. Comparison of pathology, delayed type hypersensitivity, and antibody.

In the present study, it was demonstrated that there were marked strain differences in susceptibility to the induction of our new murine model of experimental autoimmune orchitis (EAO; definite orchitis with hypospermatogenesis) induced by two or three sc injections with viable syngeneic testicular germ cells (TC) without any adjuvants. Among 12 inbred strains of mice examined, the A/J (H-2a), C3H/He (H-2k), and C3H/HeN (H-2k) strains were highly susceptible, whereas the C57BL/6N (H-2b), C57BL/10Sn (H-2b), BALB/cAnN (H-2d), AKR/N (H-2k), CBA/JN (H-2k), C3H/HeJ (H-2k), and MRL/lpr (H-2k) strains were low susceptible, and the DBA/2N (H-2d) as well as C3H/BiKi (H-2k) strains were resistant. In particular, mice of the H-2k haplotype demonstrated varying degrees of susceptibility, from highly to totally resistant, to the induction of EAO. Disease susceptibility to this type of EAO does not seem to be associated with a particular H-2 haplotype. All mice of the highly susceptible strains that received two injections of TC (TC x 2) developed a significant increase in both levels of delayed footpad reaction (DFR) to TC and anti-TC antibodies measured by ELISA. In the low susceptible and the resistant strains receiving TC x 2 or TC x 3, there was no correlation between the immune responses and the susceptibility to disease in these strains, with the exception of the BALB/cAnN mice receiving TC x 3. The low susceptible and the resistant mice that received TC x 2 were classified into four groups based on the DFR and antibody response: the C57BL/6N, BALB/cAnN, CBA/JN, and C3H/HeJ strains were both positive, and the C57BL/10Sn and AKR/N strains were both negative or very low; the DBA/2N and MRL/lpr strains showed negative DFR and positive antibody response, and the C3H/BiKi strain showed quite the opposite. Almost all mice of the 12 inbred strains that received TC x 3 showed positive antibody response, although its level varied. There seems to be no linkage between the cell-mediated and humoral immune responses and the H-2 locus in our new EAO model.

Animals↗
PubMed1993

Preoperative combined treatment with radiation, intraluminal hyperthermia, and 5-fluorouracil suppositories for patients with rectal cancer.

A clinical trial of a novel modality consisting of preoperative irradiation and intraluminal hyperthermia therapy, with or without 5-fluorouracil (5-FU) suppositories, was conducted on 30 patients with rectal cancer. To create hyperthermia in rectal cancer, an intraluminal electrode connected to a radiofrequency system was devised. Patients were treated preoperatively with a total irradiation dose of 30 Gy, being 3 Gy every 2 days, and 5 applications of hyperthermia given twice a week, with or without 5-FU suppositories, given as 100 mg a day to a total of 2,000 mg. Twenty patients received irradiation, intraluminal hyperthermia, and 5-FU suppositories, being the three-combination treatment, and the remaining 10 received irradiation and intraluminal hyperthermia, being the two-combination treatment. Shrinkage of the rectal cancer was observed macroscopically in 26 patients, resulting in a flattened cancerous crater or shallow ulcer. Microscopic examination revealed a marked decrease in the number of cancer cells. In fact, three resected specimens showed no evidence of cancer cells microscopically. These striking reductions in cancer size enabled us to successfully perform super-low anterior resections in four patients, with anastomoses being made just above the dentate line with a sufficiently safe margin. No serious complications were encountered in this series.

Aged↗
PubMed1993

Low R-wave amplitude in the right precordial leads in children with symptomatic doxorubicin cardiomyopathy.

Electrocardiographic (ECG) findings were studied in four patients with doxorubicin cardiomyopathy. In all patients with congestive heart failure (CHF), the ECGs had a low R-wave and low R/S ratio in lead V1. Our study suggests that increased injury to myocardial cells in the regions of the anterior septum and anterior left ventricular wall may be important in the pathogenesis of doxorubicin cardiomyopathy. Eight years later, cardiac recovery from CHF occurred with a normal ECG and left ventricular ejection fraction in one patient, indicating that CHF may be reversible in certain cases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Secondary spontaneous pneumothorax.

To assess the clinical manifestations and therapy of secondary spontaneous pneumothorax (SSP), 123 episodes of SSP in 67 patients were retrospectively reviewed and were compared with 254 episodes of primary spontaneous pneumothorax in 130 patients. The major underlying lung diseases associated with SSP were emphysema (22 patients) and tuberculosis (21 patients). The average age of patients with SSP was 66.8 years, and the most common symptom was dyspnea. The average arterial oxygen tension at onset of SSP was 61.1 +/- 12.1 mm Hg (mean +/- standard deviation), which was lower than that of patients with primary spontaneous pneumothorax (p < 0.01). The recurrence rate of open thoracotomy with pleural abrasion was 12.5% (3 of 24 episodes), which was not lower than that of thoracostomy tube drainage with chemical pleurodesis using tetracycline (recurrence rate, 18.8%) (p > 0.5). We concluded that considering the high age of the patients, the presence of underlying lung diseases, and the increased operative risk, thoracostomy tube drainage rather than open thoracotomy was preferred as the first choice of therapy for SSP.

Adolescent↗
PubMed1993

Serotonergic regulation of the spinal cord content of thyrotropin releasing hormone in the cerebellar ataxia mutant mouse.

The effects of serotonin (5-HT) and various serotonin receptor antagonists on the spinal cord thyrotropin releasing hormone (TRH) content were studied in the rolling mouse Nagoya (RMN) and in the unaffected C3H mouse. TRH was extracted from the cervical, thoracic, lumbar, and sacral cord, at 1 h after the intraperitoneal injection of a serotonin precursor, 2 serotonin agonists, and 5 serotonin receptor antagonists. Administration of 5-hydroxytryptophan and 2-methyl-5-hydroxytryptamine resulted in an increase of the spinal cord TRH content in C3H mice, but not in RMN. Parachlorophenylalanine decreased the spinal cord TRH content in C3H mice, while it increased TRH levels in all regions of the RMN spinal cord. The TRH contents were decreased in all regions of the spinal cord after 5,7-dihydroxytryptamine administration in both C3H mice and RMN. In C3H mice, methysergide, mianserin, ketanserin, and spiperone significantly decreased the TRH content in all regions of the spinal cord, while 3 alpha-tropanyl-1H-indole-3-carboxylic acid ester (ICS205-930) did not affect it. These antagonists paradoxically increased TRH levels in the cervical cord in RMN. The degradation of synthetic TRH by cord homogenates and the number and affinity of spinal cord serotonergic receptors (5-HT1 and 5-HT2) showed no significant difference between C3H mice and RMN. These results suggest that TRH turnover is abnormally regulated by serotonergic neurons in the RMN and that the dysfunction of the serotonergic nerves is attributable to the serotonin autoreceptor.

Animals↗
PubMed1993

6-[18F]fluorodopa metabolism in patients with hemiparkinsonism studied by positron emission tomography.

A group of 10 healthy control subjects and 10 patients with hemiparkinsonism (HD) were studied by positron emission tomography (PET) using 6-[18F]fluorodopa (FDOPA). FDOPA metabolism in the caudate nucleus and the putamen was separately estimated by measuring target-to-background ratios (TBRs) using composite images added between 30 and 60 min after FDOPA injection and by TBR-versus-time slopes during PET study. TBRs in the caudate nucleus and the putamen were 1.81 +/- 0.23 (mean +/- SD) and 1.92 +/- 0.28 in the 10 controls, respectively. In HD patients, on the dominantly affected hemisphere related to main clinical symptoms, TBRs were significantly decreased in the caudate nucleus (P < 0.01) and the putamen (P < 0.05) compared with those in the corresponding areas on the contralateral hemisphere, though those TBRs on both hemispheres were significantly decreased compared with the TBRs of normal subjects (P < 0.01). TBRs and TBR slopes in both the caudate nucleus and the putamen were correlated with disease severity according to Hoehn and Yahr. On the dominantly affected hemisphere, TBR and TBR slopes in the putamen were well correlated with individual clinical measures for bradykinesia and rigidity, and those in the caudate nucleus were also correlated with the severity of tremor. Our data suggest that in HD patients, PET study using FDOPA may provide unique and efficient information on the dysfunction of the dominantly affected caudate nucleus and the putamen which are correlated with diseased severity and individual clinical symptoms.

Adult↗