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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 955 records · Page 53Linked to original sources

Enhancement of hyperthermochemotherapy for human gastric cancer in nude mice by thermosensitization with nitroimidazoles.

Hyperthermia for human gastric cancer xenotransplanted into the hindlegs of nude mice was performed to determine whether misonidazole (MISO) or metronidazole (MTR), derivatives of nitroimidazole, would intensify the antitumour effects of hyperthermia only, or combined with mitomycin C (MMC). MISO, MTR and MMC were given i.p. at doses of 500 mg kg-1, 500 mg kg-1 and 2.0 mg kg-1 respectively, and MISO or MTR was administered 45 min before MMC. Hyperthermia was applied twice at 48 h intervals, by means of a water bath at 43.5 +/- 0.1 degrees C for 23 min. Tumour tripling times following heat alone, MTR plus heat, and MISO plus heat were about 6.7, 8.0 and 7.9 days respectively, compared with 4.6 days for the control, but tumour regression occurred in the heat plus MISO group only. Tumour tripling times for MMC plus heat, MMC plus MTR plus heat, and MMC plus MISO plus heat were 9.6, 11.6 and 17.1 days respectively, compared to 4.6 days for the control and 6.7 days for heat alone. These data suggest that the antitumour activity of MMC plus MISO plus heat is an additive phenomenon.

Animals↗

Case report of biliary atresia associated with preduodenal portal vein, ventricular septal defect and bilobed spleen.

A case report of biliary atresia associated with preduodenal portal vein is presented with a review of 27 similar cases previously reported. The occurrence of associated anomalies in these 28 cases has a much higher frequency (82%) than coincidental association. They were associated with cardiovascular anomalies in 71%, polysplenia in 68%, malrotation of the intestine in 61%, situs inversus in 22% and duodenal atresia in 9%. Developmental anomaly is considered to participate strongly in the aetiology of biliary atresia combined with preduodenal portal vein.

Bile Ducts↗

Intraperitoneal hyperthermic perfusion combined with surgery effective for gastric cancer patients with peritoneal seeding.

Fifteen patients with far-advanced gastric cancer were given surgical treatment followed by intraperitoneal hyperthermic perfusion (IPHP) with mitomycin C (MMC) and misonidazole (MIS), a thermosensitizing drug. Immediately after extensive resection of the abdominal tumors, a 2-hour IPHP was performed at the inflow temperature of 44.7 to 48.7 C, using equipment designed for treatment of cancerous peritoneal seeding as a closed circuit, and under hypothermic general anesthesia at 30 to 31 C. In nine of the 15 patients with peritoneal seeding and/or ascites, cancerous ascites was absent after this treatment. In all cases, repeated cytologic examinations of the lavage from Douglas's pouch were negative. The postoperative courses were uneventful except for Patients 1 and 10, in whom slight leakage occurred. All patients were discharged and are in good health at the time of this writing, 7.2 +/- 4.6 months after the treatment. The Case 4 Patient recently died in a traffic accident. In all patients, transient hepatic dysfunction and hypoproteinemia occurred after the operation. This extensive surgery combined with IPHP using MMC and MIS was well tolerated and is a safe antitumor treatment for gastric cancer with peritoneal dissemination. Neurotoxicity due to MIS was nil.

Adult↗

Comparison of ionic and nonionic low-osmolar contrast media in coronary arteriography. A crossover study in children.

Twenty-six patients with Kawasaki disease were observed in a prospective crossover study to compare coronary arteriography with a nonionic low-osmolar contrast medium, iopamidol 370 mgI/mL, and with an ionic low-osmolar contrast medium, ioxaglate 320 mgI/mL. A slight heart rate change and no severe arrhythmia during coronary arteriography were observed with both agents. Electrocardiographically, QTc elongation and ST-T changes were marked in ioxaglate and minimal in iopamidol. No ventricular fibrillation occurred with either agent. Both contrast media provided adequate visualization for the diagnosis of Kawasaki disease, but the contrast of the images and the visualization of details were better with iopamidol than with ioxaglate. Iopamidol seems to be superior to ioxaglate in pediatric coronary arteriography.

Angiography↗

In vitro hexagonal assembly of R-form lipopolysaccharides: effect of pH on the Mg+2-mediated hexagonal assembly.

The R-form lipopolysaccharide (LPS) from Escherichia coli K-12, from which cationic material had been removed by electrodialysis and the pH of which had fallen to 3.6, formed a rough hexagonal lattice structure with the lattice constant of about 19 nm. The rough hexagonal structure was maintained in buffers at pH 5 or lower but disintegrated into the ribbon-like structures in buffers at pH 6 or higher. However, in the presence of 10 mM Mg2+, the hexagonal lattice structure was not disintegrated even at alkaline pH levels but conversely it became more dense. At pH 8.3 to 8.9, the hexagonal lattice structure with the shortest lattice constant (15 nm) was formed. The same optimal pH levels were obtained for formation of the dense hexagonal lattice structure (lattice constant, 14 to 15 nm) by the electrodialyzed LPS from Klebsiella pneumoniae strain LEN-111 (O3-:K1-). The ability of Mg2+ to induce formation of the dense hexagonal lattice structure of the K-12 LPS depends upon the presence of buffers showing the optimal pH levels, since a very high concentration of Mg2+ such as 500 mM was required for the lattice formation in distilled water. The amount of the magnesium bound to the K-12 LPS did not significantly differ throughout the pH range of 3 to 9. Therefore, the optimal pH range is another essential factor for formation of the dense hexagonal lattice structure of the LPS in addition to binding of the magnesium to the LPS.

Dialysis↗

Formation of a hexagonal lattice structure by an R-form lipopolysaccharide of Klebsiella: effect of various divalent cations on the lattice formation.

The R-form lipopolysaccharide from Klebsiella pneumoniae strain LEN-111 (O3-:K1-), from which cationic material had been removed by electrodialysis, was previously shown to form a hexagonal lattice structure with the lattice constant of 14 to 15 nm when suspended in 50 mM tris(hydroxymethyl)aminomethane buffer at pH 8.5 containing 10 mM Mg2+. Under this experimental condition, effects of other divalent metal cations on the hexagonal assembly of the electrodialyzed LPS were compared with that of Mg2+. The Zn2+, Hg2+, Cu2+, and Ni2+ could produce essentially the same hexagonal lattice structure with the lattice constant of 14.5 to 15.0 nm as that formed with Mg2+. The Cd2+, Co2+, and Fe2+ produced the hexagonal lattice structure with the lattice constant of 15.5 to 16.0 nm, and Ba2+, Sr2+, and Ca2+ produced that with the lattice constant of 18 to 19 nm. In addition, the hexagonal lattice structures formed with the latter three cations were less orderly than those formed with the other cations. When the higher concentrations of Ba2+, Sr2+, and Ca2+ were used, the lattice constants were not shortened. The length of lattice constants of the hexagonal lattice structures formed with the divalent cations did not relate to the quantity of the cations bound to the LPS. Among the divalent cations tested, Hg2+ was bound to the LPS in the smallest amount (its atomic ratio to P, 0.07), and Zn2+ and Fe2+ were bound in very large amounts (their atomic ratios to P, 2.94 and 8.28, respectively).

Cations, Divalent↗

Clinical application of phorbol diester-induced leukemic cell differentiation for the definite diagnosis of acute leukemias.

Seventy-three patients with acute leukemias or chronic myelogenous leukemias in blast crisis were evaluated as to the susceptibility of their leukemic cells to differentiation induction by a chemical agent, 12-O-tetradecanoyl phorbol-13-acetate (TPA). Leukemic cells of myeloid origin treated with TPA showed monocyte-macrophage-lineage differentiation morphologically and functionally, whereas those of lymphoid origin did not. We applied these differentiation phenomena for the clinical diagnosis of three leukemia cases in whom it was difficult to determine whether the leukemic cells were of non-lymphoid or lymphoid origin, although all the regular diagnostic procedures available had been performed. We successfully diagnosed these three cases by utilizing the above differentiation phenomena. Furthermore, this technique was clinically beneficial as to the choice of adequate chemotherapy in each of these leukemia cases. These findings confirm that the responsiveness to TPA of leukemic cells is of clinical usefulness for the definite diagnosis of acute leukemias.

Acute Disease↗

Tourette's disorder coupled with infantile autism: a prospective study of two boys.

In a longitudinal study, two boys in the Outpatient Psychiatric Clinic at Tokyo University were found to exhibit Tourette's disorder in addition to the original diagnoses of infantile autism. This paper addresses problems of applying the diagnostic criteria of DSM-III in terms of voluntary tic suppression in diagnosing patients with both disorders. Differences between motor tics and stereotyped movements in patients with both infantile autism and Tourette's disorder have been clearly distinguished. This may enable us to identify more autistic individuals with Tourette's disorder by focusing on these differences. In contrast to Burd et al.'s findings and implications, these two boys have not manifested spurts in language and social relationships nor have their conditions significantly improved, despite the development of Tourette's disorder.

Adult↗

Light and electron microscopic study of the liver in paraquat poisoning.

Intrahepatic cholestasis in paraquat poisoning in man has been thought to be secondary to extensive bile duct injuries, though its exact mechanism remains unsettled. We have examined liver biopsy specimens from two cases of paraquat poisoning. Case 1 (fatal) presented severe intrahepatic jaundice, and liver biopsy showed centrilobular cholestasis with extensive bile duct loss. Ultrastructurally, dilatation of bile canaliculi with decrease of microvilli and thickening of pericanalicular ectoplasm was found in the hepatocytes. Case 2 (alive) showed mild liver dysfunction without jaundice. While liver biopsy showed nonspecific reactive changes with intact bile ducts and ductules, electron microscopy disclosed dilatation of bile canaliculi with decrease of microvilli and thickening of pericanalicular ectoplasm in the hepatocytes, suggesting that damage to the bile secretory apparatus in the hepatocytes develops irrespective of extensive bile duct loss. These findings suggest that bile secretory apparatus in the hepatocytes as well as biliary epithelial cells could be a target of paraquat or its metabolites.

Adult↗

Identification of a cis-regulatory element involved in accumulation of human T-cell leukemia virus type II genomic mRNA.

The X gene products of the human T-cell leukemia viruses type I and II are thought to be involved not only in viral replication but also in mediating the expression of certain cellular genes. These X gene products are known to be translated from doubly spliced viral mRNA, while viral structural proteins, such as the gag, pol, and env gene products, are translated from unspliced or singly spliced viral mRNA. One of the X gene products of human T-cell leukemia virus type II, tax2 protein, has been shown to be responsible for transcriptional stimulation from the viral long terminal repeat. The other X gene product(s) of human T-cell leukemia virus type II, the rex2 protein(s), is located in the nuclear fraction of virus-infected cells, but its function is not known. This article reports evidence that rex2 protein(s) enhances the accumulation of unspliced viral RNA by interacting posttranscriptionally, either directly or indirectly, with a cis-regulatory element downstream from the first splice donor site in the long terminal repeat.

Cell Line↗

Capillary permeability and boron distribution in ethylnitrosourea-induced rat glioma.

The vasculature and capillary permeability of gliomas induced by ethylnitrosourea in Sprague-Dawley rats were studied with horseradish peroxidase and Evans blue dye. The distribution of the boron-10 compound, Na2(10)B12H11SH, which is now in clinical use for boron neutron capture therapy (BNCT) for brain tumors, was investigated quantitatively using neutron-induced alpha-autoradiography. The vasculature and the degree of capillary permeability varied widely, depending mainly on the size of the glioma, and were often heterogeneous even in the same tumor. The distribution of boron-10 also varied, correlating to capillary permeability. The boron-10 concentration and the tumor:blood concentration ratio in large and medium-sized gliomas were adequate for successful BNCT. This study suggests that the vasculature and capillary permeability of the target brain tumor exert an important influence on the therapeutic efficacy of BNCT.

Animals↗

Ultrastructural observation in clinical and experimental myocardial infarction, with reference to pathogenesis.

Electron microscopic investigation was carried out to confirm our hypothesis, derived from a large number of macroscopic and light-microscopic observations, that impairment of the peripheral circulation of the myocardium, and not the presence of coronary thrombi, plays the fundamental role in the development of acute myocardial infarction. The peripheral coronary vessels of 5 human hearts obtained at autopsy showed severe histolytic impairment of the endothelial cells and of the tunica media muscle cells, even though no myocardial necrosis was observed either macroscopically or microscopically. An additional experimental study using 12 rabbits was performed to ascertain the induction of myocardial necrosis without coronary occlusion, by intravenous administration of either epinephrine or endotoxin alone or a combination of both. One-third of the epinephrine group and all of the combined treatment group developed myocardial necrosis. The intramyocardial vessels of these rabbits showed similar hystolytic changes to those observed in human cases. These findings support our concept that derangement of the peripheral circulation precedes the development of a coronary thrombus in cases of acute myocardial infarction.

Animals↗

Release of atrial natriuretic peptide from the isolated, blood-perfused right atrium of the dog.

Release of atrial natriuretic peptide (ANP) was investigated using the isolated right atrium (RA) cross-circulated with heparinized arterial blood of the donor dog. ANP concentration of the blood was measured by radioimmunoassay. The plasma ANP concentration of the arterial blood of the donor dog (ANP-D) which perfused the RA preparation was 111 +/- 18 pg/ml (n = 4), while the ANP concentration of venous blood leaving the RA preparation (ANP-A) was 1680 +/- 220 pg/ml (n = 4). In comparison, the plasma ANP concentration of venous blood leaving the isolated papillary muscle of the right ventricle (ANP-V) was 106 +/- 19 pg/ml (n = 4), which was not significantly different from the ANP-D concentration. When the right atrium was electrically driven at a rate of 100 beats/min, almost the same rate as the spontaneous sinoatrial rate of 98 +/- 6 beats/min (n = 4), the ANP-A concentration was not changed (1630 +/- 160 pg/ml, n = 4). When the driving rate was increased to 200 beats/min, the ANP-A concentration was significantly increased to 2250 +/- 130 pg/ml (n = 4). These results suggest that ANP is exclusively secreted from the atrium, but not from the ventricle, and that release of ANP is directly related to atrial rate.

Animals↗