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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 1,171 records · Page 65Linked to original sources

[Experimental hyperthermo-chemotherapy for human gastric carcinoma transplanted in the nude mice].

Human gastric carcinomas serially xenotransplanted into BALB/c nu/nu mice were treated by hyperthermo-chemotherapy with mitomycin C (MMC). The antitumor efficacy was assessed by both single and double treatments of 25-minute hyperthermia (43.5 degrees C) and/or 2.0 mg/kg of MMC (ip). Tumor weight was estimated using Battelle's Columbus Laboratories protocol. To assess DNA biosynthesis in the tumor cells, the xenotransplanted tumors were excised at prescribed times after these treatments 60 minutes after 3H-thymidine injection (ip), and were examined microscopically. In the group treated twice by hyperthermo-chemotherapy marked growth inhibition and microscopic damage of the tumors were observed, while such features were not recorded in groups treated twice by hyperthermia only and chemotherapy only, nor in groups given single hyperthermo-chemotherapy, or hyperhermia and chemotherapy. In the single-treated groups, DNA biosynthesis was remarkably inhibited by hyperthermo-chemotherapy over 24 hours. The present results suggest that repeated treatments of hyperthermo-chemotherapy with MMC may be effective in the treatment of human gastrointestinal cancer.

Animals↗

Inactivation of toxin B from the Indian cobra by cleavage of a specific bond during limited hydrolysis with trypsin.

Two neurotoxins, "toxin B", a long neurotoxin from Naja naja, and "cobrotoxin", a short neurotoxin from Naja naja atra, were compared with respect to their limited hydrolysis by trypsin and chymotrypsin and its effect on their neurotoxicity. Limited hydrolysis of toxin B with trypsin cleaves peptide bonds at Arg68-Lys69 and Arg33-Gly34 in the toxin molecule and causes complete loss of the neurotoxicity yielding des-carboxyl terminal toxin B(1-68) nicked at Arg33-Gly34 in the molecule. On the other hand, the des-carboxyl terminal toxin B(1-67) shows 70% of the native toxin B neurotoxicity. These results indicated that the complete loss of the toxicity may be due to hydrolysis of a specific peptide bond, Arg33-Gly34, in the toxin B molecule. Limited trypsin digestion did not affect the toxicity of cobrotoxin and limited chymotrypsin digestion had no effect on either neurotoxin.

Amino Acid Sequence↗

[Evaluation of right ventricular wall contractility in ischemic heart disease by cardiac computed tomography].

One hundred and eight cases with ischemic heart disease except for acute myocardial infarction were examined by cardiac computed tomography with ECG-gated scanning. The right ventricular (RV) wall contractility was evaluated by the long-axial and short-axial CT images in terms of (a) contraction rate of the RV area, (b) shortening rate of the RV free wall and (c) changes in the thickness of the RV free wall in cardiac cycle. These parameters were compared to the findings of coronary angiography and left ventriculography. 1. There was no difference of the contraction rate of the RV area between the cases with severe (90-100%) right coronary (RCA) stenosis and those with mild (0-75%) stenosis, while the contraction rate of the RV area was markedly decreased in the former combined with the impaired contraction of the ventricular septum. Consequently, it was assumed that RV function is hardly damaged by RCA lesion alone, and that the contraction rate of the RV area is not a suitable parameter for the assessment of the severity of RCA stenosis. 2. The shortening rate of the RV free wall in the long-axial image in cases with severe RCA stenosis was significantly decreased (14.5 +/- 4.6%) compared with that of mild stenosis (27.8 +/- 5.0%). The changes in the thickness of the RV free wall were also impaired in severe RCA stenosis. Same tendency was observed in the short-axial image, while the correlation between RCA stenosis and impaired contraction of the RV free wall was much more evident in the long-axis image than in the short-axis image. As the result, reduced RV contraction due to RCA ischemia seems to exist not only in acute myocardial infarction but also in chronic stage of the ischemic heart. 3. CT method is suitable for the evaluation of RV ischemia due to RCA lesion because the contractility of the RV free wall can be assessed independently of ventricular septal contraction. In cases with reduction of the free wall shortening rate under 20% combined with poor change in the thickness of the RV free wall, severe stenosis of the RCA should be suspected.

Angiography↗

[Aortic flow patterns in heart diseases with left-to-right shunts from the aorta, and their clinical significance: a Doppler echocardiographic study].

Aortic flow patterns were analyzed using two-dimensional Doppler echocardiography for 15 patients with patent ductus arteriosus, seven with ruptured aneurysms of the sinus of Valsalva, two with coronary artery fistulae and for 22 healthy persons, with special reference to diastolic flow patterns. The conclusions were as follows: In healthy subjects, there was a tiny and transient reversed flow signal in early diastole followed by a slow and sustained diastolic forward flow signal. The velocity of the diastolic forward flow was slower and the duration was shorter in the lower abdominal aorta than in the upper portion. In patients with shunts from the aorta to the right-sided chambers, the early diastolic reverse flow was enhanced, and another reversed flow developed in mid- and late diastole, which was the most evident in the lower portion of the abdominal aorta. The extent of the reversed flow correlated significantly with Qp/Qs by catheterization (r = 0.73). Thus, the abdominal flow patterns in cases with left to right shunts from the aorta to the right-sided chambers of the heart provided information for estimating the size of the shunt volume. In patients with bi-directional shunts, the dominant direction of the shunt during diastole can apparently be determined by analyzing the aortic flow patterns.

Adolescent↗

Increased anticonvulsant effect of phenytoin in aging BDF1 mice.

The anticonvulsant effect of phenytoin was examined in BDF1 mice of both sexes and various ages (6, 12, 24 and 30 months old) using the abolition of the tonic hindlimb extensor component of maximal electroshock seizure as the index. The minimal effective plasma concentration of phenytoin was significantly lower in 24- and 30-month-old mice compared with young adult (6 month old) mice. Similarly, all older groups (24 and 30 month old, both sexes) showed significantly lower minimal effective brain concentrations compared with respective younger (6 and 12 month old) animal groups. Studies using nearly 2-fold different intensities of electroshock (30 and 55 mA) showed almost identical results. The results provide evidence that, in adult mice, the brain becomes more sensitive with age to phenytoin with regard to its anticonvulsant effect.

Aging↗

[Clinical effect of human lymphoblastoid interferon in patients with multiple myeloma].

Five patients with multiple myeloma were treated with human lymphoblastoid interferon (HLBI). HLBI, 3 X 10(6) IU/day, was administered daily for more than two weeks by intramuscular injection. Out of four evaluable patients, a minor response was obtained in 3 patients. In these responders, one patient developed pleural effusion due to the infiltration of myeloma cells during the administration of HLBI, and drug resistance was observed in another patient during the re-administration of HLBI. Therefore, out of six evaluable courses, a minor response was obtained in 3 courses of HLBI treatment. No severe side effects were observed. Thrombocytopenia, general malaise, liver dysfunction and anorexia were the main reasons for discontinuation of HLBI administration. On the basis of the preliminary study, it is concluded that HLBI is worth trying in the management of refractory multiple myeloma.

Anorexia↗

Resonance Raman study on the flavin in the purple intermediates of D-amino acid oxidase.

Resonance Raman (RR) spectra were measured for the purple intermediates of D-amino acid oxidase reconstituted with isotopically labelled FAD's, i.e., [4a-13C]-, [4,10a-13C2]-, [2-13C]-, [5-15N]-, and [1,3-15N2]flavin adenine dinucleotides, and compared with those with the native enzyme. The RR lines around 1605 cm-1 with D-alanine or D-proline as a substrate and at 1548 cm-1 with D-alanine undergo isotopic shifts upon [4a-13C]- and [4,10a-13C2]-labelling. These lines are assigned to the vibrational modes associated with C(10a) = C(4a) - C(4) = O moiety of reduced flavin, providing the first assignment of RR lines of reduced flavin and conclusive evidence that reduced flavin is involved in this intermediate.

Animals↗

Microvascular abnormalities in ethylnitrosourea (ENU)-induced rat brain tumors: structural basis for altered blood-brain barrier function.

The fine structure, histometric characteristics, and permeability of microvessels were studied by electron microscopy in normal and in ethylnitrosourea (ENU)-induced glioma tissue from rats, using horseradish peroxidase (HRP) as a tracer. The tumor vessels were classified into (1) capillary buds (Type I); (2) round small to large capillaries (Type II); (3) sinusoidal or venule-like microvessels (Type III), and (4) abnormal arteriole-like microvessels (Type IV). All endothelial cells, basement membranes and periendothelial cells in the tumor tissue demonstrated changes in structure. The most striking alterations occurred in the endothelial cells; there were abnormal endothelial tight junctions, altered pinocytotic activity, and thickening. In the tracer study, the reaction product of HRP was present around some sinusoidal or venule-like microvessels (Type III) and extended to the widened extracellular spaces around the microvessels. The endothelial cells of Type III microvessels showed decreased nuclear and mitochondrial fractions, and increased euchromatin content and a rough endoplasmic reticulum fraction. The pinocytotic vesicles with the HRP reaction product in the endothelial cells were not increased in number. Fenestrations and gaps of the endothelial cells were observed. These alterations of the endothelial cells of sinusoidal or venule-like microvessels (Type III) are considered to be the main cause of breakdown of the blood-brain barrier in this tumor.

Animals↗

P300 and stimulus evaluation process in autistic subjects.

Cognitive functioning in autistic subjects was investigated by employing ERP recordings. The sample included four autistic patients, with five normal subjects and four Down's syndrome patients serving as the two control groups. The P300 component was investigated under three different experimental conditions, that is; "No-task," "Counting," and "Keypress." Two out of four autistic subjects were able to perform the required task under the Counting condition. However, none of them were able to complete the task for the Key-press condition. Autistic subjects demonstrated a lower amplitude of the P300 component under the No-task condition as compared to the other two groups. It was speculated that the autistic, as opposed to the other two groups, had some cognitive difficulties in the "active stimulus evaluating process."

Adolescent↗

Severe hepatitis during ketoconazole therapy.

Ketoconazole is an imidazole derivative recently developed as an antifungal agent. There have been only a few established cases of hepatotoxicity in the literature. This report describes a case of presumed ketoconazole hepatotoxicity characterized by the development of severe hepatitis with marked centrilobular necrosis. The lack of hypersensitivity reactions in clinical findings and centrilobular location of necrosis suggested a host idiosyncrasy with metabolic abnormality as the effect of ketoconazole in the present case.

Adult↗

A quantitative study of the muscle satellite cells in various neuromuscular disorders.

The regenerative ability of muscles was studied in various neuromuscular disorders by quantitative electron microscopy using two indices of both the satellite cell population and the euchromatin percentage of satellite cell nucleus. Both the number of satellite cells and the euchromatin percentage were increased in polymyositis. Duchenne muscular dystrophy and myotonic dystrophy showed only an increased number of satellite cells without increased euchromatin percentage, while amyotrophic lateral sclerosis had only an increased euchromatin percentage without increased satellite cell number. These results suggest that some defects of satellite cell function probably exist in progressive muscular dystrophy and amyotrophic lateral sclerosis, while in polymyositis the muscle fiber may have the ability to regenerate completely. The euchromatin percentages of myonuclei were increased in polymyositis and Duchenne muscular dystrophy, but not in amyotrophic lateral sclerosis or myotonic dystrophy compared to those of controls. This suggests the activated function of the remaining muscle fibers in polymyositis and Duchenne muscular dystrophy.

Adult↗

Differentiation of human leukemia cells and its usefulness for clinical diagnosis.

Various chemical inducers have effects on the induction of terminal differentiation of human myelogenous leukemia cell lines. We studied morphological and functional changes of human leukemia cells freshly obtained from patients using 12-0-tetradecanoyl phorbol-13-acetate (TPA), retinoic acid (RA) or dimethyl sulphoxide (DMSO). The myeloid leukemia cells cultured with TPA became adherent to plastic culture dishes, and then developed macrophage-like morphology with long filamentous pseudopods within 48 h incubation. They showed marked enhancement of the ability to phagocytose latex particles. But these acquired properties did not always parallel each other, suggesting that the mechanism of functional maturation of leukemic cells induced by chemical agents was not identical with that of morphological changes. On the other hand, the lymphoid leukemia cells did not show morphological and functional changes when cultured with the above inducers. It is suggested that exposure of leukemic cells to TPA for relatively short times (12-24 h) may be useful for determining whether they are of myeloid or lymphoid origin. These characteristic changes were also observed in leukemic cells from the myeloid or lymphoid crisis of chronic myelogenous leukemia.

Cell Differentiation↗

Spectroscopic studies on the photoreaction of choline oxidase, a flavoprotein, with covalently bound flavin.

Formation of the anionic flavosemiquinone was observed spectrophotometrically during the anaerobic photo-irradiation of Alcaligenes sp. choline oxidase in the presence of EDTA. Further irradiation slowly converted the semiquinone form into the fully reduced state. The presence of a catalytic amount of riboflavin greatly enhances the photoreduction rate not only to the semiquinone state but also to the fully reduced state. This semiquinone species has low reactivity toward the substrate, choline or betaine aldehyde, as well as toward oxygen. This low reactivity toward oxygen is unique to the semiquinone form of a flavoprotein oxidase. The oxidized enzyme forms a complex with betaine, the product of the enzymatic reaction of choline oxidase. The dissociation constant for this complex was found to be 17 mM by spectroscopic titration. Anaerobic photo-irradiation of the enzyme with a saturating amount of betaine in the absence of EDTA produces, with no detectable semiquinone formation, an absorption spectrum which resembles (but significantly differs from) that of the fully reduced form. This species was found to comprise two flavin species. One of them is rapidly oxidized to the oxidized form by oxygen and is thus assigned as the fully reduced state. The other is converted slowly to the oxidized form upon aerobic standing in the dark. We tentatively assigned this latter species as a C(4a)-adduct. Formaldehyde was detected as a product of this photoreaction. The amount of formaldehyde formed coincided with that of the fully reduced enzyme. On the basis of the results obtained we propose a mechanism of the photoreaction of the enzyme in the presence of betaine where a C(4a)-adduct and the fully reduced enzyme via an N(5)-adduct are formed. Betaine also affects the dithionite reduction. In the dithionite reduction of the oxidized enzyme, the semiquinone species is an intermediate in the conversion of the oxidized to the fully reduced form, while the reduction of the oxidized enzyme-betaine complex with dithionite produces the fully reduced form without any significant formation of the semiquinone species.

Alcaligenes↗

On the structures of flavoprotein D-amino acid oxidase purple intermediates. A resonance Raman study.

Resonance Raman (RR) spectra were obtained in H2O or D2O solution for the purple intermediates of D-amino acid oxidase (DAO) with isotopically labeled substrates, i.e., [1-13C]-, [2-13C]-, [3-13C]-, [15N]-, and [3,3,3-D3]alanine; [carboxyl-13C]- and [15N]proline. RR spectra were also measured for the intermediates of DAO reconstituted with isotopically labeled FAD's, i.e., [4a-13C]-, [4,10a-13C2]-, [2-13C]-, [5-15N]-, and [1,3-15N2]FAD in D2O. The isotopic shift of the 1692 cm-1 band upon [15N]- or [2-13C]-substitution of alanine indicates that the band is due to the C = N stretching mode of an imino acid derived from D-alanine, i.e., alpha-iminopropionate. The 1658 cm-1 band with D-proline was also assigned to the C = N stretching mode of an imino acid derived from D-proline, i.e., delta 1-pyrrolidine-2-carboxylate, since the band shifts to 1633 cm-1 upon [15N]-substitution and its stretching frequency is generally found in this frequency region. Since the band shifts to low frequency in D2O, the imino acid should have a protonated imino group such as the C = N+1H form. The intense band at 1363 cm-1 with D-alanine was assigned to a mixing of the CO2- symmetric stretching and CH3 symmetric deformation modes in alpha-iminopropionate, based on the isotope effects. The 1359 cm-1 band with D-proline has probably contributions of CO2- symmetric stretching and CH2 wagging, considering the isotope effects with [carboxyl-13C]proline. The 1359 cm-1 band with D-proline was split into 1371 cm-1 and 1334 cm-1 bands in D2O. As this splitting of the 1359 cm-1 band with D-proline in D2O can not be interpreted only by the replacement of the C = N+1-H proton by deuterium, the carboxylate of the imino acid probably interacts with the enzyme through some proton(s) exchangeable by deuterium(s) in D2O. The bands around 1605 cm-1 which shift upon [4a-13C]- and [4,10a-13C2]-labeling of FAD are derived from a fully reduced flavin, because the isotopic shifts of the band are very different from those of the bands of oxidized or semiquinoid flavin observed near 1605 cm-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine↗

The Klebsiella O3 lipopolysaccharide isolated from culture fluid: structure of the polysaccharide moiety.

In a series of our earlier studies, the O3 antigen isolated from culture supernatant of Klebsiella pneumoniae strain Kasuya (O3:K1) (KO3) was shown to exhibit very strong adjuvant activity in mice. KO3 obtained was homogeneous in analyses by either gel filtration or ultracentrifugation. Its molecular weight determined by ultracentrifugal analysis was greater than 2 X 10(6). It contained 37.9% C, 6.20% H, 0.24% N, and less than 0.1% P. KO3 was degraded into the polysaccharide moiety and lipid moiety (about 20%) by hydrolysis with 1% acetic acid at 100 C for 1 hr. The molecular weight of the polysaccharide moiety obtained by the hydrolysis was 16,200 as determined by the Somogyi-Nelson method. Chemical analyses using methylation analysis and Smith degradation as the principal methods indicated that the polysaccharide moiety consisted of a mannan which has a pentasaccharide repeating unit of alpha-mannosyl-1,3-alpha-mannosyl-1,2-alpha-mannosyl-1,2-alpha-mannosyl-1, 2-alpha-mannose joined through alpha-1,3-mannosyl linkages. The number of repetitions was less than 20. The fact that minor components such as 2-keto-3-deoxyoctonate and glucose were detected suggests the presence of a core oligosaccharide, but its precise structure is unknown.

Antigens↗