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Biomedical subjects

M Tsuchiya

Publications and source records attributed to M Tsuchiya.

At least 253 records · Page 14Linked to original sources

Elevated ratio of late measles among subacute sclerosing panencephalitis patients in Karachi, Pakistan.

Subacute sclerosing panencephalitis (SSPE) in Western countries and Japan is found more often in early- than in late-measles sufferers. Recent SSPE findings in Karachi, however, present a different picture. Age at measles contraction was obtained and analyzed for 44 SSPE patients identified in Karachi between 1983 and 1988. The ratios of early- (< 2 years of age) and late- (> or = 2 years of age) measles sufferers among 36 of these patients who had experienced only one attack of measles were 0.33 and 0.67, respectively. This is in striking contrast to the predominance of early measles in the SSPE histories reported in Japan and an number of Western countries.

Age Factors↗

[Application of the limulus amebocyte lysate test to measurement of endotoxin in therapeutic human plasma protein fraction. Comparison with the rabbit pyrogen test].

We applied the limulus amebocyte lysate (LAL) test to the detection of bacterial endotoxins in therapeutic human plasma protein fraction (PPF) and compared the LAL-test with the rabbit pyrogen test. Two endotoxin-specific LAL-reagents were used for the colorimetric method and turbidimetric kinetic method. The amounts of added endotoxin to the PPF were correctly estimated by either method. The results of four independent assays for the 53 samples of PPF corresponded well with each other (correlation coefficient: 0.851-0.959, regression coefficient: 0.898-1.151). The amounts of endotoxin in the PPF estimated by the LAL-test significantly correlated with the rise of body temperature in rabbits (correlation coefficient: 0.547-0.642, and 0.911-0.934 for the endotoxin added samples). These results suggest that the LAL-test could be used as an alternative method for the rabbit pyrogen test to PPF.

Animals↗

Quantitative analysis of mesenteric microcirculatory disturbances induced by autonomic nervous irritation.

In this study, we have demonstrated that repeated electrical stimuli to the artery of the mesenteric pedicle can produce mesenteric microcirculatory disturbance by autonomic nervous irritation in rats. The parameters to demonstrate microcirculatory damage were observed and quantitatively analyzed using the intravital microscopy after electrical stimulation for 40 minutes. The blood flow of arterioles and venules in the mesentery showed ischemia-reperfusion pattern during the repeated electrical stimulations. The diameter of arterioles did not show significant change, while RBC velocity of arterioles was significantly decreased at 30 min after the irritation. The RBC velocity in venules was decreased from the early period to about 20%. But this values were not significantly dropped during the later observation period, suggesting the formation of short circuit flow by passing the collapsed capillary beds. The number of rolling WBC in the venules was notably increased at the time immediately after irritation, and thereafter the number of rolling WBC number was rather reduced. The number of sticking WBC in venules was time-dependently increased and reached its maximum at 30 min. When permeability of venular wall was determined by the injection of pontamine sky blue, significant increase in permeability was already shown immediately after irritation, suggesting that the integrity of microvascular wall was disturbed in this early period. The permeated area expanded thereafter in parallel with the increase in sticking WBC number. From these observations, it is suggested that endothelial cell damage and following leukocyte-endothelium interaction induced by autonomic nerve irritation appear to be an important factor in microcirculatory disturbances.

Animals↗

Recent advances in the study of hepatocellular carcinoma.

Among the known causes for the occurrence of hepatocellular carcinoma (HCC), chemical carcinogens, chronic alcoholic intake and hepatitis B virus (HBV), especially in Asia, has been emphasized. HBV has been industriously studied and many queries about the relationship between HBV infection and hepatocarcinogenesis have been clarified. Recent discovery of hepatitis C virus (HCV) revealed that there may be the participation of this virus in hepatocarcinogenesis. However, a precise mechanism in such a viral infection has not been known. Host immunological defence mechanisms including the role of cytokines should be also taken into consideration. Cellular gene abnormalities have been noted in the late period of cancer cell progression. The technical development in the clinically available diagnostic procedures have enabled us to detect early phase of HCC. Some new concepts in the pathological diagnosis of precancerous lesions of HCC and also early HCC have been reported recently. We gave an outline of the recent advances and references in the study of HCC.

Carcinoma, Hepatocellular↗

Lipoate prevents glucose-induced protein modifications.

Nonenzymatic glycation has been found to increase in a variety of proteins in diabetic patients. The present study examined a possibility of preventing glycation and subsequent structural modifications of proteins by alpha-lipoic acid (thioctic acid) as lipoate, a substance which has gained attention as a potential therapeutic agent for diabetes-induced complications. Incubation of bovine serum albumin (BSA) at 2 mg/ml with glucose (500 mM) in a sterile condition at 37 degrees C for seven days caused glycation and structural modifications of BSA observed by SDS-PAGE, near UV absorption, tryptophan and nontryptophan fluorescence, and fluorescence of an extrinsic probe, TNS (6-(p-toluidinyl)naphthalene-2-sulfonate). When BSA and glucose were incubated in the presence of lipoate (20 mM), glycation and structural modifications of BSA were significantly prevented. Glycation and inactivation of lysozyme were also prevented by lipoate. These results suggest a potential for the therapeutic use of lipoic acid against diabetes-induced complications.

Diabetes Mellitus↗

Endotoxin removed from hemoglobin solution using polymyxin-B immobilized fibre (PMX-F) followed by a new turbidometric endotoxin assay.

Endotoxin contamination in modified hemoglobin can result in side effects. Accurate measurement and effective elimination of endotoxin are important in producing safe hemoglobin preparation. A new turbidometric endotoxin assay (Toxinometer) was studied, in which absorbance of wavelength was applied at 660 nm. This method is not affected by the presence of hemoglobin in solution. This way, toxinometer can accurately measure endotoxin concentration in hemoglobin solution. For the elimination of endotoxin, polymyxin-B immobilized fiber (PMX-F) was studied in-vitro and compared with commercial materials. The PMX-F was found to be a convenient and less expensive approach.

Animals↗

Endogenous arginine-specific ADP-ribosyltransferases and target proteins.

We investigated vertebrate arginine-specific ADP-ribosyltransferases and target proteins for the enzyme. ADP-ribosyltransferase found in each organelle ADP-ribosylated preferentially an endogenous acceptor protein co-localized with the enzyme. We propose that the ADP-ribosylation of tissue-specific target protein by the endogenous ADP-ribosyltransferase may participate in the regulation of cellular processes, including signal transduction.

ADP Ribose Transferases↗

Effect of dexamethasone, dimethylsulfoxide and sodium butyrate on a human hepatoma cell line PLC/PRF/5.

The effects of agents which are known to be differentiation inducers on a human hepatoma cell line PLC/PRF/5 were investigated. Dexamethasone (DEX), sodium butyrate (SB) or dimethylsulfoxide (DMSO) were examined. They all reduced cell proliferation but differ from each other in effect on the secretion of alphafetoprotein (AFP) and hepatitis B surface antigen (HBsAg), changes in morphology and RNA transcription. SB changed the cell from polygonal into a fibroblast-like type and decreased AFP secretion. DMSO decreased the cell size and changed AFP secretion in the same manner as SB. DEX changed the cell into a larger size, as well as increased AFP secretion. HBsAg secretion and also HB virus DNA transcription was enhanced by 3 agents. AFP and myc gene transcriptions were reduced by SB but DMSO reduced only AFP. Albumin gene transcription was enhanced by SB and DEX. These results indicate that the decrease of PLC/PRF/5 proliferation is induced through different mechanisms by these 3 agents.

Butyrates↗

Oxiradical-dependent photoemission induced by a phacoemulsification probe.

Oxygen free radical formation by conventional phacoemulsification devices has been postulated as a possible mechanism of corneal endothelial damage during surgery. To test this hypothesis, phacoemulsification probe-induced free radical production was visualized using a single photon-counting camera and an O(2-)-sensitive luciferin derivative, 2-methyl-6-[p-methoxyphenyl-3,7-dihydroimidazo [1,2-a]pyrazin-3-one (MCLA), which allows the visualization of spatial and temporal alterations in free radical production. Within 1 min after starting ultrasound emission, MCLA-dependent chemiluminescence was increased significantly, the intensity of which was maximal at the tip of the probe and tapered along a gradient toward distal portions. The chemiluminescence was suppressed significantly by adding either superoxide dismutase (300 U/ml) or sodium azide (20 mmol/l). By adding deuterium to the medium, MCLA-dependent chemiluminescence significantly increased, suggesting the involvement of singlet oxygen in the reaction.

Azides↗

Topographic dissociation between mitochondrial dysfunction and cell death during low-flow hypoxia in perfused rat liver.

BACKGROUND: Although it has been postulated that mitochondrial dysfunction and oxygen radicals may play a role in the mechanisms of hypoxic liver injury, little is known about the intralobular topographic relationship between a disorder in oxygen metabolism and cell death during hypoxia. EXPERIMENTAL DESIGN: Intralobular heterogeneity of mitochondrial dysfunction and its topographic relationship to cell death during 25% low-flow hypoxia was visually demonstrated in perfused rat hepatic microcirculatory units by dual-color digital microfluorography using rhodamine 123, a fluorochrome sensitive to the mitochondrial membrane potential, and propidium iodide, which labels the nuclei of nonviable cells with a concomitant enhancement of fluorescence. RESULTS: In the normoperfused liver from fasted rats, no significant depletion of the mitochondrial membrane potential values was observed in any portion of lobules during 100 minutes. In the liver treated with the 40-minute hypoxia, the mitochondrial membrane potential values within the entire lobule were significantly decreased. After a longer period of hypoxia, the pericentral fluorescence decreased to background levels, and the intralobular gradient showed a steep decline midway between the periportal and pericentral regions. Cell death was at first prominent in the midzone at 40 minutes, and then extended towards the pericentral regions, forming centrilobular necrosis at 100 minutes. Although allopurinol diminished the early midzonal cell death and retarded the development of centrilobular necrosis, it did not attenuate depression of the mitochondrial membrane potential. CONCLUSIONS: It is conceivable that mitochondrial dysfunction per se may not be related to the intralobular distribution of cell death during hypoxia. On the other hand, mitochondrial dysfunction in the centrilobular regions seems to be an important event leading to early midzonal oxidative tissue damage in that this change may involve ATP breakdown and the subsequent enhancement of xanthine oxidase-mediated oxidative cell injury in the midzonal regions, which are incompletely oxygenated.

Animals↗

Endogenous urinary 3-hydroxyproline has 96% specificity and 44% sensitivity for cancer screening.

A method for determining the endogenous urinary excretion levels of both 3-hydroxyproline and 4-hydroxyproline that may be useful for cancer screening of the general population and at the workplace is evaluated in this report. The excretion levels of 3-hydroxyproline and 4-hydroxproline were estimated in 97 patients with cancer and in 99 patients with various nonmalignant diseases and were compared with those of 211 healthy persons. Measurable 3-hydroxyproline peaks (by amino acid autoanalyzer) were absent from 93 samples from 211 healthy persons (44%), 50 of 99 patients with nonmalignant disease (50%), and 10 of 96 patients with cancer (10%). The levels of both 3-hydroxyproline and 4-hydroxyproline in cancer patients were significantly higher than those in healthy persons (p < 0.001 and p < 0.01, respectively) and those in patients with nonmalignant diseases (p < 0.05 and p < 0.01, respectively). Cancer patients were classified into three groups according to grade of cancer growth and invasion. The sensitivity of 3-hydroxyproline was 44% and higher than that of 4-hydroxyproline for the detection of stage II cancers (no distant metastasis); the sensitivities of both hydroxyprolines for the detection of stage I (very early cancer) were low. The specificity of these assays for healthy persons and patients with nonmalignant disease was 96% and 92% for 3-hydroxyproline, and 97% and 79% for 4-hydroxyproline, respectively. Urinary 3-hydroxyproline level should be further investigated as a cancer screening method for healthy persons in the community or the workplace, but appears unlikely to detect many cancers in the earliest stages.

Adult↗

Adenine nucleotide content of thymoma-derived lymphocytes.

Purine and pyrimidine metabolites are essential substances for cells. We have measured the adenine nucleotide (AN) contents of thymocytes from 15 human thymomas, 11 adjacent non-neoplastic thymuses and 3 children's thymuses. There was no significant difference in AN content of thymocytes between thymoma and children's thymus. But, AN content of adjacent non-neoplastic thymuses was significantly lower than that of thymoma or children's thymus. In mixed type thymoma, ATP content in thymocytes was significantly higher than that in lymphocytic type thymoma. These data indicate that thymocytes in thymoma may show further T cell maturation probably associated with the functional microenvironment of the neoplastic epithelial cells just like the children's thymus.

Adenine Nucleotides↗

[Effects of lidocaine on stimulation-coupled responses of neutrophils and protein kinase C activity].

The effects of lidocaine on superoxide generation and other stimulation-coupled responses of neutrophils induced by 12-phorbol myristate 13-acetate (PMA) were studied. Depolarization of membrane potential, superoxide generation and chemiluminescence response were inhibited by lidocaine in a concentration dependent manner. Lidocaine inhibited protein kinase C (PKC) activity in a manner competitive with phosphatidylserine. Lidocaine also inhibited the phosphorylation of 47 kDa neutrophil cytoplasmic protein, a phosphorylated protein required for activation of NADPH oxidase. The inhibitory action of lidocaine on PKC activity may correlate with the inhibition of superoxide generation induced by PMA.

Animals↗

HA1077, a novel calcium antagonistic antivasospasm drug, increases both cerebral blood flow and glucose metabolism in conscious rats.

The effects of a novel calcium antagonistic antivasospasm drug, HA1077, on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were studied in 33 anatomically discrete regions of the brain in conscious rats, using the quantitative autoradiographic [14C]iodoantipyrine and [14C]2-deoxyglucose techniques. HA1077 was infused i.v. over a 30-min period (1 or 3 mg/kg). HA1077 significantly increased LCBF in 9 of 33 sites in rats given 1 mg/kg, and in 14 of 33 sites in rats given 3 mg/kg compared to the control group given vehicle. Significant increases in LCGU were also noted in 16 of 33 sites in rats given 3 mg/kg. HA1077 increased both cerebral blood flow and glucose metabolism in conscious rats.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗