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Biomedical subjects

K Miyaji

Publications and source records attributed to K Miyaji.

At least 19 recordsLinked to original sources

Effects of protein kinase C modulators on multidrug resistance in human glioma cells.

To identify the role of protein kinase C (PKC) in multidrug resistance, the effects of phorbol-12-myristate-13-acetate (PMA), a PKC activator, or calphostin C, a PKC inhibitor, on intracellular vincristine accumulation and expression of P-glycoprotein phosphorylation were studied in one multidrug-resistant and three multidrug-sensitive human glioma cell lines. Basal PKC activities and immunoreactivities of PKC-alpha and -zeta were higher in multidrug-resistant cells than in multidrug-sensitive cells. There was no significant difference in the immunoreactivity of PKC-delta between multidrug-resistant and -sensitive cells, and immunoreactive PKC-beta, -gamma, and -epsilon were not detected in either multidrug-resistant or -sensitive cells. The treatment of multidrug-resistant cells with 100 nM PMA for 2 hours resulted in the activation not of PKC-zeta but of PKC-alpha, with concomitant decrease in vincristine accumulation and increase in P-glycoprotein phosphorylation. The exposure of multidrug-resistant cells to 100 nM PMA for 24 hours induced down-regulation not of PKC-zeta but of PKC-alpha, with concurrent decrease in vincristine accumulation, and reduced but still increased P-glycoprotein phosphorylation. The treatment of multidrug-resistant cells with 100 nM calphostin C for 2 hours decreased immunoreactive PKC-zeta and not immunoreactive PKC-alpha, inducing increase in vincristine accumulation, with concomitant decrease in P-glycoprotein phosphorylation. There was no evidence of significant change in vincristine accumulation in multidrug-sensitive cells treated with PMA or calphostin C. This may suggest that at least two isozymes of PKC, PKC-alpha and -zeta, are involved in P-glycoprotein phosphorylation and that vincristine efflux function in multidrug-resistant human glioma cells is closely associated with P-glycoprotein phosphorylation and is decreased by PKC inhibitor.

ATP Binding Cassette Transporter, Subfamily B, Mem

Development of intestinal flora of human-flora-associated (HFA) mice in the intestine of their offspring.

Development of intestinal flora in newborn human-flora-associated (HFA) mice was compared with that in newborn conventional (CV) mice. Facultative anaerobes were detected from the first day after birth in both CV and HFA mice but anaerobes were not detected in the first week. Anaerobes rapidly increased from the 2nd week after birth and became predominant in newborn intestine. Most of the intestinal bacteria in adult CV and HFA mice were colonized in the intestine of CV and HFA mice, respectively, within 3 weeks after birth. The human intestinal flora established in the intestine of HFA mice finally reproduced without any remarkable change in composition in the intestine of newborn HFA mice. The development of intestinal flora in HFA mice was similar to that in CV mice but not that in human infants. These results indicated that human flora associated in HFA mice could be transferred from mothers to their offspring although HFA mice could not simulate the development of intestinal flora of the human infant.

Adult

Inhibition by 5'-methylthioadenosine of cell growth and tyrosine kinase activity stimulated by fibroblast growth factor receptor in human gliomas.

Stimulation of three human glioma cell lines with basic fibroblast growth factor (bFGF) led to the enhancement of cell growth and the rapid tyrosine phosphorylation of cellular proteins, including major substrates of 90 kD. A methyltransferase inhibitor, 5'-methylthioadenosine (MTA), inhibited dose dependently the bFGF-stimulated cell growth and protein tyrosine phosphorylation in glioma cells by blocking both receptor autophosphorylation and substrate phosphorylation, as shown by immunoblotting with antiphosphotyrosine antibodies and cross-linking bFGF to receptors. The antiproliferative activity of MTA correlated quantitatively with its potency as an inhibitor of bFGF-stimulated protein tyrosine kinase activity. The methyltransferase inhibitor MTA had no effect on either epidermal growth factor- or platelet-derived growth factor-stimulated protein tyrosine phosphorylation in glioma cells, but inhibited specifically bFGF-stimulated protein tyrosine kinase activity. The concentration of MTA required for inhibition of protein methylation correlated well with the concentration required for inhibition of bFGF-stimulated cell growth and protein tyrosine phosphorylation. Because MTA had no effect on numbers and dissociation constants of high- and low-affinity bFGF receptors, the inhibition of bFGF-stimulated bFGF receptor tyrosine kinase activity is not likely to be the result of a reduction in bFGF receptor and bFGF binding capacity. In fact, MTA delayed and reduced the internalization and nuclear translocation of bFGF, and the internalized bFGF was submitted to a limited proteolysis that converted it to lower molecular peptides whose presence remained for at least 22 hours. The effect of MTA on bFGF-stimulated tyrosine phosphorylation was immediate and readily reversible.

Antibodies

[Cisplatin, 5-fluorouracil and leucovorin combination chemotherapy-added radiation therapy for advanced esophageal cancer--a case report].

Cisplatin, 5-fluorouracil and leucovorin combination chemotherapy added radiation therapy was performed for the treatment of 62-year-old male patient with advanced esophageal cancer who had liver cirrlosis. After the treatment, esophageal lesion disappeared. Only minimal side effect occurred during the treatment. Biochemical modulation chemotherapy combined with radiation therapy is useful for advanced esophageal cancer.

Antineoplastic Combined Chemotherapy Protocols

Stimulation of protein-tyrosine phosphorylation in gerbil hippocampus after global forebrain ischemia.

Tyrosine phosphorylation in the gerbil hippocampus after a transient ischemia was analyzed by immunoblotting and immunohistochemistry. In control hippocampus, the phosphotyrosine was detected in many proteins of 165 to 10 kDa and the immunostain showed a distinct distribution. The ischemic insult induced various alterations of the phosphotyrosine immunoreactivities in both ischemia-resistant and -vulnerable neurons which were associated with alterations in the expression of 165 to 19 kDa-immunoreactive bands. These results suggest that tyrosine phosphorylation is involved in the ischemic hippocampus to play a role in the development of early and delayed neuronal deaths in CA4 and CA1 neurons, respectively.

Animals

Effects of hexoses and their derivatives on glucagon secretion from isolated perfused rat pancreas.

Although it has been firmly established that D-glucose inhibits glucagon secretion from pancreatic A cells, the regulatory mechanism of glucagon secretion by D-glucose has not been elucidated. To study this regulatory mechanism by D-glucose, the effects of hexoses and their derivatives on glucagon secretion from the A cells of isolated perfused rat pancreas were investigated. When these cells were perfused with D-glucose, D-fructose, D-sorbitol, D-galactose, 2-deoxy-D-glucose, D-gluconic acid sodium salt and D-glucosamine HCl salt, glucagon secretion was significantly inhibited. None of the hexoses or their derivatives tested were found to stimulate glucagon secretion. The effects of these sugars on glucagon secretion were independent of their metabolism in the cells. From the findings that the sugars both metabolized and unmetabolized in the cells demonstrated comparable inhibition of glucagon secretion from the isolated perfused rat pancreas, it is speculated that the recognition system for these sugars may be probably present on the A cell membrane and responsible for mediating these inhibitory effects of glucagon secretion.

Animals

Effect of tyrphostin on cell growth and tyrosine kinase activity of epidermal growth factor receptor in human gliomas.

The effects of tyrphostin, a selective protein tyrosine kinase inhibitor, on epidermal growth factor (EGF)-stimulated cell growth and EGF-receptor tyrosine kinase activity were studied in four human glioma cell lines. Stimulation by EGF induced variable enhancements of cell growth as well as tyrosine phosphorylation of EGF receptor and intracellular target proteins in all glioma cell lines. The level of immunoreactive EGF receptor detected with antibodies against extra- and intracellular domains was moderate in all four glioma cell lines, but markedly decreased with the latter antibody in two glioma cell lines. This variation was associated with considerable reduction of the EGF-stimulated tyrosine autophosphorylation level. Tyrphostin inhibited dose-dependently the EGF-stimulated cell growth and tyrosine autophosphorylation in all glioma cell lines, and the optimum time for the maximum inhibitory effect on tyrosine autophosphorylation was 12 to 18 hours after treatment with tyrphostin. The antiproliferative activity of tyrphostin nearly correlated quantitatively with its potency as an inhibitor of the EGF-stimulated EGF receptor tyrosine kinase activity. Tyrphostin had no significant effect on the immunoreactive EGF receptor levels, on the affinity constants and numbers of EGF receptor, or on the down-regulation and specific internalization of EGF receptor in any glioma cell line, suggesting that the effects of tyrphostin are not likely to be the results of reduction in EGF receptor and EGF binding capacity. In addition, the serum-stimulated cell growth was also inhibited dose-dependently by higher concentrations of tyrphostin in all glioma cell lines. It might be suggested, therefore, that tyrphostin inhibits EGF-stimulated cell growth by a specific suppression of EGF receptor tyrosine kinase activity, and at higher concentrations there appears to be some degree of either nonspecific inhibition or inhibition of serum-stimulated protein tyrosine kinase activity to induce the cell growth inhibition of gliomas.

Catechols

[Superior vena cava-right atrial appendage direct anastomosis for repair of partial anomalous pulmonary venous connection to superior vena cava].

Successful repair was performed for a 7-year-old male with a diagnosis of partial anomalous pulmonary venous connection (PAPVC) to superior vena cava (SVC) and superior sinus venosus atrial septal defect (ASD). The SVC was divided above the orifice of the anomalous pulmonary vein and the cephalad end of the SVC was anastomosed directly to the right atrial appendage. A patch was used to divert pulmonary venous flow from the orifice of the SVC through superior sinus venosus ASD into the left atrium. Postoperative course was uneventful with normal sinus rhythm. There was no evidence of vena caval or pulmonary venous obstruction. At 3-month after surgery, sinus node function was confirmed to be normal by electrophysiological study. This is useful alternative method for repair of PAPVC to high or middle SVC.

Anastomosis, Surgical

[Successful treatment of fungal endocarditis and mediastinitis after fenestrated Fontan operation--a case report].

Fenestrated Fontan operation was performed in a 19-year-old male with a diagnosis of right isomerism syndrome. Postoperatively, fungal endocarditis due to Candida Albicans and mediastinitis by Methicilin resistant Staphylococcus Aureus (MRSA) occurred. For Candida endocarditis, combined surgery and medical treatment with amphotericin B was effective. MRSA mediastinitis was successfully treated by continuous closed irrigation with 0.5% povidone-iodine solution. This is the 17th reported case of fungal endocarditis after open heart surgery in Japanese literature.

Adult

[Myocardial protection during aortic cross-clamping for more than 240 minutes].

The efficacy of cold crystalloid cardioplegia (St. Thomas II solution) during aortic cross-clamping more than 240 minutes was evaluated in 5 patients with non-coronary diseases undergoing heart surgery. The ischemic time ranged from 257 to 302 minutes with the mean of 274 minutes. As the technique of myocardial protection, multidose antegrade crystalloid cardioplegia was used at an interval of 20 minutes. These patient were compared with another patient group with clamping time 120-180 minutes. There was no difference between the two groups in terms of mortality, cardiac index, CK, CK-MB, GOT, LDH. These findings suggest that cold crystalloid cardioplegia provided clinically satisfactory myocardial protection during the aortic cross-clamping for more than 240 minutes.

Adult

[A case of mediastinal neurinoma originated from the left vagal nerve].

A 46-year-old man was admitted to our hospital because of an abnormal shadow on the chest roentgenogram. The operation was performed through left posterolateral thoracotomy. A tumor mass, 4.5 x 2.5 x 2.5 cm in size, was found and its origin was the left main vagal nerve 0.5 cm distal the branching root of the recurrence nerve. The tumor and a part of the left vagal nerve was resected en bloc. Pathological study revealed tha the tumor was neurinoma of Antoni A+B. Postoperative course was uneventful. This is the 34th reported case in Japanese literature of neurinoma with its origin from the intrathoracic vagal nerve.

Cranial Nerve Neoplasms

[Clinical evaluation of the intraluminal ultrasonography].

Although for the diagnosis of rectal diseases barium-enema and colonoscopy have been commonly carried out, by the methods neither information on the layer structure of the intestinal wall nor swelling of the regional lymphnodes can be provided. Therefore we tried intraluminal ultrasonography (IUS) for further evaluation of the rectum and peri-rectal lesion, and the usefulness of IUS in the rectal disease was described. In 46 cases of rectal cancer, the following results were obtained. Five layer structures were distinguished in the normal rectal wall by the IUS. Intraluminal invasion showed destruction of the layer structures of the colonic wall. The swelling of the regional lymphnodes was revealed as low echoic round mass. In 43 cases with benign diseases, characteristic variations of the layer structures in the colonic wall can be distinguished by the IUS. In conclusion, the IUS was of great use to observe the variation of the layer structure of colonic wall and to provide valuable information on metastasis into the regional lymphnodes.

Adult

Interspecies comparison of c-myc gene in human and rat glioma cell lines.

Interspecies difference in expression of the c-myc gene between two human and three rat glioma cell lines was studied with use of a human c-myc probe. The c-myc deoxyribonucleic acid (DNA) fragments detected at higher stringency in Southern blotting, showed a difference in size and gene copy number between human and rat glioma cells. The c-myc transcript was detected at both higher and lower stringencies in Northern blotting in human glioma cells, whereas it was demonstrated only at lower stringency in rat glioma cells, and the c-myc transcript was seen in cytoplasms of both glioma cells by in situ hybridization. The c-myc protein, if examined with anti-human c-myc protein monoclonal antibody, was observed as two separate components in Western blotting and localized immunocytochemically in nuclei in human glioma cells, whereas it was detected as three separate forms in Western blotting and shown in both nuclei and cytoplasm in rat glioma cells. The above discrepancy in manifestation of c-myc DNA fragments, transcript and protein could be due to the difference in nucleotide sequence of c-myc gene between human and rat glioma cells.

Animals

Residual neutron-induced radionuclides in samples exposed to the nuclear explosion over Hiroshima: comparison of the measured values with calculated values.

Residual radionuclides induced by neutrons from the Hiroshima atomic bomb have been measured at Kanazawa University for 14 years. The results of 152Eu, 154Eu and 60Co are reviewed in this paper. Where appropriate, an attempt is made to provide our new data with the aim of reinterpreting our published data. From the comparison of the measured values with the calculated values by DS86 methodology, we may point out here: (1) that close agreement was found between measured and calculated values for the specific radioactivity of 152Eu in the samples exposed at ground ranges between 320 m and 720 m; (2) that the calculated/measured ratios for the specific radioactivity of 152Eu were, however, larger than unity in the vicinity of ground zero and smaller than unity at locations more than 1000 m apart from ground zero; (3) that, in the vicinity of ground zero, epithermal neutron fluence evaluated from a set of measured specific radioactivities of 152Eu, 154Eu and 60Co showed a close agreement with the calculated result, whereas thermal neutron fluence evaluated in the same way was different from the calculated result; and (4) that the depth distribution of the specific radioactivity of 152Eu in a wall sample which was exposed at the location 320m from ground zero approximately agreed with the calculated result.

Humans

Application of the Karhunen-Loeve expansion to evaluate regional cardiac excitation in body surface potential maps.

The authors investigated the usefulness of the Karhunen-Loeve technique applied to body surface maps to study regional cardiac excitation. Eigenvectors were derived from the body surface potential maps of 120 healthy adults using the Karhunen-Loeve expansion theory. Then, in the maps of various types of ventricular hypertrophy, each eigenvector coefficient was calculated for a statistical comparison. The first eigenvector coefficient in early QRS and the second in mid QRS were larger in patients with asymmetrical septal hypertrophy and in patients with left ventricular hypertrophy, respectively. The third was larger in patients with right ventricular hypertrophy. In the maps of patients with previous anteroseptal myocardial infarction, the second eigenvector coefficient decreased with asynergy of the anterior to apical wall, and the first decreased with the asynergy of the interventricular septum. They conclude that some eigenvector components and coefficients at particular times in the QRS are sensitive to changes in regional cardiac excitation and that they may facilitate the detection of local excitation changes such as occur in hypertrophy or infarction.

Adult

[Eigenvector analysis in body surface potential maps for evaluating right ventricular hypertrophy in primary pulmonary hypertension].

This study related the eigenvectors derived from the QRS complex in body surface isopotential maps of normal subjects to regional myocardial excitation, with special emphasis on the right ventricle. The subjects consisted of 120 normal healthy adults and eight patients with primary pulmonary hypertension and right ventricular hypertrophy (PPH). According to the Karhunen-Loève theory, eigenvectors were derived from the normal group and the eigenvector coefficient of each subject was obtained against time for the first three components. The cumulative proportion of the first three eigenvectors was 90.3% in normals and 80.2% in PPH. The first eigenvector had a peak of eigenvector coefficients early in the QRS and had a bottom late in the QRS. The peak of the second was in the middle of the QRS. The coefficients of the third eigenvector were low compared to the former two eigenvectors, and had no characteristic time pattern. PPH had a similar time pattern of coefficients in the first eigenvector, reduced coefficients in the second, and a definite peak in the mid-QRS in the third. The average eigenvector coefficient of the third eigenvector in PPH was significantly higher than those in normal subjects (p less than 0.01). We conclude that the third eignevector derived from normal subjects strongly reflects right ventricular excitation.

Adult