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Biomedical subjects

M Takeda

Publications and source records attributed to M Takeda.

At least 901 records · Page 50Linked to original sources

[Role of radiation therapy in the multi-modal treatment of head and neck cancer--with special emphasis on oral and maxillary sinus cancer].

The role of radiation therapy as part of the multi-modal treatment of head and neck cancer appeared to be important with respect to functional and cosmetic morbidity. As for oral cancer, the value of brachytherapy was excellent in cases of localized disease. As far as the latter technique was applicable, patients with tongue cancer at T1, T2 and T3 could be treated by radiation as the initial choice unless palpable neck node metastasis was present. In contrast, cure of the lesion would not be expected from external irradiation alone even when combined with chemotherapy. Accordingly, in such advanced cases, salvage surgery should be applied with or without radiation and/or chemotherapy. As for maxillary cancer, the introduction of "trimodal therapy" has improved the local control rate only to a slight degree. After the application of conservative surgery followed by conventional trimodal combination therapy, local control and five-year survival rates have been improved markedly.

Brachytherapy↗

[Results of radiation therapy of carcinoma of the salivary glands].

The results of radiation therapy in 152 patients with carcinoma of the major and minor salivary glands during the past 30 years were analyzed. Long-term survivors with recurrent disease and/or distant metastasis were common in the minor salivary glands as compared to the major salivary glands. The effects of radiation therapy depend on the degree of residual tumor after surgery. The treatment of choice for the tumor must be the surgery. However, local control was obtained by radiation therapy in many patients treated with brachytherapy or intracavitary electron beam in the minor salivary glands with a slight degree of residual tumor.

Adolescent↗

Nuclear genes coding the yeast mitochondrial adenosine triphosphatase complex. Primary sequence analysis of ATP2 encoding the F1-ATPase beta-subunit precursor.

The yeast nuclear gene ATP2 encodes a F1-ATPase beta-subunit protein of 509 amino acids with a predicted mass of 54,575 daltons. In contrast to the ATPase beta-subunit proteins determined previously from Escherichia coli and various plant sources, the yeast mitochondrial precursor peptide contains a unique cysteine residue within its immediate amino terminus. Expression of an in-frame deletion in ATP2 between residues 28 and 34 to eliminate this single cysteine residue located near the processing site of the matrix protease does not prevent the in vivo delivery of the subunit to mitochondria or its assembly into a functional ATPase complex. Thus, the import F1 beta-subunit into mitochondria does not require a covalent modification of the type utilized for the secretion of the major lipoprotein from E. coli. In addition, analysis of the level of the major F1-ATPase subunits in mitochondria prepared from an atp2- disruption mutant demonstrates that the in vivo import of these catalytic subunits is not dependent on each other. These data and additional studies, therefore, suggest that the determinants for mitochondrial delivery reside within the amino terminus of the individual precursors.

Amino Acid Sequence↗

Comparison of tyrosine protein kinases in membrane fractions from mouse liver and Ehrlich ascites tumor.

Tubulin was phosphorylated mainly at tyrosine residues by membranes from mouse liver and Ehrlich ascites tumor with ATP in the presence of MnCl2, ZnCl2, NaVO3, and Nonidet P-40 in an epidermal growth factor (EGF)- and insulin-independent manner. The tyrosine tubulin kinase activity in the tumor membranes is comparable to the activity in liver membranes. Two tyrosine tubulin kinases, namely I (Mr = 64,000) and II (Mr = 46,000), were purified 5-17-fold and were free of the EGF receptor and the insulin receptor. Phosphorylation of endogenous proteins produced major alkali-resistant phosphoproteins of 56 and 53 kDa in kinase I preparations and of 46 and 37 kDa in kinase II preparations. These kinases phosphorylated tubulin stoichiometrically at tyrosine and had a preference of alpha-subunit to beta-subunit of tubulin. Apparent Km values of kinases I and II for tubulin were about 4 and 8 microM and for ATP were about 2 and 4 microM, respectively. Thiol reagents inhibited their reactions. N alpha-p-Tosyl-L-lysine chloromethyl ketone stimulated the reactions at 1 mM but inhibited them at 5 mM. Although kinases I and II also phosphorylated angiotensin II, tyrosine-glutamate copolymers, and heavy chains of anti-pp60src IgG, they differed from each other in preferences for the substrates. More than 95% of the enzyme activities was not immunoprecipitated with the anti-pp60src IgG which cross-reacts with pp60c-src. In comparison with the corresponding liver enzymes, tumor enzymes were more stable to heat and incorporated more phosphate into tubulin, but showed lower activity toward angiotensin II and anti-pp60src IgG.

Adenosine Triphosphate↗

ATP-dependent [3H]Met-enkephalin uptake by bovine adrenal chromaffin granule membrane.

Uptake of [3H]Met-enkephalin by purified chromaffin granule membrane isolated from bovine adrenal medulla was investigated. Addition of a single divalent cation, such as Mg2+ or Ca2+, did not affect the uptake. The presence of 3 mM ATP in the incubation medium stimulated the uptake to two times that of the control. The same stimulation effect was also found in the presence of ATP plus a single divalent cation. The ATP-dependent uptake reached its half-maximal level within 5 min after initiation of the reaction at 25 degrees C, and reached a plateau within 10 min. The apparent Km for [3H]Met-enkephalin uptake by the chromaffin granule membrane was about 2.3 X 10(-6) M. GTP, CTP, UTP and ADP did not stimulate enkephalin uptake. Several calcium inhibitors such as trifluoperazine, verapamil and 3,4,5-trimethoxybenzoic acid 8-(N,N-diethylamino)octylester (TMB-8) markedly inhibited enkephalin uptake. The inhibition exceeded 80%, although these chemicals inhibited Ca2+-ATPase activity in chromaffin granule membrane only 30% under the same conditions. Ethyleneglycol-bis-(beta-aminoethylether)N,N'-tetraacetic acid (EGTA), at 3 mM also inhibited uptake about 30%. The results indicate that uptake of Met-enkephalin by chromaffin granule membrane ghosts was driven not only by ATPase activity, but also by some other Ca2+-ATP-mediated mechanism(s).

Adenosine Triphosphate↗

Comparison of tyrosine phosphorylation of proteins by membrane fractions from mouse liver, Ehrlich ascites tumor and MH134 hepatoma.

When membrane fractions from mouse liver, Ehrlich ascites tumor and MH134 hepatoma were incubated with [gamma-32P]ATP at 0 degree C in the presence of MnCl2, ZnCl2 and NaVO3, proteins were phosphorylated on tyrosines to a larger extent in liver membranes than in tumor membranes. Separation of labelled proteins by SDS-gel electrophoresis showed phosphorylated alkali-resistant bands of 170, 140, 130, 80, 56, 53 and 46 kDa proteins in Ehrlich ascites tumor membranes; liver membranes exhibited more strongly phosphorylated bands of 170, 56, 53 and 46 kDa proteins. Epidermal growth factor stimulated the tyrosine phosphorylation of only a 170 kDa protein, which was more significant in liver membranes. Liver membranes exhibited slightly higher levels of tyrosine protein kinase activity compared to tumor membranes.

Animals↗

Effects of colchicine on the ultrastructure of mouse taste buds.

Effect of colchicine on the ultrastructure of taste bud cells was studied in the mouse. In untreated mice microtubules were abundant throughout the entire cytoplasm of type-III cells, but only in the apical cytoplasm of type-I cells. After 2 h of colchicine treatment, no microtubules were observed in any taste bud cells; dense secretory granules in the apical cytoplasm of type-I cells mostly disappeared, and instead, numerous phagosomes appeared. It is suggested that colchicine causes an interruption of the transport of the secretory granules in type-I cells from the Golgi apparatus to the membrane of the apical surface, from which release occurs. In type-III cells, after 4 or 5 h of treatment, dense-cored vesicles scattered throughout the cytoplasm tended to increase in number; they were often observed to accumulate in the vicinity of the Golgi apparatus. Five hours after treatment with 5-hydroxy-L-tryptophan (5-HTP) following colchicine pretreatment, monoamine specific fluorescent cells and vesicles with highly electron-dense cores of type-III cells were still present. On the other hand, 5 h after 5-HTP treatment alone both fluorescent cells and vesicles with highly electron-dense cores had already disappeared. These observations suggest that the treatment with colchicine interrupts the transport of dense-cored vesicles of type-III cells to synaptic areas, in which those vesicles are presumed to discharge the neurotransmitter substance.

Animals↗

Hepatitis due to repeated inhalation of methoxyflurane in subanaesthetic concentrations.

The authors present a case of hepatitis, which was due to repeated self-administered inhalation of methoxyflurane in subanaesthetic concentrations for insomnia. The diagnosis of viral hepatitis, type A or type B, was excluded on the basis of serologic findings. This case is of particular interest in that methoxyflurane even in subanaesthetic concentrations caused hepatic damage on repeated exposure.

Adult↗

Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia.

Lipoprotein patterns and cholesteryl ester transfer activity (CETA) were examined in 2 patients with familial hyperalphalipoproteinaemia (FHALP). The proband was a healthy 58-year-old Japanese male who had an HDL cholesterol of 7.83 mmol/l (301 mg/dl). His sister's HDL cholesterol was 4.52 mmol/l (174 mg/dl), which suggested that both were homozygous carriers of FHALP. In both subjects HDL showed a high cholesterol/apo A-I ratio and appeared to be a larger-sized particle than normal HDL on agarose gel chromatography. Two of the proband's children showed higher HDL cholesterol levels (1.74 mmol/l, 2.16 mmol/l) than normal, but another 2 children showed normal levels (1.48 mmol/l, 1.40 mmol/l). However, the ratios of HDL cholesterol to total cholesterol and to apo A-I in all children were higher than normal. These data suggest, but do not prove, that all his children were heterozygotes. Apo B levels in all of the family members studied were lower than normal (47-80 mg/dl). Deceased members of the same family had not died from cardiovascular disease. Cholesteryl-ester transfer activity was studied in both patients. When serum or lipoprotein deficient serum (d greater than 1.21) and [3H]cholesteryl ester labelled HDL3 were incubated in the presence of an LCAT inhibitor, there was no evidence of cholesteryl ester transfer from HDL to VLDL and/or LDL, unlike normal subjects. The deficiency of CETA in these patients with FHALP presumably accounted for the increase in particle size and cholesterol enrichment of HDL.

Adult↗

Chromosome aberrations in the peripheral lymphocytes induced by brachytherapy and external cobalt teletherapy.

In the present study, the induction efficiencies of chromosome aberrations were analyzed in patients receiving various modalities of interstitial radiotherapy with small radiation sources in the oral cavity area and compared with those in patients treated with external telecobalt irradiation in the thoracic region. Further, as a local nonstochastic effect, the acute mucosal reaction was investigated. The mucosal reaction in the area treated by brachytherapy reached a maximum at two to three weeks after the implantation. The frequencies of dicentrics plus rings of peripheral lymphocytes, on the other hand, revealed rapid increases and approached plateau levels as early as two days after the implantation. The whole-body effects, evaluated on the basis of the chromosome aberration frequencies of peripheral lymphocytes in the patients who underwent brachytherapy, were compared with the effects observed in those patients treated with external radiotherapy or bleomycin injection and discussed with regard to their effectiveness in control of the tumor and side effects. The radiation doses used in the patients who received brachytherapy or a single external irradiation were found to exert the same effects on the chromosome aberration induction. However, even in the case of brachytherapy in which whole-body side effects were believed to be trivial, the peripheral lymphocyte count was temporarily reduced to one half or less of the preirradiation level. An equivalent whole-body dose of 50 cGy was obtained from the frequencies of dicentrics and rings.

Adult↗

Human erythrocyte membrane acid proteinase (EMAP): sidedness and relation to cathepsin D.

An acid proteinase purified from human erythrocyte membranes (Yamamoto, K. & Marchesi, V.T. (1984) Biochem. Biophys. Acta 790, 208-218), now termed "EMAP," was further characterized with respect to its localization and relation to cathepsin D. The membrane-associated form of EMAP was shown to be latent by demonstrating that no activity was detectable in both resealed (right-side-out) ghosts and inside-out vesicles in the absence of detergents. The enzyme associated with the inside-out vesicles was unstable when exposured to acidic pH between 4.0 and 4.5, whereas the enzyme associated with the resealed ghosts was stable in the wide pH range of 3.7 to 9.0. Tryptic digestion produced the loss of activity for the enzyme associated with the inside-out vesicles but not the resealed ghosts. The antibody to rat spleen cathepsin D, which cross-reacted weakly but detectably with EMAP, selectively bound to the inside-out vesicles. These results indicate the location of EMAP on th inner surface of the membranes. Comparison of a number of enzymatic properties of EMAP with rat cathepsin D showed significant differences between these two enzymes. EMAP was less stable in the pH range of 3.5 to 6.0 than cathepsin D. The enzymes were distinguished from each other by differences in their elution profiles on DEAE-Sephacel and chromatofocusing columns and by differences in the extent of inhibition by a few specific inhibitors. Both enzymes revealed significant differences in the amino acid composition and specific activity towards bovine hemoglobin. The immunological relationship between these two enzymes is discussed.

Animals↗