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Biomedical subjects

M Tada

Publications and source records attributed to M Tada.

At least 19 recordsLinked to original sources
PubMed1992

High incidence of ras gene mutation in intrahepatic cholangiocarcinoma.

The DNA sequences around codons 12, 13, and 61 of the ras gene were analyzed by polymerase chain reaction and direct sequencing in 18 intrahepatic cholangiocarcinomas. The ras gene mutations were found in 9 of 18 (50%): 6 in K-ras codon 12, 1 in K-ras codon 13, 1 in K-ras codon 61, and 1 in N-ras codon 12. The incidence of mutations was higher in the hilar type of intrahepatic cholangiocarcinomas, especially when these tumors were large. The incidence and spectrum of the mutations were almost the same as those reported in colon cancers, possibly indicating similar etiologic agent(s) in the carcinogenesis of both cancers.

Adenocarcinoma↗
PubMed1992

Molecular mechanism of regulation of Ca2+ pump ATPase by phospholamban in cardiac sarcoplasmic reticulum. Effects of synthetic phospholamban peptides on Ca2+ pump ATPase.

The molecular mechanism of the regulation of Ca2+ pump ATPase by phospholamban in cardiac sarcoplasmic reticulum was examined using synthetic peptides of phospholamban and purified Ca2+ pump ATPase from cardiac sarcoplasmic reticulum. The phospholamban monomer of 52 amino acid residues contains two distinct domains, the cytoplasmic (amino acids 1-30) and the transmembrane (amino acids 31-52) domains. The peptide corresponding to the amino acids 1-31 of phospholamban (PLN 1-31) decreased the Vmax of the Ca(2+)-dependent ATPase activity in dose-dependent manner, while it had no effect on the affinity of the ATPase for Ca2+ (KCa). On the other hand, the peptide corresponding to the amino acids 28-47 of phospholamban (PLN 28-47) increased the KCa from 0.52 to 1.33 microM without significant change in the Vmax value when reconstituted into vesicles with the ATPase. Essentially the same results as PLN 28-47 were obtained with the peptide corresponding to the amino acids 8-47 of phospholamban (PLN 8-47). The inhibitory effects of PLN 1-31 and PLN 8-47 on the ATPase were reversed by cAMP-dependent phosphorylation of the peptides (Ser16). These results indicate that phospholamban suppresses Ca2+ pump ATPase at two different sites, the cytoplasmic domain for Vmax and the transmembrane domain for KCa, and that cAMP-dependent phosphorylation de-suppresses these inhibitory effects on the ATPase.

Amino Acid Sequence↗
PubMed1992

Tumor diagnosis by PET: potential of seven tracers examined in five experimental tumors including an artificial metastasis model.

The potential of seven tracers for the metabolic imaging of tumors by positron emission tomography was studied using five experimental tumor models. The tracers examined were 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), 2-deoxy-2-[18F]fluoro-D-galactose (2-[18F]FdGal) and 2-deoxy-2-[18F]fluoro-L-fucose (2-[18F]FdFuc) for investigating energy metabolism. L-[methyl-11C]Methionine ([11C]Met) and 6-[18F]fluoro-L-fucose (6-[18F]FFuc) were used for assessing protein and glycoprotein synthesis, while [3H]thymidine ([3H]Thd) and 2-deoxy-5'-[18F]fluorouridine ([18F]FdUrd) were used to investigate nucleic acid metabolism. The highest mean uptake by the five different tumors was found for [3H]Thd, followed in order by [18F]FDG, [11C]Met, 2-[18F]FdGal, [18F]FdUrd, 2-[18F]FdFuc and 6-[18F]FFuc. The tumor-to-tissue uptake ratios indicated that the nucleosides, [11C]Met and 6-[18F]FFuc were better tracers in the brain region. All the tracers except for the fucose analogs were suitable for the thoracic region, while [11C]Thd and [18F]FDG were superior in the abdominal region. In comparison with the primary tumor model of Lewis lung carcinoma (3LL), [3H]Thd uptake in the artificial metastatic 3LL model showed the maximum enhancement, followed by [18F]FDG, [11C]Met and the other tracers. The [18F]FDG uptake correlated with the [3H]Thd uptake. [18F]FdUrd, 6-[18F]FFuc and 2-[18F]FdGal could be used for distinguishing different types of tumors. The combined use of these radiotracers can possibly allow the assessment of tumor metabolism, and this indicates the viability of tumors.

Animals↗
PubMed1992

Investigation of tumor metastatic potential with N-[18F]fluoroacetyl-D-glucosamine.

In order to investigate the metastatic potential of tumors in vivo by measuring hyaluronic acid metabolism, C57BL/6 mice with B16 melanoma variants and C3H/He mice with FM3A tumor variants were evaluated using N-[18F]fluoroacetyl-D-glucosamine (18F-GlcNFAc). The uptake of 18F-GlcNFAc was slightly higher (P less than 0.05) in B16-F10 tumors (high metastatic potential) than in B16-F1 (low metastatic potential). Analysis of metabolites showed that acid-insoluble fraction was the largest one in the liver by 60 min, whereas in the tumors, phosphates fraction was the major metabolite. Slower metabolism in tumors was suggested, and it may be one of the reasons for the difficulty of detecting the characteristics of their hyaluronic acid synthesis. 18F-GlcNFAc uptake by FM3A variants showed no significant correlation with their metastatic potential. In addition, N-acetyl-D-[1-14C]glucosamine, 2-deoxy-D-[1-14C]glucose and [6-3H]thymidine failed to demonstrate any difference between tumors' metastatic variants in vivo.

Acetylglucosamine↗
PubMed1992

Dose-responsive effect of radiotherapy on the tumor uptake of L-[methyl-11C]methionine; feasibility for monitoring recurrence of tumor.

The L-[methyl-11C]methionine [( 11C]Met) uptake by rat AH109A tumor was decreased irradiation-dose dependently from the control to 5, 10 and 20 Gy. After 10 Gy irradiation, the [11C]Met uptake decreased earlier than the tumor volume reduction, and later, it significantly increased earlier than the recurrent growth. Double tracer autoradiography with [14C]Met and 4-[18F]fluoroantipyrine showed a decrease in the [14C]Met tumor uptake without change of blood flow after irradiation. The [11C]Met uptake representing amino acid metabolism is a sensitive indicator for monitoring radiotherapeutic effect on tumor.

Animals↗
PubMed1992

Differences in DNA damage induced by mutagenic and nonmutagenic 4-aminoazobenzene derivatives in Escherichia coli.

DNA lesions produced in Escherichia coli AB2500 (uvrA) exposed to the carcinogen N-hydroxy-3-methoxy-4-aminoazobenzene (N-OH-3-MeO-AAB) or the noncarcinogen N-hydroxy-2-methoxy-4-aminoazobenzene (N-OH-2-MeO-AAB) were investigated by alkaline sucrose gradient sedimentation and 32P-postlabeling analysis. Alkali-labile sites appeared to be formed equally in cells treated with both aminoazobenzene derivatives. 32P-Postlabeling analysis revealed that the 3-MeO-AAB-DNA adduct level was 25-fold higher than that for 2-MeO-AAB-DNA adducts. In addition to major adducts, 4 minor spots were detected in N-OH-3-MeO-AAB-treated cells, while only one major adduct was found in N-OH-2-MeO-AAB-treated cells. The mutagenicities and cytotoxicities were also determined with E. coli with different repair capacities; we found that repair of 3-MeO-AAB damages is strongly dependent on the UVR repair system. Moreover, N-OH-3-MeO-AAB, but not N-OH-2-MeO-AAB, could induce recA and umuC gene expression, which was higher in uvrA strains than in the wild type.

Bacterial Proteins↗
PubMed1992

Application of ultrasonic probes prior to endoscopic resection of early gastric cancer.

The development of a new strip biopsy technique for endoscopic mucosectomy utilizing endoscopic saline injection and a double-channel endoscope permits the safe and simple resection of superficial type early gastric cancer which has been difficult to perform with conventional polypectomy techniques. Preresection assessment of the depth of invasion and postresection assessment of efficacy are important with regard to treatment of early gastric cancer, but conventional endoscopic ultrasonography employed for this purpose requires special equipment and involves intricate procedures. An ultrasonic probe which can be used endoscopically has recently been developed and is currently in the trial stage. The authors have conducted studies with respect to a 7.5 MHz radial scanning type Miniature Ultrasonic Probe as well as a 20 MHz manual linear scanning type Sonoprobe System. Experimental studies indicated that the former type is capable of delineating postresection ulcers, while the latter permitted delineation of tumors as hypoechoic images in 9 of 11 cases of early gastric cancer.

Adenocarcinoma↗
PubMed1992

Value of endoscopic ultrasonography in the assessment of inflammatory bowel diseases.

The value of EUS in the assessment of inflammatory bowel diseases was determined. EUS was useful for estimation of the histological changes of inflammatory bowel diseases. In ulcerative colitis, EUS findings were classified into five types, which correlated with the colonoscopic and histological findings. Studies in surgical cases and further prospective investigations are necessary, however, to determine whether EUS can contribute to the management of inflammatory bowel diseases.

Adult↗
PubMed1992

mGK-6-derived true tissue kallikrein is synthesized, processed, and targeted through a regulated secretory pathway in mouse pituitary AtT-20 cells.

mGK-6-derived true tissue kallikrein was shown to be synthesized in mouse pituitary AtT-20 cells. This cell line, which is capable of processing other prohormones, only partially processed the proform of kallikrein to its active form, secreting it predominantly as the proform. The secretion of the active form was stimulated in response to a secretagogue, 8-bromo-cyclic AMP. These results imply that not only cellular elements capable of directing the processing of the proform to the active form and the intracellular transport of the kallikrein, but also a pathway that regulates the release of the active form may be present in the AtT-20 cells, thus the availability of this cell line for investigation of biosynthetic and secretory processes for tissue kallikrein in vivo being suggested.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Tissue-specific regulation of renin-binding protein gene expression in rats.

Rat gene for renin-binding protein (RnBP) was shown to be expressed in the kidney, adrenal gland, brain, lung, spleen, ovary, testis, and heart. On sodium depletion and captopril administration, the rat showed a marked increase in the adrenal RnBP mRNA level and a slight decrease in the kidney RnBP mRNA level. In two-kidney, one clip hypertensive rats, the RnBP mRNA levels of the clipped and contralateral kidneys were unchanged and also its adrenal mRNA level was maintained at the control level. The recombinant rat RnBP was synthesized in Escherichia coli cells and purified to apparent homogeneity. The RnBP existed as a homodimer and formed a heterodimer with rat renin to inhibit renin activity extensively. Intravenous injection of the RnBP into rats resulted in a rapid and strong inhibition of plasma renin activity, which persisted at least for 2 h. These results suggest that the expression of RnBP gene in the kidney and adrenal gland is regulated independently, and the function of RnBP is related to electrolyte homeostasis, probably through the interaction with renin.

Adrenal Glands↗
PubMed1992

Immunological detection and quantitation of DNA adducts formed by 4-aminoazobenzene species in vivo.

Antibodies to 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and 2-methoxy-4-aminoazobenzene (2-MeO-AAB) DNA adducts were raised in rabbits against in vitro-adducted DNA samples. The enzyme-linked immunosorbent assay (ELISA) was used to determine the sensitivity and specificity of these antibodies. They proved highly specific for the modified DNA used as the immunogen, but cross-reacted with each other. Moreover, they showed cross reactivity with DNA modified by 4-(o-tolylazo)-o-toluidine, but not by other carcinogens, such as 4-aminobiphenyl or 4-nitroquinoline 1-oxide. The 50% inhibition level of antibody binding in the competitive ELISA was at 10-20 fmol of modified base per assay (equivalent to 1-2 adducts per 10(6) bases). Immunohistochemical staining indicated that these antibodies bind specifically to nuclear components of the liver in rats given either 3-MeO-AAB or 2-MeO-AAB at the dose of 50 mg/kg body weight.

Animals↗
PubMed1992

Assessment of endothelium-derived relaxing factor from human coronary arteries using the anti-platelet aggregatory effect.

Responses of human and canine washed platelets to thrombin in the presence and absence of human and canine coronary arteries were examined to establish a simple indirect measurement system for endothelium-derived relaxing factor (EDRF). Isolated rings of coronary arteries were obtained from either adult dogs or recipient hearts of cardiac transplant patients. The addition of small segments of canine and human coronary arteries with intact endothelia inhibited thrombin-induced platelet aggregation, but those with disrupted endothelia did not. Pretreatment of human and canine coronary arteries with the cyclo-oxygenase inhibitor indomethacin markedly attenuated the observed effect. The anti-platelet aggregatory effect of indomethacin-pretreated coronary artery was enhanced by acetylcholine or histamine, stimulators of EDRF production, or superoxide dismutase, which prolongs the half-life of EDRF, and inhibited by the EDRF inhibitor hemoglobin. These results suggest that endothelial cells of the human coronary artery, like the canine coronary artery, can produce EDRF which inhibits platelet aggregation, and that this simple experimental model is useful to examine the effect of environmental chemicals on EDRF in the human coronary artery.

Animals↗
PubMed1992

Injury to cultured human vascular endothelial cells by copper (CuSO4).

The effect of copper sulfate (CuSO4) on cultured human vascular endothelial (HVE) cells and cultured human fibroblasts (HAIN-55) was investigated. HVE cells were collected from umbilical veins by enzymatic digestion with collagenase. The viability, subsequent growth and DNA synthesis of both cell types were inhibited concentration-dependently by the addition of copper. The cytotoxic effect of copper on the morphology of these cells was also concentration-dependent. However, the cytotoxic effect of copper on the viability, subsequent growth and DNA synthesis was greater in HVE cells than in HAIN-55 cells. These results suggest that HVE cells are more susceptible to concentration-dependent copper cytotoxicity than HAIN-55 cells are, and that copper could induce vascular endothelial injury, which may be involved in the pathogenesis of cardiovascular disease.

Cardiovascular Diseases↗