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Biomedical subjects

T Kamata

Publications and source records attributed to T Kamata.

At least 217 records · Page 12Linked to original sources

The effect of isosorbide dinitrate and isosorbide-5-mononitrate on prostacyclin (PGI2) and thromboxane A2 (TXA2) generation in rat and human arteries.

The mechanism by which nitrates produce relaxation of the vascular smooth muscle and anti-aggregatory effect on platelets has not been understood. Several reports have suggested that vasoactive prostaglandin generation may account for part of the pharmacological action of nitroglycerin. However, few studies have been reported that isosorbide dinitrate or its main metabolite, isosorbide-5-mononitrate, directly stimulates prostacyclin (PGI2) generation in blood vessels. We examined the effect of ISDN and 5-ISMN on PGI2 and thromboxane A2 (TXA2) generation in rat thoracic aorta and human thoracic aorta and coronary artery. The stimulation of PGI2 generation was dependent on the concentration of ISDN and the maximum PGI2 generation was effected by ISDN 5.0 ng/ml in both rat and human vessels. The ratio of peak to basal PGI2 generation was about 1.6 with rat thoracic aorta and about 1.6 with human thoracic aorta and about 1.3 with human coronary artery. On the other hand, TXA2 generation showed a smaller increase than that of PGI2 with ISDN used in the therapeutic dose range and 5-ISMN did not significantly affect PGI2 or TXA2 generation. Previous studies of the effect of cyclooxygenase inhibitor, for example indomethacin, on the vasodilating response to nitrates have given conflicting results. It is believed, however, that ISDN is partially, not wholly, associated with the hemodynamic and platelet antiaggregation effects due to vascular PGI2 generation, which may play a beneficial role in inhibiting coronary vasospasm during anginal attacks.

Aged↗

[A case of gastric cancer successfully treated with hyperthermo-chemo-radiotherapy].

A 56-year-old woman was diagnosed as having gastric cancer with lymph node metastasis and invasion to the pancreas head and was admitted to our hospital in September, 1984. She was treated with hyperthermo-chemo-radiotherapy, using radiofrequency-induced hyperthermia (8 MHz) with a daily dose of fractionations at 42-43 degrees C for 60 minutes, 5 fractions per week of irradiation at 180 cGy and systemic chemotherapy. After the total doses of hyperthermia and radiation had reached 11.8 hours and 2500 cGy, the primary tumor and lymph node metastasis measured by X-ray examination were reduced in size. On October 8th, laparotomy was done, and total gastrectomy combined with total pancreatectomy, left hepatic lobectomy and right hemicolectomy was performed. Histologically, almost all of the cancer cells in the primary tumor and lymph node metastasis had disappeared. These results show that this multimodal therapy is effective for local control of gastric cancer, when used preoperatively.

Adenocarcinoma↗

A human nucleolar antigen (pp90) associated with cell growth and its induction by Epstein-Barr virus and human cytomegalovirus.

Immunofluorescent staining of HeLa cells with rabbit antiserum raised against isolated HeLa cell nucleoli showed bright nucleolar fluorescence. Immunoprecipitation of nuclear extracts obtained from HeLa cells labelled with 35S-methionine or 32P-orthophosphate followed by gel electrophoresis of the precipitate revealed a major band of 90 kd. This antigen, called pp90, was judged to be responsible for the nucleolar fluorescence. Serine residues were predominantly phosphorylated in pp90. Similar nucleolar fluorescence was observed commonly in human cells derived from malignant tumors including acute lymphatic leukemia, adult T-cell leukemia, hepatitis B virus-associated hepatoma, adenocarcinoma, and in 5 lymphoid cells derived from Burkitt lymphoma but not in normal human lymphocytes or liver cells. In immunoprecipitation, 32P-labelled pp90 was commonly detected as the major component in all of those cells which showed nucleolar fluorescence. Resting human embryo lung (HEL) cells were negative for both nucleolar fluorescence and pp90 in immunoprecipitation, but turned positive when stimulated to grow, suggesting the involvement of pp90 in cell growth. Antigen pp90 was also induced in human lymphocytes and HEL cells by infection with Epstein-Barr virus in human cytomegalovirus, respectively, which are known to induce cell DNA synthesis in early stages of infection. A cross-reacting nucleolar antigen was detected in 2 monkey cells but not in 3 rodent cells tested.

Adult↗

Three-dimensional distribution of vasoactive intestinal polypeptide-containing structures in the rat stomach and their origins using whole mount tissue.

The three-dimensional distribution of vasoactive intestinal polypeptide (VIP)-like immunoreactive (VIPLI) structures in rat stomach and their origins were investigated using the indirect immunofluorescence method in whole mounted tissue. The present study demonstrates a very dense VIPLI fiber meshwork in the circular muscle layer, longitudinal muscle layer and myenteric plexus. In the muscle layers VIPLI immunoreactive fibers run parallel to the muscle. VIPLI fibers are distributed evenly throughout the entire stomach. We have also shown by experimental manipulations that the fibers in the stomach originate from VIPLI neurons in the myenteric plexus.

Animals↗

Microinjection of the oncogene form of the human H-ras (T-24) protein results in rapid proliferation of quiescent cells.

Using an E. coli expression-vector system we have efficiently produced, purified, and characterized the full-length, nonfused, protooncogenic and oncogenic (T-24) forms of the human H-ras gene product. These purified ras proteins have been introduced by microinjection into a variety of somatic cells in an effort to examine their function. Within several hours after injection of the oncogenic form of the human H-ras protein into quiescent cells, we observe dramatic morphological changes followed by transient proliferation of the cells. In contrast, microinjection of the normal, protooncogenic form of the ras protein at the same level appears to have only little effect on the cells. Additional experiments indicate that the effect of the ras protein requires entry into the cells, is temporary, is inhibited by cycloheximide or actinomycin D, and is seen only in established cell lines. This experimental approach demonstrates that the bacterially derived and purified human H-ras proteins retain their ability to function when put back into mammalian cells and furthermore, provides a novel assay for transformation induced in established cells by the human H-ras oncogene protein.

Animals↗

Origins and three-dimensional distribution of substance P-containing structures on the rat stomach using whole-mount tissue.

The origin and three-dimensional distribution of substance P-immunoreactive structures in the rat stomach were investigated by means of the indirect immunofluorescence method using whole-mount tissue. The present study demonstrated that the myenteric plexus contained a very high concentration of substance P-immunoreactive fibers. It also contained cells that were moderately concentrated in the greater curvature, with those closer to the lesser curvature decreasing in number. In addition, a number of fibers ran parallel to the muscles in the circular and longitudinal muscle layers; these were distributed evenly throughout the entire stomach. We further found that most of the fibers located in the myenteric plexus originated from the greater splanchnic nerve from T5 to L2, but that some originated from intrinsic substance P-immunoreactive cells in the myenteric plexus. The fibers in the circular and longitudinal muscle layers originated from the cells in the myenteric plexus.

Animals↗

Three human transforming genes are related to the viral ras oncogenes.

Three distinct transforming genes present in human tumor cell lines are all related to the viral oncogenes of Harvey and Kirsten murine sarcoma viruses, designated v-H-ras and v-K-ras, respectively. The transforming gene of a bladder carcinoma cell line has been shown to be a human homolog to v-H-ras [Parada, L. F., Tabin, C. J., Shih, C. & Weinberg, R. A. (1982) Nature (London) 297, 474-478; Santos, E., Tronick, S. R., Aaronson, S. A., Pulciani, S. & Barbacid, M. (1982) Nature (London) 298, 343-347]. The transforming gene common to one colon (SK-CO-1) and two lung carcinoma (SK-LU-1 and Calu-1) cell lines is the same human homolog of v-K-ras as is the transforming gene previously identified in a lung carcinoma cell line Lx-1 [Der, C. J., Krontiris, T. G. & Cooper, G. M. (1982) Proc. Natl. Acad. Sci. USA 79, 3637-3640]. The transforming gene of SK-N-SH neuroblastoma cells is weakly homologous to both v-H-ras and v-K-ras. NIH 3T3 cells transformed with the SK-N-SH transforming gene contain increased levels of a protein serologically and structurally related to the protein products of the v-H-ras and v-K-ras genes. Therefore, it represents a third member of the ras gene family, which we have called N-ras. Based on the homology with the v-ras genes, we have established the orientation of transcription and approximate coding regions of the cloned human K-ras and N-ras genes.

Animals↗

Biosynthesis of glycogen in Neurospora crassa. Purification and properties of the branching enzyme.

A branching enzyme was extracted from the mycelia of Neurospora crassa and was purified to electrophoretic homogeneity by procedures including DEAE-Sephacel column chromatography, 6-aminohexyl-Sepharose 4B column chromatography and gel filtration on Toyopearl HW-55S. The final yield of the branching enzyme activity was 15.1%, and the final purified enzyme preparation showed a specific activity of 702 units per mg of protein. The molecular weight of this enzyme was estimated to be 80,000 by electrophoresis in sodium dodecyl sulfate-polyacrylamide gel. The amino acid composition and the carbohydrate content of this enzyme were analyzed. The isoelectric point of this enzyme determined by polyacrylamide gel isoelectrofocusing was 5.6. The branching activity of the enzyme was confirmed by its action on amylopectin as well as by the combined action of this enzyme and N. crassa glycogen synthase. The action of this enzyme on amylopectin decreased the wavelength of the absorption maximum of the glucan-iodine complex, and increased the amount of the short unit chains of the debranched product. The product obtained by the combined action yielded beta-limit dextrin upon hydrolysis with beta-amylase. No multiplicity was found for the branching activity either by chromatography or by electrophoresis.

1,4-alpha-Glucan Branching Enzyme↗

Electron microscopic studies of myosin molecules from chicken gizzard muscle II: The effect of thiophosphorylation of the 20K-dalton light chain on the ATP-induced change in the conformation of myosin monomers.

The conformation of thiophosphorylated myosin molecules of chicken gizzard muscle was studied by electron microscopy with the rotary shadowing technique and by the light scattering method. In the absence of ATP, the radius of gyration (RG) of gizzard thiophosphorylated myosin was 478 A, and was essentially equal to that (474 A) of unthiophosphorylated myosin. In the presence of ATP, it was 355 A, and was much larger than that (146 A) of unthiophosphorylated myosin. In the presence of ATP, 84 percent of the unthiophosphorylated myosin molecules had intramolecular loops at their tails, but only 23 percent of the thiophosphorylated myosin molecules had them. There were two flexible regions in the unthiophosphorylated myosin tail. The considerable flexibility at both regions remained even when the light chain was thiophosphorylated. The two globular heads of the unthiophosphorylated myosin molecules had a tendency to bend back towards the tail in the presence of ATP, but this tendency was reduced by the light chain thiophosphorylation. The myosin molecules with "looped" tails were mostly, if not all, in one of two mirror-image forms, and the mirror-image asymmetry was independent of the thiophosphorylation.

Adenosine Monophosphate↗

Protective action of endogenous prostacyclin (PGI2) and prostaglandin E2 (PGE2) in endoscopic polypectomy-induced human ulcers.

To assess how endogenous prostaglandin (PG) in gastric mucosa acts against ulcer formation, we determined the mucosal prostacyclin (PGI2), PGE2, PGF2 alpha, and thromboxane A2(TXA2) concentrations before and after polypectomy in 6 patients in whom gastric ulcers were produced by electric burning resection of gastric polyps. These artificially induced ulcers all healed within short periods (25.7 +/- 7.4 days, mean +/- SE). Of the PGs assayed, the level of PGI2 was highest. The pG levels were increased at 4 and 7 days post-polypectomy; the most remarkable increase took place in the mucosa along the ulcer margin rather than the mucosa far from the ulcer site. We suggest that the observed increase in endogenous PGs represents a physiological response against polypectomy-induced ulcer formation.

Alprostadil↗

Role of prostaglandin E2 on human gastric ulcers.

Using radioimmunoassay, we determined the mucosal prostaglandin E2 (PGE2) concentration in normal subjects and in patients with tractable and intractable gastric ulcers. The fundic and antral mucosa of the normal subjects contained large amounts of PGE2; they were not significantly different from those found in tractable and intractable gastric ulcer patients. The mucosal PGE2 concentration at the ulcer margin was significantly higher in tractable than intractable cases. To assess the effect of PGE2 on ulcer healing, 11 intractable ulcer patients received PGE2 (1.5 or 3.0 mg/day) perorally. In 7 (64%), the ulcer healed completely within 4 to 14 weeks.

Adult↗

Adenosine triphosphate-induced reversible change in the conformation of chicken gizzard myosin and heavy meromyosin.

In 1978, we (Suzuki et al., J. Biochem. 84, 1529) reported the very interesting finding that in a medium of 0.2 M KCl (and 10 mM MgCl2), addition of ATP induced a large increase in the sedimentation velocity of chicken gizzard myosin from approximately 6S to 10S. Moreover, our flow birefringence study suggested that 10S-myosin was not much different from 6S-myosin in the particle length. Therefore, we concluded that ATP induced dimerization of gizzard myosin monomers. In the present study, we reinvestigated 6S-myosin and 10S-myosin by the sedimentation equilibrium method, and found that both myosins had the same molecular weight of approximately 500,000. We also studied the angular dependence of the light scattering intensity, and found that addition of ATP caused a large change in the radius of gyration of gizzard myosin; the radius of gyration of 6S-myosin was 545 A whereas that of 10S-myosin was only 146 A. Accordingly, our previous conclusion had to be withdrawn. Instead, we now put forward a new conclusion that ATP induces a large change in the conformation of gizzard myosin monomers. We added two new observations: (a) The ATP-induced change in the myosin conformation and the large decrease in the ATPase activity of myosin were both reversible upon increasing the KCl concentration from 0.2 M to 0.3 M. (b) The large decrease in the ATPase activity and the ATP-induced increase in the sedimentation velocity were also observed with gizzard heavy meromyosin when the KCl concentration decreased to lower than 0.3 M.

Adenosine Triphosphate↗