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Y Totsuka

Publications and source records attributed to Y Totsuka.

At least 127 records · Page 7Linked to original sources

[Fourteen cases of mucosal melanomas of the oral cavity].

Fourteen cases of mucosal melanomas of the oral cavity were treated from January, 1970 to April, 1986 in our department. The patients were 10 males and 4 females and in their fifth and sixth decades with the primary sites in the upper gingiva and palates in the majority. The 3 and 5 year survival rates were 21.4% and 14.3% respectively, with unfavorable prognosis in comparison with cutaneous melanoma. The clinical stages were as follows: stage Ia (1), Ib (8), II (5), which affected the prognosis. The depth of invasion, as described by Breslow et al., were beyond 1.50 mm except in one case, which might be a significant prognostic factor in the study of mucosal melanoma of the oral cavity. Seventy one percent had neck node metastases and 35% had distant metastases. The high occurrence of metastases might be related to their poor prognosis.

Adult↗

Histopathologic study of bone invasion by DMBA-induced carcinoma of the mouth in the hamster.

Carcinoma was induced in the floor of the mouth in the hamster, and the mechanism of bone invasion was studied microscopically. Conclusions are as follows: The periosteum is destroyed and, in general, the external surface of the cortical bone is resorbed through osteoclastic action. However, the periosteum at times resists the invasion of tumors. As the cortical bone is resorbed to some extent and tumor replaces the resorbed area, Volkmann and haversian canals begin to enlarge. Following enlargement of the canals, tumor invasion results in enlargement of the canals of the cortical bone far from the invaded area. In addition, tumors invade the periodontal space and resorb the inner surface of the alveolar bone. Tumors invade the bone marrow through the enlarged haversian canals or the periodontal space or by direct resorption of cortical bone, thus replacing the marrow spaces.

9,10-Dimethyl-1,2-benzanthracene↗

Structure of the thyrotropin receptor and thyroid adenylate cyclase system as determined by target analysis.

Bovine thyroid plasma membranes were irradiated with high-energy electrons. Analysis of the target size of the thyrotropin (TSH) receptor revealed a complex pattern composed of a TSH binding component of 71 000 daltons and a large component (several hundred thousand daltons) that masked some of the binding. Both components were also observed when binding was assayed in the presence of 50 mM NaCl. Membranes preincubated with Mg2+ and 10 microM guanosine 5'-(beta,gamma-imidotriphosphate) [Gpp(NH)p], a persistent activator of adenylate cyclase, also showed the presence of these same components. Although the receptor for TSH has been reported to have some similarities to the receptor for cholera toxin, target analysis of [125I]iodocholera toxin binding was consistent with a single small component about the size of a ganglioside. Measurement of the target size of ground-state, i.e., not preactivated, adenylate cyclase was also carried out. The basal (Mn2+) adenylate cyclase yielded a Mr of 85 000, the smallest unit capable of producing cAMP. The Gpp(NH)p-responsive adenylate cyclase has a Mr of 150 000, which may reflect the contribution of the guanine nucleotide regulatory component to the mass of the active enzyme. A similar size was previously measured for the Gpp(NH)p-preactivated, detergent-solubilized thyroid enzyme [Asbury, R.F., Cook, G.H., & Wolff, J. (1978) J. Biol. Chem. 253, 5286-5292]. Radiation inactivation of the NaF-responsive enzyme indicated two or more components to this activity, the smaller of which (140 000 daltons) was similar in size to the ground-state Gpp(NH)p-responsive enzyme and the larger of which was greater than 10(6) daltons.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

Cellular distribution of thyroid myosin.

The subcellular localization of myosin in thyroid was investigated by both immunofluorescence and biochemical techniques. Dog thyroid cells stained with antisera to gizzard or thymus myosins showed that epithelial cells from thyroid contain nonmuscle myosin but not smooth muscle myosin. The antimyosin staining appeared at the periphery of the cell and in fibrils within the cell. The nature and subcellular localization of the myosin were further probed using biochemical techniques. Bovine thyroid plasma membranes were isolated by flotation on sucrose density gradients and subsequently extracted with 1% Triton X-100 to prepare an insoluble cytoskeletal fraction. After washing to remove residual Triton X-100, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cytoskeletal fraction demonstrated two major bands and several minor bands. The higher molecular weight band of the two major bands comigrated with the 200,000 mol wt heavy chain of myosin. Phosphorylation of the cytoskeletal fraction by thyroid myosin light chain kinase demonstrated a calcium- and calmodulin-dependent phosphorylation of the 20,000 mol wt light chain of myosin. Furthermore, the cytoskeletal fraction contained a myosin-type EDTA-K+ ATPase activity which was not influenced by ouabain and sodium azide. These results demonstrate the association of myosin with thyroid plasma membranes. Little myosin was solubilized by incubation of the thyroid plasma membranes with 0.6 M KCl; however, the addition of 10 mM ATP and 10 mM MgCl2 solubilized most of the myosin, indicating that it is associated with the thyroid plasma membranes through interaction with actin filaments. The presence of myosin in the thyroid plasma membranes may be important in endocytosis and exocytosis involved in thyroid hormone secretion.

Adenosine Triphosphatases↗

Propylthiouracil-induced diffuse interstitial pneumonitis.

Cough productive of sputum, exertional dyspnea, and hypoxemia developed in two patients with Graves' disease after six months (patient 1) or three weeks (patient 2) of treatment with propylthiouracil, 300 mg/day. Chest roentgenograms and transbronchial lung biopsy specimens revealed diffuse interstitial pneumonitis. Lymphocyte transformation by phytohemagglutinin was highly stimulated by propylthiouracil. Symptoms and signs improved after cessation of the drug therapy and administration of prednisolone acetate. These cases represent the first report of a complication of diffuse interstitial pneumonitis induced by propylthiouracil.

Aged↗

Effects of forskolin on adenylate cyclase, cyclic AMP, protein kinase and intermediary metabolism of the thyroid gland.

Forskolin (40 microM) stimulated adenylate cyclase activities of bovine thyroid plasma membranes without the addition of guanine nucleotides. GDP had little effect on the forskolin-stimulated adenylate cyclase activity while Gpp[NH]p (0.1-1.0 microM) decreased it. In the presence of TSH (10 mU/0.11), Gpp[NH]p no longer caused inhibition. Forskolin did not affect phosphodiesterase activities of thyroid homogenates. Forskolin (10 microM) rapidly increased cAMP levels in bovine thyroid slices both in the absence and presence of a phosphodiesterase inhibitor. The effect of TSH (50 mU/ml) on cAMP levels was additive or greater than additive to that of forskolin. An initial 2-h incubation of slices with forskolin did not decrease their subsequent cAMP responses to either forskolin and/or TSH while similar treatment of slices with TSH induced desensitization of the cAMP response to TSH, but not to forskolin. Forskolin (10 microM) as well as TSH (50 mU/ml) activated cAMP-dependent protein kinase of slices in the absence of a phosphodiesterase inhibitor. Although forskolin activated the adenylate cyclase cAMP system, it did not stimulate iodide organification or glucose oxidation, effects which have been attributed to cAMP. In fact, forskolin inhibited these parameters and 32P incorporation into phospholipids as well as their stimulation by TSH. These results indicate that an increase in cAMP levels and cAMP-dependent protein kinase activity in thyroid slices may not necessarily reproduce the effects of TSH on the thyroid.

Adenylyl Cyclases↗

Outcome of patients with Graves' disease after long-term medical treatment guided by triiodothyronine (T3) suppression test.

The value of the T3 suppressed 20-min uptake test for the prediction of post-treatment outcome was studied in 193 unselected patients with Graves' disease treated with thionamide drugs and T3. One hundred and twenty-nine of 193 patients were studied previously and followed thereafter (Group A). Sixty-four were newly treated patients: thirty-three (Group B) were treated at the same hospital as Group A; thirty-one (Group C) were treated at another hospital. In total 126 patients out of 193 satisfied our criteria for suppression (total suppression rate, 65%). The suppression rate for new patients (55% in Group B, 52% in Group C) was similar to that for Group A in 1977 (49%) after comparable duration of treatment. The suppression rate for Group A increased with prolongation of the treatment period (49% in 1977 and 71% in 1981). As to the time course of suppression, it was observed that about two-thirds of the suppressed patients satisfied the criteria for suppression within 3 years of starting treatment. The number of suppressed patients per year decreased thereafter as the treatment periods increased. However, the yearly suppression rate did not decrease with time. The time course of suppression in each patient could not be predicted from the results of initial thyroid function tests. The overall remission rate among the 120 suppressed patients followed for 1-13 (mean, 4) years was 96%, which was almost equal to the value obtained in Group A in 1977 (95%) with the average follow-up period of 2 years. Among the 46 patients in Group A followed for 5-13 (mean, 7) years, no increase in relapse was observed with prolonged follow-up periods. Examination on the relationship between the duration of treatment and the post-treatment outcome revealed that, as a whole, the duration of treatment for the patients with relapse were rather short as compared with those for the patients in remission. These results confirm the usefulness of our T3 suppression test for predicting sustained remission of Graves' disease after treatment, and clearly indicate that long-term medical therapy could increase the number of remissions in patients with Graves' disease.

Adolescent↗

Effect of thyrotropin-induced desensitization of bovine thyroid adenylate cyclase on the nucleotide regulatory protein.

The stimulation of adenylate cyclase by TSH was decreased 50-60% in crude membranes prepared from homogenates of bovine thyroid slices that had previously been incubated for 2 h with the hormone. The diminished response was not associated with any significant change in the binding capacity or affinity for 125I-labeled TSH. The apparent affinities of the desensitized adenylate cyclase for TSH or GTP were not different from those of the enzyme prepared from thyroid slices that had been incubated without TSH. Decreased adenylate cyclase responses to NaF, cholera toxin, or guanyl-5'-yl-imidodiphosphate were also observed in the desensitized membrane, whereas the enzyme responses to prostaglandin E1, GTP, or forskolin were not decreased. However, desensitization caused no decrease in the cholera toxin-catalyzed ADP ribosylation of the 40,000 mol wt polypeptide guanine nucleotide-binding component of the adenylate cyclase. The desensitized membranes showed basal adenylate cyclase activity similar to that of the control membranes using adenyl-5'-yl-imidodiphosphate as substrate in the absence of a nucleotide-regenerating system. These results suggest that the in vitro TSH-induced desensitization of thyroid adenylate cyclase reflects an alteration in the activation processes of the nucleotide regulatory protein.

Adenosine Diphosphate Ribose↗

Roles of GTP and GDP in the regulation of the thyroid adenylate cyclase system.

Effects of guanine nucleotides on the adenylate cyclase activity of thyroid plasma membranes were investigated by monitoring metabolism of the radiolabeled nucleotides by thin-layer chromatography (TLC). When ATP was used as substrate with a nucleotide-regenerating system, TSH stimulated the adenylate cyclase activity in the absence of exogenous guanine nucleotide. Addition of GTP or GDP equally enhanced the TSH stimulation. Effects of GTP and GDP were indistinguishable in regard to their inhibitory effects on NaF-stimulated activities. The results from TLC suggested that GDP could be converted to GTP by a nucleotide-regenerating system. Even in the absence of a nucleotide-regeneration system, addition of GDP to the adenylate cyclase assay mixture resulted in the parallel decrease in ATP levels and formation of GTP indicating that thyroid plasma membrane preparations possessed a transphosphorylating activity. When an ATP analog, App[NH]p, was used as substrate without a nucleotide-regenerating system, no conversion of GDP to GTP was observed. Under such conditions, TSH did not stimulate the adenylate cyclase activity unless exogenous GTP or Gpp[NH]p was added. GDP no longer supported TSH stimulation and caused a slight decrease in the activity. GDP was less inhibitory than Gpp(NH)p to the NaF-stimulated adenylate cyclase activity. These results suggest: (1) TSH stimulation of thyroid adenylate cyclase is absolutely dependent on the regulatory nucleotides. (2) In contrast to GTP, GDP cannot support the coupling of the receptor-TSH complex to the catalytic component of adenylate cyclase. (3) The nucleotide regulatory site is more inhibitory to the stimulation of the enzyme by NaF when occupied by Gpp[NH]p than GDP.

Adenosine Triphosphate↗

Three types of desensitization of metabolic responses to thyrotropin in thyroid tissue: a review.

The evidence is reviewed that a desensitization to thyrotropin is of three distinct types. Type 1 is proximal to the production of cyclic AMP and is manifested by a fall of cyclic AMP concentration in the thyroid tissue despite the continued presence of TSH or phosphodiesterase inhibitors in the medium. Type 2 is distal to this event and involves the metabolic effects of TSH mediated by cyclic AMP such as colloid droplet formation, iodide organification and, in dog thyroid, glucose oxidation. All these effects may be due to a reduced amount of cyclic AMP which is not capable of stimulation the protein kinase. They may be prevented by a pre-exposure to similar concentrations of TSH and cannot be overcome by other stimulators acting through the same adenylate cyclase-cyclic AMP pathway. Type 3 involves the processes not regulated by cyclic AMP. Thus, a desensitization of thyroid tissue by pre-exposure to TSH results in a reduced response of phospholipid turnover, a process not mediated by cyclic AMP, either to homologous (TSH) or heterologous (acetylcholine) stimulation.

Acetylcholine↗

["Methamphetamine-stereotypy and hypermotility" in rats chronically treated with reserpine--the effect of intracerebral injection of chlorpromazine].

In rats given methamphetamine (MAPT, 10 mg/kg i.p.) 24 hrs--48 hrs after the long term-administration of reserpine (RE), we have previously found such "bizarre-biting behaviour" as persistent and bloody biting activity at their own legs and tails or those of their cage mates. The present investigation examined the effect of a blockade of the dopamine receptor in the brain on MAPT-induced "bizarre-biting behaviour" and hypermotility of RE-pretreated rats. Male albino Wistar rats aged 4 weeks were injected intraperitoneally with RE (1.25 mg/kg) or 0.9% saline solution (1.25 ml/kg) every two days for 13 days. Twenty-three hrs after the last injection, rats received chlorpromazine (CP, 150 micrograms, 250 micrograms, 625 micrograms, or 1 mg/rat) intracerebrally by Valzelli's method; and 1 hr later, MAPT (10 mg/kg i.p.) was injected. MAPT-induced hypermotility was potentiated in the RE-pretreated rats, but it was suppressed dose-dependently by CP. Stereotyped licking and biting activities of saline-pretreated rats were completely suppressed by CP at each dose given, however, the "bizarre-biting behaviour" of RE-pretreated rats was inhibited by CP only at high doses (625 micrograms or 1 mg/rat). It is suggested that the MAPT-induced hypermotility of RE-pretreated rats is mediated by activation of dopamine receptor while their "bizarre-biting behaviour" is partially related to it.

Animals↗

[Effect of alpha-methyl-para-tyrosine on "methamphetamine-induced sterotype and hypermotility" of reserpinized rats (author's transl)].

Previously we have found such "bizarre stereotypy" as persistent and bloody biting activity at the legs or the tail of himself or of the cage mate given methamphetamine (MAPT, 10 mg/kg) 24 hrs-48 hrs after long term-administration of reserpine (RE). The present investigation examined the effect of inhibition of dopamine synthesis in brain on MAPT-induced "bizarre stereotypy" and hypermotility of RE-treated rats. Male albino Wistar rats aged 4 weeks were injected intraperitoneally with RE (1.25 mg/kg) or 0.9% saline solution (1.25 ml/kg) every two days for 13 days. Twenty-two hrs after the last injection, rats received alpha-methyl-para-tyrosine ( alpha-MPT, 50 mg/kg, 125 mg/kg, 250 mg/kg i.p.) or its vehicle (1 ml/kg i.p.) and 2 hrs later, MAPT. MAPT induced continuous licking and biting at the metal wire of the cage floor in saline-treated rats and also "bizarre stereotypy" in RE-treated rats, but these activities were completely suppressed by pretreatment of alpha-MPT in each dose given (especially in 125 mg/kg, 250 mg/kg). Pertaining to the locomotor activities of saline-treated rats, the horizontal movements were especially enhanced by MAPT, however, the vertical movements remained unchanged. Alpha-MPT partially inhibited such horizontal movements while it potentiated the vertical movements. Locomotor activities of RE-treated rats were depressed one day after the last injection of RE, however, after the MAPT, these activities counts were increased considerably and were also higher in comparison to the counts of saline-treated rats given MAPT. These hypermotilities in RE-treated rats were partially antagonized by pretreatment with alpha-MPT. It is suggested that MAPT-induced "bizarre stereotypy" of RE-treated rats is mediated by the accelerative effect of RE on MAPT-induced dopamine synthesis, while MAPT-induced hypermotility of RE-treated rats is partially related to such an acceleration of dopamine synthesis.

Animals↗