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Biomedical subjects

S Mitsuyama

Publications and source records attributed to S Mitsuyama.

33 records · Page 2Linked to original sources

[Study on CAF + medroxyprogesterone acetate (MPA) therapy for advanced or recurrent breast cancer--comparison between MPA 600 mg and 1,200 mg. Kyushu CAFT Therapy Study Group (Third Study)].

To find the optimal dose of MPA for combined use with CAF therapy for advanced or recurrent breast cancer, a randomized comparative study with a MPA 1,200 mg group and 600 mg group was carried out multi-institutionally. The response rate of complete cases was 37.5% (12/32) in the 1,200 mg group and 36.6% (15/41) in the 600 mg group, showing no difference between the two groups. There were no differences in either the duration of response or the survival term. The major adverse effects and abnormal laboratory test values included alopecia, nausea and vomiting, general fatigue, anorexia and leukopenia, with no difference in incidence between the groups. Moon face, genital hemorrhage and body weight increase, which are thought to be caused by MPA, were found in both groups without a significant difference in incidence. The results of this study revealed no differences in effectiveness or safety between MPA 1,200 mg and 600 mg, suggesting that MPA for combined use with CAF is fully effective at a dose of 600 mg.

Adult↗

Breast Cancer in a Patient with McCune-Albright Syndrome.

We treated a patient with breast cancer associated with McCune-Albright syndrome. A 40-year-old woman with a history of precocious puberty visited our hospital complaining of a mass in the upper lateral quadrant of the right breast. Although bone scintigraphy revealed multiple high uptake of 99mTc, plain X-ray demonstrated ground-glass appearance, suggesting fibrous dysplasia rather than bone metastases. Serum levels of tumor markers and alkaline phosphatase were within the normal range. Breast cancer associated with McCune-Albright syndrome was diagnosed, and she subsequently underwent breast conserving surgery, excision of abdominal wall myxoma and bone biopsy of the left clavicula. The bone lesion was histologically confirmed as fibrous dysplasia. Although McCune-Albright syndrome isa rare clinical entity, it should be considered as a possible differential diagnosis of bone metastasis in patients with breast cancer. As recent molecular studies have suggested genetic mutations in McCune-Albright syndrome, this syndromemay possibly predispose patients to breast cancer.

Journal Article↗

Genotype-phenotype correlation of patients with multiple endocrine neoplasia type 2 in Japan.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperparathyroidism. MEN 2 is caused predominantly by germ-line mutations of the RET proto-oncogene. This study aimed to clarify the genotype-phenotype correlation in MEN 2 patients in Japan in order to modify the clinical management according to the genotype. METHODS: Constitutive DNA of 64 MEN 2 patients (48 kindreds) were searched for mutations at exons 10, 11, 13, 14 and 16 of the RET proto-oncogene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing and restriction enzyme digestion. The clinical characteristics of the patients were obtained from a previous nationwide questionnaire survey. RESULTS: Overall, 62 (96.9%) out of 64 patients had a germ-line point mutation at the hot spots. MTC and pheochromocytoma occurred equally in every genotype except C630S. Specific genotype had a correlation between tumor size and age at the operation for MTC or extent of MTC, i.e. C618S developed late onset type of MTC as compared with that of C634R, C634Y and M918T. Small MTC in C634R may be less aggressive than those in C634Y and M918T. CONCLUSIONS: DNA testing has good clinical implications for the management of patients with MEN 2 and the timing and operative procedures of thyroidectomy can be modified according to the genotype.

Adrenal Gland Neoplasms↗

Granular cell tumors of the breast: a report of two cases.

Granular cell tumors (GCT) are rare neoplasms, and only 173 cases of benign GCT of the breast have been documented. We report herein the cases of two patients with this tumor and discuss the methods of diagnosis and treatment. The first patient was a 60-year-old woman who presented with a firm ill-defined mass in her left breast. Mammography showed a dense shadow with spicula and skin thickness, and ultrasonography revealed a hypoechoic mass with an irregular border. Radical mastectomy was performed under the wrong preoperative diagnosis of breast cancer. The second patient was a 31-year-old woman who presented with an elastic-hard mass in her left breast. Mammography showed a well-demarcated dense mass, and ultrasonography revealed a well-defined hypoechoic mass with a large depth-width ratio. Fine-needle aspiration cytology (FNAC) showed a large number of histiocytic cells with abundant granular cytoplasm. An excisional biopsy was performed, and histological examination confirmed a diagnosis of GCT. GCT is benign, but often misdiagnosed as breast cancer both clinically and radiologically. Therefore, histological examination is essential for making a correct diagnosis, while FNAC is also useful. Local resection is still the treatment of choice, and surgeons should do their utmost to avoid performing needless radical mastectomy.

Adult↗

[Administration method and recurrence-preventing effect of medroxyprogesterone acetate (MPA) as a postoperative adjuvant endocrine therapy for stage III breast cancer. Kitakyushu Collaborative Study Group for Breast Cancer].

By a collaborative study undertaken by 11 medical institutions in the Kita-Kyushu area, we evaluated the clinical efficacy of the combination of medroxyprogesterone acetate (MPA) and Tamoxifen (TAM) as a postoperative adjuvant endocrine therapy for Stage III breast cancer. First, 1 course of CAF therapy was administered; then, in combination with the basic therapy of 5-FU 200 mg/day p. o. for 3 years, ER (+) patients were treated with either 2-week sequential therapy of TAM (30 mg/day) and MPA (800 mg/day) or TAM (30 mg/day), and ER (-) patients received either MPA (800 mg/day) or 5-FU alone. Neither survival nor disease-free rates of the 92 analyzable patients were different between these treatment groups. Furthermore, the blood levels of MPA and cortisol had no correlation with survival and disease-free periods. We studied the effect of MPA on the natural inhibitors of blood coagulation, but found no difference from the result in healthy adults. It was, however, shown that MPA had a bone marrow-protecting effect.

Adult↗

[Comparison of CAF plus MPA with CAF plus TAM for advanced or recurrent breast cancer--Kyushu CAFT Study Group of Advanced or Recurrent Breast Cancer].

A multi-center randomized comparison study of CAF + TAM therapy (Arm A) and CAF + MPA therapy (Arm B) in advanced or recurrent breast cancer was conducted at 37 institutions in Kyushu. Out of 119 registered cases, 114 were eligible and 76 were evaluable. The response rate was 42% (15/36) in Arm A and 58% (23/40) in Arm B. In the comparison of side effects, nausea/vomiting and anorexia were significantly less and moon face and body weight gain were significantly more in Arm B. Leucocytopenia was significantly inhibited in Arm B compared with Arm A, which indicated the myeloprotective effect of MPA. These results indicated that CAF + MPA therapy (Arm B) may be more advantageous than CAF + TAM therapy (Arm A) in advanced or recurrent breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[Late phase II study of KW-2307 in advanced or recurrent breast cancer. KW-2307 Cooperative Study Group (Breast Cancer Section)].

A multi-institutional late phase II study of KW-2307 (vinorelbine), a new vinca alkaloid derivative, in advanced or recurrent breast cancer was conducted in 26 nationwide hospitals. KW-2307 was intravenously administered at a dose of 20 mg/m2 once weekly. Eighty among the enrolled 82 patients were eligible. The overall response rate was 30.0% (24/80) with 4 CR, 20 PR, 5 MR, 22 NC, 17 PD and 12 unevaluable patients. The major side effect was leucopenia, which was the dose-limiting factor in this study. Other subjective or objective side effects included general fatigue, nausea-vomiting, anorexia, paresthesia, fever and stomatitis, but none of them was serious.

Adult↗

Effects of glycosaminoglycan polysulfate on extracellular matrix metabolism in human skin cells.

The effects of chondroitin polysulfate (CPS), a semi-synthetic oversulfated chondroitin sulfate, on the metabolism of extracellular matrix in human skin cells were examined. CPS accelerated the production of glycosaminoglycans (GAGs) in human dermal fibroblasts in a dose dependent manner (0.1-3.0 micrograms/ml), but did not modulate the production of noncollagenous protein and collagen, or [3H]-thymidine incorporation into DNA. However, higher concentrations (> 10 micrograms/ml) of CPS suppressed the [3H]-thymidine uptake by fibroblasts. More than 80% of total synthesized GAGs were found to be hyaluronate, whereas CPS did not alter their composition. These results indicated that CPS preferentially enhances the production of GAGs in human dermal fibroblasts, and that GAGs and DNA synthesis in the fibroblasts are independently regulated. Furthermore, CPS might be a unique material able to maintain the level of GAGs in the human skin.

Cells, Cultured↗

High-yield purification of glucokinase from rat liver.

A rapid and reliable method for the purification of rat liver glucokinase was developed. The procedure consists of DEAE-cellulose ion-exchange chromatography, Phenyl-Sepharose hydrophobic interaction chromatography, DEAE-Affi Gel Blue dye-ligand chromatography, and duplicate steps of glucosamine-Sepharose affinity chromatography. Glucokinase was purified to a specific activity of 290 units/mg protein in a yield of 55% in 6 days. The final enzyme preparations were completely homogeneous in most experiments as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The estimated molecular weight (51,000) and sigmoidal saturation function for glucose of purified glucokinase were in good agreement with published data.

Animals↗

Participation of glucokinase inactivation in inhibition of glucose-induced insulin secretion by 2-cyclohexen-1-one.

We assessed our speculation that 2-cyclohexen-1-one (CHX) impairs glucose-induced insulin secretion through inactivation of glucokinase. Treatment of pancreatic islets with CHX at concentrations (0-5 mM) that caused a dose-dependent inactivation of glucokinase activity similarly inhibited glucose-induced insulin secretion. Another glucose-phosphorylating enzyme (hexokinase) in pancreatic islets was little affected by CHX. CHX-induced inactivation of glucokinase was blocked by the presence of its substrates (glucose and mannose) and an inhibitor (N-acetylglucosamine), all of which also protected against the inhibitory effect of the drug on glucose-induced insulin secretion. CHX also impaired insulin secretion induced by D-glyceraldehyde and dimethyl succinate, which are believed to stimulate the release of the hormone by being directly oxidized by glyceraldehyde-3-phosphate dehydrogenase, by entering the midstream of the glycolytic pathway as glyceraldehyde 3-phosphate, or by entering the tricarboxylic acid cycle in mitochondria after intracellular hydrolysis. The inhibitory effect of CHX on glucose-induced insulin secretion, however, was far more marked than that on insulin secretion evoked by D-glyceraldehyde and dimethyl succinate at any CHX concentrations used. Our study revealed that the inhibitory action of CHX on glucose-induced insulin secretion is exerted mainly, but not solely, through inactivation of glucokinase. This conclusion supports the view that glucokinase is a key enzyme in the recognition of glucose as an insulin secretagogue in pancreatic islets.

Animals↗

Evidence for the presence of rat liver glucokinase in the nucleus as well as in the cytoplasm.

Subcellular distribution of glucokinase was studied in rat liver. With an immunohistochemical procedure, glucokinase immunoreactivity was clearly shown in the nucleus of parenchymal cells of rat liver, but faintly in the cytoplasm. Nuclei, cytosol (extranuclear fraction in the strict sense), and homogenate prepared in nonaqueous medium, i.e. glycerol, were analyzed for glucokinase by both immunoblotting and activity measurement. Such analyses demonstrated that glucokinase concentration was far higher in the nuclei than in the cytosol when compared on the basis of total protein content and that total glucokinase activity in the cytosolic fraction was about 1.8 times that in the nuclear fraction. These results indicate that hepatocyte glucokinase is present in the nucleus as well as in the cytoplasm in contradiction to the widespread belief of its exclusive localization in the cytoplasm.

Animals↗

Pharmacokinetic evidence for blood flow depression in dose dependent disposition of 4-aminoantipyrine in rabbits.

Pharmacokinetic relationships have been developed to characterize a one-compartment drug disposition model which includes perfusion limited elimination processes. The derived expressions have been applied to plasma concentration and urinary excretion data obtained after rapid intravenous administration of 4-aminoantipyrine to rabbits. The mathematical relationships and experimental data demonstrate that dose dependent disposition of 4-aminoantipyrine is a result of reduced renal and hepatic blood flow caused by the drug itself.

Ampyrone↗

Dynamics of swallowing in tetanus.

An 82-year-old man developed an uncommon type of swallowing disturbance with tetanus. Initially, he could masticate his food but could not pass it into the esophagus. The mechanism of swallowing in this patient was studied radiologically and endoscopically. The disturbance in the second stage of deglutition was associated predominantly with his advanced age and the slow clinical progress of the tetanus. The patient was cured by treating the disease.

Aged↗

Thyroid metastasis from hepatocellular carcinoma as an initial presentation: a case report.

Although metastases to the thyroid are not uncommon at autopsy, most of these lesions are clinically occult. To our knowledge, this is the first report of a case of hepatocellular carcinoma initially presenting as a thyroid mass. Various radiological studies suggested malignant thyroid tumor, and core needle biopsy was performed. Metastasis from hepatocellular carcinoma was histopathologically suspected, and subsequent abdominal CT revealed advanced hepatocellular carcinoma.

Aged↗