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Biomedical subjects

T Tsuchida

Publications and source records attributed to T Tsuchida.

At least 19 recordsLinked to original sources

Identification of a src family protein specifically expressed in rat astrocytes by immunohistochemistry and double immunofluorescent study.

Identification of a src-related tyrosine kinase and its regional and cellular distributions were studied in rat brain. The study was performed using a specific antibody raised against a synthetic peptide corresponding to the conserved autophosphorylation site of src-family tyrosine kinases. The antibody (alpha-src antibody) recognized a 43 kDa polypeptide in plasma membrane enriched fraction. The immunohistochemical data revealed that the polypeptide is localized in astrocytes of corpus callosum and fimbria hippocampus. The presence of this src-related protein in astrocytes suggests that it may have some control in their proliferation and differentiation.

Animals

Fluorescent dye rhodamine 6G as a molecular probe to study drug resistance of C6 rat glioma cells.

A study was made of the membrane transport of cytoplasm and mitochondria stained fluorescence dye Rhodamine 6G (R6G). In rat glioma C6 cells and 1-(4-amino-2-methyl-5-pyrymidinyl)-methyl-3-(2-chloroethyl) -3-nitrosourea hydrochloride (ACNU) and vincristine (VCR) resistant cell lines (C6/ACNU, C6/VCR), the rate of uptake of R6G decreased in C6/VCR cells, but verapamil increased the intracellular accumulation of R6G in C6/VCR. The intracellular accumulation of R6G of C6/ACNU cells was essentially the same as that of wild-type cells. C6/ACNU cells did not show cross resistance and were sensitive to VCR and cisplatin. C6/VCR cells showed cross resistance to ACNU and CDDP, but C6/VCR cells in the presence of verapamil were more sensitive to drugs than C6/VCR cells in the absence of verapamil. We conclude that the reduction of R6G fluorescence staining intensity in C6/VCR cells compared to wild-type cells may be associated with the mechanism of multidrug resistance (MDR) but does not reflect the mechanism of resistance to ACNU. Verapamil increased the accumulation of R6G in C6/VCR cells and overcame MDR, suggesting that there is a correlation between the MDR overcoming effect and enhancement of R6G accumulation, and that this correlation validates the use of the R6G staining test for clinical and laboratory investigation of MDR.

Animals

Clinical evaluation of scleroderma spectrum disorders using a points system.

We have established a new diagnostic method using a points system to evaluate patients with early scleroderma and those with scleroderma spectrum disorders (SSD). To examine the clinical usefulness of this method, it was applied to a total of 215 cases including 97 patients with scleroderma, 32 with SSD, 28 with presumed primary Raynaud's phenomenon (RP) and 58 with other connective tissue disorders (CTD). A total score was obtained for each patient as the sum of the following five factors: (1) extent of skin sclerosis (maximum, 10 points); (2) pulmonary changes (maximum, 4 points); (3) antinuclear antibodies (maximum, 5 points); (4) pattern of Raynaud's phenomenon (maximum, 3 points); and (5) nailfold bleeding (maximum, 2 points). Of the 97 scleroderma patients, 86 (89%) had 9 or more points, and of the 32 SSD patients, 28 (88%) had 5 to 8 points. In contrast, all patients with presumed primary RP and 54 of 58 (93%) patients with other CTD had 0 to 4 points. These data suggest that this diagnostic method is very useful not only for clinical evaluation of SSD, but also for the differentiation of scleroderma and SSD from other CTD and primary RP.

Connective Tissue Diseases

Evaluation of transcatheter arterial embolization with epirubicin-lipiodol emulsion for hepatocellular carcinoma.

A total of 18 patients with hepatocellular carcinoma (HCC) were treated by transcatheter arterial embolization (TAE) with a 4'-epi-doxorubicin (EDX)-lipiodol emulsion. Infusion of the EDX-lipiodol emulsion (EDX-L) via the hepatic artery was followed by the injection of gelatin sponge in 12 cases. The response and survival of these 12 patients following EDX-L treatment were compared with those of 42 subjects treated with a doxorubicin-lipiodol emulsion (DX-L) and those of 23 patients treated by TAE with gelatin sponge (GS) only. In the group treated with EDX-L, nine cases were AFP-positive in sera and four showed a decrease in serum AFP values to less than 10% of the pretreatment level. Seven cases showed a partial response, and nine cases showed no change in the size of the tumor. In the group treated with EDX-L, nine cases are alive, and the oldest has survived for more than 431 days since the treatment. The half-year survival value was 57%, and the 1-year survival value was 49%. These values did not differ significantly from those calculated for the group treated with DX-L. The 1-year survival value determined for patients treated with a lipiodol emulsion (EDX-L or DX-L) followed by GS was 65%, and the 2-year survival value was 39%. These results rates are significantly better than those obtained in patients treated with GS only (1-year survival, 39%; 2-year survival, 13%.

Aged

Effectivity and safety of mannitol treatment for acute hepatic failure in rats.

In rats with D-galactosamine-induced hepatic failure, 14C-D-mannitol transport into the brain was accelerated through an increase of vesicular transport via the blood-brain barrier and thus brain mannitol contents increased. However, the osmolarity of the brain tissue changed little and the mortality was decreased by mannitol infusion to acute hepatic-failure rats. Experimental data indicate the effectivity and safety of hypertonic mannitol therapy for cerebral edema in acute hepatic failure.

Animals

Colloid cysts of the third ventricle: immunohistochemical evidence for nonneuroepithelial differentiation.

The histogenesis of colloid cysts (CCs) of the third ventricle has been a subject of controversy. We examined, using immunohistochemical techniques, four CCs for the presence of cytokeratins (CKs), glutathione S-transferase isoenzymes (GST-pi, GST-mu), and glial fibrillary acidic protein. Antibodies to both low molecular weight CKs (anti-CK8) and to a mixture of CKs (AE1/AE3) were used. For comparison, normal fetal and adult choroid plexus, ependyma, and nasal mucosa were also examined. The epithelium lining all four CCs showed positive immunostaining for the CKs and GST-pi but not for GST-mu or glial fibrillary acidic protein. Fetal and adult nasal mucosa showed a pattern of immunohistochemical staining almost identical to that of CCs. In contrast, fetal and adult choroid plexus tissue showed positive immunostaining for GST-pi and low molecular weight CKs but not for the CK mixture (AE1/AE3). Fetal and adult ependyma were negative for both CKs and GST-pi. These results suggest that CCs differentiate along nonneural lines distinct from the neuroepithelial differentiation of the choroid plexus and ependyma.

Adult

Gangliosides of melanoma.

The relationships between the ganglioside composition of melanomas and their biologic behavior were investigated. (1) The amount of GM2 and/or GD2 in melanoma cells injected into nude mice correlated with the tumor growth rate. (2) GD2 content of melanoma cell lines correlated with sensitivity to radiation and vincristine. (3) GM2 expression of melanoma cells correlated with sensitivity to lymphokine-activated killer cells. (4) Gangliosides inhibited the proliferation of human T cells stimulated with interleukin-4 or interleukin-2. Based on these results, we proposed a hypothesis for the role of melanoma-associated gangliosides in the biologic behavior of melanomas and suggested a prospective melanoma treatment related to the gangliosides.

Animals

Radiotherapy for pediatric brain stem glioma: radiation dose, response, and survival.

An analysis of 39 patients under 20 years of age with brain stem glioma treated with radiotherapy between 1977 and 1991 was undertaken. Twenty-eight (71.2%) of the patients responded well to initial radiotherapy, and 11 (28.8%) responded poorly. Median survival for the total patient population was 10 months. Response rates and median survivals were influenced by radiation dose: 45.5% and 9 months at doses less than 4499 cGy (n = 11), 83.3% and 13 months at doses between 4500 and 5499 cGy (n = 12), 66.7% and 11.5 months at doses between 5500 and 6499 cGy (n = 9), and 100% and 10 months at doses more than 6500 cGy (n = 7). Multivariate analysis revealed the response to initial radiotherapy was the only predictor of survival with radiation doses up to 6499 cGy. Four of the patients who responded well demonstrated radiological and/or histological calcification within or around the tumor at the time of clinical deterioration. Radiation injury was confirmed in two autopsy cases. The possibility that intratumoral radiation injury causes clinical deterioration is suggested.

Adolescent

Sputum cytology-positive, bronchoscopically negative adenocarcinoma of the lung.

Among a total of 114 cases of resected lung adenocarcinoma that were examined by sputum cytologic study before bronchoscopy, 17 were sputum cytology-positive, but had no abnormal bronchoscopic findings. In most of these cases, the reason for detection was sputum and bloody sputum (58.8 percent). Pathologically, many cases were classified as stage III A or more (82.4 percent) due to mediastinal lymph node metastases. More than 70 percent of the cases showed vascular invasion. The proportion of well-differentiated cases was also high (52.9 percent). The prognosis of these cases was worse than sputum cytology-negative adenocarcinoma without abnormal bronchoscopic findings and better than sputum cytology-positive adenocarcinoma with abnormal bronchoscopic findings. There was no significant difference between these cases and sputum cytology-negative adenocarcinoma with abnormal bronchoscopic findings. Combined with the bronchoscopic findings, sputum cytologic study is useful for preoperative evaluation of lymph node metastasis and prognosis. This combined approach can provide information necessary to perform sufficient dissection of mediastinal lymph nodes and proper adjuvant therapy in sputum cytology-positive adenocarcinoma cases, even though there are no abnormal bronchoscopic findings.

Adenocarcinoma

Granulomatous hypophysitis with meningitis and hypopituitarism.

We report an unusual case of granulomatous hypophysitis in which visual impairment, meningitis and hypopituitarism in a 76-year-old female were associated with radiological evidence of a pituitary mass. The sellar lesion was indistinguishable from pituitary tumor on neuroimaging studies, but the recovery of visual acuity and visual field abnormalities together with the improvement of pituitary function after steroid administration indicated that the mass lesion was due to an inflammatory disease of the pituitary gland. The pituitary tissue obtained by transsphenoidal hypophysectomy revealed granulomatous inflammatory cell infiltration with epithelioid cells and scattered multinucleated giant cells. Although a causal relationship with meningitis was not ascertained, possible exposure of the CSF space to the autoimmune inflammatory process of the pituitary gland was likely in view of the positive pituitary antibody reaction and radiological evidence of suprasellar extension. This entity should be considered when evaluating patients with a pituitary mass, hypopituitarism and meningitis.

Aged

Retroperitoneal ganglioneuroma: a case report and review of the Japanese literature.

A rare case of retroperitoneal ganglioneuroma incidentally found during an annual health examination is presented. The patient was an asymptomatic female, age 26. Physical examination and routine laboratory studies gave normal results. The plasma concentrations and 24-h urinary excretion of catecholamine and its metabolites were within the normal range. The patient was diagnosed as having a left supra-renal mass (6.3 x 3.6 cm) by abdominal ultrasonography, although by image diagnosis the paraadrenal mass could not be discriminated from an adrenal tumor. Operation was performed under the suspicion of a nonfunctioning adrenal tumor. The tumor removed was 8 x 6 x 4 cm, 98 g and was encapsulated. Histopathological diagnosis of retroperitoneal ganglioneuroma was confirmed. Forty-one cases of retroperitoneal ganglioneuroma in the Japanese literature including the present case are reviewed.

Adult

[Intra-arterial chemotherapy with ACNU in the treatment of malignant gliomas].

Twelve patients with supratentorial gliomas were treated with intra-arterial ACNU followed by intravenous maintenance chemotherapy. Six of the patients, treated from February 1987 through May 1989, received doses of 120-200 mg/m2 (high dose treatment group); six patients, treated from June 1989 through October 1990, received doses of 80-100 mg/m2 (low dose treatment group). The drug was given via the supraophthalmic portion of the internal carotid artery or vertebral artery at a rate of 10 mg/min. The response rate (CR + PR) on CT scan was 50% (3/6) in the high dose treatment group and 17% (1/6) in the low dose treatment group. Survival periods from first operation, however, did not differ between the high and low dose treatment groups. Bone marrow suppression was dose-related and reversible at these doses. Severe neurotoxicities (hemiparesis and aphasia) developed in the patients who received 200 mg/m2 of ACNU; in one case, this was irreversible. High dose intra-arterial ACNU chemotherapy is effective in reducing tumor size on CT scan but the prognosis is not improved. The dose limiting factor of intra-arterial nitrosourea is neurotoxicity, and doses of more than 200 mg/m2 are considered to be dangerous.

Adult

Ganglioside GM2 levels in human melanoma cells: inverse correlation with lysosomal beta-hexosaminidase A activity.

GM2 is usually significantly elevated in human melanoma cells. The lysosomal hydrolase beta-hexosaminidase A (Hex A), is an isoenzyme required for terminal GalNAc hydrolysis from intact GM2 to GM3. The objective of the present studies is to determine if the elevated levels of gangliosides, particularly GM2, correlate with the activity of Hex A in cultured melanoma cells. The Hex A activity in 13 melanoma cell lines ranged from 26%-88.3% There was a inverse correlation between GM2 nmole/g and Hex A activity (r = -0.48; p less than 0.003). An inverse correlation (p less than 0.03) occurred between GD2 nmole/g and Hex A activity. There was an inverse correlation (r = -0.53; p less than 0.05 and r = -0.51; p less than 0.05, respectively) between the ratio of substrate/product (GM2/GM3) and (GD2/GD3) and Hex A activity. These results indicate that the level of GM2 in melanoma is inversely correlated with the level of activity of Hex A.

Analysis of Variance