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Biomedical subjects

T Yamane

Publications and source records attributed to T Yamane.

At least 487 records · Page 27Linked to original sources

[Mitoxantrone in the treatment of relapsed and refractory malignant lymphoma].

Mitoxantrone is an anthracenedione with structural similarities to adriamycin but without the amino-sugar moiety on the parent molecule. The compound attracted attention on the basis of animal tumor studies in which it showed equal or superior efficacy compared to adriamycin, but with diminished cardiotoxicity; and it was not fully cross-resistant to adriamycin. Our in vitro studies using human small cell lung cancer cell line (SBC-3) disclosed the absence of cross-resistance between mitoxantrone and adriamycin: SBC-3/ADM, which had developed resistance by continuous exposure to increasing concentration of adriamycin, was as equally sensitive to mitoxantrone as SBC-3 was when tested by clonogenic assay. A phase II study conducted in our Department revealed that mitoxantrone was active to malignant lymphoma refractory to conventional agents including adriamycin: 6 (33%) of 18 patients responded to the agent. Based on the results of our phase II studies of mitoxantrone, etoposide, and cisplatin in malignant lymphoma, we have conducted a phase III study of a 4-drug combination of these 3 drugs plus prednisolone in relapsed or refractory lymphoma: Out of 14 patients, 3 responded completely and 4 did partially, so far. The regimen would appear useful as a salvage therapy for refractory lymphoma.

Adult↗

Eradication of microscopic metastases with intratumoral injection of bacillus Calmette-Guerin.

The studies reported here were designed to examine the effects of intratumoral preoperative administration of Bacillus Calmette-Guerin (BCG) on the cure rates of C3H mice transplanted with MH134 tumor cells and on the metastatic rates in the regional lymph nodes. Furthermore, the morphological findings occurring in the regional lymph nodes were monitored during tumor growth using H-E stain and non-specific esterase staining. The cure rate of the Group treated with BCG intratumoral injection and surgery was significantly higher than that of the Group treated with surgery alone, and in the BCG + surgery group metastatic rates of regional lymph nodes decreased consistently after operation. Moreover, in this group, extensive sinus histiocytosis and marked swelling of the regional nodes were frequently observed. Quantitative studies of the cell kinds using the esterase staining indicated that intratumoral injection of BCG has an effect on the influx of lymphoid cells into the regional nodes, but does not aid specific cell lineage to flow into the regional nodes. In cytostatic assays, it was shown that the regional lymph node cells and spleen cells in the BCG + surgery group always have a greater per cent of inhibition than those in the surgery alone group.

Animals↗

Inhibition of luteinizing hormone secretion during quiescent interval of testicular androgen production in immature mice.

We reported [1] that the proliferation of seminal vesicle cells in mice takes place largely in the neonatal (days 0-15) and pubertal (days 25-35) periods and that between neonatal and pubertal proliferations, a quiescent interval of cell proliferation due to markedly diminished secretion of androgens occurs. The present study was carried out to investigate the mechanism for this quiescent interval of Leydig cell activity. Serum LH concentrations were moderate (0.29 ng NIH-LH-S1/ml) at 8 days of age, low (0.13 ng/ml) at 18 days, and high (0.78-0.60 ng/ml) at 30, 40 and 60 days. The LH level on day 18 was almost the same as that found in hypophysectomized adult mice (0.12 ng/ml). These changes with age in serum LH concentrations paralleled those for serum total androgen (testosterone plus 5 alpha-androgens) concentrations. The injection of HCG (1 IU/day) or LH releasing hormone (0.1 or 0.4 microgram/6h) for 1 or 2 days resulted in significant and marked increases on day 18 in testicular and serum androgen levels and/or the proliferation of seminal vesicle cells measured with 5-[125I]iodo-2'-deoxyuridine uptake by the whole seminal vesicles. These findings lead to the hypothesis that the quiescent interval of testicular androgen production due to inhibition of pituitary LH secretion occurs around day 20 in mice.

Aging↗

Thyrotoxic myopathy associated with subacute thyroiditis.

We report a case of subacute thyroiditis complicated by thyrotoxic myopathy. Previously thyrotoxic myopathy has been described as being associated with Graves' disease. The patient in this study was a 35-year-old man who developed proximal dominant muscular weakness and atrophy during the course of subacute thyroiditis. His myopathic symptoms regressed as his serum thyroxine and triiodothyronine levels returned to normal, however it took a relatively long period of time for them to do so. This suggests that marked myopathy may develop even in cases of subacute thyroiditis if the thyrotoxic state persists for a long period of time.

Adult↗

Distribution pattern of DNA template activity in the developing cerebellar cortex in rats and its alteration after transplacental administration of ethylnitrosourea.

The ultracytochemical acridine orange(AO) method has been employed to demonstrate DNA template activity in the developing cerebellar cortex in rats and its alteration after transplacental administration of ethylnitrosourea (ENU). Electron microscopic studies revealed that AO binds to DNA exclusively within the active extended euchromatin portion of the cell nucleus of the proliferating external granular layer. No or only a few AO reaction products were visible in the non-proliferating cell nuclei of the internal granular layer and of Purkinje cells. With increasing cellular differentiation of granule cells in the cerebellar cortex the number of AO positive cells as well as the number of AO reaction products per cell showed a progressive decrease. A single i.p. injection of 50 mg/kg of ENU in rats on day 15 to 21 of gestation resulted in occasional cell damage to the proliferating external granule cells of developing cerebellar cortex at 4 and 7 days after birth. Damaged cells of the external granular layer were found to have no or only a small number of AO reaction products in their nuclei. In further development from 14 to 28 days the cerebellar cortex of offspring from ENU-treated mother showed no abnormality and exhibited no definite alteration in distribution pattern of AO reaction products.

Acridine Orange↗

Electron microscopic localization of acridine orange binding to DNA within various human brain tumor cells.

The ultracytochemical acridine orange (AO) method has been employed to demonstrate DNA template activity within untreated human brain tumors. A total of 16 biopsies from brain tumors removed for frozen section examination were investigated. Ultrastructural examination revealed that AO binds to DNA exclusively within the extended euchromatin portion of the cell nucleus of brain tumors. The percentage of AO positive cells varied from 6.0 to 48.6% in various types of brain tumors. A few AO reaction products were visible in the nuclei of the endothelial cells and in the pericytes of the capillaries within neoplastic tissue. The present results suggested that untreated human brain tumors exhibit de-repression of DNA template normally repressed in the adult state. This altered DNA templates may be related to abnormal cell proliferation and differentiation diverted from the normal state.

Acridine Orange↗

Electron microscopic localization of acridine orange binding to DNA within rat astrocytoma C6 cells.

Combination of autoradiography and ultracytochemical acridine orange method in rat astrocytoma C6 cells is described. Electron microscopic examination revealed that AO binds to DNA exclusively within the euchromatin portion of the cell nucleus. X-ray microanalysis showed that AO reaction products contain lead, uranium, and osmium. These heavy metals seem to contribute to electron density of the AO reaction products. The percentage of AO positive cells was 51.8 +/- 1.9%, whereas average labeling index of C6 cells incubated with 3H-thymidine for 30 minutes was 25.6 +/- 1.7%. About 82% of 3H-thymidine-labeled cell nuclei were AO positive and the remaining 18% were free of AO reaction products. On the other hand, about 27% of AO positive cells were not labeled with 3H-thymidine. However, most of C6 cell nuclei with active 3H-uridine incorporation showed AO chromatin reaction products. The results suggest that visualization of AO chromatin reaction products might be related to RNA synthesis rather than DNA synthesis in the cell nuclei.

Acridine Orange↗

Effect of extracorporeally induced total body hyperthermia for cancer on cardiovascular function.

Total body hyperthermia (TBHT) was induced in patients with terminal cancer, using a femoral arterio-venous shunt as an extracorporeal circuit incorporating a heat exchanger. A total of 31 systemic hyperthermic treatments lasting 3 to 4 hours at 41.5 degrees C to 42 degrees C (rectal temperature) were performed on 11 patients; chemotherapy had previously been unsuccessful in all of these cases. The effect of TBHT on cardiovascular function was explored in these patients. The heart rate and cardiac output were always markedly increased during hyperthermia, however, the peripheral arterial, central venous, pulmonary arterial and pulmonary wedge pressures were little affected and no progressive metabolic acidosis occurred. TBHT was generally well tolerated and there was no instance in which this treatment had to be terminated because of severe cardiovascular failure during hyperthermia.

Adult↗

Phenotypical stability of a human hepatoma cell line, HuH-7, in long-term culture with chemically defined medium.

A chemically defined medium containing selenium was further improved, and the improved medium showed excellent ability to support growth and colony formation of a human hepatoma cell line, HuH-7. The improved defined medium (designated as IS-RPMI) contained small amounts of unsaturated fatty acids, inorganic trace elements including selenium, and HEPES buffer. Many of these additions exert only a small individual effect on the growth of cells, but their cumulative effects were substantial. HuH-7 cells replicated continuously with a doubling time of 47-51 hr in IS-RPMI. A conditioned medium from a semiconfluent population increased the colony-forming ability of HuH-7 cells in IS-RPMI. The addition of insulin to the medium gave good colony growth, thus duplicating the effect of the conditioned medium. Although some alterations of morphological and growth characteristics of HuH-7 cells were observed, the differentiated liver functions, as revealed by production of plasma proteins including high levels of alpha 1-fetoprotein, were maintained for a period of more than 3 years and through 70 passages under the above culture conditions.

Animals↗

[Combination chemotherapy with neocarzinostatin(NCS), HCFU and picibanil(NHO therapy) for advanced carcinoma of the digestive system--a comparative study with NF, and NFO therapy].

We have previously reported the clinical effects of NF therapy (NCS + 5-FU) and NFO therapy (NCS + 5-FU + Picibanil) on patients with advanced carcinoma of the digestive organs. In the present study, (NHO therapy (NCS + HCFU + Picibanil) performed in 41 patients and 30 patients were evaluated for its clinical effects. In comparison with NHO, NF and NFO, partial regression (tumor regression exceeding 50%) was noted in 5 of 30 patients (16.7%) on NHO, which was superior to 7.4% on NF, but slightly inferior to 18.8% on NFO. However, six and twelve month survival rate and 50% survival month on NHO therapy were 31.6%, 10.5% and 4.6 months, respectively and they were superior to those of NF and NFO therapy. Though the incidence of the adverse effects by NHO was almost identical with that of NFO and not more frequent than that of NF therapy. Urinary frequency, hot sensation and urgency due to HCFU administration were observed approximately in 10% on NFO therapy. In the three modalities the advantageous clinical effects on patients with hepatic carcinoma irrespective of primary or metastatic were observed.

Adult↗