Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 433 records · Page 24Linked to original sources

PubMed1991

Nuclear p53 immunoreaction associated with poor prognosis of breast cancer.

p53 protein has been frequently detected at high levels in the nuclei of human breast cancer cells. We analyzed immunohistochemically the association between nuclear localization of p53 protein and clinical and histological parameters of breast cancer patients. Surgically resected tissues of 73 primary breast cancers were processed by acetone fixation and paraffin embedding and examined using an anti-p53 monoclonal antibody, PAb1801. p53 immunoreactivity was detected in the nuclei of cancer cells in 17 cases (23%). The nuclear p53 immunoreaction was closely associated with overexpression of c-erbB-2 protein (P less than 0.05), high histologic grade (P less than 0.01), advanced clinical stage (P less than 0.05), and negative estrogen receptor status (P less than 0.01). When 31 cases which had been followed up for more than 50 months were examined, a positive nuclear p53 immunoreaction was found to be significantly associated with shorter overall survival of patients (P less than 0.01). These results suggest that immunohistochemical examination of nuclear p53 protein is clinically useful as an indicator of breast cancer aggressiveness.

Antibodies, Monoclonal↗

PubMed1991

Alterations in copy number of c-erbB-2 and c-myc proto-oncogenes in advanced stage of human breast cancer.

In our previous study, amplification of c-erb B-2 and c-myc proto-oncogenes in DNA of human breast cancer occurred in 16% and 4% of cases, respectively, and increased copy number of these genes is suggested to be associated with aggressive primary tumors. We examined change in the copy number of c-erb B-2 and c-myc proto-oncogenes between primary and multiple metastatic tumors in 10 patients with breast cancer, who underwent breast surgery and were later autopsied, by using DNAs isolated from formalin-fixed paraffin-embedded tissues and the dot blot-hybridization method. In primary tumors, amplification of c-erb B-2 and c-myc was detected in three and two cases, whereas at the stage with systemic metastasis, it was detected in four and three cases, respectively. In all four cases with amplified c-erb B-2 gene and in one of the three with amplified c-myc gene, the copy number was clearly increased in the metastatic tumors in comparison with the primary. Microscopically, more than five mitotic figures per high power field were detected in metastatic tumors of five cases including three with amplified c-erb B-2, but in only two primary. These results suggested that the aggressive nature of breast cancer is frequently enhanced in accordance with cancer metastasis.

Breast Neoplasms↗

PubMed1991

Serum beta 2-microglobulin in patients with adult T-cell leukemia.

Thirty-seven patients with adult T-cell leukemia had serum beta 2-microglobulin (beta 2M) estimated at presentation. A significant association was found between beta 2M and the subtypes of the disease: beta 2M in the acute type is significantly higher than in the chronic and smoldering types (p less than 0.01), and beta 2M in the lymphoma type is apparently higher than in the chronic and smoldering types, although the difference between the lymphoma and chronic types was not statistically significant. An apparent reduction in beta 2M levels after chemotherapy was observed in 7 patients who reached partial or complete remission. One patient who was resistant to chemotherapy showed elevated beta 2M values even after intensive chemotherapy. In another patient, who attained partial remission with a concordant reduction in beta 2M, renewed elevation of beta 2M was observed in parallel with exacerbation of other parameters such as lactate dehydrogenase (LDH), WBC, calcium and clinical manifestations. Correlation analysis was carried out between beta 2M, LDH, calcium, lymphoid cell count and the grade of clinical severity. The beta 2M level was moderately correlated with LDH, calcium, the grade of clinical severity but not with the lymphoid cell count. The clinical severity also correlated with LDH and calcium but to a lesser extent than with beta 2M. These data support the use of the beta 2M in the evaluation of adult T-cell leukemia.

Anemia, Refractory, with Excess of Blasts↗

PubMed1991

Is the diagnosis of significant residual neuromuscular blockade improved by using double-burst nerve stimulation?

This study evaluated the use of double-burst stimulation (DBS) in the diagnosis of significant post-operative residual neuromuscular blockade. Ninety patients were allocated to three equal groups. In Group A the degree of residual neuromuscular blockade was assessed by clinical criteria (CC) only; in Group B by CC and manual evaluation of the response to train-of-four (TOF) nerve stimulation; and in Group C by CC, manual evaluation of the response to TOF, and DBS stimulation. Immediately after arrival in the recovery room mechanical twitch was recorded using TOF stimulation. The mean (+/- SD) TOF ratios were 0.53 +/- 0.19 in Group A, 0.67 +/- 0.11 in Group B and 0.81 +/- 0.08 in Group C. The incidence of a TOF ratio of less than 0.7 was 83.3% in Group A, 56.7% in Group B and 6.7% in Group C. It is concluded that the use of DBS enabled the anaesthetist to recognize significant residual block and thus reduced the incidence of post-operative residual neuromuscular blockade.

Analysis of Variance↗

PubMed1991

Small cell carcinoma of the uterine cervix showing Cushing's syndrome caused by ectopic adrenocorticotropin hormone production.

A uterine cervical cancer is reported in a woman who developed Cushing's syndrome. The tumor measured 1.3 x 0.7 cm, and was a pure small cell carcinoma, identical to that in the lung. The primary tumor cells showed argyrophilia with Grimelius staining and reacted positively to the anti-chromogranin antibody. Clinically, the neoplasm behaved in an aggressive manner in spite of adjuvant chemotherapy and radiotherapy, and the patient died of widespread metastasis. Cushing's syndrome was noted after the occurrence of liver metastasis with an elevation of the serum adrenocorticotropin hormone (ACTH) level. At autopsy, metastatic tumor cells from the liver reacted immunohistochemically positively not only to anti-ACTH but also to antichromogranin, anti-gastrin and anti-calcitonin antibodies. This is the first report of an immunohistochemical analysis of, and comparison of primary and metastatic sites in cervical carcinoma showing Cushing's syndrome.

ACTH Syndrome, Ectopic↗

PubMed1991

Erythropoietin rapidly reduces phosphorylation of a membrane protein in a murine erythroleukemia cell line.

Erythropoietin (Epo) is a glycoprotein hormone that specifically regulates the proliferation and differentiation of erythroid progenitor cells. The effect of Epo on the phosphorylation of cellular proteins was investigated in a murine erythroleukemia cell line ELM-I-1 which differentiates to produce hemoglobin in response to Epo. The phosphorylation of a prominent 98 kDa phosphoprotein (pp98) (pI approximately 6.5) in the particulate fraction of ELM-I-1 cells decreased markedly upon exposure of the cells to recombinant human Epo. The effect was rapid and transient, occurring within 1 min after Epo exposure, and disappearing within 15-30 min. Interleukin 3, another hematopoietic factor which is known to act also on erythroid progenitors, did not induce this effect. Phosphoamino acid analysis revealed that pp98 is phosphorylated on serine residues. The results suggest that this rapid and transient alteration in protein phosphorylation may serve as critical trans-membrane signal for Epo.

Animals↗

PubMed1991

[Adjuvant chemotherapy using cyclophosphamide for breast cancer. National Hospital Collaborative Group for Study of Breast Cancer Treatment].

The total dosage and therapeutic value of Cyclophosphamide (CPA) administered as adjuvant chemotherapy for breast cancer were studied. The subjects were those under 65 years of age who were diagnosed as Stage II breast cancer and underwent curative operation at any of 10 national hospitals from May, 1978 to April, 1981. CPA at dose of 100mg was administered orally every day. Comparison was made between the long-term administration group (L) of patients receiving a total of 25 g/m2 over 18 months and the short-term administration group (S) receiving a total of 6 g/m2 over 6 months, in terms of survival rate (SV) and disease-free survival rate (DFV). Cases selected as the subjects were randomly allotted to the two groups by means of the envelope method. The number of cases registered was 316. Of them, 308 cases were eligible for the study. Thirty-eight cases (23.6%) in L and 15 cases (10.2%) in S dropped out due to side effects and other reasons. No difference was observed between the two groups in background factors such as age, menopausal status, type of operation, histological diameter of tumor, histological type and metastasis to lymph nodes. Results of a 10-year follow-up revealed no difference in SV and DFV between the two groups. Excluding the drop-out cases, however, DFV was significantly high in L. There was no difference in DFV between the two group in terms of menopausal status. DFV was significantly high in L, if one includes cases with metastasis to lymph nodes. DFV was high in L, even when a group with no more than 3 metastatic lymph nodes and the group with not less than 4 were included. It is of little value to administer CPA to all Stage II cases for a long period of time. CPA may be indicated for cases showing metastasis to lymph nodes.

Administration, Oral↗

PubMed1991

Selective removal of anti-DNA and anticardiolipin antibodies by adsorbent plasmapheresis using dextran sulfate columns in patients with systemic lupus erythematosus.

The effect of adsorbent plasmapheresis using dextran sulfate columns on anti-DNA and/or anticardiolipin antibodies (aCL) in 6 patients with systemic lupus erythematosus (SLE) was studied by multicenter clinical trials. The titers of anti-DNA (RI assay), IgG anti-dsDNA (ELISA), IgG and/or IgM anti-ssDNA, (ELISA), and IgG aCL (ELISA) significantly decreased or normalized after 4 treatments of plasmapheresis during a 2 to 4 week period. A patient with SLE with recurrent abortion and aCL who was successfully treated by adsorbent plasmapheresis is reported. We expect that adsorbent plasmapheresis will be an influential treatment for patients with not only SLE but aCL syndrome.

Adsorption↗

PubMed1990

Role of DT diaphorase the cytotoxicity of menadione and 4-nitroquinoline-1-oxide in cultured mammalian fibroblastic cells.

The role of DT diaphorase on the cytotoxicity (reduction in colony formation frequency) of menadione and 4-nitroquinoline-1-oxide (4NQO) was examined in two fibroblastic cell lines (Chinese hamster V79H3 cells and NG2 Syrian hamster cells). The addition of dicoumarol (10(-4) M-3 x 10(-4) M), a specific inhibitor of DT diaphorase, resulted in an intensification of the cytotoxicity of menadione, supporting the hypothesis that DT diaphorase protects cells against the oxidative stress induced by quinones. On the other hand, the toxicity of 4NQO was greatly reduced by the addition of dicoumarol (10(-5) M-3 x 10(-4) M), showing that DT diaphorase is the key (or the sole) enzyme involved in the activation of 4NQO in the above cells.

4-Nitroquinoline-1-oxide↗

PubMed1990

Inhibition of rat hepatic glutathione S-transferase placental form positive foci development by concomitant administration of antioxidants to carcinogen-treated rats.

Inhibition potential of concomitant butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), catechol or sodium ascorbate (Na-AsA) administration on development of diethylnitrosamine (DEN) initiated glutathione S-transferase placental form (GST-P) positive foci in rat liver under the influence of 2-acetylaminofluorene (2-AAF) or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) plus partial hepatectomy (PH) was investigated. Whereas BHA, BHT and catechol exerted marked inhibitory effects, Na-AsA lacked any modifying potential. The compounds that demonstrated inhibition also induced GST-P in the hepatic periportal areas, suggesting that development of GST-P positive foci is negatively influenced by extra-focal increase in this enzyme form observed with BHA, BHT or catechol.

2-Acetylaminofluorene↗

PubMed1990

Association of point mutation in c-Ki-ras oncogene in lung adenocarcinoma with particular reference to cytologic subtypes.

The correlation between clinicopathologic findings and point mutation in codon 12 of c-Ki-ras gene was examined in primary lung adenocarcinomas using polymerase chain reaction and oligonucleotide hybridization techniques. The mutation was detected in ten of 67 cases (15%). Microscopically, mutation-positive cases revealed a tendency to be well differentiated (P less than 0.01). Especially, the incidence of the mutation-positive cases was significantly higher in goblet cell type (three of four) than in other types (five of 56) (P less than 0.001). None of 21 cases of pure Clara cell type showed the mutation (P less than 0.05). The mutation was detected frequently in tumors with no lymph node metastasis (P less than 0.05), with larger tumor size (P = 0.01), and T2 cases (P less than 0.01). Cigarette smoking was not always a contributing factor for mutation. This study revealed that the point mutation of c-Ki-ras codon 12 in lung adenocarcinoma has been associated with the cytologic subtype.

Adenocarcinoma↗

PubMed1990

[Intraperitoneal administration of OK-432 and rIL-2 in a case of peritonitis carcinomatosa with chronic renal failure].

Recombinant interleukin-2 (rIL-2) was administered intraperitoneally for 15 days, 2 days after intraperitoneal administration of Streptococcal preparation OK-432 to a patient of peritonitis carcinomatosa occurred eight months after second look operation, in which residual tumor could not be removed completely. The patient had been maintained by hemodialysis three times a week for over ten years. Combination chemotherapy using CDDP and Ifosfamide, or CDDP and THP-Adriamycin had not been effective to control rapidly increasing ascites. Negative cytological exam, was achieved on day 7 and ascites disappeared by day 15. No severe side effects including fluid retention were observed. Fever up was controllable by Indomethacin. Flow cytometric analysis revealed dominant (73%) CD4+, CD29+ helper inducer subset, while CD4+, CD45RA+ was 6%, in the lymphocytes in ascites on day 8. It was suggested that intraperitoneal administration of rIL-2 after OK-432 was safe and effective for peritonitis carcinomatosa with chronic renal failure.

Adenocarcinoma↗

PubMed1990

Correlation between histologic grade of malignancy and copy number of c-erbB-2 gene in breast carcinoma. A retrospective analysis of 176 cases.

A system of histologic grade of malignancy in human breast carcinoma was devised by significantly modifying the way of evaluating number of mitoses and architectural atypia in the histologic grading of Bloom and Richardson. The modified grading system was applicable to all histologic subtypes of adenocarcinoma and showed a good association with prognosis of breast carcinoma patients in retrospective analysis of 176 consecutive surgical cases (P less than 0.0001). Of the three components of histologic grade, architectural atypia and number of mitotic figures independently had a significant effect on the prognosis. The copy number of c-erbB-2, a prognostic factor independent of tumor size and nodal status, was strongly correlated with the histologic grade, number of mitotic figures, and degree of nuclear atypia (P less than 0.001, each). Cox's regression model analysis showed that nodal status and histologic grade were two determinants of prognosis, and the independent effect of c-erbB-2 amplification was absorbed within that of the histologic grade. Although the importance of c-erbB-2 gene copy number seemed to be inferior to that of the histologic grade, both were shown to be strongly associated with the aggressiveness of the tumor itself rather than the extent of tumor spread.

Breast Neoplasms↗

PubMed1990

Involvement of the noradrenergic system in the seizures of epileptic El mice.

We studied the role of the noradrenergic system in the seizures of epileptic El mice. To this end, the anticonvulsant activity of adrenergic drugs was tested with a scoring method, and the binding of [3H]dihydroalprenolol, [3H]prazosin and [3H]yohimbine was evaluated in whole brains and various brain regions from stimulated and unstimulated El mice, and their maternal ddy mice. The seizures of El mice were inhibited by noradrenaline, phenylephrine, oxymetazoline, clonidine and yohimbine in a dose-dependent manner. These preventive effects of alpha-adrenoceptor agonists were antagonized by pretreatment with alpha-adrenoceptor antagonists. The preventive effect of yohimbine was reversed by pretreatment with clonidine or alpha-methyl-p-tyrosine, although the latter drug did not affect the anticonvulsant effect of clonidine. The binding of [3H]dihydroalprenolol was the same in the three groups of mice. More [3H]prazosin was bound in the cerebellum and striatum, and there were more [3H]yohimbine binding sites in the whole brain, cerebral cortex, hippocampus and brainstem of stimulated and unstimulated El mice than in the same areas of ddy mice. These findings suggest that up-regulated alpha 1- and alpha 2-adrenoceptors are involved in the inhibition of the seizures of El mice.

Animals↗

PubMed1990

The anticancer effect of antineoplaston A-10 on human breast cancer serially transplanted to athymic mice.

We report the effects of Antineoplaston A-10 Injection on the growth curve of human breast cancer (R-27) serially transplanted to athymic mice. The intraperitoneal administration of 1/4 LD-50 (50 mg/mouse) of Antineoplaston A-10 Injection every day and 1/2 LD-50 (100 mg/mouse) every other day for 35 days was found to significantly inhibit the growth curve and also the 3H-TdR uptake was inhibited by 73.7% in those given 1/4 LD-50 and by 77.1% in those given 1/2 LD-50. The tumor histology in both groups showed necrosis but no lymphocyte infiltration.

Animals↗

PubMed1990

Decreased benzodiazepine receptor binding in epileptic El mice: a quantitative autoradiographic study.

Benzodiazepine receptors and subtypes were examined in El mice and normal ddY mice with a quantitative autoradiographic technique. Specific [3H]flunitrazepam binding in stimulated El mice, which had experienced repeated convulsions, was significantly lower in the cortex and hippocampus than in ddY mice and unstimulated El mice. In the amygdala, specific [3H]flunitrazepam binding in stimulated El mice was lower than in ddY mice. There was a tendency for the [3H]flunitrazepam binding in these regions in unstimulated El mice to be intermediate between that in stimulated El mice and that in ddY mice, but there was no significant difference between unstimulated El mice and ddY mice. [3H]Flunitrazepam binding displaced by CL218,872 was significantly lower in the cortex of stimulated El mice than in that of the other two groups, and in the hippocampus of stimulated than of unstimulated El mice. These data suggest that the decrease in [3H]flunitrazepam binding in stimulated El mice may be due mainly to that of type 1 receptor and may be the result of repeated convulsions.

Animals↗

PubMed1990

GABA-gated chloride ion influx in brains of epileptic El mice.

GABA-gated chloride ion influx was measured in brain "microsac" preparations of epileptic El mice. There was significantly greater sensitivity to GABA in stimulated El mice (which had 14-18 convulsions induced at weekly intervals) than in unstimulated El mice (which had not experienced convulsions) or ddY mice. GABA-gated chloride ion influx was significantly decreased 20 min after a single convulsion, and returned to the preconvulsion level 60 min after a convulsion. These findings suggest that the functional state of GABA-gated chloride channel in El mice is changed secondarily by single or repeated convulsions.

Animals↗

PubMed1990

Lack of modifying effects of p-phenylenediamine on induction of gamma-glutamyl transpeptidase-positive foci in a medium-term bioassay system using F344 rats.

The modifying effects of p-phenylenediamine (p-PD) on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given p-PD at dietary levels of 1000, 330 and 110 parts per million (ppm), or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) at 600 ppm as a positive control for 6 weeks. At week 3 following DEN administration, all animals were subjected to partial hepatectomy. Slight retardation of body weight was observed in rats treated with p-PD at all dietary levels. Significant increases in relative liver weight were found in animals treated with 1000 ppm p-PD. Remarkable growth retardation and increased liver weight were found in rats given 3'-Me-DAB. p-PD did not significantly increase the level of gamma-glutamyl transpeptidase (gamma-GT) positive foci observed after DEN initiation. In contrast, 3'-Me-DAB demonstrated marked enhancing activity as evidenced by significantly increased values for gamma-GT positive foci as compared with the controls given DEN alone. The results demonstrate that p-PD does not modify liver carcinogenesis in our in vivo medium-term bioassay system.

Animals↗