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Biomedical subjects

K Nishii

Publications and source records attributed to K Nishii.

At least 91 records · Page 5Linked to original sources

Immunohistochemical detection of estrogen receptors in paraffin sections of human thyroid tissues.

The optimal demonstration of estrogen receptor binding in thyroid tissues was made under conditions of 10% protease in 50 mM Tris-HCl buffer (pH 7.6) for 10 min as the pretreatment digestion step, incubation of primary antibody (ER-ICA monoclonal kit; Abbott Laboratories) at 37 degrees C for 2 h and incubation of secondary antibody (ABC kit; Vector) at 37 degrees C for 40 min. Thyroid tissues used for assessing the reaction were 17 cases of goiter, 25 adenoma cases, 27 cases of papillary carcinoma, 14 cases of follicular carcinoma and 10 latent cancer cases. Incidences of positive estrogen receptor reaction were 22% (11/51) for all thyroid cancers, 20% (5/25) for the thyroid adenomas and 59% (10/17) for goiters. 15% (4/27) of papillary carcinomas, 21% (3/14) of follicular carcinomas and 40% (4/10) of latent cancers proved positive, the estrogen receptor reaction being limited to the nuclei of thyroid follicular/papillary type cells.

Deoxyribonucleases↗

[Molecular diagnosis of leukemia and lymphoma].

Diagnosis of leukemia and lymphoma has been made by morphological, cytochemical, and immunophenotypical methods. Recently molecular biological approaches have been introduced to clarify the cellular lineage of the tumor cells and to demonstrate the monoclonality. Southern blot analysis using immunoglobulin (Ig) and T cell receptor (TcR) genes revealed the presence of monoclonal components in some cases of angioimmunoblastic lymphadenopathy (AILD), in which demonstration of monoclonality was difficult by conventional methods. In preB-ALL, many cases had rearranged IgH and TcR genes simultaneously. These "dual genotype" cases were found to be of accidental involvement of TcR gene in the process of making effective IgH gene rearrangements by the precise analysis of rearranged IgH gene structures. The rearranged TcR gene which was detected in initial lymphoblastic lymphoma cells, was observed in relapsed blasts after lineage conversion to myeloid leukemia, which indicates the same clonal origin. Diagnosis and detection of minimal residual disease by the polymerase chain reaction (PCR) are now recognized as sensitive methods. PCR using oligonucleotides common to each VH and JH gene detects the rearranged IgH gene sensitively. PCR using primers located on the translocation boundary, such as bcr and abl in CML, is very useful in the diagnosis and pursuit of the disease course. PCR study also can be applied to the detection of alteration of some particular genes such as tumor suppressor genes.

Base Sequence↗

[Syncytial variant of nodular sclerosing Hodgkin's disease expressing T-cell antigens].

A case of syncytial variant of nodular sclerosing Hodgkin's disease in a 34-year-old woman is reported. Histologically, numerous Reed-Sternberg (RS) cells and their variants were seen in sheets. They were positive for CD30, CD15, CD25, and HLA-DR antigens. In addition, they expressed CD45 antigen and T-cell antigens (CD2, CD4). Molecular genetic analysis showed that this case had a germ line configuration for T-cell receptor (TCR) beta chain, TCR gamma chain, and immunoglobulin heavy chain genes. The percentage of the neoplastic cells in the specimen identified by CD30 positive cells was about 20% which was far above sensitivity of the molecular genetic analysis. Such analysis is reliable as to judgement of the results. Thus, these findings suggest that the RS cells and their variants in the present case are not derived from mature T cell in spite of their T-cell antigens expression.

Adult↗

Effects of estrogen on cell proliferation and leukotriene formation in transformed mouse Leydig cells cultured under serum-free conditions.

B-1 F cells from mouse Leydig cell tumor (T 124958-R) were maintained in serum-free culture. Estrogen enhanced the growth of the cells, and this growth was suppressed by antiestrogens such as 4-hydroxytamoxifen or TAT, a newly developed antiestrogen. Since the growth of B-1 F cells was recently found to be inhibited by the metabolites of arachidonic acid, we examined the relationship between this metabolism and the enhancement of cell growth by estrogen. Among the modulators affecting the metabolism of arachidonic acid, 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoqu inone, an inhibitor of 5-lipoxygenase, reproducibly stimulated the growth of the cells, whereas the cyclooxygenase inhibitor indomethacin had only the marginal growth-stimulatory effects. Phorbol ester had no growth-modulating effect. 17 beta-Estradiol and 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoqu inone had some additive effects especially in terms of restoration of antiestrogen-induced inhibition. Moreover, the inhibition of DNA synthesis elicited by the addition of arachidonic acid in concentrations of 0.05 to 0.5 micrograms/ml was partly blocked by estrogen. Analyses of extracts of media and cells by high-pressure liquid chromatography and radioimmunoassay showed that 17 beta-estradiol inhibited the synthesis of leukotrienes B4, C4, D4, and E4 and this inhibition could be restored by antiestrogen. These results suggest that the enhancement of B-1 F cell growth by estrogen is at least partly mediated through its ability to inhibit leukotriene synthesis.

Animals↗

[Patterns of relapse in patients with small cell lung cancer--the effect of chest irradiation and prophylactic cranial irradiation combined with intensive chemotherapy on long-term survival].

The pattern of relapse was analyzed in patients with small cell lung cancer (SCLC). Of 180 patients treated with intensive combination chemotherapy between 1976 and 1987, 75 achieved complete response (CR). Of 47 patients with limited disease (LD), 20 (43%) initially relapsed in the chest and 7 (15%) in the brain. Among 27 patients with extensive disease (ED), the chest was also the most frequent site of relapse (44%) followed by the brain (19%). In LD patients who had received chemotherapy plus chest irradiation, the initial relapse rate and the cumulative relapse rate in the chest at 2 years were only 29% and 35.4%, respectively. These rates were significantly lower compared with the rates of 69% and 76.5% for patients who had received chemotherapy alone (p less than 0.05). Survival was improved to some extent by the addition of chest irradiation, but not significantly, however, the long-term survival rate favored those receiving chest irradiation. Prophylactic cranial irradiation (PCI) reduced the frequency of brain relapse and significantly improved the survival of SCLC patients achieving CR. The median survival time and 5-year survival rate of patients who received PCI were 23.1 months and 26.7%, which these figures were only 14.0 months and 8.3% for those who had not respectively. Analysis using Cox's proportional hazard model showed that PCI was the greatest prognostic factor favoring the SCLC patients achieving CR. These results indicate that chest irradiation and PCI in conjunction with intensive combination chemotherapy are effective for cases of SCLC with CR.

Adult↗

[Progress and obstacles in chemotherapy and combined modality treatment of small cell lung cancer].

In order to assess the development of treatment of small cell lung cancer (SCLC), we analyzed a total of 183 patients who had been entered into our protocol studies since 1976. Between 1976 and 1981, 39 patients (20 LD and 19 ED) received COMP, a 4-drug combination of cyclophosphamide (CTX), vincristine (VCR), methotrexate and procarbazine. During the period, chest irradiation (RT) was optimal for those with LD. Between 1981 and 1986, 112 patients (56 each of LD and ED) were treated with a cyclic alternating chemotherapy (CT) of COMP and VAN, a 3-drug combination of etoposide (VP-16), adriamycin (ADM) and nimustine. In this study, we randomized patients with LD either to receive CT alone or CT plus RT of 40 Gy to assess the role of RT in the treatment of LD. Thereafter, a pilot study of CAV-PVP hybrid CT has been conducted in 32 patients (16 each of LD and ED), in which CTX, ADM and VCR were given on day 1 (CAV), and cisplatin on day 8 and VP-16 on days 8 and 9 (PVP). RT was administered mandatory to LD in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Small cell lung cancer; a retrospective analysis of results of chemotherapy and chemo-radiotherapy].

In order to assess the development of treatments and the curability of small cell lung cancer, we analysed a total of 239 patients entered in our protocol study since 1976. Median survival time was 68 weeks for 127 patients with limited disease and 48 weeks for 112 with extensive disease. Three-year survival rate was 18% for those with limited disease, whereas it was only 5% for extensive disease. The median survival time and long-term disease-free survival rate has been improved with an introduction of aggressive chemotherapy including new drugs such as etoposide and cisplatin. Chest irradiation in addition to intensive chemotherapy played a substantial, but not significant, role for prolonging patient survival in those with limited disease. Nevertheless, the pace of therapeutic advances has been slowed and appears to reach a plateau. In this paper, the authors try to find some obstacles in the treatment of the disease, and to indicate some strategies to gain a progress.

Aged↗

[Aplastic anemia which terminated in hypoplastic leukemia 10 years after diagnosis].

A 57-year-old woman was admitted to our hospital because of further examination of anemia in November, 1978. She was diagnosed as having aplastic anemia, which was not associated with any atypical findings. Treatment with oxymetholone had been effective. However, she developed pancytopenia in January, 1988. A bone marrow aspiration revealed a hypocellular marrow with 75.6% blasts. Following two courses with low dose cytosine arabinoside and vitamin D3, the leukemia improved although she needs red cell transfusions at intervals of one to two months because of persistent pancytopenia. We present a patient with aplastic anemia who developed a hypoplastic leukemia at the tenth year of the disease.

Anemia, Aplastic↗

Effect of androgen on proliferation of estrogen-responsive transformed mouse Leydig cells in serum-free culture.

We examined the effects of steroid hormones on the proliferation of transformed mouse Leydig cells (B-1) in serum-free culture condition. Among hormones examined, androgen as well as estrogen enhanced the cell proliferation rate. Hormone binding studies revealed that B-1 cells contained both androgen and estrogen receptors. In addition, androgen-enhanced cell growth was inhibited by antiandrogen, but not by antiestrogen, while estrogen-stimulated cell growth was suppressed by antiestrogen. However, the simultaneous addition of androgen and estrogen did not show an additive effect. Dose-response study on androgen-dependent cell growth revealed that relatively high concentrations (10(-7)-10(-6) M) of dihydrotestosterone were required to obtain the maximum response. This was at least partly explained by the finding that B-1 cells could metabolize dihydrotestosterone into the less active steroids. Finally, B-1 cells were found to grow more rapidly in normal than in castrated male mice. These results clearly indicate that the proliferation of B-1 cells is stimulated by both androgen and estrogen, which utilize the different receptor systems.

Androgens↗

[Beneficial effect of cisplatin based combination chemotherapy on adenocarcinoma of the lung].

Cisplatin (CDDP) based combination chemotherapy has improved the response rate of non-small cell lung cancer (NSCLC). However, the survival benefit of CDDP-based chemotherapy in patients with NSCLC is still controversial. In order to determine whether CDDP had a meaningful impact on the course of NSCLC, the survival of patients treated by combination chemotherapy containing CDDP (CDDP arm: PVB; CDDP + vindesine + bleomycin, VIP; vindesine + ifosfamide + CDDP) was compared with that treated by chemotherapy without CDDP (no CDDP arm: COMP; cyclophosphamide + vincristine + methotrexate + procarbazine, MVB; mitomycin C + vindesine + bleomycin), retrospectively. Survival in CDDP arm (median survival time [MST]; 10.2 months) was significantly longer than in the no-CDDP arm (MST; 6.9 months) (p less than 0.01). These results indicate that CDDP-based combination chemotherapy can not only improve response rate but also prolong survival of NSCLC.

Adenocarcinoma↗

[Small cell lung cancer: a retrospective analysis of results of chemotherapy and combined modality treatment].

In order to assess the development of treatments and the curability of SCLC, we analyzed a total of 181 patients entered in our protocol studies since 1976. Between 1976 and 1981, 37 patients (20 LD and 17 ED) were treated with COMP, a 4-drug combination of cyclophosphamide (CTX), vincristine (VCR), methotrexate, and procarbazine. During the period, chest irradiation (RT) was administered optionally to those with LD. Between 1981 and 1986, 112 patients (56 each of LD and ED) were treated with a cyclic alternating chemotherapy of the COMP and VAN, a 3-drug combination of etoposide (VP-16), adriamycin (ADM), and nimustine. In this study, we randomized LD patients either to receive CT alone or CT plus chest RT of 40 Gy to assess the role of chest RT in the treatment of patients in LD. Complete responders were also randomized either to receive prophylactic cranial irradiation (PCI) or not. Thereafter, a pilot phase II study of a hybrid regimen has been conducted in 32 patients (16 each of LD and ED), in which CTX, ADM and VCR (CAV) was given on day 1, and cisplatine and VP-16 (PVP) on days 8 and 9. Chest RT was administered mandatory to LD in this study. The median survival time (MST) has been prolonged with an improvement in response rate over CT in both LD and ED: MST of LD was 10 months for COMP, 14 months for COMP-VAN, and not achieved for CAV-PVP hybrid regimen (13 of 16 patients alive between 10 and months), while that of ED was 8 months for COMP, 11 months for COMP-VAN, and 13 months for CAV-PVP hybrid regimen. The randomized study comparing CT alone and CT plus chest RT revealed that chest RT played a substantial, but not significant, for long survival in LD. Finally 13 of 149 patients treated between 1976 and 1986 were long-term, disease-free survivors beyond 2 years (12 LD and 1 ED). Two of them who had not received PCI had a relapse in the brain, but the remaining 11 patients are alive and disease-free between 28 and 84 months. These results imply that SCLC is potentially curable, but it will be difficult to achieve a cure in a substantial proportion of patients with the disease.

Adult↗

[Pilot phase II study of hybrid chemotherapy of CAV-PVP in small cell lung cancer (SCLC)].

A pilot phase II study of a hybrid chemotherapy for SCLC has been conducted between October 1986 and March 1988. Dose and schedule of the regimen were as follows: CTX, 700 mg/m2, on day 1; ADM 30 mg/m2, on day 1; VCR, 1.4 mg/m2, on day 1 (CAV); and CDDP, 60 mg/m2, on day 8; VP-16, 100 mg/m2, on days 8 and 9 (PVP). Courses were repeated q. 4 weeks up to 6 cycles. Patients with LD received chest irradiation at a dose of 50 Gy when maximal response was achieved. Thirty-six patients were fully evaluated for tumor response and toxicity. All 18 patients with LD responded to the regimen including 11 CRs (61%); there were 7 CRs (39%) and 9 PRs (50%) in patients with ED. Fourteen of the 18 patients with LD have survived for 7 to 22 months, against 12.8 months in ED patients. The major toxicity was myelosuppression, but it was well tolerated. These results indicate that hybrid chemotherapy is highly effective for SCLC, and warrants further clinical trials.

Aged↗

[Prognosis in chronic pulmonary disease and cor pulmonale].

Echocardiography and cardiac catheterization were performed in 30 patients of chronic pulmonary disease and cor pulmonale. We studied the relation of echo-cardiographic data and pulmonary hemodynamics to prognosis in these patients. In the nonsurvival group (12 patients) the extent of dyspnea was worse significantly (p less than 0.05), PaO2 was decreased significantly (p less than 0.05, 7 +/- 8.2 Torr), right ventricular preejection period (RPEP)/right ventricular ejection time (RVET) ratio increased significantly (p less than 0.05, 0.51 +/- 0.07), left ventricular diastolic diameter index (LVDdI) was shortened significantly (p less than 0.05, 23.5 +/- 3.1 mm/m2), and pulmonary capillary wedge mean pressure (PCWm) rose significantly (p less than 0.05, 11.9 +/- 6.9 mmHg) in comparison with the survival group (12 patients). In the survival group PaO2, RPEP/RVET ratio, LVDdI and PCWm averaged 60.9 +/- 12.8 Torr, 0.41 +/- 0.09, 27.5 +/- 5.1 mm/m2, 6.2 +/- 3.3 mmHg, respectively. The rate of survival was decreased significantly (p less than 0.05) in pulmonary vascular resistance (PVR) of greater than 400 dyne.sec.cm-1 or stroke volume index (SVI) of less than 35 ml/m2. These factors and 3 factors of obesity, %VC and pulmonary artery mean pressure (PAPm) differentiated nonsurvivors from survivors with linear discriminant function.

Adult↗

Gel-filtration of serum gamma-glutamyl-transpeptidase with HPLC in hepatobiliary diseases and its significance.

Serum gamma-glutamyl-transpeptidase (gamma-GTP) from patients with various hepatobiliary diseases was fractionated by molecular size using HPLC to investigate the heterogeneity of serum gamma-GTP. Serum gamma-GTP eluted with HPLC showed essentially 3 elution peaks of different molecular size. In the sera of normal patients, there was little gamma-GTP in the high molecular fraction, and most occurred in the low molecular fraction. Intermediate molecular gamma-GTP appeared only in the sera of patients with hepatobiliary disease. In the sera of patients with extrahepatic biliary obstruction, the percentage of high molecular gamma-GTP to total serum gamma-GTP activity was higher than that of other patients. High molecular gamma-GTP increased in the sera of patients with extrahepatic biliary obstruction. Intermediate molecular gamma-GTP appeared in the relatively higher molecular fraction in the sera of patients in whom alcohol consumption might have caused serum gamma-GTP increase, and in the relatively lower molecular fraction in the sera of patients with extrahepatic biliary obstruction. It was concluded, therefore, that the position of elution of intermediate molecular gamma-GTP corresponded to the morbid state. It was shown that intermediate molecular gamma-GTP appeared in the relatively low molecular fraction, corresponding to the increase of serum total bile acids concentration.

Carcinoma, Hepatocellular↗

[Therapeutic effect of ceftizoxime on infection in patients with lung cancer].

Ceftizoxime (CZX) was given in daily doses of 4 approximately 6 g by intravenous drip infusion to 30 patients with infection accompanying lung cancer to investigate the usefulness of the drug for infectious disease: The rate of effectiveness (marked and moderate) was 73.3% (22/30 patients). Of the 30 patients, 2 had drug fever; 1, arthralgia; and 1, eosinophilia. These side effects improved after the drug was withdrawn. CZX is a very useful antibiotic with high effectiveness and safety in immunocompromised patients with infection accompanying advanced lung cancer.

Adenoma↗

[Sensitivity testing of anticancer drugs using the human tumor clonogenic assay].

The response to cancer chemotherapy varies from patient to patient with the same histologic type of tumor. However, anticancer drugs are considerably toxic to the patient, and it is therefore very important to have an accurate knowledge of the sensitivity of anticancer drugs against an individual patient's tumor in establishing successful chemotherapy. We have investigated the sensitivity testing of anticancer drugs using the human tumor clonogenic assay since 1980. Specimens were obtained by aspiration of ascites, pleural effusions and bone marrow and by biopsy of primary and metastatic tumors. Drugs tested in the present study were adriamycin, aclarubicin, THP-adriamycin, mitoxantrone, 40497s (an active compound derived from ifosfamide), mitomycin C, cisplatinum and methotrexate. One hundred and fifty-two specimens were obtained from cancer patients and tested for their drug sensitivity using the assay. Of the 152 specimens, 63 (41%) formed more than 30 colonies in control plates and could be used to evaluate drug sensitivity. Of these, 45 instances were evaluable for examination in an in vitro-in vivo association, and 42 (93%) showed a correlation between in vitro sensitivity and clinical response. In summary, the results indicated that the human tumor clonogenic assay was an excellent technique for testing the in vitro sensitivity of anticancer drugs. However, technical developments yielding higher colony efficiency would be required to facilitate practical use of the assay.

Antineoplastic Agents↗