Biomedical subjects

K Nishii

Publications and source records attributed to K Nishii.

At least 19 recordsLinked to original sources

PubMed1992

Phenotypical characteristics of acute myelocytic leukemia associated with the t(8;21)(q22;q22) chromosomal abnormality: frequent expression of immature B-cell antigen CD19 together with stem cell antigen CD34.

Twenty-three acute myelocytic leukemia (AML) patients with t(8;21) chromosomal abnormality, all classified as M2 (French-American-British [FAB] classification), were investigated. Blastic cells from all patients were positive for the stem cell-associated antigens, CD34 and HLA-DR, and the immature myeloid antigens, CD13 and CD33. The nonblastic leukemic cells expressed the more mature myeloid antigens, CD11b and CD15, with loss of the immature phenotype. The incidence of positivities for the stem cell-associated antigens, CD34 and HLA-DR, in t(8;21) AML cells was significantly higher in comparison with those in other AML showing granulocytic differentiation (M2 or M3). AML cells with t(8;21) also showed some phenotypic abnormalities. Frequent expression of CD19 was found in the blastic population of t(8;21) AML (18 of 23 cases) without other B-cell antigens and Ig gene rearrangements. CD19 expression was confirmed by immunocytochemistry and Northern blotting. The CD19+ blastic cells coexpressed both CD34 and HLA-DR. In addition, CD33+ cells among the blastic fraction in t(8;21) AML cells were fewer in number than in those of M2 or M3 AML without t(8;21). Our findings indicate that leukemic blasts of t(8;21) AML commonly express CD19 while preserving the stem cell-associated antigens, and differentiate into the granulocytic pathway with discordant maturation such as low CD33 expression.

Adult↗

PubMed1992

Outcome of patients with lung cancer detected via mass screening as compared to those presenting with symptoms.

We performed lung cancer resection in 721 patients between 1980 and 1989. Cancers were detected via mass screening programs by annual chest X-ray examination in the majority of cases. We evaluated the surgical results in patients with tumors detected by mass screening and compared them to those in whom the malignancy was detected by symptoms. Lesions in the mass screened group were T1 to T2 tumors in 90% of the cases, and NO in 73%. Stage I disease accounted for 65.3% in the mass screened group. The overall 5-year survival rate was 56.2% in the mass screened group, which was significantly better than the 25.3% for the symptom group (P less than 0.001). The surgical results in the lung cancer cases detected by the mass screening program had better results than the cases who presented with symptoms.

Aged↗

PubMed1992

Structural alterations of the p53 gene in human leukemias.

We have investigated alterations of the p53 gene in human leukemias by polymerase chain reaction-mediated restriction fragment length polymorphism analysis. This method detects the codon 72 polymorphism of the p53 gene, allowing identification of loss of heterozygosity (LOH) of the p53 gene. In this study, at least two specimens were obtained from each patient to compare the allele status at different points of clinical course. Of 21 cases examined 7 were heterozygous at this polymorphic site and were evaluable for LOH study. Only one patient of Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) lost the heterozygosity in the specimen of her last relapse. Leukemic cells from her repeated relapses including the last one revealed to have the clonally rearranged immunoglobulin H chain gene of the same size, indicating that alteration of the p53 gene in this patient might account for the lethal relapse as a clonal evolution event. Northern-blot analysis of the p53 gene showed that one case of CD7(+) ALL had altered p53 mRNA. Overall, it is demonstrated that alterations of the p53 gene might be involved in the pathogenesis or progression of at least some human leukemias, although the alterations in leukemias seemed to be not as frequent as in solid tumors.

Base Sequence↗

PubMed1992

Promoting effects of potassium dibasic phosphate on early-stage renal carcinogenesis in unilaterally nephrectomized rats treated with N-ethyl-N-hydroxyethylnitrosamine.

The effects of potassium dibasic phosphate (PDP), potassium aluminum sulfate (PAS) and copper sulfate (CS) on early-stage renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N-ethyl-N-hydroxyethylnitrosamine (EHEN) administration. After feeding 1,000 ppm EHEN, or basal diet for 2 weeks and removal of the left kidney at week 3, male Wistar rats were divided into 8 groups of 20 rats each. These groups received the following dietary treatments: 50,000 ppm PDP, 50,000 ppm PAS, 5,000 ppm CS or basal diet, respectively, for 18 weeks from weeks 3 to 20. The average numbers of adenomatous hyperplasias counted as preneoplastic lesions in the EHEN with 50,000 ppm PDP group were significantly higher than in the EHEN alone group or the EHEN followed by 50,000 ppm PAS or 5,000 ppm CS group. The treatment with 50,000 ppm PDP induced renal calcification and promoted the development of preneoplastic lesions in unilaterally nephrectomized rats treated with EHEN, but that with 50,000 ppm PAS or 5,000 ppm CS did not.

Animals↗

PubMed1992

c-kit gene expression in CD7-positive acute lymphoblastic leukemia: close correlation with expression of myeloid-associated antigen CD13.

Expression of human c-kit proto-oncogene and interleukin-7 receptor (IL-7R) in acute lymphoblastic leukemia (ALL) cells expressing CD7 was examined by Northern-blot analysis and reversed transcription polymerase chain reaction (RT-PCR) assay in relation to the phenotypes. Leukemic cells from four out of 12 CD7+ ALL patients, all of which fulfilled the criteria of ALL in the FAB classification, expressed c-kit genes. Surface CD3 (sCD3) was absent in all of these cases, while cytoplasmic CD3 (cCD3) was found in the two sCD3- cases. CD3 epsilon transcripts were detected in one of the sCD3- cCD3- cases. IL-7R genes were transcribed in the three cases with c-kit gene expression. In addition, there was a good correlation between c-kit gene expression and myeloid associated antigen CD13 positivity of the leukemic cells. None of the patients with c-kit gene expression had mediastinal tumor. Our results show that leukemic cells in a proportion of CD7+ ALL express receptors for cytokines that are secreted by bone marrow stromal cells. Ligands for c-kit genes and IL-7 could play an important role for the regulation of proliferation and differentiation of T-cell progenitors in bone marrow.

Antigens, CD↗

PubMed1992

[Six cases of primary pulmonary cryptococcosis].

Six patients with asymptomatic primary pulmonary Cryptococcosis are reported. In all of the patients, the disease was detected by annual chest X-ray during mass screening for lung cancer or during follow-up for pulmonary tuberculosis or gastric cancer. The chest X-ray findings consisted of a solitary pulmonary nodule in 4 patients and multiple pulmonary nodules in 2. Only one patient who could not be histologically diagnosed by bronchofiberscopy underwent surgical resection. However, the other 5 patients were histologically diagnosed by transbronchial biopsy with bronchofiberscopy. They were treated with oral antifungal agents, namely flucytosine (5-FC) and/or fluconazole, with marked improvement of chest X-ray findings. These results indicate that transbronchial biopsy with bronchofiberscopy and oral administration of antifungal agents instead of initial surgical resection are useful in the diagnosis and treatment of primary pulmonary cryptococcosis.

Adult↗

PubMed1992

Rearrangement patterns of immunoglobulin heavy chain (IgH) and light chain genes in acute lymphoblastic leukemia and chronic myelocytic leukemia lymphoid crisis cells showing oligoclonal IgH gene rearrangements.

We investigated leukemic cells with multiple immunoglobulin heavy chain (IgH) gene rearrangements from nine B-precursor cell acute lymphoblastic leukemia (ALL) patients and three chronic myelocytic leukemia lymphoid crisis (CML.Ly-BC) patients in order to determine detailed recombination patterns of the variable (V), diversity (D), and joining (J) region genes. Southern blot study, using DNA probes for DQ52 and 5'D region genes, was useful to distinguish VDJ recombination from DJ recombination at the level of each allele. Leukemic cells from seven out of eight CD10-positive ALL patients showed biallelic VDJ recombinations. Rearrangements of Ig kappa genes were found in only one case. Leukemic cells from all of the CML.Ly-BC patients had a DJ/(V)DJ IgH genotype. These findings suggest that the multiple IgH gene rearrangements in B-precursor cell ALL occurred as a consequence of continuing V-(V)DJ rearrangements after neoplastic transformation, and were closely related to the stage of bone marrow B-precursor cell differentiation. Multiple IgH gene rearrangements in CML.Ly-BC might take place earlier in the process of IgH gene rearrangements than is the case in B-precursor cell ALL. In this sense, the genotypic oligoclonality observed in ALL and CML.Ly-BC should be regarded not as 'true', but as 'pseudo' oligoclonal leukemia.

Blast Crisis↗

PubMed1991

Inhibition of murine transformed Leydig cell proliferation by leukotrienes in serum-free culture.

We have previously shown that estrogen-dependent growth enhancement of murine transformed Leydig cells (B-1 F) is mediated through inhibition of arachidonic acid metabolite formation. In the present study, the growth-inhibitory ability of leukotrienes (LTs) on B-1 F cells in serum-free culture was directly addressed. All peptidyl LTs (LTC4, LTD4, and LTE4) inhibited B-1 F cell growth in a dose-dependent manner and exhibited maximum inhibition of DNA synthesis (60-80%) compared with that of untreated cells in a range of 10(-9) to 10(-8) M. To examine the mechanism of this LT-dependent inhibition, binding studies of LTD4 toward plasma membrane were conducted. Specific binding sites for LTD4 were identified. Scatchard analyses indicated the presence of a single class of high-affinity sites (Kd = 0.9 +/- 0.2 nM; maximum binding sites, 61 +/- 18 fmol/mg protein). This binding of LTD4 to the high-affinity site was markedly inhibited by ICI 198615, a specific inhibitor for LTD4. These results would suggest that inhibitory effects of LTs, at least LTD4, are elicited as a receptor-mediated event. In addition, this LT-dependent growth inhibition could not be blocked by simultaneous exposure of cells to estrogen, whereas estrogen partially protected arachidonic acid-dependent growth inhibition. Furthermore, treatment of cells with estrogen resulted in marked suppression of 5-lipoxygenase activity. Collectively, the present data clearly show that LTs play an important role as intermediates in an autocrine loop for B-1 F cells to exhibit estrogen-dependent growth.

Animals↗

PubMed1991

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↗

PubMed1991

[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↗

PubMed1991

[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↗

PubMed1990

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↗

PubMed1990

[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↗

PubMed1990

[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↗

PubMed1990

[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↗

PubMed1990

[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↗

PubMed1989

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↗

PubMed1989

[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↗