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Biomedical subjects

E Shimizu

Publications and source records attributed to E Shimizu.

At least 109 records · Page 6Linked to original sources
PubMed1994

Cell-mediated immune response in acute poststreptococcal glomerulonephritis.

To evaluate the role of cell-mediated immunity in acute poststreptococcal glomerulonephritis (APSGN), we identified the immune cell population infiltrating the glomeruli. Renal biopsies were obtained from 22 patients with APSGN, 16 with overt and 6 with asymptomatic disease, one to 30 days after onset. Samples of normal renal tissue were used as controls. Frozen sections were examined using monoclonal antibodies that recognize various leukocyte surface markers. Double staining for granulocytes and monocyte/macrophages (M phi) was performed using chloro-esterase staining and indirect immuno-alkaline-phosphatase staining with Leu M-5 sequentially. In overt APSGN, there was a substantial increase in the total number of granulocytes and M phi with a slight increase in T cells. Numbers correlated with time after onset, as more leukocytic infiltration was observed when the tissue was taken earlier. Furthermore, a significant positive linear correlation was seen between helper/inducer T cells and M phi (r = 0.86, p < 0.01). Helper T cells tended to be increased to a higher proportion during the early stage, while suppressor T cells remained constant throughout the course. Analysis with anti-proliferating cell nuclear antigen antibody revealed increased glomerular cell proliferation in the early phase of APSGN. In asymptomatic patients, the total number of leukocytes was less than in the overt patients, but the proportions of infiltrating cells were similar. These data suggest that M phi are important effector cells causing endothelial and mesangial cell proliferation in APSGN. M phi infiltration in the glomeruli appears to be mediated by complement-induced chemotaxis and probably be an antigen-specific event related to the delayed type hypersensitivity mediated by helper/inducer T cells.

Acute Disease↗
PubMed1994

RB protein status and clinical correlation from 171 cell lines representing lung cancer, extrapulmonary small cell carcinoma, and mesothelioma.

We have studied RB protein expression in 171 cell lines derived from patients with small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), pulmonary carcinoid, mesothelioma, and extrapulmonary small cell cancer (EPSC) and have correlated this data with clinical outcome. We detected absent or aberrant RB protein expression in 66/75 SCLC, 12/80 NSCLC, 1/6 carcinoid, 0/5 mesothelioma, and 4/5 EPSC samples. In addition, we observed integration of human papilloma virus (HPV) DNA in the single EPSC cell line that retained wildtype RB protein. We did not detect integration of HPV, SV40 or adenoviral DNA in other tumor samples with wildtype RB status. We also noted a stable, hypophosphorylated mutant RB in 12 SCLC and 3 NSCLC samples which might have been falsely interpreted as wildtype by current immunohistochemical techniques. Analysis of the matched clinical data showed no associations between RB status and age, sex, extent of disease, performance status, smoking history, and previous treatment. In addition, retrospective analyses showed no consistent correlation of RB protein expression with either best clinical response, overall survival, or in vitro chemotherapeutic drug sensitivity. The stable expression of RB after gene transfection into RB(-) SCLC cells, however, resulted in a trend toward increased in vitro resistance to etoposide, cisplatin and doxorubicin.

Adult↗
PubMed1993

Loss of heterozygosity on chromosome arm 17p in small cell lung carcinomas, but not in neurofibromas, in a patient with von Recklinghausen neurofibromatosis.

BACKGROUND: It has been suggested that the genetic abnormality responsible for von Recklinghausen neurofibromatosis (NF1) increases a patient's risk of various kinds of malignancies. The incidence of small cell lung carcinoma (SCLC) as a complication of NF1, however, is rare. To clarify the relationship between NF1 and SCLC, possible loss of heterozygosity of chromosome 17 in a patient with SCLC combined with NF1 was analyzed. METHODS: Possible loss of heterozygosity for chromosome 17 was analyzed by a molecular genetic approach using several chromosome 17-specific polymorphic DNA markers. RESULTS: In both primary tumor and metastatic tumors of SCLC, loss of heterozygosity was detected on chromosome arm 17p, but not on 17q. Loss of heterozygosity, however, was detected on neither 17p nor 17q in neurofibromas and normal tissue. CONCLUSIONS: The formation of SCLC may result from several genetic alterations, including inactivation of tumor-suppressor gene on chromosome 17p, most likely P53, although it still is unknown whether or not a mutation of the NF1 gene on 17q was involved in the development of SCLC in this patient.

Alleles↗
PubMed1993

Effect of alternating combination chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, cisplatin, and etoposide for small cell lung cancer on hematopoietic progenitors in the peripheral blood.

The effects of a combination chemotherapy (CAV-PVP) consisting of cyclophosphamide, doxorubicin, hydrochloride (dox) and vincristine (CAV) alternating with cisplatin and etoposide (PVP) on peripheral blood hematopoietic progenitor cells (PBHPs) were studied in five patients with small cell lung cancer (SCLC). The kinetics of the CFU-GM levels were different during the CAV and PVP phases. None of the five patients displayed a rebound increase in the level of peripheral blood CFU-GM during the CAV phase. In contrast, all five patients displayed a rebound increase in peripheral blood CFU-GM levels during the PVP phase of the alternative combination chemotherapy (3-5 weeks after the initiation of PVP regimen). These findings indicate the optimal timing for leukapheresis to obtain PBHPs in SCLC patients which have been treated with an alternating combination chemotherapy consisting of CAV-PVP.

Adult↗
PubMed1993

Comparison of cisplatin plus vindesine with cisplatin plus mitomycin C for treatment of advanced non-small-cell lung cancer. The Eastern Shikoku Lung Cancer Chemotherapy Group.

Seventy-six patients with advanced non-small-cell lung cancer were randomly allocated to two groups and treated with cisplatin (CDDP; 80 mg/m2 on day 1) plus either vindesine (VDS; 3 mg/m2 on days 1 and 8) or mitomycin C (MMC; 8 mg/m2 on days 1 and 8) every 3-4 weeks. The objective response rates were 26% (10/38) for CDDP plus VDS and 32% (11/34) for CDDP plus MMC; the corresponding response rates in patients with adenocarcinoma were 7% (1/14) and 43% (6/14), respectively. The median survival times of patients treated with CDDP plus VDS and CDDP plus MMC were 33 and 30 weeks, respectively, the difference in survival times in the two groups not being significant. There was no significant difference in toxic effects in the two groups except that alopecia and leukopenia were more frequent in patients treated with CDDP plus VDS.

Adult↗
PubMed1993

RB-mediated tumor suppression of a lung cancer cell line is abrogated by an extract enriched in extracellular matrix.

To examine whether the expression of retinoblastoma (RB) protein could mediate tumor suppression in a lung carcinoma cell line carrying multiple genetic defects, we transfected the Rb gene into a non-small cell lung cancer cell line with absent RB protein. We observed that the stable expression of a functional RB product was associated with a decreased efficiency of soft agar cloning and partial suppression of tumorigenicity in nude mice. The suppression of tumorigenicity was marked when 10(6) cells were injected into the flanks of nude mice but was less prominent when 10(7) cells were injected. RB-mediated tumor suppression, however, was consistently blocked by preincubation of the transfected cells with an extract enriched with an extracellular matrix (Matrigel). Analysis of tumors harvested from nude mice showed that they continued to express detectable levels of human RB protein which retained functional E1A binding activity and nuclear localization. RB-mediated inhibition of soft agar cloning was also blocked in a dose-dependent manner by the addition of Matrigel. These observations demonstrate that the expression of wild-type RB may suppress certain parameters of tumorigenicity in lung carcinoma cells that contain multiple genetic alterations. In addition, the reversal of tumor suppression by an extract enriched in basement membrane components may offer clues for further investigations into the mechanism of RB-mediated tumor suppression.

Animals↗
PubMed1992

Functional analysis at the Cys706 residue of the retinoblastoma protein.

A missense mutation at cysteine 706, resulting in a retinoblastoma (RB) protein defective in phosphorylation and oncoprotein binding, has been isolated from a human tumor cell line. Since this residue is conserved in murine RB and in the related p107 protein, we studied the activity of in vitro mutants flanking this position. These experiments demonstrated that the thiol atom at codon 706 does not possess intrinsic functional activity as small polar or nonpolar residues could substitute at either codons 706 or 707, while bulkier R-group changes in these positions interfered with in vitro oncoprotein binding or in vivo protein phosphorylation. A series of missense mutants in an adjacent leucine repeat domain also demonstrated a loss of oncoprotein binding that was proportional to the magnitude of amino acid substitutions. To determine whether the cysteine 706 --> phenylalanine RB mutant retained any protein binding activity, we examined its ability to precipitate MYC, which was recently identified as a potential RB-associated protein. These experiments demonstrated that the mutant RB product is capable of binding in vitro to c-myc and L-myc proteins with comparable affinity as wild-type RB. These findings raise questions about the functional role of the RB:MYC interactions and emphasize important differences in the binding patterns between MYC and the other RB-associated proteins.

Amino Acid Sequence↗
PubMed1992

Oncogenes in human lung cancer.

The rapid pace of research in the genetics of human cancer will predictably render any review of the topic out of date by the time of its publication. Prospects for the near future will likely include the identification of a chromosome 3p gene(s) linked with the development of familial renal cancer and, perhaps, also lung cancer. In addition, the availability from the Human Genome Project of an increasing number of well-characterized markers will accelerate the search for additional human recessive oncogenes. Many questions still remain about the etiology of lung cancer and how to apply this information for patient care. For example, identification of the cell of origin for small cell and non-small cell lung cancers will facilitate our understanding of the development of these tumors and improve the possibilities for future preventive strategies. In addition, we now realize that these cancers arise from the sequential accumulation of multiple genetic mutations (Table 3; Fig. 1). Therefore, a central question is which of these targets are essential for the process of carcinogenesis, and whether there is a critical temporal order for this process with a defined premalignant phase in a discrete field of bronchial tissue. In addition, are there genetically inherited susceptibilities to the development of lung cancer (either directly or via variabilities in carcinogen metabolism) that could be accurately identified in the general population? Finally, is there a rate-limiting mutation and will the genetic correction of this defect suffice to restore growth regulation, or will the replacement of multiple gene products be required for tumor suppression? We are already witnessing the beginnings of the use of molecular diagnostic markers as a research tool for assigning prognostic information. The expression of neuroendocrine markers in non-small cell lung cancer has recently been applied as an indicator of the potential response to combination chemotherapy [15]. Similar methods are being applied to the expression of tumor suppressor genes or the presence of somatic mutations in dominant oncogenes such as the ras gene. However, the clinical benefit of this prognostic information with currently available treatment programs is still uncertain.(ABSTRACT TRUNCATED AT 400 WORDS)

Carcinoma, Non-Small-Cell Lung↗
PubMed1992

Granulocyte-colony-stimulating factor enhances the circulating hematopoietic progenitors in lung cancer patients treated with cisplatin-containing regimens.

A phase II study examining the effects of human recombinant granulocyte-colony-stimulating factor (G-CSF) on the growth of colony-forming unit-granulocyte macrophage (CFU-GM) in the bone marrow and in the peripheral blood was performed in lung cancer patients treated with cisplatin-containing regimens. Treatment with G-CSF following chemotherapy significantly increased the absolute granulocyte count. No significant effect of G-CSF on either the platelet or the red blood cell count was observed. Treatment with G-CSF did not affect the CFU-GM levels in the bone marrow, but did have a significant effect on peripheral blood CFU-GM levels 14 days after initiation of chemotherapy (P less than 0.05). Four patients demonstrated a rebound increase in the level of peripheral blood CFU-GM during the first course of chemotherapy without G-CSF. In contrast, eight patients displayed increase in peripheral blood CFU-GM levels during the second course of chemotherapy with G-CSF treatment. These findings demonstrate that G-CSF is a potent stimulator of granulocyte proliferation as well as a potent agent for promoting transport of hematopoietic progenitors from the bone marrow into the peripheral blood.

Aged↗
PubMed1992

Effect of chemotherapy on colony-forming unit-granulocyte macrophage from bone marrow and peripheral blood in patients with lung cancer.

The effects of chemotherapy on the growth of colony forming unit-granulocyte macrophage (CFU-GM) from the bone marrow (BM) and peripheral blood (PB) of 8 patients with lung cancer were studied by using recombinant interleukin-3, granulocyte macrophage-colony stimulating factor, and granulocyte-colony stimulating factor. After chemotherapy, the kinetics of CFU-GM depend on the type of chemotherapeutic regimens used: a rebound overshoot of CFU-GM in the PB was seen in the 4 patients treated with cisplatin plus etoposide (PVP) but not in the 4 patients treated with cisplatin plus mitomycin plus vindesine (CMV). In the BM, the recovery of CFU-GM was more retarded in patients treated with CMV relative to that seen in patients treated with PVP. The results obtained in simultaneous cultures revealed the differences between CMV and PVP in the kinetics of chemotherapy-induced myelosuppression. Determination of the optimal timing of in vivo use of hematopoietic growth factors after cytoreductive chemotherapy requires careful experimental design.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Pharmacokinetics of bronchial artery infusion of mitomycin in patients with non-small cell lung cancer.

The pharmacokinetics of bronchial artery infusion of 20 mg (11.4-14.0 mg/m2) mitomycin was studied in 14 patients with non-small cell lung cancer (NSCLC). The mean elimination half-life was 34.3 min (range 6-72), and the area under the plasma concentration-time curve (AUC) was 166 ng h/ml (39-312). The mean maximum plasma drug concentration (Cmax) was 178 ng/ml (12-540) and back-extrapolated plasma drug concentration was 308 ng/ml (17-1423). The mean volume of distribution in the one-compartment model was 0.183 l/kg (0.010-0.887) and the rate constant for unchanged drug appearing in the urine was 1.91/min (0.57-7.27). There was considerable variation among individuals with respect to the pharmacokinetics of mitomycin, and the mean Cmax and AUC were lower than those reported after intravenous administration.

Bronchial Arteries↗
PubMed1991

Alternating chemotherapy with cyclophosphamide/adriamycin/vincristine (CAV) and cisplatin/etoposide (PVP) against small cell lung cancer. Eastern Shikoku Lung Cancer Chemotherapy Group.

Seventy-four confirmed small cell lung cancer (SCLC) patients received alternating combination chemotherapy with CAV and PVP. The CAV comprised of cyclophosphamide 800 mg/m2 on day 1, adriamycin 50 mg/m2 on day 1 and vincristine 1.4 mg/m2 on day 1, administered every 3-4 weeks. The PVP comprised cisplatin 80 mg/m2 on day 1 and etoposide 75 mg/m2 on day 1-5 administered every 3-4 weeks. Of these 74 patients, 63 (85.1%) achieved complete or partial responses with 16 (21.6%) obtaining a complete response. The median survival time was 13.2 months: 10.4 months in patients with extensive disease (ED), 16.3 months in those with limited disease (LD). A three-year disease-free period was achieved in eight patients (11.2%: 4.8% with ED, 16.8% with LD). The median duration of response was 28.3 weeks: 20.1 weeks with ED and 44.0 weeks with LD. The most commonly encountered side effects were nausea, vomiting, alopecia and myelosuppression but all were tolerable. We consider CAV-PVP to be an effective combination regimen for treating SCLC.

Adult↗
PubMed1991

[Burkitt's lymphoma with monoclonal pattern (IgG, kappa type) of cytoplasmic immunoglobulin--clinical report and review of Japanese literature].

A 52-year-old male was admitted to the hospital because of abdominal mass. Bone marrow examination revealed 26% blasts, which morphology was L3 in FAB criteria. Abdominal tumor was resected and histologic feature of the tumor was malignant lymphoma, small non-cleaved cell, Burkitt's. Lymphoma cells from the resected tumor were cultured and a cell line was established. Cytological studies of the original tumor cells and the cell line revealed that the lymphoma was negative both for EBNA and EBV DNA, and possessed t(8;14) (q24;q32) in chromosome analysis. Surface antigens were positive for HLA-DR, CD19 and CD20, but negative for CD10. The lymphoma also expressed a monoclonal pattern (IgG, kappa type) both of surface immunoglobulin and cytoplasmic immunoglobulin. Thus, the lymphoma was originated from mature B-lymphocyte. We analysed clinicopathological findings of 216 patients who were reported as Burkitt's lymphoma in Japan. Of 35 cases examined for cell EBNA, 7 (20%) were positive for EBNA. Of 86 cases tested for surface immunoglobulin of tumor cells, 67 expressed IgM alone and 10 IgG alone on tumor cells. Cytoplasmic immunoglobulin of tumor cells was positive in 61% of patients. Of 11 cases positive for cytoplasmic immunoglobulin, IgM was detected in 8 patients and IgG only in our patient.

Burkitt Lymphoma↗
PubMed1991

[An elderly case of small cell lung cancer showing a good partial response by chronic daily administration of oral etoposide].

An 86-year-old man was admitted to our hospital with complaints of dyspnea and productive cough, and diagnosed as small cell lung cancer with sputum cytology. We concluded that he was unsuitable for standard aggressive intravenous chemotherapy because of an old age, a poor performance status and cardiac complication. He was treated with oral etoposide (100 mg/day x 16.5 days), and showed a good partial response and improvement of clinical symptoms. Toxicities were leukopenia, alopecia, and anorexia. Daily oral administration of etoposide is considered to be effective and useful for elderly patient with small cell lung cancer.

Administration, Oral↗
PubMed1991

[Sex hormones and calcium regulating hormones in rheumatoid arthritis].

Rheumatoid arthritis (RA) occurred frequently in women. Exogenous estrogen has been reported to alleviate the symptoms of patients with RA. But the implications of sex hormones and immunological abnormalities in RA remain to be elucidated. Therefore, we measured sex hormones (LH, FSH, estradiol, testosterone and prolactin), bone metabolic markers (midregion and carboxy terminal mainly recognized PTH1-84, intact PTH1-84, bone GLA protein and alkaline phosphatase), bone mineral, in lumbal bone with quantitative tomography (QCT) and with of cortex with microdensitometry in 52 females with RA and 46 females with osteoarthritis (OA) as a control group. Sex hormones and bone metabolic markers were analyzed as independent variables of serum LH, FSH and estradiol levels, using one way analysis, in patients with RA and OA. The more increased serum FSH and LH levels were, the more decreased serum estradiol levels were in both RA and OA groups, when they were considered as independent variables. These results indicate that the secretory function of pituitary and ovary axis hormones are normally enacted in RA. On the other hand, when the sex hormones of the patients under 53 years of age were studied in both groups, serum FSH adn LH showed significantly higher levels, while serum estradiol levels revealed decreased tendency in RA, compared with these in RA. Thus the pituitary ovary secretory function in patients with RA was suggested to be disturbed in early stage of age, indicating that the sex hormones would be partly implicated in calcium and bone metabolism in patients with RA.

Adolescent↗
PubMed1990

Effects of recombinant human G-CSF, GM-CSF, IL-3, and IL-1 alpha on the growth of purified human peripheral blood progenitors.

The effects of recombinant products of granulocyte colony-stimulating factors (G-CSF), granulocyte/macrophage CSF (GM-CSF), human interleukin-3 (IL-3), and interleukin-1 (IL-1) were studied using purified target cell populations from patients undergoing peripheral blood stem cell transplantation after myeloablative therapy. Cells were subjected to combined purification procedures including negative selection with a panel of monoclonal antibodies (CD2, 3, 5, 10, and 20). The purified cells were enriched for HLA-DR+ (51% to 71%) and My-10+ (CD34; 37% to 54%) and had a plating efficiency of up to 20%. In the liquid-suspension limiting dilution clonal assay (LDA), purified progenitors responded directly to IL-3 by proliferation with single-hit kinetics. The ability of GM-CSF to support progenitor growth was inferior to that of IL-3, and the cells were virtually unresponsive when cultured with G-CSF, supporting the notion that these blood-derived progenitors belong to a primitive population of hematopoietic progenitor cells. The results obtained in simultaneous methycellulose cultures (MC) showed the same trend and provided additional information on the ability of GM-CSF and IL-3 to support erythroid progenitor growth. The combination of IL-3 plus G-CSF, but not IL-3 plus GM-CSF, resulted in a synergistic increase in colony number. IL-1 alpha increased both the size and number of colonies when added to IL-3 or G-CSF. Study of this enriched progenitor cell population in MC and LDA represents an excellent model for the investigation of myeloid and erythroid differentiation and for evaluating the influence of various cytokines on human hematopoiesis.

Antigens, CD↗
PubMed1990

Circulating hematopoietic progenitors in patients with primary lung cancer.

The levels of circulating hematopoietic progenitors were measured in 28 patients with primary lung cancer. The average numbers of progenitors per milliliter of blood were 33 (range 0-360) for colony-forming unit-granulocyte macrophage (CFU-GM), 23 (range 0-140) for burst-forming unit-erythrocyte (BFU-E), and 4 (range 0-50) for colony-forming unit-mixed lineages (CFU-mix). No significant influence of age, sex, histological type, or clinical stage of the tumor on the progenitor levels was detected. After cytoreductive chemotherapy of the patients by treatment with cisplatin plus etoposide, the cells showed 6- to 50-fold rebound overshoots, but no rebound was observed after treatment with cisplatin alone, cisplatin plus mitomycin C or cisplatin plus vindesine plus mitomycin C, or in 4 of 5 patients treated with cyclophosphamide plus adriamycin plus vincristine. Peripheral blood hematopoietic progenitors should be useful as an alternative source of stem cells for lung cancer patients treated with marrow ablative chemotherapy.

Adult↗