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Biomedical subjects

M Miyauchi

Publications and source records attributed to M Miyauchi.

At least 181 records · Page 10Linked to original sources

Antigenic variations of retrovirus in Japanese cancer patients.

Previously we demonstrated the prevalence of human T lymphotropic virus type I (HTVL-I) infection among cancer patients in Japan. This study was carried out to examine antigenic properties of retroviruses prevalent among Japanese cancer patients. Sera of 126 Japanese patients with cancer of different organs and with no history of blood transfusion, 94 in adult T cell leukemia (ATL)-endemic area and 32 in ATL-nonendemic area, were surveyed for antibodies to HTLV-I and HTLV-II by enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and indirect immunogold electron microscopy. Among patients who were seropositive to HTLV-I, 39 of 56 (69.6%) in ATL-endemic area and 9 of 9 (100%) in ATL-nonendemic area were seropositive also to HTLV-II. Of 48 sera positive to both HTLV-I and HTLV-II, 34 (70.8%) showed stronger reactivities to HTLV-I than to HTLV-II. Among patients who were seronegative to HTLV-I, 3 of 38 (7.9%) in ATL-endemic area and 5 of 23 (21.7%) in ATL-nonendemic area were seropositive to HTLV-II. Antibodies appearing and disappearing in sera of patients examined during the clinical course reacted with peptide species of HTLV-I and/or HTLV-II not always consistent with peptide species cross-reactive between HTLV-I and HTLV-II. These results indicate the antigenic diversity of retroviruses prevalent among Japanese cancer patients.

Antigenic Variation↗

Interleukin 2 activity in peripheral blood mononuclear cells of patients with gynecologic malignancies.

We studied production of, absorption of and response to interleukin 2 (IL-2) by peripheral blood mononuclear cells (PBMC) from 66 patients with gynecologic malignancies, in addition to measurement of the OKT 4/OKT 8 cell ratio. Patients with benign tumor served as controls. The OKT 4/OKT 8 cell ratio in patients with advanced (but not early) gynecologic malignancies was significantly lower than that in patients with benign tumor. PBMC from advanced cancer patients activated with phytohemagglutinin (PHA) had significantly lower IL-2 production compared to that from patients with benign tumors, while significant changes in their ability to respond to IL-2 and to absorb IL-2 were not observed. Absolute numbers of OKT 8 positive cells in PBMC of patients with good prognosis were significantly decreased after surgery and chemotherapy, while those of OKT 4 positive cells remained unchanged. Although IL-2 production in PBMC of patients with good prognosis was significantly elevated after chemotherapy, that in PBMC of patients with poor prognosis declined to about a half of pre-operative levels. The ability of PBMC to respond to IL-2 was significantly elevated not only in patients with good prognosis but also in patients with poor prognosis after termination of chemotherapy. On the other hand, the ability of PBMC to absorb IL-2 remained unchanged during the course of treatment. These findings may contribute to the understanding of tumor-induced immune suppression.

Antigens, Surface↗

Adjuvant effects of prostaglandin D2 to cisplatin on human ovarian cancer cell growth in nude mice.

Adjuvant effects of prostaglandin D2 to cisplatin on tumor growth were studied by using nude mice bearing HR cells derived from human ovarian carcinoma. Combinations of 0.2 or 0.4 microgram/ml cisplatin and 0.05 or 0.1 microgram/ml prostaglandin D2, which did not affect the HR cell proliferation alone, resulted in a significant inhibition of cell proliferation. In addition, tumor take of HR cells by nude mice in groups treated with a combination of cisplatin and prostaglandin D2 was inhibited. Although there was no significant difference between tumor volumes in mice treated with prostaglandin D2 alone or cisplatin alone and untreated mice, when cisplatin was administered with 1 mg/kg prostaglandin D2 the tumor volume was significantly smaller on days 21 and 35, compared to that of untreated mice. When cisplatin and 2 or 4 mg/kg prostaglandin D2 were combined, the tumor growth was significantly inhibited after day 21, compared not only to that of untreated mice but also of mice treated with cisplatin alone or prostaglandin D2 alone. Such a combination therapy by cisplatin and prostaglandin D2 seemed to result in prevention by prostaglandin D2 of immunological suppression which may be induced by cisplatin. Thus, such a combination therapy brought about a significant prolongation to the survival time.

Animals↗

Effects of cimetidine on interleukin-2 production by peripheral blood lymphocytes in advanced ovarian carcinoma.

The present study was designed to elucidate the effect of cimetidine on CD4 and CD8 positive cells, interleukin-2 (IL-2) production and IL-2 receptor expression in peripheral blood lymphocytes (PBL) from patients with advanced ovarian carcinoma during the course of combination chemotherapy. The absolute number of CD8 (but not CD4) positive cells in PBL from patients with advanced ovarian carcinoma before surgery was significantly higher than that with benign ovarian tumor, while the IL-2 productivity was significantly lower. However, the IL-2 receptor expression was comparable to that with benign ovarian tumor. When a combination chemotherapy consisting of cisplatin, adriamycin and cyclophosphamide was given to these ovarian cancer patients, the IL-2 production was markedly depressed. If cimetidine was given with the combination chemotherapy, the inhibition of IL-2 production by chemotherapy was significantly diminished with a significant increase of CD4 positive cells. On the other hand, the IL-2 receptor expression was not affected by this treatment. When treatment with cimetidine was initiated after completion of chemotherapy, the depressed IL-2 production was restored to the level of control patients with benign ovarian tumor. The restoration seemed to result from an increase in proportion of CD4 positive cells. However, the expression of IL-2 receptor remained unchanged even if cimetidine was given.

Adult↗

The mechanism of acquired resistance to cisplatin by a human ovarian cancer cell line.

The present study was designed to elucidate the mechanism of resistance to cisplatin. A cisplatin-resistant cell line (KFr) was established from KF cells derived from human serous cystadenocarcinoma of the ovary. The DNA histogram revealed an increase of S-phase cells and a decrease of G1-phase cells in cultured KFr cells, compared to that in cultured KF cells. Although the cisplatin content in the KF cells incubated with cisplatin at 10 micrograms/ml increased in a time-dependent manner, that in the KFr cells remained unchanged during the experimental period. When 0.5 mg of cisplatin was administered ip to nude mice with KF or KFr tumor, the cisplatin content in the KFr tumor was significantly lower than that in the KF tumor. The KFr cells showed a cross-resistance to L-phenylalanine mustard, while no cross-resistance to vincristine or 5-fluorouracil was observed. These findings suggest that the mechanism of cisplatin resistance in the KFr cells involves a decrease of cisplatin accumulation in the tumor cells.

Cell Line↗

Emergence of fluoroquinolone resistance in Bacteroides fragilis accompanied by resistance to beta-lactam antibiotics.

The in vitro susceptibilities of a group of 93 isolates of Bacteroides fragilis collected from 1983 to 1984 to six fluoroquinolones were compared with those of a group of 93 isolates collected from 1986 to 1987. The recently collected strains were less susceptible than the older strains to all of the agents tested. Norfloxacin-resistant (MIC, greater than 100 micrograms/ml) strains were less susceptible to cefoxitin and piperacillin than norfloxacin-susceptible strains.

Anti-Bacterial Agents↗

Complement activation by vascular prostheses and its role in progression of arteriosclerotic lesions.

This study, using C3a, C4a, and C5a assay and crossed immunoelectrophoresis in vitro and in vivo, was designed to determine whether vascular prostheses activate the complement system. The degree of complement activation and the pathway of activation were also studied. The complement levels (C3, C4, CH50) in different arterial diseases were measured, and the relationship of complement levels to serum lipids in patients with arteriosclerosis obliterans (ASO) was also investigated, in order to clarify a relationship between the complement system and arteriosclerosis or other arterial diseases. Bovine graft, dacron, and PTFE activated the complement system in vitro. In order of the degree of complement activation, bovine graft ranked first, followed by dacron and PTFE. The patient group with acute arterial occlusion showed high C3 and C4 levels. The healthy elderly group showed higher C3 and C4 levels than the healthy persons in their twenties. In ASO patients, C3 levels correlated with serum lipid levels. Judged from the relation of complement activation by vascular prostheses to the progression of arteriosclerotic changes, vascular prostheses should be assessed with regard to complement activation.

Arterial Occlusive Diseases↗

[Effect of calmodulin antagonists (W-5 and W-7) on antitumor activity of Tegafur and UFT (Tegafur plus uracil)].

The effect of calmodulin antagonists (W-5 and W-7) on antitumor activity of 1-(2-Tetrahydrofuryl)-5-fluorouracil (Tegafur; FT) and FT plus uracil (UFT) was examined by using nude mice bearing human ovarian carcinoma (KF cells). All nude mice developed a palpable tumor 17 days after KF cell inoculation unless treatment was done. A combination of UFT and calmodulin antagonists (W-5 or W-7) resulted in a delay in tumor formation in nude mice. One of 10 nude mice treated with a combination of UFT and W-5 and 3 of 10 nude mice treated with UFT and W-7 did not develop tumors during the experimental period. Tumor volume in the treatment groups combined with calmodulin antagonists was significantly less than in those in the untreated group after 31 days of tumor inoculation. In addition, tumor volume in a UFT plus W-7 treated group was significantly less than those not only in the untreated group but also in the UFT alone, FT alone, W-5 alone and W-7 alone treated groups, suggesting a synergistic inhibitory effect on tumor growth. The longest median survival time was also observed in a UFT plus W-7 treated group. 5-Fluorouracil (5-FU) content in the tumor of groups treated with FT plus W-5 or W-7 was similar to that in a group treated with FT alone. On the other hand, that of a group treated with UFT plus W-7 was about 2-fold higher than that of a UFT -only treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Morphological characteristics, especially the malignant features, of chordoma in comparison with the notochord].

Twelve cases of the chordoma, including 4 cases with metastases, have been examined by light and electron microscopy for a comparison with 5 cases of the human notochord. Observed similarities in the histological and ultrastructural characteristics of the chordoma with those of the notochord suggested the histogenetic origin of the chordoma from the remnant of notochord. A "diffuse pattern" that was seen in the histological appearance of 4 cases of the chordoma, including 2 cases with metastases, was not observed in the notochord and was considered to indicate the malignant nature of such chordoma. Electron microscopy of the physaliphorous cells characteristic of the chordoma demonstrated intracytoplasmic large vacuoles containing glycogen.

Adult↗

[Reduced cisplatin-uptake by cisplatin-resistant human ovarian cancer cells].

We have developed a human ovarian carcinoma cell line (KFr) which is relatively stable and resistant to cis-diamminedichloroplatinum (cisplatin) after repeated exposure to escalating doses of the drug. This resistant cell line (KFr) was 9.7-fold resistant to carboplatin (JM-8), 8.8-fold resistant to (glycolato-O, O') diammineplatinum (II) (254S), and 7.1-fold resistant to Cis-1, 1-cyclobutanedicarboxylato (2R)-2-methyl-1, 4-butanediammineplatinum (II) (NK121), respectively. The KFr cell line proved to be 3.1-fold resistant to L-phenylalanine mustard (L-PAM). On the other hand, no cross-resistance to vincristine (VCR), 5-fluorouracil (5-FU) and daunomycin (DM) was observed. In addition, we examined the level of platinum in whole cells after 1-16 h exposure to 20 micrograms cisplatin. The parent cell line (KF) took up cisplatin in a time-dependent manner until 4 h. The uptake reached the plateau level after 4 h. On the other hand, the uptake by the KFr cell line reached the plateau level at 1 h-exposure time; after 4 h the uptake was about 1/3 of that by the KF cell line. The release of cisplatin from both cell lines showed a similar pattern, reaching the plateau within the first 30 min. Based upon these results, we assumed that the impairment of transport of influx systems of cisplatin into cells was the mechanism of resistance.

Animals↗

[A clinical study of extended profundaplasty for severely ischemic limbs].

Between January 1986 October 1987, extended profundaplasty was performed on 11 severely ischemic limbs of eight patients with extended arteriosclerotic occlusions, associated with surgery for improvement in inflow. The subjects were all males, and ages ranged from 62 to 84 years (mean: 72.8 years). Symptoms were disabling claudication in one limb (1 case), rest pain in 5 (4 cases), and gangrene of the foot or ulcer of the toes in 5 (3 cases). Preoperative ankle pressure index (API) was 0 in 7 limbs (5 cases), and between 0.11 and 0.27 in the remaining 4 limbs (3 cases). Thrombectomy was performed in two cases, axillo-bifemoral bypass in 5, femoro-femoral bypass in one, and aorto-bifemoral bypass in one, as surgery for improvement in inflow. Although postoperative API remained 0 in 4 limbs, it increased between 0.36 and 0.56 in the remaining limbs. One subject died of heart failure on the 22nd postoperative day, and two limbs required below-knee amputation. Limb salvage rate was 81.8%. Extended profundaplasty seems to be a worthwhile choice of treatment as a limb salvage operation for severely ischemic limbs due to extended arteriosclerotic occlusions involving not only aorto-iliac but also femoro-popliteal or crural segment.

Aged↗

[Ultrastructural diagnosis of early neoplasia in man].

Recent progress in cancer detection technology has resulted in the increasing need for pathological diagnosis of small cancers at their early stage of development. Electron microscopy of early cancers may reveal ultrastructural markers characteristic of certain cell lineage and help classify these cancers in terms of aberration in differentiation of neoplastic cells. Furthermore, electron microscopy of early cancers may detect certain cellular gene products at cellular as well as subcellular levels, and help understand the process of malignant progression in situ of transformed cells.

Diagnosis, Differential↗

[Potentiation of the antitumor effect of cisplatin by calmodulin antagonists (W-7 and W-5) in nude mice bearing human ovarian carcinoma].

The present study was designed to potentiate the antitumor effects of cisplatin by combination with calmodulin antagonists (W-7 and W-5) by using nude mice bearing human ovarian carcinoma. Tumor growth in nude mice treated with W-7 or W-5 combined with cisplatin was significantly inhibited, compared to that in nude mice treated with W-7 alone, W-5 alone or cisplatin alone. Although treatment with cisplatin alone markedly inhibited lytic activity of the spleen cells from tumor bearing nude mice against the tumor cells, the inhibitory effect was eliminated by combination with W-7 or W-5. There was no significant difference in the survival time among untreated, cisplatin-treated, W-7-treated and W-5-treated groups. Only when cisplatin was followed by W-7 or W-5, a significant enhancement by W-7 or W-5 of the antitumor effect of cisplatin was observed with respect to inhibition of the tumor growth as well as prolongation of the survival time.

Animals↗

[Establishment of a cisplatin-resistant human ovarian cancer cell line and the mechanism of resistance].

A cisplatin-resistant cell line was established by using KF-1 cells derived from human serous cystadenocarcinoma of the ovary. This resistant cell line, designated "KFr", was capable of proliferating in the presence of 1.0 microgram/ml cisplatin. It had doubling times of 24.8 and 27.2 hr in the presence of 0.5 and 1.0 microgram/ml cisplatin, respectively. The morphologic characteristics of the KFr cells were an enlarged nucleus and prominent nucleoli, unlike the nucleus and nucleoli of the parent KF-1 cells. The degree of resistance to cisplatin of the KFr cells was about 20 times as great as that of the KF-1 cells, with regard to the concentrations of cisplatin required for 50% inhibition of cell proliferation. Although the cisplatin content in the KF-1 cells incubated with 10 micrograms/ml cisplatin was increased in a time-dependent manner, that in the KFr cells reached the plateau level after 1.5 hr incubation with cisplatin. After about 4 hr incubation, the cellular content in the KFr cells was about a half of that in the KF-1 cells. When 0.5 mg cisplatin was administered i.p. to nude mice with KF-1 or KFr tumor, the cisplatin content in the KFr tumor was significantly lower than that in the KF-1 tumor. The KFr cells showed a cross-resistance to melphalan, while no cross-resistance to vincristine or 5-fluorouracil was observed. When 5 microM W-5 or W-7 was added in the presence of concentrations of cisplatin that hardly inhibited cell proliferation, the KFr cell proliferation was markedly inhibited. These findings suggest that the cisplatin resistance in the KFr cells may be due to an impaired cisplatin-transport mechanisms and can be overcome by calmodulin antagonists.

Animals↗

Enhancement of antineoplastic effects of cisplatin by calmodulin antagonists in nude mice bearing human ovarian carcinoma.

The present study was designed to potentiate the antineoplastic effects of cisplatin by combination with calmodulin antagonists [N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5)] in nude mice bearing human ovarian carcinoma. Tumor growth of nude mice treated with W-7 or W-5 combined with cisplatin was significantly inhibited, compared to that of nude mice treated with W-7 alone, W-5 alone, or cisplatin alone. Although treatment with cisplatin alone markedly inhibited lytic activity of spleen cells from tumor-bearing nude mice against the tumor cells, the inhibitory effect was eliminated by combination with W-7 or W-5. There was no significant difference in survival time among untreated, cisplatin-treated, W-7-treated, and W-5-treated groups. Only when cisplatin was followed by W-7 or W-5 was a significant enhancement by W-7 or W-5 of the antitumor effect of cisplatin observed with respect to inhibition of tumor growth as well as prolongation of survival time.

Adenocarcinoma↗