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Biomedical subjects

Y Nakabayashi

Publications and source records attributed to Y Nakabayashi.

At least 37 records · Page 2Linked to original sources

Calcium channels in embryonic chick skeletal muscle cells after cultivation with calcium channel blocker.

The effects of chronic treatment with calcium channel blockers were studied on the expression of voltage-dependent calcium channels (VDCCs) in chick skeletal muscle cells developing in culture. Myotubes were treated after 2 days in culture with either 20 microM D600 or 10 microM nifedipine, and measurements were made of the maximum rate of rise (M.R.R.) of the two components of action potential, operated by T- and L-type VDCCs, respectively. Treatment with either blocker reduced the M.R.R. of the action potential component operated by the L-type VDCC throughout the culture period examined. The M.R.R. of the T-type VDCC component, on the other hand, was unaffected by either treatment. The reduction in the M.R.R. of the L-type component in blocker-treated cells is thought to be due to the down-regulation of the expression of L-type VDCC. Thus, it appears that the expression of L-type VDCC in the chick skeletal muscle cells can be regulated by a function of L-type VDCC, which mediate the entry of Ca2+ into the cells. The physiological significance of the L-type VDCC, which expressed prominently early in the development of skeletal muscle cells, for the differentiation of excitability is discussed.

Action Potentials↗

Chronic treatment with D600 enhances development of sodium channels in cultured chick skeletal muscle cells.

We have studied the long-term effects of D600, a blocker of L-type voltage-dependent Ca channels (VDCC), on the development of voltage-dependent Na channels (VDNC) that are sensitive to tetrodotoxin (TTX), by electrophysiological measurements of the maximum rate of rise of the TTX-sensitive Na spike in cultured chick skeletal muscle cells. Chronic treatment with D600 (2-20 microM) caused a dose-dependent increase in the density of VDNC. The density of VDNC was increased by 150-250% when D600 was added to the cultures at 20 microM from the second day of culture onward. Co-treatment with an inhibitor of the transcription of RNA from DNA, alpha-amanitin, or with cycloheximide, an inhibitor of protein synthesis, prevented the up-regulation by D600. Nifedipine, a different type of blocker of L-type VDCC, was also effective in increasing the density of VDNC, and BAY K 8644, an agonist of L-type VDCC, had the opposite effect. It is suggested that the effect of D600 was mediated via a mechanism specific for L-type VDCC that involves regulation of cytosolic levels of Ca2+ and protein synthesis de novo.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Pharmacological properties of two types of calcium channel in embryonic chick skeletal muscle cells in culture.

We have studied the effects of organic and inorganic Ca channel blockers on the two-component action potentials (low- and high-threshold components) in cultured chick skeletal muscle cells, which are generated by the T- and L-type voltage-dependent Ca channels (VDCCs), respectively. Nifedipine and D600 effectively blocked the high-threshold component of the action potential, whereas omega-conotoxin and phenytoin had no effect on this component. By contrast, the low-threshold component was insensitive to all of these organic Ca channel blockers. Blocking effects of polyvalent cations were observed with the following rank order of relative potency (mean apparent dissociation constant in microM): La3+ (14.7) greater than Ni2+ (20.7) greater than Cd2+ (51.2) greater than Co2+ (912) for the low-threshold component, and Cd2+ (0.7) greater than La3+ (29.2) greater than Co2+ (431) greater than Ni2+ (1241) for the high-threshold component. Taken together, these findings suggest that the pharmacological properties of the T- and L-type VDCCs in cultured chick skeletal muscle cells may differ from those in other preparations.

Action Potentials↗

Aromatase inhibitors in cigarette smoke, tobacco leaves and other plants.

A chance observation that cigarette smoke interferes with the aromatase assay led us to investigate tobacco leaf and smoke extracts for the presence of aromatase inhibitors. The highest inhibitory activity was found in the basic fraction of cigarette smoke. Further purification of this fraction led to the identification of N-n-octanoylnornicotine. Synthesis and testing of a series of acylated nornicotines and anabasines for their ability to inhibit aromatase showed an interesting correlation of activity with the length of the acyl carbon chain, with maximum activity at C-11. The acylated derivatives showed activity which was significantly greater than that of nicotine and anabasine. In vivo studies in rats indicated that administration of this inhibitor delayed the onset of NMU-induced breast carcinoma and altered the estrus cycle. These in vivo studies suggest that tobacco alkaloid derivatives exert their effects by suppression of the aromatase enzyme system. Toxicity studies indicated relatively low toxicity with LD50 for N-n-octanoylnornicotine = 367 mg/kg body weight. When extracts from thirty five varieties of vegetables, plant leaves, and fruits were analyzed, seventeen showed quantitatively significant aromatase inhibition which was comparable to that of green tobacco leaf, suggesting that naturally occurring substances may affect endocrine function through aromatase inhibition.

Anabasine↗

[An experimental study of bone remodeling influenced by mechanical stress].

Bone remodeling influenced by mechanical stresses was studied using ambulatory chickens. They were divided into four groups with the different mechanical forces applied to the leg. I: running along a circular track, II: walking or standing on one leg, III: control, IV: casting. The animals were sacrificed after 12 weeks and undecalcified cross-sections of femurs and tibias were examined using a tetracycline labeling method. Bone formation was evident at both metaphyses of the femur and at the proximal metaphysis of the tibia. More bone formation was observed at the medial quarter of both femur and tibia than in comparison with the lateral quarter. There was, however, no difference in the membraneous ossification between the medial and lateral quarters in Group II. The lack of significant cortical drift at the medial side of the femur and tibia suggests that no bending moment is generated by standing on one leg.

Animals↗

[Biochemical activity in peritoneal effusion of ovarian malignancy].

This study was provided biochemical findings on ascitic fluid following the treatment of patients with ovarian tumors. The results were as follows: LDH and LDH isozyme. The ascitic fluid from patients with germ cell tumors showed an LDH1 value of 38.8% with an H/M ratio of 2.82, which were significantly higher than those found in the benign tumor group (LDH1, 15.2%: H/M ratio, 1.05). In cases of adenocarcinomas, the LDH5 value was 27.2%, compared to 15.7% in cases of benign tumors. Of 28 patients with adenocarcinoma, 15 patients (53.6%) were positive for this elevation. The decline in total LDH activity and elevation of H/M ratio were observed as a general tendency in patients satisfactorily responding to treatment. ALP and ALP isozyme. The malignant tumor group displayed higher values for both total ALP activity and HSAP in ascitic fluid, as compared with the benign tumor group. In the malignant tumor group, alpha 2 and alpha 2-beta regions were prominent in the isozyme pattern and the isozymes of the same regions remained even after inactivation by heat. The total activity decreased significantly in the responders to treatment. TP, alpha 1-AT, alpha 1-AG, alpha 2-M and IgG. The ascitic fluid levels of alpha 1-AT, alpha 2-M and IgG did not significantly differ among the group of patients with germ cell tumors, the group of patients with ovarian gonadal stroma and the group of patients with benign tumors. In the adenocarcinoma group the alpha 1-AT and alpha 2-M levels were higher than those in the benign tumor group. The ascitic fluid alpha 1-AG level and alpha 1-AG/TP ratio were elevated in tumors of germ cell origin and in adenocarcinomas; they tended to correlate with the degree of malignancy of the tumor. The results of the present study suggest that simultaneous measurement of the ascitic fluid levels of LDH isozymes, ALP isozymes, alpha 1-AG, alpha 1-AT, alpha 2-M and IgG may play a potential adjunctive role in providing information for diagnostic differentiation between benign and malignancy, estimation of the histologic type and extent of neoplastic growth, evaluation of the therapeutic response and prediction of the clinical progress.

Adenocarcinoma↗

[Experimental chemotherapy of germ cell tumor heterotransplanted to nude mice].

While the treatment of ovarian cancer has made remarkable progress in recent years, the chemotherapy of ovarian germ cell tumor has not as yet been fully established and remains to be improved. We investigated the effectiveness of a single-agent therapy with Vincristine (VCR), Actinomycin D (ACD), and Cyclophosphamide (CPM) against a human undifferentiated dysgerminoma's cell line (JOHYL-1) with the following results. The ratio of the number of viable cells to the total cell population treated for JOHYL-1 cells of ascitic type was 70% with VCR, 58% with CPM and 25% with ACD; hence the efficacy on this malignant cell line was the greatest with ACD followed by VCR and CPM in that descending order. Notably with CPM, a striking antitumor effect was observed from 48 to 24 hours after treatment. The L.I. attained a peak at 24, 18 and 30 hours, respectively, after treatment with VCR, ACD and CPM. The M.I. was as high as a little more than 6% at 36 hours after treatment with VCR. There also was noted a shift in the cell cycle with any of the test drugs. Morphological changes observed in the cell were most obvious with ACD followed in order by VCR and CPM. LDH & isozyme pattern: In these respects there were no striking differences among the three drugs, even though the total enzyme activity was somewhat higher with VCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Experimental study of the mechanism of peritoneal dissemination--with special reference to scanning electron microscopic observations].

Most malignant ovarian tumors metastasize by peritoneal dissemination and have a poor prognosis. Few studies have been made to determine how free ovarian tumor cells act on the peritoneum and become lodged and proliferate therein and much still remains to be clarified concerning this issue. In the present study, we transplanted 2 X 10(6) cells of JOHYL-1 strain established from an atypical dysgerminoma into the peritoneal cavity of nude mice observed serially morphological changes in the peritoneum resulting from tumor cell dissemination both by light microscopy and SEM. The findings thus obtained may be summarized as follows: From 5 to 7 days after intraperitoneal transplantation of tumor cells, mesothelial cells of the peritoneum began to swell, with the intercellular boundaries becoming distinct. Microvilli of the mesothelial cells increased in number, forming a mesh-like structure, and in some places were found to be in direct contact with a tumor cell. From 10 days after tumor cell transplantation onwards the mesothelium showed enlarged intercellular spaces in some places, and at these sites tumor cells were seen to have adhered. On other sites mesothelial cells were being partially lost. From 11 days after being transplanted, the tumor cells started proliferating and infiltrating in the muscle layer. Concerning the site of tumor cell implantation, evidence was obtained showing that tumor cells adhered to intercellular spaces of mesothelial cells, and/or in defects formed on connective tissue by a loss of mesothelial cells. The study thus demonstrated a salient usefulness of the JOHYL-1 ascites type cell line, with a reliably great capacity for growth in vivo, as an experimental model for the study of peritoneal dissemination of tumor cells.

Animals↗

[In vitro sensitivity test of a cultured human ovarian cancer cell line to anticancer agents].

In vitro tests were performed to assess the sensitivity to six anticancer agents-ACT-D, ADM, CDDP, CQ, 5-FU and MMC-of a JOHYL-1 (ascites type) cell line from human dysgerminoma which was used as challenge strain. For comparative assessment, anticancer sensitivity was expressed as the ratio of IC50 and IC90 to LD50 (i.v.) in mice. Drug dose-response and time-response curves were plotted, and the IC50 ratio was calculated, for each test compound in order to investigate the mechanism of anticancer action. The results obtained were as follows. CQ proved to be remarkably active and ADM fairly active against JOHYL-1 (ascites), but 5-FU, CDDP and MMC varied remarkably with the parameter of measurement employed. Analysis of IC50 ratio data and patterns of cell growth inhibition indicated the growth-inhibitory effect of CDDP to be concentration-and time-dependent. The results of the present study are in close accord with the pattern of action reported in the literature.

Animals↗

[A study on factors influencing survival in stage I ovarian cancer].

Early diagnosis is difficult in ovarian cancer and the prognosis is unfavorable even in stage I case. A total of 131 cases with stage I ovarian carcinoma were treated at our institution, 73 were stage Ia, 13 were stage Ib, 45 were stage Ic and 39 were LPM. To define the criteria for selection of therapy, we retrospectively reviewed the stage I ovarian cancer. The results were as follows: The best survival rate was demonstrated in 96% of LPM cases followed by 73% of endometrioid adeno-carcinoma. Cases with rupture of capsule and with ascites at surgery influenced the 5 year survival rate. We observed no difference in survival rate between the conservative operation (unilateral salpingo-oophorectomy) group and the complete operation (bilateral salpingo-oophorectomy and total hysterectomy) group. Those who had received postoperative chemotherapy showed the longest survival rate of 86%. Evaluation of deaths; 9 of 21 with stage Ic died within 12 months after surgery, and 4 of 7 with stage Iai between 1 and 3 years. The analysis has shown the importance of adequate postoperative treatment and of strict follow-up to guard against recurrence of malignancy in patients with ruptured tumor capsules as well as in those with ascites.

Adenocarcinoma↗

Clear-cell syringoma. Association with diabetes mellitus.

Only one case of clear-cell syringoma has been reported in the United States, whereas six cases have already been reported in Japan, and ours described herein constitute an eighth and ninth. Eight of the total of nine cases of clear-cell syringoma were associated with diabetes mellitus. In this report, we summarize these nine cases and emphasize the close relationship between clear-cell syringoma and diabetes mellitus.

Adenoma↗

In vitro transformation by bovine papillomavirus.

We have studied tumorigenic transformation of mouse tissue culture cells by bovine papillomavirus (BPV) as a model of papillomavirus-induced cell proliferation. When BPV or its 7.9-kb full-length viral DNA genome induces focal transformation of mouse calls, the viral DNA is maintained in the transformed cells as multiple extrachromosomal copies. The transforming capacity was initially localized to a 69% subgenomic fragment of the viral DNA genome. We have further characterized the BPV DNA sequences that can encode the transforming function by generating and analyzing the transforming activity of a series of BPV DNA deletion mutants. The results indicated that two discontinuous segments of the viral DNA are required for transformation. One segment, near the 5' end of the 69% transforming fragment, probably represents a control element of the viral DNA. The second segment, which lies within the 3' end of the 69% fragment, encodes transforming sequences of the viral DNA. A retroviral control element (the long terminal repeat DNA. A retroviral control element (the long terminal repeat DNA of Harvey murine sarcoma virus) will activate the 2.3-kb segment at the 3' end of the 69% fragment to transform the mouse cells.

Animals↗

[Clinical significance of new tumor marker CA 125 in gynecological cancer--particularly usefulness in diagnosis of ovarian cancer].

A concentration in sera of a new antigen CA125 related to cancer of the ovary was measured by radioimmunoassay which used a monoclonal antibody, and its usefulness as a tumor marker in the diagnosis of cancer of the ovary was investigated. The mean values for CA125 in sera of healthy controls (80 females) were 14.2 +/- 12.2 U/ml. Mean values for CA125 in sera of various patients were 29.0 +/- 39.6 for myoma uteri (30 cases), 26.7 +/- 30.1 for benign ovarian tumors (10 cases), 64.4 +/- 146.2 for cervical carcinoma (14 cases), and 31.5 +/- 19.8 for endometrial carcinoma (6 cases), whereas the mean values for ovarian cancers (23 cases) were as high as 311.3 +/- 250.4. On the other hand, positive rates for CA125, when the cut-off value was set to 65 U/ml, were 1.3% for healthy controls (1 out of 80 cases), 10.0% for myoma uteri (3 out of 30 cases), 10.0% for benign ovarian tumors (1 out of 10 cases), 14.3% for cervical carcinoma (2 out of 14 cases), and 16.7% for endometrial carcinoma (1 out of 6 cases), whereas the positive rate for ovarian cancers was 78.3% (18 out of 23 cases). Especially for serous cystadenocarcinoma, the positive rate was 100% (10 out of 10 cases). From the above, the measurement of CA125 in sera was considered to be significant in the diagnosis of ovarian cancer.

Adolescent↗

Antinuclear antibodies in localized scleroderma.

When HeLa cells were used as the substrate for detection by the indirect immunofluorescence method, antinuclear antibodies were demonstrated in 16 of 22 (72.7%) sera from patients with localized scleroderma. When mouse kidney sections were used, the positive rate for antinuclear antibodies was 50% (11 of 22). In the 3 subgroups of localized scleroderma, frequencies of antinuclear antibodies on HeLa cells were as follows: morphea, 50% (2 of 4), generalized morphea, 100% (6 of 6), linear scleroderma, 67% (8 of 12). Antibodies to centromere, Scl-70, nuclear RNP, Sm, and SS-B antigens were not detected in any patients with localized scleroderma. The high frequency of antinuclear antibodies in localized scleroderma sera suggests that localized scleroderma is a disease which, though different from diffuse scleroderma, also involves an immunologic abnormality.

Adolescent↗