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Biomedical subjects

Y Segawa

Publications and source records attributed to Y Segawa.

At least 91 records · Page 5Linked to original sources
PubMed1994

Histomorphological confirmation of the preventive effect of beta-alanyl-L-histidinato zinc on bone loss in ovariectomized rats.

The effect of beta-alanyl-L-histidinato zinc (AHZ), in which zinc is chelated to beta-alanyl-L-histidine, on bone loss was investigated in the femur of ovariectomized rats. AHZ (10, 30 and 100 mg/kg/d) was orally administered to ovariectomized rats for 3 months. Ovariectomy significantly decreased the estradiol concentration in the serum as compared with that from sham-operated rats. This decrease was not altered by the dose of AHZ. The bone ash weight and mineral density in the femur of ovariectomized rats significantly decreased in comparison with those from sham-operated rats. Moreover, the trabecular bone at the femoral metaphysis was clearly decreased by ovariectomy. The decreases in the femoral ash content and mineral density and the metaphyseal trabecular bone were clearly prevented by the tested doses of AHZ (10, 30 and 100 mg/kg/d). The present finding with histomorphological study further supports the view that the administration of AHZ can prevent bone loss by ovariectomy.

Administration, Oral↗
PubMed1994

Antiallergic effect of ZCR-2060: antihistaminic action.

The antihistaminic effect of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate (ZCR-2060), a newly synthesized antiallergic agent, was investigated in both in vitro and in vivo studies. ZCR-2060 clearly antagonized histamine-induced contraction of isolated guinea pig ileum and trachea. In contrast, carbachol-, BaCl2- and 5-hydroxytryptamine-induced contractions of isolated guinea pig ileum were slightly inhibited by higher concentrations of ZCR-2060. 3H-Mepyramine specific binding to membranes from guinea pig lung and brain were markedly inhibited by ZCR-2060 in a concentration-dependent fashion. In the in vitro studies, the antihistaminic effect of ZCR-2060 was greater than those of cetirizine and terfenadine, but was less than that of ketotifen. In the in vivo studies, ZCR-2060 significantly inhibited the histamine-induced cutaneous reaction in rats, when administered orally 1 hr before the histamine injection. Moreover, ZCR-2060 has a long-lasting antihistaminic effect. In the in vivo studies, the antihistaminic effect of ZCR-2060 was found to be greater than that of cetirizine and terfenadine, and it was the same as that of ketotifen. Thiopental-induced sleep and spontaneous ambulatory activity in mice, however, were unaffected by ZCR-2060 at higher doses. These results indicate that ZCR-2060 has a potent, selective and long acting histamine H1-receptor antagonistic action without causing any unwanted CNS side effect.

Animals↗
PubMed1994

Antiallergic effects of ZCR-2060: effect on allergic cutaneous reactions and rhinitis models in mice and rats.

The antiallergic action of 2-[2-[4-(diphenylmethyl)-1-piperadinyl] ethoxy] benzoic acid maleate (ZCR-2060) was investigated on allergic cutaneous reactions and nasal vascular permeability in mice and rats. ZCR-2060 markedly inhibited immediate allergic cutaneous reactions, including passive cutaneous anaphylaxis (PCA) in rats and mice; histamine-, compound 48/80- and calcium ionophore A 23187-induced cutaneous reactions in rats; and biphasic skin reactions mediated by monoclonal IgE antibody and epicutaneous challenge with antigen in mice, but did not affect 5-hydroxytryptamine-induced cutaneous reaction in rats. The antigen-induced nasal vascular permeability increase in actively and passively sensitized rats and histamine-induced nasal vascular permeability increase in rats (allergic rhinitis model) were clearly inhibited in a dose-dependent fashion by ZCR-2060. Moreover, ZCR-2060 significantly inhibited antigen-induced anaphylactic histamine release from rat peritoneal mast cells and carrageenin-induced paw edema in rats. These results suggest that ZCR-2060 has antiallergic effects on allergic cutaneous reactions and experimental rhinitis, probably due to histamine H1-receptor blockage and the inhibition of histamine release.

Animals↗
PubMed1994

[Efficacy and endocrinological analysis of combined buserelin-pure FSH-hCG therapy in patients with polycystic ovary syndrome].

The study was designed to investigate the efficacy of combined buserelin-pure FSH-hCG therapy in patients with polycystic ovary syndrome (PCO) and to analyse its underlying hormonal changes. Buserelin was intranasally administered daily to 13 patients (35 cycles) for 4-10 weeks with a mean week of 5.4 +/- 1.6 (SD), followed by concomitant pure FSH administration. Out of the 13 patients, 8 were the ones who had experienced ovarian hyperstimulation syndrome (OHSS) using pure FSH alone. Hormonal analyses were performed on these 8 patients. This combined regimen resulted in a 97.1% ovulation rate (34/35) and a 37.1% incidence rate of OHSS (13/35). In 4 out of the 8 patients who had experienced OHSS, no OHSS was observed in the first cycle of the therapy. Eight patients became pregnant with the therapy. Excluding one patient whose husband had oligozoospermia, 7 patients conceived at the first cycle of the therapy and the pregnancy rate per cycle was 25.0% (7/28). No abortion or multiple pregnancy was observed in any of the 8 cases. Pretreatment with buserelin resulted in significantly decreased serum LH, FSH, LH/FSH ratio, estradiol (E2), testosterone (T), and androstenedione (ASD). Serum E2, T and ASD levels at both preovulatory and midluteal phases were significantly lower with the combined regimen than with pure FSH alone. These results indicate that this combined regimen improves the characteristic endocrine profile of PCO and enables pure FSH to achieve ovulation regularly with a high pregnancy rate, although it does not always inhibit OHSS.

Adult↗
PubMed1994

[A clinical study on memory function in climacteric and periclimacteric women].

This study was designed to investigate memory function in climacteric and periclimacteric women who lived a normal, ordinary life. Two hundred women treated at the gynecological outpatient clinic of Koshigaya Hospital were divided into 7 groups: groups A(31-35 yr), B(36-40 yr), C(41-45 yr), D(46-50 yr), E(51-55 yr), F(56-60 yr) and G(61-65 yr). Each group consisted of 30 women except group G(n = 20). The memory function of each group was determined and the mean scores for 10 paired hard-associates after three trials of presentation were compared. The mean scores (+/- SD) for groups A and B were 8.0 +/- 2.0 and 8.2 +/- 1.7, respectively, which were not statistically different. The scores for both groups were significantly higher than those for the other groups (p < 0.01). The mean scores for groups C and D were 5.9 +/- 2.1 and 5.6 +/- 2.4, respectively, which were not statistically different. The score for group C was significantly higher than those for groups E(4.5 +/- 2.4), F(4.2 +/- 2.2), and G(3.3 +/- 1.6) (p < 0.05). The score for group D was significantly higher than those for groups F and G(p < 0.05). The score for group E was significantly higher than that for group G(p < 0.01). The decrease in memory function was the greatest in group C. In the climacterium, memory impairment was also observed in group E. The former corresponds to the climacteric commencement age group where cyclic changes in serum estrogen levels decrease or cease, and the latter corresponds to the age group for menopause.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Comparative study of prophylactic cranial irradiation in patients with small cell lung cancer achieving a complete response: a long-term follow-up result.

Between 1981 and 1986, a total of 46 patients with small cell lung cancer (SCLC) achieving a complete response by chemotherapy with or without chest irradiation were randomized either to receive prophylactic cranial irradiation (PCI) or not. With a median follow-up time of 8.5 years for both groups, only five of 23 patients (22%) in the PCI group developed brain relapse, while 12 out of 23 (52%) in the no PCI group did so (P < 0.05). The frequency of patients developing a sole brain relapse during their whole clinical course was 4% for the PCI group and 17% for the no PCI group, however, the difference was not statistically significant. Patient survival was better for the PCI group (median survival time of 21 months, and 5-year survival rate of 22%) as compared with the no PCI group (median survival time of 15 months, and 5-year survival rate of 13%), showing a marginal significance (P = 0.097). Late neurologic toxicity was infrequent; only one developed a mild deterioration among seven long-term disease-free survivors in the PCI group. These results appear to warrant further clinical trials to clarify the utility of PCI in patients with SCLC achieving a complete response.

Adult↗
PubMed1993

Beta-alanyl-L-histidinato zinc enhances various bone-regulating factors' effects on bone alkaline phosphatase activity in tissue culture.

The present investigation was undertaken to clarify the interaction of beta-alanyl-L-histidinato zinc (AHZ) and other bone-regulating factors on bone alkaline phosphatase in tissue culture. Calvariae were removed from weanling rats (3-week-old males) and cultured for periods up to 48 h in Dulbecco's modified Eagle medium. The experimental cultures contained 10(-5) mol/l AHZ which reveals in maximum effect on bone formation. Bone alkaline phosphatase activity was significantly increased by the presence of AHZ (10(-5) mol/l), insulin (10(-8) mol/l), sodium fluoride (10(-2) mol/l), aluminium sulfate (2 x 10(-3) mol/l), while the enzyme activity was not altered by estradiol (10(-9) mol/l), calcitonin (3 x 10(-8) mol/l), hydrocortisone (10(-8) mol/l), indomethacin (10(-6) mol/l) and imidazole (10(-3) mol/l). The presence of AHZ (10(-5) mol/l) clearly enhanced the calcitonin-, sodium fluoride- or diltiazem-increased bone alkaline phosphatase activity. Meanwhile, AHZ did not interact for the effects of other hormones and reagents. Moreover, the presence of cycloheximide (10(-6) mol/l), an inhibitor of protein synthesis, completely blocked the enhancement of bone alkaline phosphatase activity by AHZ. These findings suggest that AHZ has an effect different from bone cellular response for other bone-regulating factors, and that bone protein synthesis was a necessary component for AHZ action.

Alkaline Phosphatase↗
PubMed1993

Preventive effect of beta-alanyl-L-histidinato zinc on the deterioration of bone metabolism in ovariectomized rats.

The preventive effect of beta-alanyl-L-histidinato zinc (AHZ) on the deterioration of bone metabolism was investigated in the femoral diaphysis of ovariectomized rats. AHZ (10, 30 and 100 mg/kg body weight/d) was orally administered to ovariectomized rats for 6 weeks. Ovariectomy produced a significant decrease in estradiol, calcitonin, calcium and inorganic phosphorus concentrations in the serum as compared with those from sham-operated rats. The dose of 30 and 100 mg AHZ/kg prevented any decrease in serum inorganic phosphorus concentration caused by ovariectomy. Alkaline phosphatase activity, deoxyribonucleic acid (DNA) and calcium contents in the femoral diaphysis of ovariectomized rats significantly decreased in comparison with those from sham-operated rats. These decreases were completely prevented by the dose of AHZ (10, 30 and 100 mg/kg). Electron microscopical analysis showed a rough alteration of bone matrix in the femoral diaphysis of ovariectomized rats. This alteration was clearly modified by the doses of AHZ (10, 30 and 100 mg/kg). Also, dosages of AHZ (30 and 100 mg/kg) restored the atrophy of osteoblasts and cartilage cells caused by ovariectomy. The present study suggests that oral administration of AHZ can prevent the deterioration of bone metabolism by ovariectomy. AHZ may have a therapeutic role in the treatment of osteoporosis.

Alkaline Phosphatase↗
PubMed1993

Effect of beta-alanyl-L-histidinato zinc on bone metabolism in rats with adjuvant arthritis.

The effect of a new zinc compound, beta-alanyl-L-histidinato zinc (AHZ), on osteopenia was investigated in rats with adjuvant arthritis. Arthritis was induced in female rats by administering 1% Mycobacterium butyricum (MB) into the subplantar surface of the right hind paw. AHZ (10, 30 and 100 mg/kg body weight) was orally administered to MB-treated rats 28 times at 24-h intervals, and the rats were bled 24 h after the last administration. Treatment with MB caused a remarkable increase in paw volume and a corresponding decrease in the ratio of albumin per globulin in serum, indicating that the treatment induces inflammation. These alterations were not significantly changed by the administration of AHZ (10, 30 and 100 mg/kg). Serum calcium and zinc concentrations are significantly decreased in rats with adjuvant arthritis. These decreases were completely restored by the administration of AHZ (30 and 100 mg/kg). Furthermore, the inflammation-induced decreases in alkaline phosphatase activity and calcium content in the femoral diaphysis were clearly blocked by the administration of AHZ (30 and 100 mg/kg). Also, the larger doses of AHZ (30 and 100 mg/kg) produced a significant increase in femoral-diaphyseal deoxyribonucleic acid and in the zinc content in rats with adjuvant arthritis. These results suggest that AHZ has a stimulating effect on bone formation in the femoral diaphysis of rats with adjuvant arthritis, although the compound did not have an anti-arthritic effect.

Alkaline Phosphatase↗
PubMed1993

Antitumor activity of platinum analogs against human lung cancer cell lines and tumor specimens.

Antitumor activities of five platinum analogs, including cisplatin, carboplatin, 254-S, DWA2114R, and NK121, were compared using five human lung cancer cell lines and 19 tumor specimens obtained from lung cancer patients. The antitumor activity was evaluated by determining the ratio of the maximum tolerated dose of each drug to the 70% tumor growth inhibitory concentration in a colony assay. Cisplatin was the most potent agent, followed by 254-S and carboplatin. DWA2114R and NK121 were less potent than cisplatin and 254-S. Cross-resistance to adriamycin was also investigated using an adriamycin-resistant small cell lung cancer subline, SBC -3/ADM30. SBC-3/ADM30 was 1.7- to 4.0-fold more resistant to cisplatin, carboplatin, NK121, and DWA2114R, than was the parent line, SBC-3, and the subline was 2.0-fold more sensitive to 254-S. Using SBC-3, in vitro combination effects of etoposide and cisplatin, carboplatin, or 254-S were evaluated by the median-effect principle. Synergism was noted when cisplatin and etoposide were combined at a fixed molar ratio of 1:1. Combination of carboplatin and etoposide showed an additive effect. The combination of 254-S and etoposide was antagonistic at low concentrations, but was markedly synergistic at higher concentrations. These data suggested the efficacy of 254-S in the treatment of lung cancer.

Antineoplastic Agents↗
PubMed1993

Neural cell adhesion molecule expression and clinical features in small cell lung cancer: a semi-quantitative immunohistochemical approach using an immunogold-silver staining method.

The neural cell adhesion molecule (NCAM) is a family of cell surface sialoglycoproteins mediating homotypic and heterotypic cell-cell adhesion. In tumors, NCAM is supposed to be involved with the malignant features characterized by invasive growth and metastasis. In the present study, we evaluated the correlation between NCAM expression of tumors obtained from small cell lung cancer (SCLC) patients and the clinical outcome. NCAM expression was determined semi-quantitatively by an immunogold-silver staining method using the SCLC cluster 1 monoclonal antibody NCC-LU-243. Of 20 SCLC patients studied, six patients with tumors with high NCAM expression had a poor response to chemotherapy, and a short disease-free (p = 0.011) and overall (p = 0.003) survival as compared with 14 patients having tumors with low NCAM expression. These findings indicate that the therapeutic outcome of SCLC may be partly predicted by determining the NCAM expression of the tumor.

Adult↗
PubMed1993

Immunohistochemical detection of P-glycoprotein and carcinoembryonic antigen in small cell lung cancer: with reference to predictability of response to chemotherapy.

In an attempt to elucidate the tumor properties relating to responsiveness to chemotherapy, we examined immunohistochemically the expression of P-glycoprotein (P-gp) and carcinoembryonic antigen (CEA) in small cell lung cancer (SCLC) tumors. Tumor specimens from 33 patients were obtained at the time of diagnosis and relapse. Four patients expressed P-gp in their initial tumors, and 7 others did in recurrent tumors. The overall response rate to chemotherapy of the initial tumors was 75% for P-gp-positive initial tumors and 86% for P-gp-negative tumors, whereas the disease-free and overall survival times were significantly shorter in the former than the latter. Three patients showed CEA in their initial tumors, and 5 others did in recurrent tumors. The patients with CEA-positive initial tumors tended to relapse earlier than those with CEA-negative tumors. In addition, recurrent tumors expressing CEA were resistant to salvage chemotherapy. A clear correlation between CEA expression by tumors and the CEA level in the serum was observed at diagnosis as well as at relapse. These findings indicate that P-gp and/or CEA expression by a tumor and elevated CEA level in the serum may predict refractoriness of the tumor to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Long-term results of combination chemotherapy with or without irradiation in small cell lung cancer: a 5- to 11-year follow-up.

Between April 1981 and December 1987, 148 patients with newly diagnosed small cell lung cancer (SCLC) were treated using combination chemotherapy with or without thoracic irradiation and prophylactic cranial irradiation (PCI) in a series of cooperative therapeutic trials. With a minimum follow-up of 4.7 years, 13 (9%) patients survived and were free of SCLC. These included 11 (15%) of 76 patients with limited disease and two (3%) of 72 patients with extensive disease. Three died without any evidence of SCLC (one each from second leukemia, non-small cell lung cancer, and unrelated disease). The remaining 10 (7%) patients are currently alive and free of SCLC beyond 4.7 years. Since late relapse beyond 5 years is a very rare event, these patients may have been cured. However, late toxicity of PCI must be kept in mind. Three among the 10 patients have suffered from neuropsychologic symptoms of varying degrees in severity. Although the long-term survival rate is a benchmark in the treatment of SCLC, modifications of therapy that may potentially avoid such toxicities should be considered hereafter.

Aged↗
PubMed1993

[In vitro comparison of podophyllotoxin analogues; etoposide, teniposide and NK 611 using human lung cancer cell lines].

In an attempt to predict the antitumor activity of a new podophyllotoxin analogue, NK 611, in the treatment of lung cancer, we compared the drug with etoposide and teniposide using four human small cell lung cancer (SCLC) cell lines, SBC-2, -3, -4, -7, and two non-small cell lung cancer cell lines, ABC-1, EBC-1. In terms of the fifty percent tumor growth inhibitory concentration (IC 50) determined by MTT assay, teniposide was most potent among the drugs. The degree of cross-resistance of each drug was investigated using an etoposide-resistant SCLC subline (SBC-3/ETP), an adriamycin-resistant subline (SBC-3/ADM 100), and a cisplatin-resistant subline (SBC-3/CDDP). As for relative resistant (the ratio of IC 50 for resistant subline to that for the parent subline), NK 611 was least cross-resistant to etoposide, adriamycin, and cisplatin among drugs tested. These results indicate that NK 611 may play a role in a salvage chemotherapy for patients with resistant SCLC.

Adenocarcinoma↗