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Biomedical subjects

S Sakamoto

Publications and source records attributed to S Sakamoto.

At least 379 records · Page 21Linked to original sources
PubMed1992

Suppression of the development of uterine adenomyosis by danazol treatment in mice.

Inhibitory effects of danazol, an isoxazol derivative of synthetic steroid 17 alpha-ethinyl-testosterone, on the development of uterine adenomyosis, a pathological disorder of endometrial tissue defined as the presence of endometrial glands and stroma in the myometrium, were investigated in mice of SHN strain. Mice treated with 0.5 microgram danazol for 5 weeks during 4-9 weeks of age and killed at 21 weeks of age showed significantly lower incidence of the spontaneous development of adenomyosis than the age-matched intact control mice. The inhibitory effects of danazol were also evident in mice bearing pituitary isografts which were effective in inducing an early and a high incidence of adenomyosis. Furthermore, the treatment with danazol resulted in the decrease of serum levels of luteinizing hormone (LH) and prolactin (PRL) associated with hypofunction of ovaries and persistent diestrus. These results support the usefulness of danazol for the clinical treatment of gynecological disorders except for hypofunction of ovaries.

Animals↗
PubMed1992

Triterpenoid saponins from Sophora subprostrata.

From Sophora subprostrata Radix, the roots of Sophora subprostrata, six triterpenoidal saponins having soyasapogenol A, B, sophoradiol and kuzusapogenol A as aglycones, were isolated as their methyl esters. The structure of a new saponin was established to be 3-O-[alpha-L-rhamnopyranosyl(1----2)-D-galactopyranosyl(1----2)-beta-D- glucuronopyranosyl] kuzusapogenol A methyl ester by means of 1H and 13C NMR spectroscopy and chemical evidence.

Carbohydrate Sequence↗
PubMed1992

Saponins from Trifolium repens.

From the whole plant of white clover, Trifolium repens, five new triterpenoid saponins, designated cloversaponins I-V, were isolated together with four known saponins, beta-D-glucoronopyranosylsoyasapogenol B, soyasaponin I, soyasaponin II and azukisaponin II as their methyl esters. Their structures were determined by 2H NMR and 13C NMR spectroscopy and chemical evidence.

Carbohydrate Sequence↗
PubMed1992

Activities of thymidylate synthetase and thymidine kinase in gastric cancer.

In a previous clinical study, sequential methotrexate and 5-fluorouracil has shown improved efficacy for treating advanced gastric cancer of the poorly differentiated type. In this study, we investigated whether difference in the levels of thymidylate synthetase (TS) and thymidine kinase (TK) activities in gastric cancer tissue account for selectivity of the treatment. Activity of TS was higher in 19 cases of the poorly differentiated type than in 16 cases of the well differentiated type (P < 0.02), whereas TK activity was lower in the poorly differentiated type than in the well differentiated type (P < 0.01). Thus, the TS/TK ratio was significantly higher in poorly differentiated gastric cancers than in well differentiated cancers (P < 0.001). These results suggest that a greater dependence upon the de novo pathway of pyrimidine synthesis in poorly differentiated gastric carcinomas may enhance the efficacy of sequential methotrexate and 5-fluorouracil treatment.

Adenocarcinoma↗
PubMed1992

The effects of ICRF-154 in combination with other anticancer agents in vitro.

We studied the effects of ICRF-154 in combination with 11 anticancer agents on four human leukaemia cell lines. Cells were incubated for 3 days in the presence of two drugs (ICRF-154 and one other), and cell growth inhibition was determined by MTT assay. Effects of drug combinations at the ID50 level were analysed using the isobologram method (Steel). In the lymphoblastic leukaemia cell lines, MOLT-3, HSB, and B-ALL, supra-additive effects were observed for ICRF-154 in combination with amsacrine, bleomycin, doxorubicin, and etoposide. Additive effects were observed for its combinations with cisplatin, CPT-11, cytosine arabinoside, 5-fluorouracil, mitomycin C, and vincristine. Sub-additive to protective effects were observed in combination with methotrexate. In an erythroleukaemia cell line, K-562, no drug showed supra-additive effects with ICRF-154, while sub-additive to protective effects were observed for ICRF-154 in combination with cisplatin and methotrexate. The other drugs showed additive effects with ICRF-154. These results indicate that the combined effects of ICRF-154 with other agents vary, depending on the cell line. Against lymphoid malignancies, ICRF-154 would be advantageous when administered simultaneously with many anticancer agents. Of such agents, amsacrine, bleomycin, doxorubicin, and etoposide are the most suitable, while methotrexate is least suitable for such combined treatment.

Antineoplastic Agents↗
PubMed1992

Effects of carcinogenesis on colonic thymidine kinase activity in familial adenomatous polyposis.

Thymidine kinase (TK) activity of polyp tissue from patients with familial adenomatous polyposis (FAP) was measured and compared with that of non-tumorous colon, sporadic polyp and colorectal carcinoma tissues. Total TK activity in colonic carcinoma was 3-fold that of non-tumorous colon; its increase seems attributable mainly to increased activity of cytosolic TK isozyme activity. By using DEAE-cellulose column chromatography, the colorectal TK isozymes were separated into two types, i.e. two isozymes, referred to as the fetal (predominantly cytosolic) and adult (predominantly mitochondrial) types. However, FAP polyp samples from 15 patients showed an average elevation of only 1.8-fold over non-tumorous region of colon. Examined individually, only 5 of the 15 FAP samples showed significant elevations in total TK activity. Furthermore, TK isozyme analysis revealed variable patterns of the cytosolic isozyme activity, which was elevated in some cases (8/15) and remained low in others. Thus FAP polyps seem to be a heterogeneous population with respect to DNA replicative activity, and cytosolic TK isozyme activity may constitute a biochemical marker for the subsequent development of colorectal carcinoma in FAP.

Adenomatous Polyposis Coli↗
PubMed1992

Involvement of arachidonate cyclooxygenase products in bronchial hyperresponsiveness induced by subthreshold concentration of aerosolized thromboxane A2 analogue (STA2) in guinea pigs.

Effects of a thromboxane synthetase inhibitor (OKY-046) and a cyclooxygenase inhibitor (indomethacin) on bronchial hyperresponsiveness induced by subthreshold concentration of aerosolized thromboxane A2 analogue (STA2) were investigated in anesthetized, artificially ventilated guinea pigs in order to examine the role of the cyclooxygenase pathway in bronchial hyperresponsiveness. Pretreatment with aerosolized OKY-046 significantly inhibited the bronchial hyperresponsiveness to histamine, but pretreatment with intravenous indomethacin showed a tendency to potentiate bronchial hyperresponsiveness. These results suggest that subthreshold concentration of thromboxane A2 contributes to bronchial hyperresponsiveness through activating the cyclooxygenase pathway including thromboxane A2 synthesis, and that the released cyclooxygenase products have an inhibitory effect on the bronchial hyperresponsiveness in guinea pigs.

Aerosols↗
PubMed1992

Effects of methacholine induced bronchoconstriction and procaterol induced bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric acid.

BACKGROUND: The direct effect of bronchoconstriction on cough receptor sensitivity is unknown, and the antitussive effect of beta 2 adrenergic agonists in man has been controversial. This study was designed to throw light on these questions. METHODS: The threshold of the cough response to inhaled capsaicin, a stimulant acting on C fibre endings, and tartaric acid, a chemostimulant, was measured before and 10 minutes after inhalation of methacholine, which caused a nearly 20% fall in forced expiratory volume in one second (FEV1), in 14 normal subjects (study 1), and also before and 30 minutes after inhalation of procaterol (30 micrograms), placebo, and saline in eight normal subjects (study 2). Progressively increasing concentrations of capsaicin and tartaric acid solutions were inhaled for 15 seconds by mouth tidal breathing at one minute intervals and cough threshold was defined as the lowest concentration of capsaicin and tartaric acid that elicited five or more coughs. RESULTS: In study 1 the geometric mean values of the cough threshold of response to capsaicin and tartaric acid before methacholine callenge, 2.98 (GSE 1.30) micrograms/ml and 46.6 (1.22) mg/ml, were not significantly different from those of the response to methacholine inhalation, 3.45 (1.33) micrograms/ml and 32.9 (1.37) mg/ml. In study 2 the geometric mean value of the cough threshold of response to capsaicin before inhalation of procaterol (4.61 (GSE 1.84) micrograms/ml) was not different from that after inhalation of procaterol (4.61 (GSE 1.84) micrograms/ml), which had significant bronchodilator effects. The cough threshold was not altered by placebo or saline. CONCLUSIONS: These findings suggest that muscarinic receptor stimulation, bronchoconstriction, beta 2 receptor stimulation, or bronchodilation might have no direct effect on the sensitivity of the cough receptors in normal subjects.

Adult↗
PubMed1992

Pharmacotherapeutic effects of kuei-chih-fu-ling-wan (keishi-bukuryo-gan) on human uterine myomas.

Kuei-chih-fu-ling-wan (Keishi-bukuryo-gan; KBG), a traditional Chinese herbal remedy contains five components: bark of Cinnamomum cassia Bl. (Lauraceae), root of Paeonia lactiflora Pall. (Paeoniaceae), seed of Prunus persica Batsch. or P. persiba Batsch.var.davidiana Maxim. (Rosaceae), carpophores of Poria cocos Wolf. (Polyporaceae), and root bark of Paeonia suffruticosa Andr. (Paeoniaceae). This prescription has been frequently used in the treatment of gynecological disorders such as hypermenorrhea, dysmenorrhea and sterility. We previously reported that KBG might act as a LH-RH antagonist and a weak anti-estrogen on the uterine DNA synthesis in immature rats. In the present study, we investigated the effects of KBG on 110 premenopausal patients with uterine myomas. Clinical symptoms of hypermenorrhea and dysmenorrhea were improved in more than 90% of the cases with shrinking of uterine myomas in roughly 60% of the cases.

Adult↗
PubMed1992

Hepatocellular carcinoma not detected with plain US: treatment with percutaneous ethanol injection under guidance with enhanced US.

To evaluate the usefulness of contrast material-enhanced ultrasound (US) in detection and treatment of hepatocellular carcinoma (HCC), carbon dioxide was injected as a contrast agent into the hepatic artery in 22 patients with HCC. Plain US had enabled detection of 24 HCC nodules in these patients. Contrast material-enhanced US enabled detection of seven additional nodules, which were confirmed as HCC by means of fine-needle aspiration biopsy performed under guidance with contrast-enhanced US. Six of these seven nodules were detected incidentally during examination of other suspected HCC nodules. Five of the seven nodules were treated with percutaneous ethanol injection (PEI) performed under guidance with contrast-enhanced US; the two other nodules were resected. Contrast-enhanced US made the HCC lesions visible for 15-60 minutes, sufficient time to mark the nodule with an iodized oil-ethanol solution for PEI. Because contrast-enhanced US enabled detection of additional nodules and performance of PEI in lesions not detected with plain US, it may help improve the treatment of HCC.

Adult↗
PubMed1992

Increase of DNA synthesis in uterine adenomyosis in mice with ectopic pituitary isograft.

Ectopic pituitary isografts (EPI) have been found to induce a high incidence of uterine adenomyosis in SHN mice. All the SHN mice given EPI in the right uterus at 40 days of age developed uterine adenomyosis, and more than 80% of mice showed the genesis of subserosal nodules, an advanced state of adenomyosis, 65 days after EPI. Activities of both thymidylate synthetase and thymidine kinase, i.e. DNA-synthesizing enzymes in de novo and salvage pathways of pyrimidine metabolism, respectively, were significantly increased in EPI-induced uterine adenomyosis to approximately 2-fold those in normal control uteri. Bromodeoxyuridine-immunoreactive cells were regarded as the cells in S phase, and the number in the endometrial epithelium and stroma in EPI-induced uterine adenomyosis was more than 1.5-fold that in normal control uteri. EPI may affect the genesis of uterine adenomyosis generally, but not locally, because there were no differences between the right uterus with EPI and the left without EPI in the incidence of adenomyosis, histology or DNA-synthesizing enzyme activities.

Animals↗
PubMed1992

Effects of insulin-like growth factor-II on proliferation and differentiation of ovarian granulosa cells.

The effects of insulin-like growth factor-II (IGF-II) on the proliferation and differentiation of ovarian granulosa cells were studied in cultured human and porcine granulosa cells. IGF-II significantly increased basal progesterone secretion in granulosa cells at concentrations of 1-100 ng/ml. A stimulatory effect was also observed in gonadotropin-stimulated porcine granulosa cells treated with IGF-II. The secretion of estradiol by basal and gonadotropin-stimulated porcine granulosa cells was also significantly increased by adding IGF-II. IGF-II led to dose-dependent increases in [3H]thymidine incorporation into DNA and in the number of granulosa cells. To further characterize the cellular mechanisms underlying the stimulatory effects of IGF-II on the proliferation and differentiation of granulosa cells, we investigated the intermediary roles of cyclic AMP and intracellular Ca2+ concentration ([Ca2+]i). Treatment with 100 ng/ml IGF-II produced a significant increase in the basal accumulation of cyclic AMP in porcine granulosa cells. However, no change of [Ca2+]i by IGF-II was noted. IGF-II produced effects in accumulation that were similar to those of IGF-I. Our findings suggest that IGF-II may be a general stimulator in the proliferation and differentiation of granulosa cells, and that cyclic AMP may be a second messenger for the effects of IGF-II in ovarian granulosa cells.

Animals↗
PubMed1992

Striosomal organization of substance P-like immunoreactivity in parkinsonian patients.

We designed this study to evaluate the expression of substance P (SP) in the striatum and the globus pallidus in normal controls, idiopathic Parkinson's disease (PD), and striatonigral degeneration (SND). We determined immunohistochemically the expression of SP in formalin-fixed, paraffin-embedded brain tissues using the free-floating method. In normal controls, we observed SP-like immunoreactivity in the internal segment of the globus pallidus, where the SP-positive fibers showed typical "woolly fiber" patterns. SP expression in the striatum had the characteristic patchwork of striosomes. Patients with PD showed the normal distribution pattern of SP. By comparison, in patients with SND, there was a striking diminution of SP in the putamen, while the SP-positive patches persisted in the caudate nucleus. This study represents the first unequivocal immunohistochemical demonstration of SP-positive striosomes in the human striatum.

Aged↗
PubMed1992

Thymidine kinase activity in familial adenomatous polyposis.

Thymidine kinase (TK) activity of polyp tissue from patients with familial adenomatous polyposis (FAP) was measured and compared with that of normal colon, sporadic polyp and colorectal carcinoma tissues. Total TK activity in colonic carcinoma was 3-fold that of normal; this increase seems attributable mainly to increased activity of cytosolic TK isozyme activity; the colorectal TK isozymes were separated into two types, i.e., fetal type and adult type isozymes predominantly in, respectively, cytosolic and mitochondrial fractions, by DEAE-cellulose column chromatography. However, FAP polyp samples from 15 patients showed an average elevation of only 1.8-fold over normal. Examined individually, only 5 of the 15 FAP samples showed significant elevations in total TK activity. Furthermore, TK isozyme analysis revealed variable patterns of the cytosolic isozyme activity being elevated in some cases (8 of 15) and remaining low in others. Thus FAP polyps seem to be a heterogenous population with respect to DNA replicative activity, and cytosolic TK isozyme activity may constitute a biochemical marker for the subsequent development of colorectal carcinoma in FAP.

Adenomatous Polyposis Coli↗
PubMed1992

Cough threshold to inhaled tartaric acid and bronchial responsiveness to methacholine in patients with asthma and sino-bronchial syndrome.

To evaluate the effect of chronic airway inflammation on cough sensitivity and bronchial responsiveness, we measured the cough threshold to tartaric acid and bronchial responsiveness to methacholine (PC20-FEV1) in 13 asthmatic, 13 bronchitic (sino-bronchial syndrome) and 49 healthy non-atopic subjects. All subjects were non-smokers. The geometric mean value of the cough threshold was 9.55, 5.62 and 12.3% in asthmatic, bronchitic and normal subjects, respectively. The value in bronchitic subjects was significantly (p less than 0.02) lower than that in normal subjects. The geometric mean value of PC20-FEV1 in asthmatic subjects (0.63 mg/ml) was significantly lower than those in bronchitic (8.7 mg/ml) (p less than 0.01) and normal subjects (21.4 mg/ml) (p less than 0.01). There was no correlation between cough threshold and PC20-FEV1 values [correlation coefficient (r) = 0.06, p greater than 0.1]. These results indicate that cough sensitivity is potentiated by chronic airway inflammation in bronchitis but not in asthma and suggest that cough sensitivity and bronchial responsiveness may be independently potentiated by different mechanisms resulting from chronic airway inflammation.

Adult↗
PubMed1992

Two cases of acute myeloid leukemia evolving into a chronic myelomonocytic leukemia-like state after induction therapy.

Two patients with acute myeloid leukemia (AML) developed a chronic myelomonocytic leukemia (CMMoL)-like state after chemotherapy. Both patients showed morphological evidence of myelodysplasia together with acute leukemia at presentation (Case 1: M5b with trilineage myelodysplasia and Case 2: M4 with dysmegakaryocytopoiesis). They also showed persistent monocytosis without prominent blast cell proliferation after induction therapy. The possibility was suggested that these two patients were in acute transformation from CMMoL at presentation and returned to a CMMoL-like state after induction therapy.

Aged↗