Search PubMed⌕ Search

Biomedical subjects

K Morimoto

Publications and source records attributed to K Morimoto.

At least 307 records · Page 17Linked to original sources
PubMed1995

[Effect of progesterone, cortisol and dehydroepiandrosterone-sulfate on prostaglandin production by cultured human myometrial cells].

Prostaglandins (PGs) are considered to play important roles as contraction regulating factors in the mechanism of human uterine contraction. On the other hand, steroid hormones released in large amounts in late pregnancy appear to be closely related to the maintenance of pregnancy, fetal growth, and onset of delivery. To clarify the interactions between PGs and steroid hormones, we studied PGE2 and 6-keto-PGF1 alpha production on human myometrial cell culture. Cultures of myometrial cells from premenopausal patients with benign uterine diseases were established, and PG production in serum-free media and in the presence of various concentrations of progesterone (P), cortisol (F) and dehydroepiandrosterone-sulfate (DHAS) was studied. The following results were obtained: 1) The PGE2 and 6-keto-PGF1 alpha concentrations were 1,410.4pg/ml and 600pg/ml at 10 minutes after changing the medium, decreased transiently at 30-60 minutes, and increased thereafter. 2) When the cells were cultured with various concentration of P for 24 hours, PGE2 production was suppressed in the presence of P at 10(-7)M or above, but 6-keto-PGF1 alpha production showed a significant dose-dependent increase. 3) In the presence of F, PGF2 production shows a dose-dependent increase at high doses, but 6-keto-PGF1 alpha production markedly decreases at 10(-6)M or above. 4) In the presence of DHAS, PGE2 production increased markedly at 10(-6)M or above. These findings indicate that steroid hormones are regulatory factors in the production of PG by the myometrium.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

[The mechanism of beta-receptor desensitization in human myometrial culture cell].

Beta-adrenoceptor desensitization is considered to be primarily due to phosphorylation of receptors by protein kinase A (PKA) and beta-adrenaline receptor kinase (beta-ARK) and sequestration of receptors themselves. But in the human uterine muscle, the desensitization mechanism has been evaluated only as a phenomenon, and there are few studies on its mechanism. We evaluated cAMP production by beta-agonist and changes in the number of beta-receptors in cultured human myometrial cells. Uterine muscle cell were obtained from patients with benign disease before menopause and cultured. 1) At the confluent stage, dl-Isoproterenol Hydrochloride (ISP) was added under various conditions, and the intracellular cAMP concentration was determined by EIA. 2) After the addition of ISP (10(-6) M), plates were incubated at 37 degrees C, and beta-AR on the cell membrane surface (S beta-AR) and total beta-AR (T beta-AR) was measured in a binding assay with 125I-pindolol. The production of cAMP dose-dependently increased 30 minutes after the addition of ISP at 10(-6) M or higher, but rapidly decreased thereafter. T beta-AR was similar in the cells treated with ISP (10(-6) M) and the untreated cells. On the other hand, S beta-AR decreased by about 50% in the ISP treated cells. These result suggest the desensitization of beta-AR in human uterine muscle, and the involvement of the sequestration mechanism as its cause.

Cells, Cultured↗
PubMed1995

[A dose-comparative study on TAP-144-SR, an LH-RH agonist depot formulation, in premenopausal patients with advanced or recurrent breast cancer. TAP-144-SR Breast Cancer Study Group].

A comparative phase II study was performed with different doses of TAP-144-SR in ER-positive or ER-unknown premenopausal patients with advanced or recurrent breast cancer. One hundred and six patients were randomly allocated to either 3.75 mg or 7.5 mg treatment by a centralized telephone registration system. TAP-144-SR was administered sc at 4-week intervals for 12 weeks (a total of 3 injections). Ninety-five cases were evaluated with the response rate of 30.4% (14/46) in the 3.75 mg group and 24.5% (12/49) in the 7.5 mg group, respectively. Serum estradiol was decreased to postmenopausal level (< 30 pg/ml) within 3-4 weeks after the first dose in the both dose groups, and this suppression was maintained throughout the treatment period. The adverse reactions most frequently observed were climacteric disturbances like hot flashes which was likely to be due to the hypoestrogen status. In conclusion, there was no significant difference between both dose groups in terms of response rates, adverse effects, and hormonal suppression. Therefore, the lower dose is recommended for the further study.

Adult↗
PubMed1995

[Long-term clinical study on TAP-144-SR, an LH-RH agonist depot formulation, in premenopausal patients with advanced or recurrent breast cancer. TAP-144-SR Breast Cancer Study Group].

Efficacy and safety of long-term treatment with an LH-RH agonist, TAP-144-SR were studied in premenopausal patients with advanced or recurrent breast cancer. The drug was given sc every 4 week at the dose of 3.75 or 7.5mg. The best objective response rates were 37.0% (17/46) in 3.75mg group, 30.6% (15/49) in 7.5mg group, respectively. The median duration of 12 PR patients in 3.75mg group was 280 (range: 84-830+) days. Serum estradiol level was maintained at < 30pg/ml in most patients given 3.75mg or 7.5mg as scheduled. There was no adverse reactions specific to the longterm administration subsequent to the foregoing 12-week administration study in both dose groups. In conclusion, TAP-144-SR is expected to be one of the first line therapies for patients with premenopausal breast cancer.

Adult↗
PubMed1995

[Effects of lifestyle on health status].

We followed up 2,148 male and female workers for 6 years and assessed the relationship between lifestyle and physical health status. The physical health status was significantly higher in the group with a good lifestyle than in the group with a poor lifestyle. When we analyzed the effects of lifestyle on chronic diseases using multiple logistic regression, the incidence of gastric and duodenal ulcers and cardiovascular diseases was several times higher in the group with a poor lifestyle than in the group with a good lifestyle. We also introduced several biological markers, including natural killer (NK) cell activity and chromosome alterations such as sister chromatid exchanges, chromosome aberrations and micronucleus formation, to predict the participants' future health status. All these markers were significantly correlated with lifestyle. Our findings indicate that lifestyle is the most important environmental factor which quantitatively affects the development of adult diseases and the changes of biological markers.

Adult↗
PubMed1995

[Study on evaluating methods for the quality control of glycoprotein products. (1). Erythropoietin products].

The ability of high performance anion exchange chromatography (HPAEC) with pulsed amperometric detection was studied for evaluation of carbohydrate moieties of erythropoietin (EPO) products. The N-linked oligosaccharides were released from EPO by the treatment with N-glycosidase F. HPAEC analysis of oligosaccharide standards revealed that elution time of sialylated oligosaccharides were dependent on the number of sialic acid, which contributed to the activity of EPO. Using HPAEC, N-linked oligosaccharides of two kinds of recombinant human EPO (rhEPO) produced in chinese hamster ovary (CHO) cells and baby hamster kidney (BHK) cells were compared. The HPAEC profiles of oligosaccharides of these EPO products indicated that there were some differences in the carbohydrate moieties between CHO rh-EPO and BHK rh-EPO. In conclusion, HPAEC method is useful to evaluate the quality of EPO products.

Animals↗
PubMed1994

Calyculin A, a non-phorbol ester type tumor promotor, induced oxidative DNA damage in stimulated human neutrophil-like cells.

Calyculin A(CA) induced 8-hydroxydeoxyguanosine (8OHdG), typical of mutagenic oxidative DNA damage, in N-Formyl-Methionyl-Leucyl-Phenylalanine (FMLP)-stimulated dimethyl sulfoxide(DMSO)-differentiated HL60(DMSO-HL60), which has characteristics similar to those of human neutrophils. CA enhanced O2-generation in FMLP-stimulated DMSO-HL60. CA by itself neither induced 8OHdG nor O2-generation. FMLP by itself induced O2-generation, however, it did not induce 8OHdG. These findings suggest that CA exerts its tumor promotion activity through modulating O2-generation and through inducing oxidative DNA damage and that a common bioactive peptide induces oxidative DNA damage under a certain condition.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

Establishment of a human system that generates O2- and induces 8-hydroxydeoxyguanosine, typical of oxidative DNA damage, by a tumor promotor.

We have established a system in which a human cell line generated reactive oxygen species (ROS), using a dimethyl sulfoxide-differentiated promyelocytic leukemia cell line HL60 (DMSO-HL60), which has characteristics similar to those of human neutrophils. DMSO-HL60 generated O2- upon stimulation with a tumor promoter, phorbol myristate acetate (PMA). O2- generation, determined as O2- release from the PMA-stimulated cells by the reduction of cytochrome c, was dependent on the dose of PMA and reached almost maximal with 2.0 nM PMA. PMA dose-dependently increased 8-hydroxydeoxyguanosine (8OHdG) in DMSO-HL60, typical of mutagenic oxidative DNA damage. The 8OHdG level, determined by electrochemical detection with high performance liquid chromatography, also became almost maximal with 2.0 nM PMA. The amount of O2- generation and that of the 8OHdG induction by PMA in human neutrophils were similar to those in DMSO-HL60. Superoxide dismutase inhibited the 8OHdG induction by about 60%, whereas catalase, deferoxamine, or thiols inhibited it almost completely. Dilution of PMA-stimulated DMSO-HL60 decreased the concentration of ROS releasing to the media from the cells. However, it did not decrease the ROS generation per cell or the 8OHdG induction. The addition of H2O2 to unstimulated DMSO-HL60 did not increase the 8OHdG level. These findings indicate that DMSO-HL60 could be used as a substitute for human neutrophils, that the concentration of ROS is not the only determinant for the 8OHdG induction, but that it requires both acquisition of susceptibility to ROS by reduction of iron by O2- and formation of H2O2, and that ROS increase 8OHdG by attacking the ROS-generating cell.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

Preparation of F(ab')2 mu fragments from rat IgM monoclonal antibodies and their application to the enzyme immunoassay of mouse interleukin-6.

F(ab')2 fragments, herein designated as F(ab')2 mu, were prepared from rat IgM monoclonal antibodies (mAbs). The IgM was digested at a pepsin-to-IgM ratio of 1:200 (w/w) in 100 mM citrate buffer (pH 4.5) at 37 degrees C for 2 h. During digestion, the light (L) chain (27 kDa) of IgM remained undegraded, whereas the heavy (H) chain disappeared and two new bands of 44 and 48 kDa appeared. The digests were fractionated by means of hydrophobic interaction HPLC with TSKgel Phenyl-5PW. The fraction containing F(ab')2 mu was homogeneous and the recovery of antigen-binding activity was 41-52%. The molecular mass of F(ab')2 mu was estimated to be 147-153 kDa, and we concluded that the fragment was composed of two truncated H chains and two intact L chains. F(ab')2 mu was used in an enzyme immunoassay of mouse interleukin-6 and the interaction of IgM with non-specific proteins was greatly reduced, when it was converted to F(ab')2 mu fragments.

Animals↗
PubMed1994

Antiepileptogenic and anticonvulsant effects of NBQX, a selective AMPA receptor antagonist, in the rat kindling model of epilepsy.

To investigate the role of non-NMDA receptors in epileptic seizures, we examined the antiepileptogenic and anticonvulsant effects of NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline), a potent and selective AMPA receptor antagonist, in the rat kindling model. Systemic administration of 10-40 mg/kg NBQX significantly and dose dependently suppressed previously kindled seizures from the amygdala (AM), assessed in terms of the motor seizure stage and afterdischarge (AD) duration. The maximal effects were observed at 0.5-1 h after drug injection. When the intensity of electrical stimulation was increased to twice the generalized seizure-triggering threshold (GST), the anticonvulsant effects of NBQX on AM-kindled seizures were not reversed, suggesting that the effects were not due to non-specific elevation of the GST. In contrast to AM-kindled seizures, 20-40 mg/kg NBQX significantly suppressed only the motor seizure stage without reducing the AD duration of previously hippocampal-kindled seizures. Daily administration of 15 or 30 mg/kg NBQX prior to each electrical stimulation of the AM markedly and significantly suppressed the development of kindling. During drug sessions, the growth of the AD duration was blocked almost completely, while the waveform of ADs became more complex. These results indicate that NBQX has potent antiepileptogenic and anticonvulsant actions on kindling, at least from the AM and that non-NMDA receptors have an important role in seizure propagation.

Amygdala↗
PubMed1994

CD44 mediates hyaluronan binding by human myeloid KG1A and KG1 cells.

Hyaluronan-binding function of the CD44 molecule has not been so far detected in myeloid cells. To study pure populations of primitive myeloid cells, we investigated the hyaluronan-binding function of the CD44 molecule from three myeloid cell lines: KG1a, KG1, and HL60. Both KG1a and KG1 cells express the CD34 antigen characteristic of the hematopoietic stem cells and HL60 cells do not; accordingly, KG1a and KG1 cells are generally considered as the most primitive and HL60 cells as the most mature of these cell lines. Measurement of cell adhesion to hyaluronan-coated surfaces (using 51Cr-labeled cells) and of aggregate formation in hyaluronan-containing solutions, showed that 45% of KG1 cells and 22% to 24% of KG1a spontaneously bind to hyaluronan, whereas HL60 cells do not either spontaneously or after treatment with a phorbol ester. Hyaluronan binding by KG1a and KG1 cells is mediated by CD44, because it is specifically abolished by monoclonal antibodies (MoAbs) to this molecule. The binding might require phosphorylation by protein kinase C and perhaps also by protein kinase A, because it is prevented by staurosporine, which inhibits these enzymes. 12-O-tetradecanoylphorbol-13-acetate (TPA) which activates protein kinase C, rises to 80% the proportion of KG1 and KG1a cells that bind hyaluronan; this activation is dependent on protein synthesis, for it is abrogated by cyclophosphamide, a protein synthesis inhibitor. Binding of TPA-treated cells to hyaluronan is only partly inhibited by MoAb to CD44: this suggests that TPA may induce synthesis of a hyaluronan-binding protein distinct from CD44. Considering the abundance of hyaluronan in human bone marrow, these results suggest that CD44 may be involved in mediating precursor-stroma interaction.

Alkaloids↗
PubMed1994

Behavioral lifestyle and mental health status of Japanese factory workers.

BACKGROUND: Lifestyle factors, sometimes associated with physical health and mortality, have also been known to be associated with mental health status. This study seeks to correlate behavioral lifestyles with major components of mental health among Japanese factory workers. METHOD: We administered the 28-item version of the General Health Questionnaire (GHQ-28) and a questionnaire concerning eight personal health practices to 2,132 male and 668 female factory workers at a camera-manufacturing company in Japan. RESULTS: There were strong negative relationships of a higher total number of favorable lifestyles as indicated by the Health Practice Index (HPI) to psychological distress and its components: somatic symptoms, anxiety-insomnia, and social dysfunction. After controlling for the effects of confounding factors that included age, marital status, and somatic condition, multiple logistic regression analysis indicated that five of the eight health factors among male workers--mental stress, nutritional balance, eating breakfast regularly, physical exercise, and working hours--were significantly related to the grade of psychological distress or its three components. Among female workers, five health practices, i.e., mental stress, physical exercise, sleeping hours, working hours, and cigarette smoking, were significantly associated with the grade of psychological distress or its three components. CONCLUSION: Good health practices might be individually and as a whole associated with better mental health status in factory workers.

Adult↗
PubMed1994

Characterization of the three genotypes of low Km aldehyde dehydrogenase in a Japanese population.

A deficiency in low Km aldehyde dehydrogenase (ALDH2) is regarded as the main factor responsible for "Oriental flushing" and other symptoms due to alcohol sensitivity. In this study, the relationship of the ALDH2 genotype to alcohol-associated symptoms and drinking behavior was investigated in 524 Japanese workers, using a new, rapid, and nonisotopic polymerase chain reaction (PCR) method. Differences in the frequency of alcohol-associated manifestations between the normal homozygote and the other deficient types were apparent. In addition, among the ALDH2-deficient individuals, the atypical homozygote was obviously more hypersensitive to alcohol than the heterozygote, judging from the frequency of flushing or other drinking-associated manifestations with a small dose of alcohol. Drinking frequency also apparently decreased in the following order: typical homozygote, heterozygote, atypical homozygote. Similarly, mean amounts of alcohol consumption also decreased in the same order, although considerable variation existed within the typical homozygote and the heterozygote group. In contrast, neither the manifestations nor the drinking behavior were, in general, influenced by polymorphism of the alcohol dehydrogenase beta-subunit (ADH2) gene in males. These findings further indicate the important contribution of the ALDH2 genotype to alcohol sensitivity in Orientals.

Adult↗
PubMed1994

Transport of thyrotropin-releasing hormone across rat alveolar epithelial cell monolayers.

It has been recently shown that epithelial cell monolayers of rat type II pneumocytes cultivated on tissue culture-treated polycarbonate Transwell filters are tight (> 2,000 ohm-cm2) and exhibit morphological and phenotypic characteristics of in vivo type I pneumocytes. We studied, utilizing these tight monolayers, the transepithelial transport of thyrotropin-releasing hormone (TRH). Either [125I]TRH or [3H]TRH was used to measure the transalveolar epithelial radiolabel fluxes across the monolayer. Radiochromatography was performed, utilizing reverse-phase HPLC techniques, to determine the presence of TRH and its subspecies in dosing, donor and receiver fluids. The apparent permeability coefficient (Papp) estimated from 125I-radiolabel fluxes was approximately 1.7 x 10(-7) cm/sec in both the apical-to-basolateral (AB) and basolateral-to-apical (BA) directions. In contrast, the Papp for 3H-radiolabels was approximately 4.2 x 10(-7) cm/sec in both directions. Radiochromatography results indicated that neither apical nor basolateral receiver fluid collected at the end of 4 h flux studies contained metabolites of [125I]TRH or [3H]TRH. In the presence of 1,000-fold excess of unlabeled TRH in the donor fluid, the Papp of neither [125I]- or [3H]-TRH in either direction was altered. These data taken together provide evidence for restricted diffusional transport of intact TRH across the rat alveolar epithelial cell monolayer, most likely via paracellular pathways. Thus, it appears that TRH delivery via pulmonary alveolar epithelium in the distal airspaces of the mammalian lung may be feasible without significant interference from peptidase activities.

Animals↗
PubMed1994

Age-related decreases in the reconstituting ability of hemopoietic cells and the ability of hemopoietic microenvironment to support hemopoietic reconstitution in senescence accelerated (SAM-P) mice.

The effect of the aging process on the hemopoietic system in senescence-accelerated (SAM-P) mice with respect to the reconstituting ability of hemopoietic cells and the ability of the microenvironment to support hemopoietic reconstitution was investigated by bone marrow transplantation (reconstitution assay). When the bone marrow cells, obtained from young or old mice, were transplanted to lethally irradiated young SAM-P mice no difference in the reconstituting pattern of femoral spleen colony-forming units (CFU-S), splenic CFU-S and splenic granulocyte macrophage colony-forming units (CFU-GM) was observed between the mice transplanted with young and old donor cells. However, the reconstitution of femoral CFU-GM in mice transplanted with old donor cells was delayed compared to that in mice transplanted with young donor cells. Moreover, the recovery of WBC in mice transplanted with old donor cells was noticeably delayed. When the bone marrow cells obtained from young mice were transplanted to young or old recipient mice, no difference in the reconstituting pattern of femoral CFU-S and CFU-GM as well as splenic CFU-S and CPU-GM was observed between young and old recipient mice. However, the recovery of WBC in old recipient mice was noticeably delayed. These data indicate that the functions of both the hemopoietic cells and the hemopoietic microenvironment deteriorated with age in SAM-P mice.

Aging↗
PubMed1994

Elevated chromosome aberration frequency after X-ray exposure of cultured fibroblasts derived from patients with porokeratosis.

Porokeratosis (PK) is a rare genetic skin disorder inherited as an autosomal dominant trait and regarded as a disease predisposing to cancer. To evaluate chromosomal radiosensitivity of PK cells, we examined chromosome aberration frequency after X-irradiation of cultured skin fibroblasts derived from PK patients and controls. Without X-ray exposure, frequencies of chromosome-type aberrations (exchanges or deletions) were not different between the patients and controls. Following X-ray irradiation, frequencies of deletions in the patient group were significantly increased, whereas those of exchanges were not elevated. No differences in chromatid-type aberration frequency were found between the patients and controls with or without exposure to X-ray. The observed radiosensitivity, though not as high as in ataxia telangiectasia (AT) cells, agrees well with the previously reported higher radiosensitivity of PK fibroblasts in survival analysis.

Analysis of Variance↗
PubMed1994

The effects of perinatal anoxia or hypoxia on hippocampal kindling development in rats.

The effects of anoxia and hypoxia (3% oxygen) at 10-12 post days of age on the development of ventral hippocampal kindling and its transfer to the contralateral ventral hippocampus were studied in adult male Sprague-Dawley rats. During oxygen deprivation, the heart rate decreased to 15% of the prehypoxic value in the animals exposed to anoxia and 40% in those exposed to hypoxia. As is observed in asphyxia of human newborns, our study included both ischemia and hypoxia. The susceptibility to kindling, which was measured by kindling rate, afterdischarge threshold, generalized seizure threshold, and total afterdischarge duration to stage 5, had a tendency to be enhanced in rats exposed to hypoxia compared with controls. The facilitating effects on primary site kindling were enhanced in the animals exposed to hypoxia compared with those exposed to anoxia. Transfer, which was indicated by kindling rate and afterdischarge threshold, was also slightly facilitated in the rats exposed to anoxia or hypoxia in the perinatal period. These results reveal that perinatal oxygen deficiency may not be sufficient to lead to the development of temporal lobe epilepsy. However, it is possible that perinatal hypoxia results in some pathophysiological change in the brain which leads to greater seizure susceptibility in adulthood.

Aging↗