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Biomedical subjects

K Hoshi

Publications and source records attributed to K Hoshi.

At least 181 records · Page 10Linked to original sources

Pronuclear formation and cleavage of mammalian eggs after microsurgical injection of freeze-dried sperm nuclei.

A study was conducted to evaluate the ability of mammalian oocytes to develop to the pronuclear stage and beyond if injected with freeze-dried sperm nuclei. The rate of development of hamster eggs to the pronuclear stage after microinjection of freeze-dried hamster sperm nuclei was 90%. The pronuclear formation rate of hamster eggs injected with freeze-dried human sperm nuclei was 85%. On the other hand, the rates for eggs injected with untreated sperm nuclei were 84% and 89% respectively. The survival rate of rabbit eggs microinjected with freeze-dried rabbit sperm nuclei was 64%, the fertilisation rate 56% and the cleavage rate 38%. The survival, fertilisation and cleavage rates of eggs injected with non-freeze-dried sperm nuclei were 78%, 45% and 34%, respectively. There was no difference between eggs injected with freeze-dried sperm nuclei and those injected with sperm nuclei that had not been freeze-dried. Of the viable rabbit eggs injected with freeze-dried rabbit sperm nuclei, 6% developed to the 6- to 8-cell stage 62 h after injection.

Animals↗

A case of ovarian Brenner tumor with stromal estrogenic activity.

An 88-year-old menopausal Japanese female suffering from atypical genital bleeding received a left oophorectomy for a tumor of the left ovary. A vaginal smear before removal of the tumor revealed high estrogenic activity. The patient's ovarian tumor was a benign Brenner tumor and contained theca-like cells in its stroma. The pathological findings relating to these theca-like cells suggested their estrogenic activity, and a vaginal smear after removal of the tumor revealed that estrogenic activity had disappeared.

Aged↗

Calcaneus and vertebrae bone mineral density values and fracture threshold.

The calcaneus bone mineral density values (BMDs) of healthy Japanese women peaked at 20 to 25 years of age with 435 +/- 66 mg/cm2 (mean +/- S.D.), decreased 0.51% on the average every year thereafter until 45 years of age, 1.72% between 45 and 55 years (menopause) and 0.55% thereafter. The vertebrae bone mineral density value peaked at 30 to 35 years of age with 1.06 +/- 0.13 g/cm2 (mean +/- S.D.), decreased 0.67% on the average every year thereafter until 45 years of age, 1.23% between 45 and 55 years (menopause) and 0.70% thereafter. Mean -2.0 S.D. of the peak bone mass was considered appropriate as the fracture threshold for both the calcaneus and vertebra, judging from the BMDs of osteoporosis patients.

Absorptiometry, Photon↗

Species differences in the inhibiting effect of fluvastatin, a new inhibitor of HMG-CoA reductase, on cholesterol biosynthesis.

Cholesterol synthesis both ex vivo and in vivo in liver and ileum of hamsters was significantly inhibited by fluvastatin. This ex vivo inhibition was considerably lower in fluvastatin-treated hamsters than in fluvastatin-treated rats. In hamsters and rats, fluvastatin was more potent than pravastatin on inhibitory activities of sterol synthesis in liver, but not in the hamster ex vivo. This may indicate that, in part, the hydrophobicity of the fluvastatin molecule confers the selectivity and metabolism in the liver of hamsters and rats to originate from the species differences.

Animals↗

[Development of new drugs for intractable vasculitis--lipo-PGE1 and monoclonal antibody].

"Lipo-PGE1", PGE1 incorporated into lipid microspheres (LM), has marked antiplatelet and vasodilatory actions. Since LM largely accumulate in inflamed vascular lesions, lipo-PGE1 shows a marked efficacy for treating vascular diseases such as atherosclerosis and vasculitis. Another recently developed drugs against intractable vasculitis are monoclonal antibodies to surface antigens of lymphocytes. Treatment with humanized anti-CDw52, and subsequent anti-CD4 monoclonal antibodies was reported to have brought remission up to 42 months.

Alprostadil↗

Vitamin K2 (menatetrenone) inhibits prostaglandin synthesis in cultured human osteoblast-like periosteal cells by inhibiting prostaglandin H synthase activity.

Prostaglandin (PG) E2, a potent bone-resorbing agent, is synthesized in osteoblast-like cells. Since vitamin K reportedly plays an important role in bone metabolism, we investigated the effects of vitamin K2 (menatetrenone) on PGE2 production by human osteoblast-like periosteal cells. In cells incubated with menatetrenone (1 microgram/mL = 2.25 x 10(-6) M) for 2 days, PGE2 production was reduced to 50% of that in untreated control cells. This inhibition was dose and time dependent for up to 10 micrograms/mL and 20 days, respectively, and involved two major steps. In one of these menatetrenone at doses of 0.5-10 micrograms/mL dose dependently inhibited the calcium ionophore A23187-induced release of arachidonic acid (AA) from membrane phospholipids, and in the other the conversion of AA to PG was inhibited, as evidenced by the PG-synthesizing activity in the homogenates of menatetrenone-treated cells with AA being lower than that in untreated cells. The inhibitory effect was almost identical to that for PG production. The PG synthesizing activity in cell homogenates was inhibited only by a high concentration of menatetrenone (10 micrograms/mL) when this was added directly. Menatetrenone (1 microgram/mL) also inhibited 52% of the purified PGH synthase activity from a ram seminal vesicle. This study shows that menatetrenone inhibited PGE2 release from cells by inhibiting both PG production steps, AA release from the membrane and PG synthesizing activity with AA. Inhibition of PGE2 production by menatetrenone might be important in improving bone metabolism.

Adult↗

Involvement of p53 gene mutations in human endometrial carcinomas.

Mutations in the p53 gene are associated with a wide variety of human malignancies. Point mutation in one allele and loss of the remaining one generally lead to inactivation of p53 protein. A high frequency of allelic losses corresponding to the 17p13.3 region that contained the p53 gene sequence was also noted in human endometrial carcinoma. Thus, in order to confirm involvement of the p53 gene in endometrial carcinogenesis, we searched for nucleotide sequence change in this gene in 42 endometrial carcinomas that had been subjected to previous LOH analyses. Using the polymerase-chain-reaction-single-strand conformation polymorphism (PCR-SSCP) method, we detected p53 gene mutations in 4 specimens. Two adenocarcinomas with allelic loss on 17p contained a mutant p53 gene in the allele that was retained. One specimen with a p53 gene mutation contained a 17q deletion but was uninformative for LOH on 17p. p53 gene mutation was also noted in the remaining stage-I carcinoma, though the 17p deletion was not detected in the previous LOH examination. However, 5 specimens with the LOH on 17p retained the wild-type p53 gene. In the remaining 33 specimens, both alleles of p53 gene seemed to be normal. The mutations observed in 2 specimens (cases 10 and 24), involving C-to-T and T-to-G substitutions, were located in a highly conserved region. However, the mutations identified in the remaining 2 cases (29 and 35) were at regions positioned outside conserved stretches.

Adenocarcinoma↗

The influence of prostaglandins on the contractile response to electrical field stimulation in rabbit myometrial and cervical smooth muscles.

Indomethacin (10 microM) significantly reduced the contractile responses to electrical field stimulation (EFS) in the non-pregnant myometrium (5-50 Hz by an average of 25.7%) and the pregnant myometrium (30-50 Hz by an average of 16.5%). On the other hand, it significantly increased the contractile responses of the cervix in non-pregnant (2.5-30 Hz by an average of 21.5%) and pregnant (2.5-10 Hz by an average of 12.5%) muscular strips. Prostaglandin (PG) E2 (0.1-1000 nM) strongly and PGI2 (0.1-1000 nM) slightly and dose-dependently inhibited the contractile response to EFS of the non-pregnant cervical muscle, but not of the myometrium. In the pregnant uterus, the contractile responses of the cervical muscle were similar to those of the non-pregnant cervix, while the response of the myometrium was increased significantly and dose-dependently by the application of PGE2 or PGI2.PGF2 alpha (1000 nM) significantly increased the contractile response of the myometrium but not cervical muscle to EFS in the pregnant rabbits. In non-pregnant muscles, the contractile responses of the myometrium and cervical smooth muscle to EFS were not influenced by the treatment with PGF2 alpha.PGE2 (0.1-1000 nM) also inhibited the contractile response to direct muscle stimulation, but the inhibition was significantly less than that of the response to indirect stimulation. PGI2 slightly inhibited the contractile responses to both indirect and direct stimulation. These findings indicate that PGE2, PGI2 and PGF2 alpha increase the contractile response of pregnant myometrium to EFS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Oxytocin, PGE2 and PGF2 alpha stimulate the production of inositol phosphates in the rabbit myometrium.

Phosphoinositide breakdown is thought to be important in regulating a variety of transmembrane signal transduction in the action of oxytocic agent during uterine smooth muscle contraction. We investigated the effects of oxytocin and prostaglandins (PGE2 and PGF2 alpha) on phosphoinositide hydrolysis in the myometrium taken from non-pregnant and pregnant rabbits by measuring the accumulation of total inositol phosphates (IP). Oxytocin strongly, and PGE2 and PGF2 alpha slightly but significantly, stimulated IP production in both the non-pregnant and pregnant myometria. Oxytocin more markedly accelerated the IP production in pregnant myometrium than in non-pregnant myometrium. However, IP production stimulated by PGE2 and PGF2 alpha was much the same in non-pregnant and pregnant myometria. The amount and time course of the increase in the production of the total IPs by oxytocin are quite different from those by PGs. It seems that the mechanism by which oxytocin stimulates phospholipase C is different from that of the PGs. It is suggested that transmembrane signalling pathways of phosphoinositide hydrolysis play an important role in the each mechanism.

Animals↗

The bone mineral density change with aging of Japanese women measured by single energy X-ray absorptiometry and dual energy X-ray absorptiometry.

The calcaneus bone mineral density of 473 Japanese women was measured by single energy X-ray absorptiometry (SXA) and the vertebrae bone mineral density of 198 Japanese women was measured by dual energy X-ray absorptiometry (DEXA). The calcaneus bone mineral density of Japanese women starts decreasing from age 30, and the rate of decrease accelerates from the age of 50. The vertebrae bone mineral density starts decreasing from the age of 35, and a conspicuous decrease can be seen from the age of 50 as well. Because bone deterioration of Japanese women is thought to start earlier than Caucasian, the necessity of osteoporosis screening before menopause was suggested. A high positive correlation (r = 0.804) between calcaneus bone mineral density and vertebrae bone mineral density was found, and a high degree of precision of SXA was shown.

Absorptiometry, Photon↗

Induction of the acrosome reaction in human spermatozoa by human zona pellucida and effect of cervical mucus on zona-induced acrosome reaction.

OBJECTIVES: To investigate the induction of the acrosome reaction in human spermatozoa by the zona pellucida (ZP), cumulus oophorus, and cervical mucus (CM), and to examine the effect of cumulus oophorus and CM on the zona-induced acrosome reaction. DESIGN, PATIENTS, MAIN OUTCOME MEASURES: The acrosome status of spermatozoa from healthy donors that were cultured with salt-stored human ZP, cumulus oophorus, and/or cervical mucus was assessed using fluoresceinated pisum sativum agglutinin. RESULTS: The acrosome reaction rate after sperm attachment to the zona for 6 hours was 35.7% +/- 17.7%, which was higher than controls (2.8% +/- 1.9%). The acrosome reaction was not observed after passage through cumulus oophorus or CM; however, the acrosome reaction rate of spermatozoa passed through CM after the attachment to zona was 51.6% +/- 6.8%, a higher value in comparison with spermatozoa that had not passed through CM (25.6% +/- 9.4%). CONCLUSION: These data indicate that human ZP are capable of inducing the acrosome reaction in human spermatozoa; however, cumulus oophorus and CM are unable to do so. The data further provide evidence that CM promotes the zona-induced acrosome reaction in human spermatozoa.

Acrosome↗

Limitation of stunning in dog myocardium by nucleoside and nucleotide mixture, OG-VI.

BACKGROUND: OG-VI is a nucleoside-nucleotide solution composed of 30 mM inosine, 30 mM cytidine, 30 mM sodium 5'-guanylate, 22.5 mM uridine, and 7.4 mM thymidine. It is expected to enhance the efficacy of intravenous hyperalimentation in surgically stressed patients. One of the main causes of ischemic myocardial damage is loss of adenine nucleotides from heart cells. The aim of the present study, therefore, was to examine the effect of OG-VI on myocardial mechanical function and energy metabolism in stunned myocardium. METHODS: Pentobarbital-anesthetized dogs were subjected to 20 min ligation of the left anterior descending (LAD) coronary artery, followed by reperfusion for 30 min. OG-VI at 0.1 or 0.2 ml/kg/min or saline was infused from the left femoral vein throughout the experiment. The tissue levels of high-energy phosphates in the hearts were determined after 30 min reperfusion. RESULTS: LAD flow, first derivative of left ventricular pressure (LVdp/dt), and segment function were increased by OG-VI in a dose-dependent manner. OG-VI infusion resulted in a significant improvement in LVdP/dt and segment shortening in the ischemic/reperfused myocardium compared with saline infusion. The levels of segment shortening with saline, 0.1, and 0.2 ml/kg/min OG-VI after reperfusion for 30 min were -0.3, 75, and 82% of the preligation levels, respectively. The tissue level of adenosine triphosphate (ATP) after reperfusion in OG-VI-infused animals was significantly higher than that in saline-infused animals. CONCLUSION: OG-VI has a positive inotropic action, and its infusion results in a marked cardioprotective effect in stunned myocardium associated with the restoration of tissue ATP level.

Animals↗

Pharmacological characteristics of contractile responses of rabbit uterine cervices to electrical field stimulation.

The pharmacological characteristics of contractile responses to electrical field stimulation (EFS) of uterine cervical muscular strips taken from non-pregnant and pregnant rabbits were investigated, in vitro. The contractile responses to EFS of both non-pregnant and pregnant muscular strips were markedly depressed by treatment with prazosin 1 microM, while the responses were only slightly depressed by treatment with atropine 1 microM. Propranolol 1 microM did not affect the responses. Guanethidine 10 microM and tetrodotoxin (TTX) 10 microM also depressed the contractile responses to EFS of both non-pregnant and pregnant muscular strips. However, the depressive effects of the latter 2 drugs were more marked in non-pregnant muscular strips than in pregnant ones. These findings indicate that the uterine cervical smooth muscle is predominantly innervated with adrenergic excitatory nerve fibers. The cholinergic innervation in uterine cervical smooth muscle seems minor. Furthermore, during pregnancy, a TTX-resistant, non-adrenergic, non-cholinergic component might increase the contractile response of uterine cervical smooth muscle to EFS.

Animals↗

Prostaglandins biosynthesis in the rabbit uterine cervix at various stages of pregnancy.

The accumulation of prostaglandins (PGs: 6-keto PGF1 alpha, PGE2, PGF2 alpha and TXB2) elicited by A-23187, a Ca(2+)-ionophore, was studied in the uterine cervical tissue taken from non-pregnant and pregnant (10th, 20th and 30th day of pregnancy) rabbits in vitro. At every stage of pregnancy, the accumulation of PGs levels increased as follows; 6-keto PGF1 alpha, PGE2, PGF2 alpha and TXB2. Biosynthesis of each began to increase from the 20th day of pregnancy, and was significantly elevated at the 30th day. Especially, 6-keto PGF1 alpha and PGE2 were remarkably higher than PGF2 alpha and TXB2 at term, and so they are thought to play a more important role in cervical dilation and ripening than the other PGs. Six-keto PGF1 alpha was significantly elevated on the 20th day, when other PGs had not yet began to increase. It is thus conceivable that PGI2 plays an important role in the predispositing of cervical ripening.

Animals↗