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Biomedical subjects

H Nagase

Publications and source records attributed to H Nagase.

At least 325 records · Page 18Linked to original sources
PubMed1994

Assessment of the mechanical properties of peripheral arteries in chain saw operators using a photosensor.

In order to evaluate the severity of peripheral vascular disorders, and to detect changes in the digital arteries of workers who use chain saws, the mechanical properties of the digital arteries of 22 such workers were examined using a photosensor. The elastic properties and the nonlinearity of digital arteries were assessed through observation of the changes in the vascular volume ratio (V/Vo) against the volume (Vo) at mean blood pressure (Pm). A significant negative correlation was found between age and V/Vo at a transmural pressure of 30 mmHg (V30/Vo), which suggested that V30/Vo tended to decrease with aging. Although it was impossible to calculate V30/Vo for chain saw operators because of the vague changes in the volume pulse wave, this nonlinearity was more clearly observed through changes in the relative vascular volume (V/V40) along with a reduction in cuff pressure (Pc) to 40 mmHg below systolic blood pressure. A group of similarly aged healthy controls and three groups of workers with a different severity of vibration-induced white finger (VWF), i.e., no symptoms of VWF, mild VWF and severe VWF, were classified according to the changes in their V/V40 and the reduction in Pc. The results obtained in the present study suggest that the peripheral vascular disorders in workers using chain saws are due to the opening disturbance of the arteries with nonlinear changes in the peripheral artery, which is related to functional and organic abnormality of the arteries.

Adult↗
PubMed1994

Amino acid sequence of hen ovomacroglobulin (ovostatin) deduced from cloned cDNA.

The complete amino acid sequence of the hen ovomacroglobulin (ovostatin) subunit has been determined from cDNA and partial peptide sequence analysis. Ovostatin is a tetrameric member of the alpha-macroglobulin (alpha M) family of proteins. The 4715 nt ovostatin cDNA encodes a 36- or a 16-residue signal peptide and a 1437-residue mature protein (162.2 kDa). At the protein level the overall score of sequence identity between ovostatin and mammalian alpha Ms is 39-44%, indicating an early divergence from the line leading to the mammalian alpha Ms. Ovostatin contains 56 mol glucosamine per mol subunit, and 12 of its Asn-residues are likely to be N-glycosylated. Including carbohydrate, the size of the ovostatin subunit is approx. 185 kDa. The ovostatin subunit is predicted to contain 12 intrachain disulfide bridges, and two subunits are predicted to be disulfide bound by two interchain bridges. One Cys residue may be unpaired or participate in dimer formation as a third interchain disulfide bridge. Ovostatin contains a unique 40-residue bait region. In contrast to other alpha Ms, ovostatin contains no internal beta-Cys-gamma-Glu thiol ester, as a result of a Cys-to-Asn replacement (TGC or TGT to AAT), but the Gln-moiety of the thiol ester is preserved. By comparing the sequences of the receptor binding domain in alpha Ms with the corresponding region of ovostatin possible determinants for receptor recognition of mammalian alpha Ms are proposed.

Amino Acid Sequence↗
PubMed1994

Serum gamma-glutamyl transferase level in predicting hypertension among male drinkers.

In a 10 year prospective study, we investigated the utility of the level of serum gamma-glutamyl transferase (GGT), a biological marker of alcohol consumption, in predicting the development of hypertension in Japanese male drinkers, all of whom lived in a rural community. The study included 77 men, aged 30-69 years, who were normotensive (SBP < or = 140 mmHg and DBP < or = 90 mmHg) and who had no prior history of antihypertensive treatment at baseline (1979-80). Hypertension was defined as SBP of > 140 mmHg and/or DBP of > 90 mmHg and/or starting antihypertensive medication. The age-adjusted relative risk for subjects with a serum GGT level of 20 U/l or higher compared with those with a level of < 10 U/l was 4.18 (95% confidence interval, 1.59-11.01, P = 0.004). The relative risk remained significant after adjustment for baseline BP level and the amount of alcohol consumption. These results suggest that the serum GGT levels may predict the future development of hypertension among drinkers.

Adult↗
PubMed1994

Antitussive effect of (+/-) pentazocine in diabetic mice is mediated by delta-sites, but not by mu- or kappa-opioid receptors.

The effects of streptozotocin-induced diabetes on the antitussive effect of (+/-) pentazocine were examined in mice. Intracerebroventricular (i.c.v.) administration of (+/-) pentazocine produced a dose-dependent antitussive effect in both diabetic and non-diabetic mice. There were no significant differences in the antitussive effect of (+/-) pentazocine in diabetic and non-diabetic mice. The antitussive effect of i.c.v. (+/-) pentazocine was partially, but significantly, reduced in non-diabetic mice following pretreatment with either beta-funaltrexamine, a selective mu-opioid antagonist, or rimcazole, a specific sigma-site antagonist. The antitussive effect of (+/-) pentazocine in diabetic mice was significantly antagonized by pretreatment with rimcazole. However, beta-funaltrexamine had no effect on the antitussive effect of (+/-) pentazocine in diabetic mice. Furthermore, nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antitussive effect of (+/-) pentazocine in either non-diabetic or diabetic mice. These results suggest that although the antitussive effect of i.c.v. (+/-) pentazocine in non-diabetic mice is mediated by both mu-opioid receptors and sigma-sites, in diabetic mice this effect is mainly mediated by sigma-sites.

Animals↗
PubMed1994

Human breast carcinoma cells cultured in the presence of serum shed membrane vesicles rich in gelatinolytic activities.

Human breast carcinoma cell lines, 8701-BC and MCF-7, in culture shed membrane vesicles with similar morphology. Vesicles shed in the presence of serum were rich in gelatinolytic activities, but not those obtained in the absence of serum. Zymographic analyses of the vesicles from 8701-BC and MCF-7, using gelatin as substrate, showed three predominant activities at 68-kDa, 97-kDa, and above 200-kDa. The ratio of the three activities was similar in the vesicles recovered from the two cell lines, but the vesicles from 8701-BC cells contained greater amounts of activities than those from MCF-7 cells. Optimal pH and sensitivity to protease inhibitors suggest that all gelatinolytic activities detected in vesicles are metalloproteinases. Treatment of the vesicles extracts with 4-aminophenylmercuric acetate and comparison with the purified enzyme indicate that 97-kDa gelatinase is the precursor of matrix metalloproteinase-9 (gelatinase B). These results support the early hypothesis that vesicle shedding from the plasma membrane may participate in metastatic cascade of cancer cells.

Blood Proteins↗
PubMed1994

Effects of diabetes on the antinociceptive effect of (+/-)pentazocine in mice.

The antinociceptive effect of (+/-)pentazocine was examined in streptozotocin-induced diabetic mice. Although intracerebroventricular (i.c.v.) administration of (+/-)pentazocine (10 nmol) produced a significant antinociceptive effect in both non-diabetic and diabetic mice, the antinociceptive effect of (+/-)pentazocine was greater in diabetic mice than in non-diabetic mice. The antinociceptive effects of (+/-)pentazocine in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of nor-binaltorphimine, a selective kappa-opioid receptor antagonist. On the other hand, the antinociceptive effects of (+/-)pentazocine were potentiated when non-diabetic mice were pretreated with beta-funaltrexamine, a selective mu-opioid receptor antagonist. Furthermore, there was no significant difference in the antinociceptive effect of (+/-)pentazocine between diabetic mice and beta-funaltrexamine-treated non-diabetic mice. These results suggest that the hypo-responsiveness of mu-opioid receptors may account for the enhanced kappa-opioid receptor-mediated antinociceptive effect of (+/-)pentazocine in diabetic mice.

Analgesics↗
PubMed1994

[Effects of vibration on uterine circulation in pregnant rats].

With the recent remarkable development of transportation facilities, pregnant women are frequently exposed to mechanical vibration. To experimentally demonstrate that vibration disorders normal pregnancy, uterine blood flow (UBF) and the several kinds of endocrine indicators were examined in pregnant rats exposed to vibration (10m/s2, 8Hz, 90 min). The exposure to vibration decreased UBF in the rats significantly. The UBF of the rats pretreated with peritoneal administration of angiotensin II (AII) was increased when they were not exposed to vibration. In contrast to this, in AII pretreated rats simultaneously exposed to vibration, a significant decrease in the UBF was recognized. Vibration decreased the plasma level of progesterone (PRO), but pretreatment with AII induced no difference in PRO in vibration-exposed and unexposed rats. The level of prostaglandin E2 (PGE2) was decreased in rats exposed to vibration, but not in control rats. Pretreatment with AII still decreased PGE2 in rats exposed to vibration. These results indicate that vibration may play an important role in the development of abnormal pregnancy through uterine circulatory and ovarian dysfunctions. It seems that a decrease in UBF is induced primarily via an inhibitory effect of vibration on PGE2, and secondarily via a direct action on the uterus.

Animals↗
PubMed1993

Involvement of protein kinase C in the interleukin 1 alpha-induced gene expression of matrix metalloproteinases and tissue inhibitor-1 of metalloproteinases (TIMP-1) in human uterine cervical fibroblasts.

The role of protein kinase C in the interleukin 1 (IL-1)-mediated production of pro-matrix metalloproteinases (proMMPs) and tissue inhibitor-1 of metalloproteinases (TIMP-1) in human uterine cervical fibro-blasts has been investigated. IL-1 and a protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA) augmented the production of proMMP-1 (interstitial procollagenase), proMMP-3 (prostromelysin-1) and TIMP-1, but their effects were inhibited by the protein kinase C inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and staurosporine in a dose-dependent manner. The suppressive effect of H-7 and staurosporine on the IL-1-induced production of proMMPs-1 and -3 and TIMP-1 resulted from the decrease in the steady-state levels of their mRNAs. When protein kinase C was down-regulated by treating the cells with a high level of TPA, the inductive effect of IL-1 upon proMMP-3 production was reduced considerably. These results indicate that protein kinase C mediates the IL-1-induced production of proMMPs-1 and -3 and TIMP-1 at the pretranslational level in human uterine cervical fibroblasts. On the other hand, neither IL-1 nor TPA modulated the production of proMMP-2 (progelatinase A). Both IL-1 and TPA also accelerated the production of prostaglandin E2 (PGE2) by cervical fibroblasts. However, the treatment of the cells with staurosporine in the presence of IL-1 or TPA further augmented PGE2 synthesis, suggesting that the increased synthesis of PGE2 by IL-1 treatment is mediated via signalling pathways distinct from those of proMMPs-1 and -3 and TIMP-1.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Antitussive effects of naltrindole, a selective delta-opioid receptor antagonist, in mice and rats.

The effects of naltrindole, a selective delta-opioid receptor antagonist, on the capsaicin-induced cough reflex in mice and rats were studied. Intraperitoneal administration of naltrindole decreased the number of coughs both in mice and rats dose dependently. The cough-depressant effects reached a peak 15 min after the administration of naltrindole and lasted more than 120 min. Pretreatment with [D-Pen2,D-Pen5]enkephalin, a selective delta-opioid receptor agonist, partially but significantly reduced the antitussive effect of naltrindole. Blockade of kappa-opioid receptors by pretreatment with nor-binaltorphimine also partially antagonized the antitussive effect of naltrindole. However, the antitussive effect of naltrindole was not antagonized by beta-funaltrexamine, a selective mu-opioid receptor antagonist. Thus, it is possible that the antitussive effect of naltrindole may be mediated, in part, by kappa-opioid receptors. The present results provide evidence for the development of delta-opioid antagonists, especially naltrindole, for use as antitussive drugs.

Animals↗
PubMed1993

Disruption of the cysteine-75 and zinc ion coordination is not sufficient to activate the precursor of human matrix metalloproteinase 3 (stromelysin 1).

Matrix metalloproteinases (MMPs) are activated in vitro from their precursors (proMMPs) by multiple means such as treatment with proteinases, mercurial compounds, chaotropic agents, sodium dodecyl sulfate, HOCl, and heat. The latency of proMMPs is stabilized by intramolecular interaction of the single cysteine residue in the conserved sequence PRCG(V/N)PD of the propeptide and the zinc atom at the active site. The activation of proMMP-1 (interstitial procollagenase) by multiple treatments has been explained by the "cysteine switch" model, in which the disruption of the Cys-Zn interaction is considered to be critical for activation [Springman, E. B., Angleton, E. L., Birkedal-Hansen, H., & VanWart, H. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 364-368]. To further test this hypothesis we dissociated the Cys-Zn interaction by specifically modifying Cys-75 of proMMP-3 (prostromelysin 1) with iodoacetamide, (4-aminophenyl)mercuric acetate (APMA), or 5,5'-dithiobis(2-nitrobenzoate) and examined the expression of enzymic activity. The enzymic assays of the modified proMMP-3s against protein and synthetic substrates did not reveal any significant activity. The modified 57-kDa proMMP-3s were stable and did not show spontaneous activation. Activation of the modified proMMP-3s required further treatment with APMA or a proteinase and was accompanied by conversion of the proMMP-3 to a 45-kDa species. Circular dichroism studies of proMMP-3 treated with HgCl2 demonstrated time-dependent conformational changes in proMMP-3 prior to the expression of proteolytic activity and processing of the zymogen to lower molecular weight species. These results indicate that the disruption of the Cys-Zn coordination alone is not sufficient to activate proMMP-3.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkylation↗
PubMed1993

Effect of diabetes on the antinociceptive effect of beta-endorphin.

We examined whether streptozotocin-induced diabetes can modulate beta-endorphin-induced antinociception in mice. While beta-endorphin administered i.c.v. produced a dose-dependent inhibition of the tail-flick response in both diabetic and non-diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The ED50 value of beta-endorphin administered i.c.v. in diabetic mice was significantly lower than that in non-diabetic mice. The antinociceptive effects of beta-endorphin administered i.c.v. in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective delta-opioid receptor antagonist. beta-Endorphin administered i.t. also produced a dose-dependent antinociception in both diabetic and non-diabetic mice. However, the ED50 value of kappa-opioid receptor antagonist. On the other hand, the antinociceptive potency of DPDPE, a selective delta-opioid agonist, administered i.t. is significantly increased in diabetic mice, as compared with non-diabetic mice, whereas, the antinociceptive potency of U-50,488H, a kappa-opioid receptor agonist, administered i.t. is significantly less than in non-diabetic mice. These results suggest that diabetes may modulate beta-endorphin-induced antinociception differently at the spinal and supraspinal levels.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Modification of morphine-induced locomotor activity by pertussis toxin: biochemical and behavioral studies in mice.

The effect of pertussis toxin (PTX) on the locomotor-enhancing action of systemic and intracerebroventricular (i.c.v.) morphine was investigated in mice. Mice were i.c.v. injected with either PTX (0.25 and 0.5 micrograms) or saline as a control. The s.c. (5-20 mg/kg) and i.c.v. (7-30 nmol) administration of morphine produced a dose-related locomotor-enhancing action in control mice. The peak effect of morphine (30 nmol, i.c.v.)-induced hyperlocomotion was observed 90 min after the morphine injection. At the same time, morphine significantly increased dopamine (DA) metabolism in the limbic forebrain (nucleus accumbens and olfactory tubercle). Similarly, the selective mu-opioid receptor agonist [D-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAGO, 4 nmol, i.c.v.) also significantly increased locomotor activity and DA metabolism in the limbic forebrain. Both morphine- and DAGO-induced hyperlocomotion and elevation of DA turnover were antagonized by pretreatment with the mu antagonist beta-funaltrexamine (beta-FNA). These results suggest that the locomotor-enhancing action of morphine results from the activation of central mu-opioid receptors, and that the activation of the mesolimbic DA system may be involved in the expression of morphine-induced hyperlocomotion in mice. Furthermore, pretreatment with PTX (0.5 micrograms, i.c.v., 6 days prior to the testing) significantly reduced hyperlocomotion and elevation of DA turnover in the limbic forebrain which had been induced by administrations of morphine (30 nmol, i.c.v.) and DAGO (4 nmol, i.c.v.). These findings suggest that the central PTX-sensitive GTP-binding protein (G-protein) mechanism may play an important role in opioids-induced locomotor-enhancing action. Furthermore, the activation of mesolimbic DA transmission by mu-opioid agonists may also be mediated by a PTX-sensitive G-protein mechanism in mice.

Analgesics↗
PubMed1993

The role of the mu 2-opioid receptor in the antitussive effect of morphine in mu 1-opioid receptor-deficient CXBK mice.

The effect of morphine on the capsaicin-induced cough reflex was studied in mu 1-opioid receptor-deficient CXBK mice. There was no significant difference between the morphine-induced antitussive effect in CXBK mice and C57BL/6 mice, a progenitor strain. Furthermore, the antitussive effects of morphine in both the CXBK and C57BL/6 mice were antagonized by pretreatment with either naloxone or beta-funaltrexamine, a mu-opioid receptor antagonist, whereas pretreatment with naltrexonazine, a selective mu 1-opioid receptor antagonist, had no effect. Moreover, naltrindole, a selective delta-receptor antagonist, also had no significant effect on the antitussive effects of morphine in either CXBK or C57BL/6 mice. These results support our previous hypothesis that mu 2- rather than mu 1-opioid receptors are involved in morphine-induced antitussive effects.

Animals↗
PubMed1993

Species specificity of pharmacological characteristics of CCK-B receptors.

Novel CCK-B receptor antagonists, tetronothiodin and L-156,586, showed different affinities for CCK-B receptors in brain membranes from human, rat, guinea pig and mouse. [125I]CCK-8 bound to these membranes with a similar affinity. However, tetronothiodin was most potent in rat (IC50 = 3.6 nM), followed by guinea pig (96 nM), human (210 nM) and mouse (280 nM). L-156,586 bound with highest affinity to membranes from guinea pig (11 nM), and with lowest affinity to membranes from mouse (220 nM). These results suggest the existence of species specificity of CCK-B receptors, and that these two compounds are useful tools for discrimination between these receptors.

Aged↗
PubMed1993

Antitussive effects of mu- and kappa-agonists in diabetic rats.

We evaluated the antitussive effect of morphine and U-50,488 in diabetic and non-diabetic rats. The antitussive potency of morphine (0.3 mg/kg, i.p.) in diabetic rats was significantly reduced as compared to the results in non-diabetic rats. The antitussive effect of U-50,488, a kappa-agonist, was also significantly lower in diabetic rats than in non-diabetic rats. When naltrindole (0.03 mg/kg, i.p.), a delta-antagonist, was administered 15 min before morphine or U-50,488, there was no difference between the antitussive potencies of these two opioid agonists in non-diabetic rats and in diabetic rats. Furthermore, naltrindole produces a reduction of the number of coughs in diabetic rats, but not in non-diabetic rats. It is possible that the enhancement of the antitussive potency of morphine and U-50,488 in naltrindole-treated diabetic rats is the result of the antitussive synergy produced by these opioid agonists and naltrindole. It seems likely, therefore, that delta-receptor-mediated endogenous inhibitory systems in mu- and kappa-receptor-mediated antitussive processes may be activated under diabetic conditions.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗