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H Nagase

Publications and source records attributed to H Nagase.

At least 307 records · Page 17Linked to original sources
PubMed1994

Vagal-central nervous system interactions modulate the feeding response to peripheral enterostatin.

Enterostatin selectively inhibits the intake of dietary fat after both peripheral and central administration. We have investigated the role of the hepatic vagus nerve in modulating the peripheral response to enterostatin in Sprague-Dawley rats adapted to a high fat (HF) diet. Intraperitoneal (ip) enterostatin reduced intake of HF diet after overnight starvation. This response was abolished by selective vagal hepatic branch transection. Immunohistochemical techniques were used to identify the location of Fos protein in brain nuclei after ip enterostatin. Fos protein was evident in the nucleus tractus solitarius (NTS), parabrachial, paraventricular and supraoptic nuclei. The pattern of expression of Fos-like immunoreactivity differed from that induced by the lipoprivic agent beta-mercaptoacetate. Transection of the hepatic vagus blocked the central Fos responses to ip enterostatin. We conclude that afferent hepatic vagal nerve activity is required for the feeding response to peripheral enterostatin.

Animals↗
PubMed1994

Distribution of gelatinase B (MMP-9) and type IV collagen in colorectal carcinoma.

Gelatinase B (92 kD, matrix metalloproteinase-9, MMP-9), an enzyme capable of degrading several connective tissue components, was demonstrated by immunolocalization in all specimens of colorectal carcinoma (n = 40), but its distribution between specimens was variable. MMP-9 expression was more frequently observed in advanced tumour stages and was especially prevalent at the side and deep margins of the tumours, and ulceration sites. MMP-9 staining was observed for transformed epithelial cells, macrophages and neutrophils, but seldom for vascular or stromal cells. By contrast, the enzyme was absent from epithelial cells of normal mucosal tissue. Immunostaining of type IV collagen, the major structural component of basement membranes, revealed a general depletion or loss of these structures both within the tumours and at the tumour margins. Dual immunolocalization of MMP-9 and type IV collagen demonstrated that MMP-9 expression at specific sites in the tumour was often inversely related to the distribution of type IV collagen. MMP-9 expression was most pronounced at the invasive tumour margins and in microfoci where tumour cells were in close proximity to inflammatory cells. Such observations support the concept that localized proteolytic and collagenolytic activities contribute to the invasive properties of colorectal tumours.

Aged↗
PubMed1994

Changes of cerebral vasoactive intestinal polypeptide- and somatostatin-like immunoreactivity induced by noise and whole-body vibration in the rat.

To clarify the role of vasoactive intestinal polypeptide (VIP) and somatostatin, somatotropin-release inhibiting factor, (SRIF) neurons in the response to organisms to noise or whole-body vibration stress, VIP- and SRIF-like immunoreactivity were determined in various regions of the rat brain following exposure for 90 min to noise (broad band, 102 dB) or whole-body vibration (20 Hz, 4.0 g). Both noise and whole-body vibration significantly increased VIP-like immunoreactivity in the amygdala. A significant reduction of VIP-like immunoreactivity in the hippocampus was induced only by whole-body vibration. On the other hand, SRIF-like immunoreactivity was decreased significantly in the hypothalamus and increased significantly in the amygdala by noise and whole-body vibration, respectively. The present findings would seem to indicate that the amygdalofugal VIP neural system is involved in regulating hypothalamic and pituitary hormone secretions in non-specific reactions to stress. Responses of hippocampal VIP and the amygdalofugal SRIF to whole-body vibration stress are assumed to be activated as specific reactions to the stress.

Animals↗
PubMed1994

Involvement of adenosine A1 receptors in antitussive effect in mice.

The effects of N6-cyclohexyladenosine, a selective adenosine A1 receptor agonist, on the capsaicin-induced cough reflex in mice were examined. I.c.v. administration of N6-cyclohexyladenosine in doses that ranged from 0.03 to 0.3 nmol decreased the number of coughs in a dose-dependent manner. Pretreatment with 8-cyclopentyl-1,3-theophylline, a selective adenosine A1 receptor antagonist, significantly reduced the antitussive effect of N6-cyclohexyladenosine. On the other hand, CGS21680 (0.3 and 1 nmol, i.c.v.), a selective adenosine A2 receptor agonist, had no significant effect on the number of capsaicin-induced coughs. These data suggest that adenosine A1 agonists may have a marked antitussive effect in mice.

Adenosine↗
PubMed1994

The role of delta-opioid receptor subtypes in cocaine- and methamphetamine-induced place preferences.

The effects of delta-receptor antagonists on cocaine- and methamphetamine-induced place preferences were examined in rats. Cocaine- and methamphetamine-induced place preferences were significantly attenuated by naltrindole (NTI: a non-selective delta-opioid receptor antagonist). Furthermore, naltriben (NTB: a selective delta 2-opioid receptor antagonist), but not 7-benzylidenenaltrexone (BNTX: a selective delta 1-opioid receptor antagonist), attenuated the cocaine- and methamphetamine-induced place preferences. These results suggest that delta-opioid receptors, particularly delta 2-opioid receptors, may be involved in the reinforcing effects of cocaine and methamphetamine.

Animals↗
PubMed1994

Streptozotocin-induced diabetes selectively enhances antinociception mediated by delta 1- but not delta 2-opioid receptors.

We assessed the effect of diabetes on antinociception produced by intracerebroventricular injection of delta-opioid receptor agonists [D-Pen2,5]enkephalin (DPDPE) and [D-Ala2]deltorphin II. The antinociceptive effect of DPDPE (10 nmol), administered i.c.v., was significantly greater in diabetic mice than in non-diabetic mice. The antinociceptive effect of i.c.v. DPDPE was significantly reduced in both diabetic and non-diabetic mice following pretreatment with 7-benzylidenenaltrexone (BNTX), a selective delta 1-opioid receptor antagonist, but not with naltriben (NTB), a selective delta 2-opioid receptor antagonist. There were no significant differences in the antinociceptive effect of [D-Ala2]deltorphin II (3 nmol, i.c.v.) in diabetic and non-diabetic mice. Furthermore, the antinociceptive effect of i.c.v. [D-Ala2]deltorphin II was significantly reduced in both diabetic and non-diabetic mice following pretreatment with NTB, but not with BNTX. In conclusion, mice with diabetes are selectively hyper-responsive to supraspinal delta 1-opioid receptor-mediated antinociception, but are normally responsive to activation of delta 2-opioid receptors.

Analgesia↗
PubMed1994

Differential mediation of cold water swim stress-induced antinociception by delta-opioid receptor subtypes in diabetic mice.

The involvement of delta-opioid receptor subtypes in cold water swim stress (CWSS)-induced antinociception in diabetic mice was compared with that in non-diabetic mice. Three-minute swim stress produced significant antinociception in both diabetic and non-diabetic mice as determined by the tail-pinch test. However, the extent of CWSS-induced antinociception in diabetic mice was significantly greater than that in non-diabetic mice. Pretreatment with naltriben, a selective delta 2-opioid receptor antagonist, significantly attenuated CWSS-induced antinociception in both non-diabetic and diabetic mice. In contrast, although 7-benzylidenenaltrexone, a selective delta 1-opioid receptor antagonist, significantly attenuated CWSS-induced antinociception in diabetic mice, it had no effect in non-diabetic mice. These results suggest that CWSS-induced antinociception in non-diabetic mice is mediated by delta 2-opioid receptors, whereas CWSS-induced antinociception in diabetic mice is mediated by both delta 1- and delta 2-opioid receptors. Furthermore, the enhanced CWSS-induced antinociception in diabetic mice may be due to the activation of delta 1-opioid receptors.

Analgesia↗
PubMed1994

Evidence for differential modulation of mu-opioid receptor-mediated antinociceptive and antitussive activities by spleen-derived factor(s) from diabetic mice.

The effects of spleen-derived factor(s) from diabetic mice on the antinociceptive and antitussive effects of mu-opioid receptor agonists were examined in mice. The antinociceptive effects were examined 1 week after adoptive transfer of the supernatant of spleen cell homogenate (SSCH) from diabetic mice (SSCH-D). Naive mice which had been injected with SSCH-D were less sensitive to the antinociceptive effects of mu-opioid receptor agonists, such as morphine and [D-Ala2, N-MePhe4, Gly-ol5]enkephalin (DAMGO), than mice which had been injected with SSCH from non-diabetic mice. The antinociceptive effects of DAMGO was also significantly lower in naive mice injected with SSCH-D than in SSCH from non-diabetic mice (SSCH-ND)-treated naive mice, when assessed 2 weeks after adoptive transfer of SSCH. The sensitivity to the antinociceptive effect of [D-Pen2,5]enkephalin (DPDPE), a delta-opioid receptor agonist, was significantly enhanced 2 weeks, but not 1 week, after adoptive transfer of SSCH-D. On the other hand, adoptive transfer of SSCH-D to naive mice had no significant effect on the recipients' antitussive sensitivities to morphine and DAMGO when assessed 1 week after transfer of SSCH-D. However, when the antitussive effect was assessed 2 weeks after adoptive transfer of SSCH, the antitussive effect of DAMGO was significantly lower in naive mice injected with SSCH-D than in SSCH-ND-treated naive mice. The reduction in the antitussive effect of DAMGO in naive mice had been injected with SSCH-D 2 weeks before testing was abolished when they were pretreated with naltrindole, a selective delta-opioid receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1994

Effects of clenbuterol, a beta 2-adrenoceptor agonist, on macronutrient selection in rats.

In these studies, clenbuterol, a beta 2-adrenergic agonist, was injected into male rats and the intake of a three-choice macronutrient diet was measured. The intakes of fat and protein were selectively inhibited by clenbuterol in both overnight-fasted and freely fed rats. There was no effect of clenbuterol on carbohydrate intake. Prior administration of nadolol, a beta-adrenergic antagonist, which does not easily pass the blood-brain barrier, completely antagonized the anorectic effect of clenbuterol. However, section of the hepatic branch of the vagus nerve did not abolish the nadolol effect. These results suggest that the anorectic effect of clenbuterol is mediated by peripheral beta 2-adrenergic receptors rather than central beta 2-adrenoceptors, and is not related to information transmitted from the liver via the vagus nerve.

Afferent Pathways↗
PubMed1994

Cellular localization of matrix metalloproteinases in the abdominal aortic aneurysm wall.

PURPOSE: This study explores the source(s) of the matrix-degrading proteinases, matrix metalloproteinase 1 (MMP-1; interstitial collagenase), matrix metalloproteinase 3 (MMP-3; stromelysin 1), and matrix metalloproteinase 9 (MMP-9; gelatinase B), previously implicated in abdominal aortic aneurysm (AAA) development. The possible involvement of the plasmin cascade in the activation of these proteinases was also explored by examining the presence of the urokinase-type plasminogen activator (uPA) in aneurysm wall. METHODS: Immunohistochemical techniques were used to detect the presence of MMP-1, MMP-3 and MMP-9 proteins and uPA in fixed, paraffin-embedded tissue sections from AAA (n = 10) and control (n = 2) aortas. RESULTS: The MMP-9 protein was localized to mononuclear cells in the AAA wall. Dual-labeling techniques confirmed the identity of these cells as macrophages. The MMP-3 protein and uPA were also detected primarily in the macrophage-like mononuclear cells infiltrating the aneurysmal aorta. Immunoreactive material to MMP-1 was demonstrated in mesenchymal cells of the AAA wall suggesting alternative expression and delivery of this enzyme in AAA. CONCLUSIONS: This work establishes the role of macrophages in the delivery, expression, and possible activation of matrix destructive proteinases during AAA pathogenesis and suggests a role for the activation of MMPs in the progression of the disease.

Antibodies, Monoclonal↗
PubMed1994

Serum creatinine level in predicting the development of hypertension. Ten-year follow-up of Japanese adults in a rural community.

In a 10-year prospective study, we investigated the utility of the serum creatinine level in predicting the development of hypertension in Japanese adults, all of whom lived in a rural community. The study included 229 subjects, 91 men and 138 women aged 30 to 69 years, who were normotensive (systolic blood pressure 140 mm Hg or less and diastolic blood pressure 90 mm Hg or less) and had no prior history of antihypertensive treatment at baseline (1979 to 1980). Hypertension was defined as systolic blood pressure more than 140 mm Hg and diastolic blood pressure more than 90 mm Hg and starting antihypertensive medication. Stepwise proportional hazard analysis selected serum creatinine (P < .001) as an independent, significant predictor of hypertension together with systolic blood pressure (P < .001), age at entry (P < .001), body mass index (P = .008), and diastolic blood pressure (P = .011). The age- and sex-adjusted relative risk for subjects with a serum creatinine level of 1.2 mg/dL or higher compared with those with a level less than 1.1 mg/dL was 0.42 (95% confidence interval, 0.25 to 0.71). The mechanism of this association might relate to muscle mass and physical exercise or, possibly, to a primary renal abnormality. It appeared that the serum creatinine level may be useful in predicting future hypertension.

Adult↗
PubMed1994

Alternative splicing of the NF2 gene and its mutation analysis of breast and colorectal cancers.

To investigate a potential role of NF2, the gene responsible for hereditary bilateral acoustic neurinomas, during carcinogenesis of non-neurogenic tissues, we screened somatic mutations of NF2 in 55 breast cancers and 44 colorectal carcinomas by an RNase protection assay coupled with the reverse-transcriptase polymerase chain reaction (RT-PCR). By screening the entire coding region of the gene in these tumors, we detected missense mutations in the exon encoding the alpha-helical domain of the NF2 product in two colorectal carcinomas. No mutations were detected in any of the breast cancers. Our results suggested that inactivation of the NF2 gene was associated with carcinogenesis in some, but not the majority of, colorectal tumors. In the course of these analyses, we found various alternatively-spliced forms of NF2 transcript. These variants showed no specificity among the tissues examined except for one that resulted from alternative splicing at the 3'-region; this form was more abundantly expressed in skeletal and cardiac muscles than in other tissues.

Amino Acid Sequence↗
PubMed1994

Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm.

A prominent metalloproteinase activity with an apparent molecular mass of 80 kD and additional activities at 67 through 70, 50, and 32 kD have been observed on casein, gelatin, and elastin gel zymography in extracts from abdominal aortic aneurysms (AAAs). The forms at 80, 50, and 32 kD were isolated by affinity to recombinant tissue inhibitor of metalloproteinases, and the 80-kD and 50-kD components were shown to be derived from matrix metalloproteinase-9 (MMP-9). The relative electrophoretic mobility of these forms under reducing and nonreducing conditions corresponds to those of MMP-9 generated by MMP-3 (stromelysin-1) cleavage, and the active forms of MMP-3 at 45 and 35 kD were detected in aneurysmal extracts under reducing conditions by using specific antibody. Confirmation that the major proteolytic activity observed at 80 kD is MMP-9 was also demonstrated by immunoprecipitation of the activity with specific antibody. Comparative immunoblots of tissue extracts from 10 typical AAA patients, using specific antibody against MMP-9, revealed bands at 92, 82, 67, 51 through 53, 27, 23, and 20 kD under reducing conditions; six aortic control specimens displayed negligible immunoreactivity. This report is the first to show that known activated forms of MMP-3 and MMP-9 are present in the aneurysmal aortic wall and that they may play a role in the destruction of aortic matrix in AAA disease.

Aorta, Abdominal↗
PubMed1994

Proteolysis of insulin-like growth factor binding protein-3 during rat pregnancy: a role for matrix metalloproteinases.

Insulin-like growth factor binding protein-3 (IGFBP-3) is degraded by a cation-dependent protease(s) present in the serum of late gestation rats. Proteolysis of IGFBP-3 results in an increase in IGF-I clearance and possibly in IGF bioavailability. Based on our previous findings that matrix metalloproteinases (MMPs) degrade IGFBP-3 in fibroblast conditioned media, we hypothesized that MMPs might be involved in the degradation of IGFBP-3 by rat pregnancy serum. In the present study, we demonstrate that tissue inhibitor of metalloproteinases (TIMP-1), a specific inhibitor of all MMPs, inhibited significantly the degradation of 125I-rhIGFBP-3 by both rat pregnancy serum and rat placental extracts. Purified human MMPs (principally MMP-1 and MMP-3) degraded IGFBP-3 in solution; MMP-3 produced a pattern of IGFBP-3 degradation products identical in size to the fragments produced by pregnancy serum. Furthermore, the combined addition of antihuman MMP-1 IgG and anti-human MMP-3 IgG to rat pregnancy serum blocked almost completely the degradation of 125I-rhIGFBP-3, suggesting that these two MMPs are the principal MMPs involved in IGFBP-3 degradation in rat pregnancy serum. Together, these data suggest that MMPs function as IGFBP-3-degrading proteases in the serum of late gestational pregnant rats.

Animals↗
PubMed1994

Matrix metalloproteinase production by cultured human endometrial stromal cells: identification of interstitial collagenase, gelatinase-A, gelatinase-B, and stromelysin-1 and their differential regulation by interleukin-1 alpha and tumor necrosis factor-alpha.

Matrix metalloproteinases (MMPs) together degrade virtually all the components of the extracellular matrix and are likely to play a role in remodeling of endometrial tissue during the normal menstrual cycle. Primary cultures of human endometrial stromal cells secreted a number of MMPs. MMP-1 (interstitial collagenase) and MMP-3 (stromelysin-1) were measured in culture medium by specific enzyme assays. Production of the enzymes did not correlate with the time of the menstrual cycle at which the tissue was collected. Identities of MMP-1 and MMP-3 were confirmed by Western blots, by comparison of mol wt with those of purified enzymes on casein zymography, and by inhibition of these activities with EDTA and 1,10-phenanthroline. Northern analysis demonstrated specific messenger ribonucleic acid for pro-MMP-1 and pro-MMP-3 in phorbol myristate acetate-stimulated stromal cells. Two gelatinases were detected by gelatin zymography: MMP-2 (gelatinase-A) was present in two forms (72 and 67 kilodaltons), and MMP-9 (gelatinase-B) was present as a homodimer with a mol wt of approximately 180 kilodaltons. MMP-9, but not MMP-2, secretion was stimulated by phorbol myristate acetate. All enzymes could be activated in vitro by (4-aminophenyl)mercuric acetate. Both interleukin-1 alpha and tumor necrosis factor-alpha stimulated the secretion of MMP-1, MMP-3, and MMP-9, but not MMP-2, from the cells in a concentration-dependent manner. MMP production by endometrial stromal cells has a potentially important role in the processes of menstruation and implantation.

Blotting, Western↗
PubMed1994

Blockade of delta-opioid receptors prevents morphine-induced place preference in mice.

Effects of highly selective delta-opioid receptor antagonists on the morphine-induced place preference in ddY and mu 1-opioid receptor deficient CXBK mice were investigated. Pretreatment with naltrindole (NTI: a non-selective delta-opioid receptor antagonist), 7-benzylidenenaltrexone (BNTX: a selective delta 1-opioid receptor antagonist) or naltriben (NTB: a selective delta 2-opioid receptor antagonist) abolished the morphine-induced place preference in ddY mice in a dose-dependent manner. These findings suggest that the morphine-induced place preference may be mediated by both delta 1- and delta 2-opioid receptors. On the other hand, in mu 1-opioid receptor deficient CXBK mice, pretreatment with these selective delta-opioid receptor antagonists did not affect the morphine-induced place preference, although pretreatment with beta-funaltrexamine (beta-FNA: a selective mu-opioid receptor antagonist) significantly inhibited the morphine-induced place preference. [D-Pen2,D-Pen5]enkephalin (DPDPE: a delta 1-opioid receptor agonist) and [D-Ala2,Glu4]deltorphin (deltorphin II: a delta 2-opioid receptor agonist) induced a significant place preference in ddY mice, but not in CXBK mice. These results suggest that delta 1- and delta 2-opioid receptors in the nucleus accumbens that are related to the DPDPE- and deltorphin II-induced place preference may be dysfunctional and/or poor in CXBK mice. These findings also indicate that delta 1- and delta 2-opioid receptors may be involved in the modulation of the reinforcing effect of morphine.

Analgesics↗
PubMed1994

Modulation of production of matrix metalloproteinases from ovine endometrial cells by ovine trophoblast interferon.

Ovine trophoblast interferon modulates the secretion of a number of proteins by ovine endometrium, but only one of these proteins has so far been identified. We examined the effects of trophoblast interferon on the secretion of matrix metalloproteinase-1, -2 and -3 by cultured ovine endometrial cells and determined whether they are mediated via effects on prostaglandin synthesis. Both ovine trophoblast interferon (30 ng ml-1) and human recombinant interferon alpha (50 U ml-1) inhibited the production of latent matrix metalloproteinase-1 and -3 (P < 0.05), as measured by enzyme assays, but had no effect on the secretion of latent matrix metalloproteinase-2. These inhibitory effects were not overcome by PGE2 or PGF2 alpha (each 10 mumol l-1) either alone or in combination. Indomethacin (12 mumol l-1) similarly inhibited the production of latent matrix metalloproteinase-1 and -3, but production was partially restored by adding the prostaglandins either singly or in combination. PGE2 and PGF2 alpha together had no effect on enzyme production. These data were confirmed by gelatin and casein zymography. Northern analysis showed a 4.5-fold increase in the abundance of specific mRNA for latent matrix metalloproteinase-1 following treatment of cells with phorbol myristate acetate, but a marked decrease following interferon treatment. Thus, ovine trophoblast interferon inhibits the production of the latent forms of matrix metalloproteinase-1 and -3 by ovine endometrial cells, and this is independent of its effect on prostaglandin production.

Animals↗