Biomedical subjects

H Nagase

Publications and source records attributed to H Nagase.

At least 145 records · Page 8Linked to original sources

PubMed1999

kappa-Opioid receptor-mediated antinociceptive effects of stereoisomers and derivatives of (+)-matrine in mice.

The antinociceptive effects of seven matrine-type lupin alkaloids were examined using the acetic acid-induced abdominal contraction test (the writhing test) and the tail-flick test in mice. (+)-Allomatrine, the C-6 epimer of (+)-matrine, produced the antinociceptive effect at 1/3 potency of (+)-matrine or pentazocine. It was demonstrated that the antinociceptive effects of (+)-allomatrine were mediated through the activation of kappa-opioid receptors, while the antinociceptive effect of (+)-matrine was mediated by both mu- and kappa-opioid receptors. (-)-Sophoridine, the C-6 epimer of (+)-matrine, (+)-sophoranol, (-)-14 beta-hydroxymatrine and (+)-matrine N-oxide, which possess a hydrophilic group, and (-)-sophocarpine and (-)-sophoramine having a double bond(s) did not show significant antinociceptive activity.

Alkaloids↗

PubMed1999

Interaction of cyclomaltononaose (delta-CD) with several drugs.

The effects of delta-cyclodextrin (delta-CD; cyclomaltononaose) on solubility of 14 drugs that are slightly soluble or insoluble in water were studied and compared with those of conventional cyclodextrins (CDs) such as alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), and gamma-cyclodextrin (gamma-CD). In general, delta-CD had a weak complex-forming ability with the drugs examined in comparison with beta-CD and gamma-CD. However, in the case of digitoxin, delta-CD enhanced solubility of the guest molecules. To determine the mechanism of inclusion complex formation of delta-CD with digitoxin, the interaction of both drugs was investigated by the solubility method and spectroscopic methods such as ultraviolet (UV) and 1H-NMR (nuclear magnetic resonance). The changes in chemical shift (1H) and hypsochromic shift of UV suggested that digitoxin was partially included in the cavity of delta-CD.

Chemistry, Pharmaceutical↗

PubMed1999

Endoproteinase-protein inhibitor interactions.

Nature uses protein inhibitors as important tools to regulate the proteolytic activity of their target proteinases. Most of these inhibitors for which 3D structures are available are directed towards serine proteinases, interacting with their active-sites in a substrate-like "canonical" manner via an exposed reactive-site loop of conserved conformation. More recently, some non-canonically binding serine proteinase inhibitors, two cysteine proteinase inhibitors, and three zinc endopeptidase inhibitors have been characterized in the free and complexed state, displaying novel mechanisms of inhibition with their target proteinases. These different interaction modes are briefly discussed, with particular emphasis on the interaction between matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors of metalloproteinases (TIMPs).

Animals↗

PubMed1999

n-Hexane neuropathy caused by addictive inhalation: clinical and electrophysiological features.

To assess the clinical and electrophysiological features of n-hexane neuropathy caused by addictive inhalation, 4 patients were studied in the progressive phase. The neurological manifestations were characterized by subacute predominantly motor polyneuropathy and disease progression despite discontinuance of the chemicals, which were similar to those reported in industrial exposure, although with a severer degree associated with anorexia and body weight loss. Electrophysiological studies showed that all showed multifocal conduction block and profound conduction slowing, as well as features of axonal degeneration. Sural nerve biopsy showed axonal loss, axonal swelling, and thin myelin probably due to retraction by axonal swelling. n-Hexane abuse causes severe subacute polyneuropathy. The mixed axonal and demyelinating electrophysiological features were consistent with peculiar pathological findings. Conduction block, probably due to paranodal myelin retraction or ongoing wallerian degeneration, is very frequent and could be responsible for the clinical deficits, especially in the early phase of illness.

Administration, Inhalation↗

PubMed1999

Acquired factor VIII inhibitor in a non-hemophilic patient with chronic hepatitis C viral infection.

Production of coagulation factor VIII inhibitor is rarely encountered in non-hemophilic patients. A 63-year-old Japanese male suffered from severe bleeding tendency caused by this inhibitor. Although he did not have malignancy or collagen disease, he had chronic hepatitis C virus (HCV) infection. Although HCV is known to induce production of various autoimmune antibodies, this may be the first report of a case with both acquired factor VIII inhibitor and HCV infection.

Blood Coagulation Factors↗

PubMed1999

[Cross-sectional study of factors related to Achilles bone mineral density measured by an ultrasound system].

A cross-sectional study was conducted to examine the relationship between bone mineral density (BMD) and life-style related factors including exercise and dietary habits in 1016 pre-menopausal women and 856 post-menopausal women in Ishikawa Prefecture, Japan. The achilles BMD in 1,872 women ages between 19 and 85 years were measured from 1995 to 1996 by an ultrasound system. The stiffness index calculated by the Lunar Achilles ultrasound machine was used as the BMD in this analysis. Self-administered questionnaires were used to obtain the following information: medical history, pregnancy, delivery and menstrual history, height at 20-years of age, present number of teeth, fracture history, sports exercise history, food intake frequency, smoking and drinking history, and daily physical activity. Analysis of covariance and multiple regression analysis were performed to evaluate the contribution of life-style related factors to BMD after adjustment for age and BMI (Body mass index) in pre- and post-menopausal women, respectively. Results were as follow: 1) BMD was inversely associated with increasing age in pre- and post-menopausal women. The BMD level of post-menopausal women were lower than that of pre-menopausal women in each 5-year age group. The pearson's correlatin coefficient between age and BMD was significant at -0.25 and -0.44 in pre- and post-menopausal women, respectively. 2) Body mass index (BMI) and BMD were positively correlated in pre- and post-menopausal women. 3) In pre-menopausal women, lower BMD was associated with the following factors: age, lower BMI, no history of joining a sports club in junior high school, absence of current regular sports, being inactive in daily life, having joint pains, lower number of remaining teeth and lower dairy product intake. 4) In post-menopausal women, lower BMD was associated with the following factors: age, lower BMI, no history of joining a sports club in junior high school, past history of fracture and longer post-menopausal years. Factors associated with lower BMD in this study were regarded as risk factors for future osteoporotic fractures in the elderly, or signs of lower BMD. Therefore, the information of these factors should be employed in health education for the prevention of osteoporosis. Especially, participating in a sports club while in junior high school may be a recommendation for acquiring higher BMD even in the post-menopausal period.

Adult↗

PubMed1999

Involvement of spinal delta 1-opioid receptors in forced walking stress-induced antinociception in the tail-flick test in mice.

The purpose of this study was to elucidate the involvement of spinal delta-opioid receptor subtypes in forced walking stress-induced antinociception mice. We first confirmed that forced walking stress produced walking duration-dependent antinociception in mice as determined by the tail-flick test. Intrathecal treatment with 7-benzylidenenaltrexone, a selective delta 1-opioid receptor antagonist, significantly attenuated forced walking stress-induced antinociception. In contrast, intrathecal treatment with naltriben, a selective delta 2-opioid receptor antagonist, had no significant effect on forced walking stress-induced antinociception. Intracerebroventricular treatment with either 7-benzylidenenaltrexone or naltriben had no effect on the forced walking stress-induced antinociception. These results suggest that forced walking stress-induced antinociception is mediated by spinal delta 1-opioid receptors in mice.

Analgesics↗

PubMed1998

Interleukin-12 expression in B cells by transformation with Epstein-Barr virus.

Although interleukin (IL)-12 was originally purified from an Epstein-Barr (EBV)-transformed B cell line and the high correlation of EBV infection and IL-12 expression has been suggested, no study has reported whether EBV infection is directly linked to IL-12 expression. To address this issue, we have investigated IL-12 expression in B cells during in vitro transformation with EBV. Human peripheral B cells became capable of constitutively producing p40 by in vitro transformation with EBV, coincident with the expression of latent membrane protein 1 (LMP1) of EBV. These B cells expressed p40 and p35 mRNA, and phorbol myristate acetate (PMA) stimulation strongly enhanced p40 and p70 production. Furthermore, transfection with LMP1 expression vector into a human B lymphoma cell line, Daudi, led to p40 production with nuclear factor (NF)-kappaB activation. These results suggest that transformation of primary B cells with EBV induces IL-12 expression potentially through LMP1 expression.

B-Lymphocytes↗

PubMed1998

Selective localization of matrix metalloproteinase 9, beta1 integrins, and human lymphocyte antigen class I molecules on membrane vesicles shed by 8701-BC breast carcinoma cells.

The shedding of membrane vesicles from the cell surface is a vital process considered to be involved in cell-cell and cell-matrix interactions and in tumor progression. By immunoelectron microscopic analysis of surface replicas of 8701-BC human breast carcinoma cells, we observed that membrane vesicles shed from plasma membranes contained densely clustered gelatinase B [matrix metalloproteinase 9 (MMP-9)], beta1 integrins, and human lymphocyte antigen class I molecules. By contrast, alpha-folate receptor was uniformly distributed on the smooth cell membrane and shedding areas. Both cell surface clustering of selected molecules and membrane vesicle release were evident only when cells were cultured in the presence of serum. Vesicle shedding occurred preferentially at the edge or along narrow protrusions of the cell. Specific accumulation of proMMP-9 and active forms of MMP-9 in shed vesicles was also demonstrated by gelatin zymography. In addition, Western blotting analysis showed the presence of a large amount of proMMP-9/tissue inhibitor of metalloproteinase 1 complex. The release of selected areas of plasma membranes enriched with MMP-9 and beta1 integrins indicates that membrane vesicle shedding from tumor cells plays an important role in the directional proteolysis of the extracellular matrix during cellular migration. The presence of human lymphocyte antigen class I antigens suggests a mechanism for tumor cells to escape from immune surveillance.

Breast Neoplasms↗

PubMed1998

Plasma membrane-bound tissue inhibitor of metalloproteinases (TIMP)-2 specifically inhibits matrix metalloproteinase 2 (gelatinase A) activated on the cell surface.

The cell-surface activation of pro-matrix metalloproteinase 2 (pro-MMP-2) is considered to be critical for cell migration and invasion. Treatment of human uterine cervical fibroblasts with concanavalin A activates pro-MMP-2 on the cell surface by converting it to the 65-kDa form with a minor form of 45 kDa. However, the 65-kDa MMP-2 was inactivated by tissue inhibitor of metalloproteinases (TIMP)-2 that was bound to the plasma membrane upon concanavalin A treatment. TIMP-2 binds to the plasma membrane through its N-terminal domain by two different modes of interaction as follows: one is sensitive to a hydroxamate (HXM) inhibitor of MMPs and the other is HXM-insensitive. TIMP-2 bound to the membrane in a HXM-insensitive manner, comprising about 40-50% of TIMP-2 on the membrane, is the inhibitor of the cell surface-activated MMP-2. It, however, does not inhibit MMP-3, MMP-9, and the 45-kDa MMP-2 lacking the C-terminal domain. The inhibition of the 65-kDa MMP-2 by TIMP-2 is initiated by the interaction of their C-terminal domains. Subsequently, the MMP-2.TIMP-2 complex is released from the membrane, and the activity of MMP-2 is blocked by TIMP-2. In the presence of collagen types I, II, III, V, or gelatin, the rate of inhibition of the 65-kDa MMP-2 by the membrane-bound TIMP-2 decreased considerably. These results suggest that the pericellular activity of MMP-2 is tightly regulated by membrane-bound TIMP-2 and surrounding extracellular matrix components.

Animals↗

PubMed1998

Involvement of mu- and delta-opioid receptors in the ethanol-associated place preference in rats exposed to foot shock stress.

The purpose of this study was to establish the ethanol-induced place preference in rats exposed to foot shock stress using the conditioned place preference paradigm. We also investigated the role of the endogenous opioid system in the development of the ethanol-induced place preference. The administration of ethanol (300 mg/kg, i.p.) with foot shock stress, but not without such stress, induced a marked and significant place preference. Naloxone (1 and 3 mg/kg, s.c.), a non-selective opioid receptor antagonist, significantly attenuated the ethanol-induced place preference. Moreover, the selective mu-opioid receptor antagonist beta-funaltrexamine (3 and 10 mg/kg, i.p.) and selective delta-opioid receptor antagonist naltrindole (1 and 3 mg/kg, s.c.), but not the selective kappa-opioid receptor antagonist nor-binaltorphimine (1 and 3 mg/kg, i.p.), significantly attenuated the ethanol-induced place preference. Furthermore, 150 mg/kg ethanol (which tended to produce a place preference, although not significantly) combined with each dose (that did not produce a place preference) of the mu-opioid receptor agonist morphine (0.1 mg/kg, s.c.) or selective delta-opioid receptor agonist 2-methyl-4aalpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12, 12aalpha-octahydroquinolino [2,3,3-g] isoquinoline (TAN-67; 20 mg/kg, s.c.), but not the selective kappa-opioid receptor agonist trans-3, 4-dichloro-N-(2-(1-pyrrolidinyl)cyclohexyl)benzenacetamide methanesulfonate (U50,488H; 1 mg/kg, s.c.), produced a significant place preference. These data indicate that stress may be important for development of the rewarding effect of ethanol, and that mu- and delta-opioid receptors may be involved in the rewarding mechanism of ethanol under stressful conditions.

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

PubMed1998

TIMP-1 contact sites and perturbations of stromelysin 1 mapped by NMR and a paramagnetic surface probe.

Surfaces of the 173 residue catalytic domain of human matrix metalloproteinase 3 (MMP-3(DeltaC)) affected by binding of the N-terminal, 126 residue inhibitory domain of human TIMP-1 (N-TIMP-1) have been investigated using an amide-directed, NMR-based approach. The interface was mapped by a novel method that compares amide proton line broadening by paramagnetic Gd-EDTA in the presence and absence of the binding partner. The results are consistent with the X-ray model of the complex of MMP-3(DeltaC) with TIMP-1 (Gomis-Rüth et al. (1997) Nature 389, 77-81). Residues Tyr155, Asn162, Val163, Leu164, His166, Ala167, Ala169, and Phe210 of MMP-3(DeltaC) are protected from broadening by the Gd-EDTA probe by binding to N-TIMP-1. N-TIMP-1-induced exposure of backbone amides of Asp238, Asn240, Gly241, and Ser244 of helix C of MMP-3(DeltaC) to Gd-EDTA confirms that the displacement of the N-terminus of MMP-3(DeltaC) occurs not only in the crystal but also in solution. These results validate comparative paramagnetic surface probing as a means of mapping protein-protein interfaces. Novel N-TIMP-1-dependent changes in hydrogen bonding near the active site of MMP-3(DeltaC) are reported. N-TIMP-1 binding causes the amide of Tyr223 of MMP-3(DeltaC) bound by N-TIMP-1 to exchange with water rapidly, implying a lack of the hydrogen bond observed in the crystal structure. The backbone amide proton of Asn162 becomes protected from rapid exchange upon forming a complex with N-TIMP-1 and could form a hydrogen bond to N-TIMP-1. N-TIMP-1 binding dramatically increases the rate of amide hydrogen exchange of Asp177 of the fifth beta strand of MMP-3(DeltaC), disrupting its otherwise stable hydrogen bond.

Amides↗

PubMed1998

Epithelial carcinogenesis in the mouse: correlating the genetics and the biology.

Tumour formation relies on a complex combination of genetic and environmental factors. In particular, the contributions from inherited predisposition genes as well as carcinogens, for example from cigarettes or in the diet, are amongst the major contributors to tumorigenesis. Since the study of such processes in particularly difficult in human cancers, the availability of a well-defined model system is of obvious benefit. The mouse skin model of multistage carcinogenesis offers an excellent tool for the study of the target cells, the target genes and the biological events associated with neoplasia. In this system, tumorigenesis occurs in a series of defined stages, each of which is characterized by specific and reproducible alterations in genes such as H-ras, cyclin D1, p53 and p16INK4A. Additional changes occur in the production of, or response to, factors such as transforming growth factor beta (TGF beta). These genetic and biological alterations are mirrored in human tumours of epithelial origin. Hence, research into the general principles of tumour initiation, promotion and progression in the context of the mouse skin model is likely to prove valuable in the continual search for new methods for the diagnosis, prevention, and therapeutic treatment of human cancers.

Animals↗

PubMed1998

Characterization of endomorphin-1 and -2 on [35S]GTPgammaS binding in the mouse spinal cord.

In the present study, G-protein activation by newly-isolated opioid peptides, endomorphin-1 and -2, was examined in the mouse spinal cord by monitoring the binding of the non-hydrolyzable analog of GTP, guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS). Both endomorphin-1 and -2 increased [35S]GTPgammaS binding to mouse spinal cord membranes in a concentration-dependent and saturable manner and reached a maximal stimulation of 57.3+/-5.0 and 60.2+/-3.2%, respectively, at 10 microM. In contrast, the synthetic selective micro-opioid receptor agonist [D-Ala2,NHPhe4,Gly-ol]enkephalin (DAMGO) had a much greater efficacy and produced 103.4+/-5.4% of the maximal stimulation. The receptor specificity of endomorphin-stimulated [35S]GTPgammaS binding was verified by co-incubating membranes with endomorphins in the presence of specific micro-(beta-funaltrexamine and D-Phe-Cys-D-Tyr-Om-Thr-Pen-Thr-NH2 (CTOP)), delta-(naltrindole) or K-(nor-binaltorphimine) opioid receptor antagonists. Co-incubation with either beta-funaltrexamine or CTOP blocked both endomorphin-1- and-2-stimulated [35S]GTPgammaS binding in a concentration-dependent manner, whereas neither naltrindole nor nor-binaltorphimine had any effect on the [35S]GTPgammaS binding stimulated by either endomorphin-1 or -2. The data presented indicate that either endomorphin-1 or -2 activate G-proteins by specific stimulation of micro-opioid receptors, and may act as partial agonists with moderate catalytic efficacies in the mouse spinal cord.

Animals↗

PubMed1998

Temperature change of the lamellar structure of DPPC/disaccharide/water systems with low water content.

Temperature change in l-alpha-dipalmitoyl phosphatidylcholine (DPPC)/disaccharide systems with low water content (less than 8 wt. %) was investigated using X-ray diffraction within a range of two transition temperatures. X-ray diffraction above the higher transition temperature showed a broad symmetric peak, indicating the Lalpha phase. Below the higher transition temperature, two overlapping diffraction peaks were observed. After peak separation, temperature change in these systems was analyzed using peak parameters of the two peaks. Peak parameters of the lower angle peak changed continuously up to and above the higher transition temperature, suggesting the systems to be in a liquid crystal phase below the higher transition temperature. Fourier-transform infrared (FT-IR) spectra of the DPPC/trehalose system with 5.5 wt.% water showed the wave number of asymmetric stretching of phosphate groups to change at the lower transition temperature and that of symmetric stretching of CH2 groups, to change between the lower and higher transition temperatures. Thus, below the lower transition temperature, the system is shown to be in a gel phase. Conformational change in phosphate groups occurred at the lower transition temperature. Within the lower and higher transition temperatures, two phases were found to coexist and transition from the gel phase to Lalpha phase to occur continuously. Above the higher transition temperature, the system is in the Lalpha phase.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1998

Augmentation of allergic reactions by several pesticides.

The augmentative effects of several pesticides on histamine release from mast cells of rats that had been sensitized passively by anti-dinitrophenol (DNP) monoclonal IgE antibodies were investigated in vitro. Various pesticides, especially phenthoate (PAP), chlornitrofen (CNP) and paraquat (PQ), increased histamine release. This increase was not observed in histamine release with non-antigen or induction by calcium ionophore A23187 or compound 48/80. Passive cutaneous anaphylaxis (PCA) was examined, and an increase of PCA was observed with PAP and PQ, but not with CNP, while an increase of tumor necrosis factor-alpha (TNF-alpha) production was observed with CNP and PQ, but not PAP. These results suggest that various pesticides as environmental pollutants exacerbate allergic diseases.

Anaphylaxis↗

PubMed1998

Calmodulin antagonists increase the expression of membrane-type-1 matrix metalloproteinase in human uterine cervical fibroblasts.

The treatment of human uterine cervical fibroblasts with concanavalin A (ConA), or a specific calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) or trifluoperazine resulted in accumulation of an active form of matrix metalloproteinase 2 (MMP-2, gelatinase A). In contrast, N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5), a weaker antagonist of calmodulin, did not modulate the activation of proMMP-2. The activation of proMMP-2 was confirmed by the enhanced activity on gelatin and the conversion of proMMP-2 to a 62-kDa form by zymography and western blotting. The plasma membrane, but not the conditioned medium, of the W-7- or trifluoperazine-treated cells activated proMMP-2; this activation was blocked by membrane-type-1 MMP (MT1-MMP) antibody and EDTA. The plasma membrane from trifluoperazine- or ConA-treated cells contained MT1-MMP and tissue inhibitor of metalloproteinases 2. Both trifluoperazine treatment and ConA treatment increased the steady-state levels of MT1-MMP mRNA and proMMP-2 mRNA. These results, together with our previous observations on the production of proMMP-1 (interstitial procollagenase) and proMMP-3 (prostromelysin 1) [Ito, A., Sato, T., Ojima, Y., Chen, L.-C., Nagase, H. & Mori, Y. (1991) J. Biol. Chem. 266, 13598-13601], suggest that calmodulin negatively regulates the matrix turnover by suppressing the production of a number of proMMPs including proMMP-1, proMMP-3 and MT1-MMP, and the activation of proMMP-2 in human uterine cervical fibroblasts.

Calmodulin↗

PubMed1998

Novel mutant mice secreting soluble CD4 without expression of membrane-bound CD4.

Mutant mice derived from C57BR/cdJ mice were found to have a novel genetic defect in CD4 expression. Flow-cytometric analysis demonstrated that there were no CD4+ cells in either the thymus or the peripheral lymphoid organs of the mutant mice. Thymocytes of the mutant mice expressed an amount of CD4 mRNA comparable to normal mouse thymocytes, but the mutant CD4 mRNA was slightly smaller in size than normal CD4 mRNA. The sequence analysis of the mutant CD4 cDNA obtained from thymic RNA revealed that the defect in the CD4 expression was attributable to the deletion of the entire exon VIII, encoding a transmembrane domain of the CD4 molecule. Moreover, soluble CD4 was detected both in the culture supernatant of thymocytes and sera from mutant mice. The analysis of the genomic DNA sequence elucidated that one thymine was substituted for 14 base pairs at the junction between exon VIII and intron VIII in the mutant mice, which could possibly account for the alternative splicing of CD4 mRNA. These mutant mice showed reduced delayed-type hypersensitivity reactions against sheep red blood cells and antibody production against T-dependent antigen but not against T-independent antigen. Thus, these mutant mice have a novel defect in CD4 expression where CD4 mRNA is alternatively spliced to delete a transmembrane domain, giving rise to secretion of soluble CD4 instead of expression of membrane-bound CD4.

Amino Acid Sequence↗