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Biomedical subjects

K Iwata

Publications and source records attributed to K Iwata.

At least 181 records · Page 10Linked to original sources
PubMed1995

Disposition of diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) in rats.

The disposition of diadenosine 5'5"'-P1,P4-tetraphosphate (Ap4A), an endogenous dinucleotide, was investigated in rats. The degradation of Ap4A in rat plasma was very rapid and could be explained by a Michaelis-Menten equation: Km and Vmax values were 1.69 micrograms/ml and 4.32 micrograms/min/ml, respectively. Ap4A was degraded in rat plasma to ATP and AMP, but not to 2 ADP molecules, and these nucleotides were further degraded through adenosine. The degradations kinetics were examined. After intravenous bolus injection, Ap4A in plasma declined rapidly and the rate of elimination was dose-dependent: the biological half-life was about 3s at the dose of 1 mg/kg and was longer at 3 mg/kg. When Ap4A was administered by intravenous infusion (0.5 or 1.0 mg/kg/min), the plasma level rapidly reached a steady-state, which then rapidly declined after stopping the infusion.

Adenosine↗
PubMed1995

Ca2+ dependency of diadenosine 5',5"'-p1,p4-tetraphosphate degradation in dog plasma.

Diadenosine 5',5"'-p1,p4-tetraphosphate (Ap4A) degradation in dog plasma was inhibited by the addition of EDTA. The Ap4A degrading activity seemed to be recovered by the addition of metal ions, Ca2+, Co2+, Cu2+, Mg2+, Mn2+ or Zn2+ to plasma in which the activity was lost by the addition of EDTA. Especially, the degradation was accelerated by the addition of Ca2+ to the plasma, and the degradation rate was dependent on the concentration of Ca2+. The results of this study suggested that the enzymatic degradation of Ap4A in dog plasma was modulated by the concentration of Ca2+.

Adult↗
PubMed1995

[The uptake of nalidixic acid and enoxacin by rat renal cortical slices in rat].

The mechanisms involved in the renal excretion of quinolone and new quinolone antibacterial drugs are still incompletely understood. The purpose of this study was to examine the renal handling of nalidixic acid (NA) and enoxacin (ENX), using the renal cortical slices uptake techniques in rats. It was demonstrated that both NA and ENX were taken against a concentration gradient by a saturable processes resulting from the ratio of slice to medium (ratio of S/M) being dependent on the time and the concentration. It was indicated that the inhibition of uptake by 2,4-dinitrophenol, ouabain and sodium cyanate was shown to be an energy dependence. Probenecid and cimetidine exhibited that they might inhibit NA uptake slightly. ENX uptake was inhibited by probenecid, cimetidine, guanidine and disopyramide, suggesting that ENX might possess an affinity for both anionic and cationic transport mechanisms.

Animals↗
PubMed1995

Mucosal protective effect of leminoprazole on reflux esophagitis induced in rats.

We examined the effect of leminoprazole (an acid pump inhibitor) on reflux esophagitis induced in rats. Intragastrically administered leminoprazole significantly and dose-dependently protected the esophageal mucosa against the reflux of gastric contents, without affecting gastric acid secretion. However, it had no effect on the esophagitis when administered intraduodenally, despite its significant inhibition (about 40%) of gastric acid secretion. Omeprazole significantly prevented the development of esophagitis, most probably through potent inhibition of gastric acid secretion. Indomethacin significantly reduced the synthesis of prostaglandin E2 in the esophagus. Since indomethacin pretreatment had no effect on the esophageal protection by leminoprazole, omeprazole or sucralfate, the involvement of endogenous prostaglandins can be ruled out as a possible underlying mechanism. Intragastrically, but not intraduodenally, administered sucralfate significantly prevented the esophagitis even at a dose not affecting gastric acid secretion. These results strongly suggest that both leminoprazole and sucralfate protect the esophageal mucosa directly.

Animals↗
PubMed1995

Cloning, purification, and properties of a cofactor-independent glutamate racemase from Lactobacillus brevis ATCC 8287.

A glutamate racemase gene of Lactobacillus brevis ATCC 8287 was cloned into Escherichia coli TM93 by the phenotypic complementation of a phosphoenolpyruvate carboxylase deficiency on minimum agar medium containing D-glutamate. The gene was localized to a 1.4-kb HindIII-EcoRI DNA fragment and the total nucleotide sequence of the fragment was analyzed. The gene has typical promoter and SD sequences which appeared to function in E. coli. The deduced amino acid sequence of the enzyme had 276 amino acids and the molecular weight was calculated as 29,426. Two cysteine residues and their surrounding regions of the enzyme are homologous to those of other cofactor-independent racemases. The glutamate racemase was purified from recombinant E. coli to homogeneity and characterized. The enzyme required no cofactors for the activity, and retained its activity even in 2 M (300 g/l) L-glutamate.

Amino Acid Isomerases↗
PubMed1995

New thermoluminescent BaSO4:Eu sheet for in vivo measurement of spatial dose distribution in radiation therapy.

A new highly sensitive thermoluminescent (TL) sheet has been studied as a means of in vivo measurement of spatial dose distribution of radiation therapy. This TL sheet (40 cm x 50 cm x 0.2 mm), which is composed of teflon mixed with BaSO4:Eu doped powder, is very flexible and can be cut to the desired size. The TL sheet was found to have a linear response with a very wide dynamic range of at least 0.002 cGy to 5000 cGy absorbed dose. In addition, this sheet does not need be shielded, because of its insensitivity to room light, and therefore the sheet can detect low-energy electrons decreased by a few millimeter thick air for 3H(maximum beta-ray energy: 18 KeV). The spatial dose distribution was printed out with a newly developed digital readout system. In addition, another high-resolution dosimetry system, which exposes X-ray film with TL photons emitted from the irradiated TL sheet at constant room temperature, is reported. Clinically, the in vivo dose distribution on the surface of the rectal cancer for intracavitary radiation therapy was determined. The applicability of TL sheet for in vivo measurement of dose distribution is discussed.

Humans↗
PubMed1995

Mechanism of the hyperthermic effect of the novel thyrotropin-releasing hormone analogue Na-((1S,2R)-2-methyl-4-oxocyclopentylcarbonyl)-L-histidyl-L- prolinamide monohydrate in mice with reserpine-induced hypothermia.

To investigate the mechanism of the antagonistic effect of Na-((1S,2R)-2-methyl-4-oxocyclopentylcarbonyl)-L-histidyl-L-prolin amide monohydrate (CAS 131404-34-7, JTP-2942) on reserpine-induced hypothermia, the role of the autonomic nervous system, adrenal gland, and thyroid gland regarding the effects of JTP-2942 has been studied in mice. Both phenoxybenzamine and propranolol significantly attenuated the hyperthermic effect of JTP-2942 on reserpine-induced hypothermia, although neither drug caused complete inhibition. A high dose of hexamethonium also significantly antagonized the hyperthermic effect of JTP-2942. The hyperthermic effect of JTP-2942 was almost abolished by adrenal demedullation. In mice with thiouracil-induced hypothyroidism, both thyrotropin-releasing hormone (TRH) and JTP-2942 significantly increased the rectal temperature. However, the increase induced by TRH was smaller in hypothyroid mice than in control mice, while the temperature increase induced by JTP-2942 was similar in both hypothyroid and control mice. These results suggest that the hyperthermic effect of JTP-2942 is mainly mediated by the adrenal gland and the autonomic nervous system. In addition, the hypothalamic-pituitary-thyroid axis does not regulate the hyperthermic effect of JTP-2942, unlike that of TRH.

Adrenal Medulla↗
PubMed1995

[Stromelysin-1 (MMP-3) level in the sera from patients with rheumatoid arthritis and other connective tissue diseases--clinical significances in early onset rheumatoid arthritis].

Stromelysin-1 (MMP-3) is a metalloproteinase that degrades articular cartilage matrix in patients with rheumatoid arthritis (RA). We measured MMP-3 in the sera from patients with RA and other connective tissue diseases using specific sandwich EIA and studied its clinical significance in early onset RA. MMP-3 level in healthy control (n = 170) was significantly higher in male than in female. The level of MMP-3 in RA was significantly and dramatically higher than in healthy control, osteoarthritis, systemic lupus erythematosus, progressive systemic sclerosis, primary sjogren's syndrome, mixed connective tissue disease, gouty arthritis and traumatic arthritis. Serum MMP-3 significantly correlated with serum BUN or serum creatinine levels in SLE patients but not in RA patients. In early onset RA, serum MMP-3 level was significantly elevated. Furthermore, when the relationship between the serum MMP-3 level and X-ray findings of the joints in RA was studied, it was found that MMP-3 level was elevated even in stage I or II and that there was no statistical differences between stage I or II and stage III or IV, suggesting that serum MMP-3 level is elevated in the early stage of initial inflammatory process when only mild cartilage degradation is seen. These results suggest that measurements of serum MMP-3 is an important tool for establishing diagnosis of early onset RA, and that serum MMP-3 level may be a marker of cartilage destruction and of estimating therapeutic efficacy in early onset RA.

Aged↗
PubMed1995

[Matrix metalloproteinase in the cynomolugus monkey optic nerve heads].

Gelationolytic and caseinolytic activity of matrix metalloproteinase in normal cynomolugus monkey optic nerve heads was investigated. Optic nerve heads of three eyes were incubated in the media for 20 hours. Each media was applied to the gelatin or casein containing gels, and zymography was performed. Major bands of 94 kDa and 62 kDa gelatinase activities were demonstrated in all three eyes. In one eye gelatinolytic activity of the 58 kDa band was also demonstrated. Caseinase activity was not detected in any of the three optic nerve heads.

Animals↗
PubMed1995

Blocking measles virus infection with a recombinant soluble form of, or monoclonal antibodies against, membrane cofactor protein of complement (CD46).

Human membrane cofactor protein (MCP, CD46) functions as an inhibitor of the complement (C) cascade to protect host cells from C attack, and as a receptor for measles virus (MV). Normal human sera contains 10-60 ng/ml of naturally produced soluble forms of MCP, which is also a cofactor for the factor I-mediated inactivation of C3b. We produced monoclonal antibodies (mAb) against MCP and a recombinant soluble form of MCP similar to the natural soluble forms, and tested their ability to block MV infection. Vero cells and CHO cells expressing human MCP were the targets. Of the antibodies tested, M75 and M177, which blocked the C regulatory activity of MCP, efficiently blocked MV infection. More than 50 micrograms/ml of the soluble form moderately blocked MV infection of CHO cells expressing MCP, but barely blocked that of Vero cells. The two mAb and the soluble form also inhibited MV H protein-mediated green monkey erythrocyte rosette formation. A quantitative analysis suggested that 30 micrograms/ml of the soluble form functionally corresponded to 0.2 microgram/ml of M177 or M75. These data established that the C regulatory function and the MV receptor function of MCP were blocked simultaneously by the individual mAb, and that soluble forms of MCP could inhibit MV infection in cells expressing human MCP, although doses far higher than the natural concentration of soluble MCP were required.

Animals↗
PubMed1995

[Changes of expression in matrix metalloproteinase and its inhibitor level in the sclera from axially elongated eyes].

We studied the gelatinolytic activity, caseinolytic activity and the level of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the sclera from experimentally induced axially elongated eyes. The animal models were made by the injection of 250U alpha-chymotrypsin into the posterior chamber of young albino rabbits. Animals were killed with overdoses of intravenous pentobarbital and eyes were enucleated gently. Sclera from the equatorial area was then subjected to organ culture. The enzyme activity in the media was investigated by zymography using gelatin- or casein-containing gels together with an image analyzer system. TIMP-1 levels in each medium were measured by enzyme immunoassay (EIA). All samples showed three major bands of gelatinolytic activity at molecular weights of 87, 61, and 57 kDa. Gelatinolytic activity of 87 kDa increased 1.1 to 2.9 times compared with control sclera. All of the caseinolytic activity (87, 82, 52, and 50 kDa) was also elevated 1.8 to 6.6 times in samples from experimental eyes. TIMP-1 levels were mildly increased (up to 1.41 times) in the experimental eyes. These data suggest that degradation processes might be accelerated in the sclera from experimentally induced elongated eyes.

Animals↗
PubMed1995

[Ultrastructural changes in the lamina cribrosa in experimental monkey glaucoma].

We examined the ultrastructural changes in the lamina cribrosa in monkeys with experimental chronic glaucoma. In normal monkey eyes, the extracellular matrix consists of tightly packed collagen fibers, elastic fibers and less ground substance in the beams, and basement membranes associated with vascular cells and astrocytes in the lamina cribrosa. In the experimental glaucomatous eyes there was a marked destruction of collagenous bundles. The empty spaces were expanded and filled with fine fibrillar materials. There were normal by appearing parts and clearly destroyed parts mixed in the same region. Elastic fibers looked isolated from the collagenous bundles around them. Basement membranes were generally thick, multi-laminated, and bent. In addition, basement membrane-like materials, separated from the cells, were often seen in the laminar beams. The lamina cribrosa in experimental chronic glaucoma showed evidence of both destruction and healing or remodeling. These changes might have a influence to the worse for the tissue characterization of the lamina cribrosa, such as resistence to intraocular pressure changes. In conclusion, this may be a factor related with the progression of glaucomatous optic nerve damage.

Animals↗
PubMed1994

Characterization of a vitamin D3-resistant human chronic myelogenous leukemia cell line.

A variant of the chronic myelogenous leukemia cell line, RWLeu-4, that is resistant to the antiproliferative effects of vitamin D3 was established. Although RWLeu-4 proliferation is inhibited by 1 nmol/L vitamin D3, the resistant cells (JMRD3) continue to proliferate in the presence of 100 nmol/L vitamin D3. Both cells express similar patterns of differentiation-specific antigens after treatment with vitamin D3, and both express the retinoblastoma gene product (p110Rb). Vitamin D3 treatment of the sensitive RWLeu-4 cells decreased the level of the p110Rb protein, as well as its phosphorylation. In contrast, vitamin D3 treatment of JMRD3 had no effect on p110Rb expression or phosphorylation. Both RWLeu-4 and JMRD3 express similar vitamin D3 receptors and vitamin D3-inducible enzyme activities. Differences were detected in the DNA binding characteristics of the vitamin D3 receptors as determined by electrophoretic mobility shift studies. However, sequence analysis of the DNA-binding domain and immunoblot analysis showed no differences in the receptors. We conclude that some process subsequent to vitamin D3 receptor activation is altered in JMRD3 that partially separates vitamin D3-induced inhibition of proliferation from the induction of differentiation.

Base Sequence↗
PubMed1994

Modulation of complement regulatory function and measles virus receptor function by the serine-threonine-rich domains of membrane cofactor protein (CD46).

Three major membrane cofactor protein (MCP) phenotypes with different serine-threonine (ST)-rich regions, namely STc (L-phenotype), STBC (H or U phenotype) and STABC, and the MCP without the ST domain (delta ST) were expressed in Chinese hamster ovary (CHO) cells by transfecting the respective cDNAs. The expressed molecules migrated with a larger molecular mass on SDS/PAGE than those expected from their amino acid sequences. O-Glycanase digestion showed that this was due to O-linked sugar chains. The apparent sugar contents in each ST segment were compatible with their serine and threonine contents in the ST regions. The functional properties of these phenotypes as inhibitors of human complement (C) and receptors of measles virus (MV) were compared. The classical pathway-dependent CHO cell lysis by human C was more effectively suppressed by the expressed delta ST and STC than by the STABC and STBC phenotypes, although the difference was not so prominent. In contrast, alternative C pathway-dependent CHO-cell lysis was most effectively suppressed by the STABC phenotype and was only slightly blocked by the ST-deleted mutant. MV infection occurred with all of the phenotypes, but the infectious dose required to cause the same level of syncytium formation was 100-times higher in large ST (STABC and STBC) than in small ST (STC and delta ST) phenotypes. Thus, the ST domain serves as a functional modulator in MCP: MCP with a large ST domain having high O-linked sugar contents is favourable to the effective suppression of both the alternative C pathway-mediated cytolysis and MV infection, whereas MCP with a small ST domain is favourable to the suppression of the classical C pathway.

Animals↗
PubMed1994

Prevalence of serum and salivary antibodies to HTLV-1 in Sjögren's syndrome.

There is accumulating evidence that human T-lymphotropic virus-1 (HTLV-1) infection contributes to the development of various inflammatory disorders. To elucidate the relation between the infection and Sjögren's syndrome, seroepidemiological and virological studies were conducted on patients with this syndrome in Nagasaki Prefecture, Japan, an area heavily endemic for HTLV-1. The HTLV-1 seroprevalence rate among the patients with Sjögren's syndrome (17/74, 23%) was significantly higher than that among blood donors (916/27,284, 3%), whereas the difference between patients with systemic lupus erythematosus and blood donors was insignificant. Moreover, among Sjögren's syndrome patients the seroprevalence was high irrespective of age, unlike that among blood donors, which rose with age. Titres of serum antibodies in the HTLV-1 seropositive patients with Sjögren's syndrome were similar to those among patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and significantly higher than those among healthy carriers. IgM class antibodies were commonly detected in the serum of patients with Sjögren's syndrome. However, unlike that in HAM/TSP patients, the viral load in peripheral-blood mononuclear cells was not necessarily high in the seropositive Sjögren syndrome group. Salivary IgA antibodies to HTLV-1 were common among seropositive patients with Sjögren's syndrome (5/7), which might be due to increased viral activity in the salivary glands. These antibodies were barely detectable in HAM/TSP patients (prevalence 1/10) or in healthy carriers (0/11). The findings strongly suggest that HTLV-1 is involved in the pathogenesis of the disease in a subset of patients with Sjögren's syndrome in endemic areas.

Adolescent↗
PubMed1994

Effects of transfected complement regulatory proteins, MCP, DAF, and MCP/DAE hybrid, on complement-mediated swine endothelial cell lysis.

We established several swine endothelial cell (SEC) lines, expressing human MCP (CD46), DAF (CD55), and MCP/DAF hybrid by transfection of cDNA, and assessed the function of these transfectant molecules on complement-mediated cell lysis as an in vitro hyperacute rejection model of swine to human discordant xenograft. Discordant organ xenografts are hyperacutely rejected by complement activation. Amelioration of complement-mediated lysis by these transfectant molecules was tested in each SEC line by lactate dehydrogenase assay. Naive swine endothelial cells were markedly damaged by human complement mainly via the classical pathway, activating only minimally the alternative pathway of human complement. Both MCP and DAF protected SEC from human complement attack in parallel with the expression density, with DAF being more effective than MCP. The MCP/DAF hybrid was more effective than MCP alone, and as effective as DAF in this system. The results suggest that the transfection of DAF or the MCP/DAF hybrid cDNA into organs to be transplanted could protect against hyperacute rejection.

Animals↗