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Biomedical subjects

K Iwata

Publications and source records attributed to K Iwata.

At least 145 records · Page 8Linked to original sources
PubMed1996

Increased matrix metalloproteinase activity and reduced tissue inhibitor of metalloproteinases-1 levels in amniotic fluids from pregnancies complicated by premature rupture of membranes.

OBJECTIVES: It has been suggested that increased matrix metalloproteinases activity promotes the weakening of the amniochorion during normal and premature rupture of membranes. This study was designed to determine whether levels of matrix metalloproteinases and the tissue inhibitor of metalloproteinases-1 in amniotic fluid change in a pattern consistent with this hypothesis. STUDY DESIGN: Gelatinolytic activity, measured by a soluble substrate assay and zymography, and the concentrations of tissue inhibitor of metalloproteinases-1 were estimated in amniotic fluid obtained from (1) normal early gestations, (2) normal term pregnancies with labor, (3) normal term pregnancies without labor, and (4) pregnancies complicated by premature rupture of membranes. The 92 kd type IV collagenase (matrix metalloproteinase-9) was also detected in amniotic fluid by Western blotting. RESULTS: Matrix metalloproteinase activities were higher in amniotic fluid from normal term pregnancies with labor and pregnancies complicated by premature rupture of membranes than from early pregnancies and term gestations without labor. The amniotic fluid from term pregnancies with labor or pregnancies with premature rupture of membranes contained several gelatinases, as revealed by zymography. The major amniotic fluid gelatinolytic activity in premature rupture of membranes and term pregnancies with labor corresponded to matrix metalloproteinase-9. Tissue inhibitor of metalloproteinases-1 concentrations were highest in early-pregnancy amniotic fluid, followed by term gestation with labor, term gestation without labor, and premature rupture of membranes. CONCLUSIONS: Normal labor and premature rupture of membranes are associated with increased levels of matrix metalloproteinases, particularly matrix metalloproteinase-9 in amniotic fluid. Premature rupture of membranes is associated with reduced levels of tissue inhibitor of metalloproteinases-1. The imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 in amniotic fluid may reflect a disorder that promotes premature rupture of membranes.

Amniotic Fluid↗
PubMed1996

Relationship between QRS duration and repolarization abnormalities in patients with Wolff-Parkinson-White syndrome.

Marked T wave abnormalities in 12-lead electrocardiograms often appear after radiofrequency ablation in patients with Wolff-Parkinson-White (WPW) syndrome. Durations of the QRS complex before ablation have been reported to be significantly greater in patients with repolarization abnormalities after ablation than in those with normal repolarization. However, there has been no report concerning the relationship between QRS duration and repolarization abnormalities before ablation. It has been reported that QRST isointegral maps are dependent on local cellular repolarization properties but largely independent of activation sequence, and that they provide quantitative information about repolarization abnormalities. Isointegral maps were constructed from data recorded in 34 patients with WPW syndrome and QRS durations of 0.1 second or longer (21 patients with left-sided accessory pathways and 13 with right-sided pathways) in order to investigate the relationship between QRS duration and abnormalities in repolarization properties during preexcitation. Body surface ECGs were recorded with an 87-lead system at a sampling interval of 1 ms. The QRST values (mean +/- 2SD) from 607 normal individuals were taken to represent the normal range. The area with abnormally low QRST values was designated as the -2SD area and the sum of the QRST values (sigma QRST) in this area was calculated. The QRS duration was found to be significantly related to sigma QRST. These results demonstrate that the patients with WPW syndrome had abnormalities in local repolarization properties that were significantly related to QRS duration during preexcitation. The degree of preexcitation may be important in producing these abnormalities in patients with manifest WPW syndrome. This may result in T wave abnormalities after ablation of the accessory pathway attributable to cardiac memory.

Adolescent↗
PubMed1996

Deficiency of antibody response to hypervariable region of hepatitis C virus in patients with chronic hepatitis C.

BACKGROUND/AIMS: Frequent mutations in the hypervariable region of hepatitis C virus have been suggested to be a cause of persistent infection by providing a way for the virus to escape host immunity. However, the variation rate in the hypervariable region is often low in patients with chronic hepatitis. The aim of this study was to elucidate the mechanism of persistent infection in patients with chronic hepatitis by investigating the relationship between the antibody response to and the variation in hypervariable region. METHODS: The hypervariable regions of 26 clones of six patients with chronic hepatitis C were expressed as proteins fused with glutathione S-transferase, and sera of the patients were serially tested for antibody to these proteins. RESULTS: The extent of antibody response to the hypervariable region differed considerably among the patients. Three patients showed no or only scanty antibody response. These had a lower variation rate in the hypervariable region (0-1.3/year) than in the others with frequent or persistent antibody response (2.1-14.6/year). In two patients, serum samples were found to be reactive with the clones even before the appearance of the clones. In three patients, coexistence of the antibodies and corresponding clones were noted. An augmentation of antibody response always followed rises in serum alanine aminotransferase levels. CONCLUSION: Deficiency of antibody response to the hypervariable region may be one of the causes of persistency in hepatitis C virus infection.

Adult↗
PubMed1996

Three-dimensional dental cast analyzing system using laser scanning.

The purpose of this article is to introduce the outline of our newly developed three-dimensional dental cast analyzing system with laser scanning, and its preliminary clinical applications. The system is composed of a measuring device with a slit-ray laser projector and two sets of coupled charged devised video cameras, an image processing unit, a 16-bit personal computer as a controller, and an engineering workstation as a post processor. The dental cast is projected and scanned with a slit-ray laser beam. The raster coordinates of the target are determined with an image processor. Triangulation is applied to determine the location of each point. Generation of three-dimensional graphics of the dental cast takes approximately 40 minutes. About 90,000 sets of X, Y, Z coordinates are stored in the main memory of the microcomputer. The measurement error is less than 0.05 mm. Besides the conventional linear and angular measurements of the dental cast, we are also able to demonstrate the size of the palatal surface area and the volume of the oral cavity. The advantage of this system is that it facilitates the otherwise complicated and time-consuming mock surgery necessary for treatment planning in orthognathic surgery.

Computer Graphics↗
PubMed1996

Sequence analysis of hypervariable region of hepatitis C virus (HCV) associated with immune complex in patients with chronic HCV infection.

Immune complex (IC) frequently exists in sera of patients with hepatitis C virus (HCV) infection. When circulating HCV particles are fractionated by differential flotation ultracentrifugation, HCV in the bottom fraction appears to be in the form of IC. Flotation ultracentrifugation of serum was done in 7 patients positive for serum anti-C3d-binding circulating IC and in 7 negative patients. In all IC-positive patients, HCV RNA was detected in the bottom fraction but not in the top fraction of 3 patients. Amino acid sequences of hypervariable region (HVR) of HCV in the bottom fraction of IC-positive patients were almost the same as those of whole serum, while those of the top fraction considerably differed from those of whole serum except for 1 case. These data suggest that the major population of HCV forms IC in IC-positive patients, and antibody response to the HVR of HCV is responsible for IC formation.

Aged↗
PubMed1996

Human cell receptor CD46 is down regulated through recognition of a membrane-proximal region of the cytoplasmic domain in persistent measles virus infection.

Monkey cells persistently infected by measles virus (MV) Biken strain (Biken-CV-1 cells) showed no cytopathic effects and lacked surface expression of a homolog of human cell receptor, membrane cofactor protein CD46. Transfection of a human CD46 gene into these cells induced extensive cell fusion, indicating that down regulation of the endogenous CD46 homolog was essential for the maintenance of a noncytopathic mode of infection. Surface expression of the exogenously introduced human CD46 was also drastically down regulated in the persistently infected cells compared with uninfected cells. The down regulation was specific for CD46 and did not affect surface expression of exogenously introduced CD4. Exogenous human CD46 was synthesized efficiently in the persistently infected cells, but it did not accumulate on the cell surface. Fusion of Biken-CV-1 cells required the extracellular hemagglutinin (H-protein)-binding domain but not the cytoplasmic domain. Replacing the transmembrane and cytoplasmic domains of CD46 with a glycosylphosphatidylinositol anchor did not prevent cell fusion but completely alleviated down regulation of the glycosylphosphatidylinositol-anchored CD46 in Biken-CV-1 cells. Deletion analyses revealed that the membrane-distal sequences of the CD46 cytoplasmic domain were not only unnecessary but also inhibitory for CD46 down regulation. By contrast, the six amino acid residues proximal to the membrane contained a sequence required for CD46 down regulation in the persistently infected cells. These results indicate that CD46 is down regulated in the persistently infected cells by a mechanism that recognizes a membrane-proximal sequence in the CD46 cytoplasmic domain.

Amino Acid Sequence↗
PubMed1996

A review of tissue inhibitor of metalloproteinases-3 (TIMP-3) and experimental analysis of its effect on primary tumor growth.

The family of tissue inhibitors of metalloproteinases (TIMPs) presently numbers four distinct gene products that are specific inhibitors of the matrix metalloproteinases (MMPs). The local balance between MMPs and TIMPs is believed to play a major role in extracellular matrix (ECM) remodeling during development and in diseases such as cancer and arthritis. Unlike the other TIMPs, which are soluble. TIMP-3 is unique in being a component of ECM. Mutations in the human TIMP-3 gene cause a dominantly inherited, adult-onset blindness (Sorsby's fundus dystrophy or SFD). In this article, we summarize what is currently known about TIMP-3, discuss possible mechanisms leading up to SFD, and investigate the effect of TIMP-3 on tumor growth. Breast carcinoma and malignant melanoma cell lines were transfected with TIMP-3 expression plasmids and injected subcutaneously into nude mice. Growth curves of the resulting tumors over a period of 6 to 8 weeks demonstrated that increased expression of TIMP-3 resulted in a statistically significant suppression of tumor growth. Deposition of TIMP-3 in the surrounding ECM by tumor cells may inhibit tumor growth by preventing local expansion of tumor, retarding the release of growth factors sequestered in ECM, or inhibiting angiogenesis. TIMP-3 over-expression had no effect on the growth of the two tumor cell lines in vitro. Because recombinant TIMP-3 inhibits endothelial cell migration and tube formation in response to angiogenic factors, we believe that the effect of TIMP-3 on tumor growth seen in this study may be a consequence of its angiostatic action.

Animals↗
PubMed1996

Mitosis-specific phosphorylation of smooth muscle regulatory light chain of myosin II at Ser-1 and/or -2 and Thr-9 in sea urchin egg extract.

We analyzed the kinase activities capable of phosphorylating the regulatory light chain of myosin-II (MRLC) from chicken gizzard in unfertilized and fertilized sea urchin egg extracts. Total kinase activity phosphorylating MRLC in vitro did not fluctuate throughout the first cell cycle. Phosphopeptide mapping analysis showed that MRLC was phosphorylated at two different sites corresponding to myosin light chain purified from chicken gizzard (MLCK) and protein kinase C (PKC) phosphorylation sites, namely MLCK and PKC sites, respectively. The activity of the kinase(s) responsible for phosphorylation of MRLC at PKC sites showed a significant increase at metaphase. Phosphoamino acid analysis revealed that this increase in MRLC phosphorylation was due to phosphorylation at serine residue (Ser-1 and/or Ser-2) and a threonine residue (Thr-9). This increase in phosphorylation at PKC sites is occurred concomitantly with an increase in histone H1 kinase activity. In contrast, MRLC phosphorylation at MLCK sites showed no significant changes during the first cell cycle. Butyrolactone I, a selective inhibitor of p34cdc2 kinase, inhibited the activity of the kinase(s) responsible for phosphorylation of MRLC at PKC sites at metaphase. These results suggest that the increase in MRLC phosphorylation at PKC sites (Ser-1 and/or -2, and Thr-9) at metaphase may be induced by p34cdc2 kinase. Thus, p34cdc2 kinase may be involved in the regulation of MRLC phosphorylation during cell division.

4-Butyrolactone↗
PubMed1996

Disposition of intravenously administered adenosine 5'-phosphosulfate (APS) in rats.

The disposition of adenosine 5'-phosphosulfate (APS), an endogenous nucleotide, was investigated in rats. The degradation of APS in rat plasma was very rapid. APS was degraded in rat plasma to AMP and ATP, and these nucleotides were further degraded through adenosine. The degradation kinetics was examined. For the in vivo study, the method to protect APS from degradation in blood was examined, and it was found that the addition of EDTA to APS-containing blood and storage at 4 degrees C can protect against APS degradation. After intravenous bolus injection, APS in plasma declined rapidly and the rate of elimination was dose-dependent: the biological half-life was about 2s at the dose of 0.3 mg/kg and was longer at 3 mg/kg. When APS was administered by intravenous infusion, the plasma level rapidly reached a steady-state, which then rapidly declined after the infusion was stopped. The total body clearance of APS could not be fully explained by metabolism in plasma or glomerular filtration, therefore the contribution of other elimination processes to the total body clearance was suggested.

Adenosine Phosphosulfate↗
PubMed1996

Antinociceptive activity of a novel non-steroidal anti-inflammatory drug (M-5011) with low ulcerogenic effects in mice.

Both analgesic and ulcerogenic activities of d-2-[4-(3-methyl-2-thienyl)phenyl] propionic acid (M-5011), a novel non-steroidal anti-inflammatory drug (NSAID), were compared with those of indomethacin (IND), ketoprofen (KP), diclofenac sodium (DIF), zaltoprofen (ZLT) and tiaprofenic acid (TIA) in mice. All orally administered NSAIDs including M-5011 inhibited kaolin-induced writhing in a dose-dependent manner. M-5011 had an effective antinociceptive activity (ED50 value) of 0.63 mg/kg, being more potent than ZLT (16.80 mg/kg) and TIA (4.78 mg/kg), equipotent to DIF (0.68 mg/kg), and less potent than IND (0.21 mg/kg) and KP (0.28 mg/kg). All drugs tested significantly reduced peritoneal 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) levels at the peak kaolin-induced writhing time (7.5 min post-kaolin injection) without affecting peritoneal bradykinin (BK) levels. Antinociceptive effects of all drugs were closely correlated with inhibition of peritoneal 6-keto-PGF1 alpha levels. Ulcerogenic activities (UD50 value) of M-5011 in the stomach and small intestines were 88.23 and 46.09 mg/kg, respectively. UD50 values of other drugs in the stomach and small intestines were as follows: 8.96 and 4.78 mg/kg, 20.04 and 10.75 mg/kg, 4.19 and 2.24 mg/kg, 62.86 and 46.55 mg/kg, and 110.92 and 54.78 mg/kg for IND, KP, DIF, TIA, and ZLT, respectively. Thus, the safety indexes (UD50/ED50) of the stomach (or small intestine) for M-5011, IND, KP, DIF, TIA and ZLT were 140.05 (73.16), 42.67 (22.76), 71.57 (38.39), 6.16 (3.29), 13.15 (9.74) and 6.60 (3.26), respectively. These findings suggest that M-5011 is a useful NSAID that shows potent antinociceptive effects with low ulcerogenic activities.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Purification and substrate specificity of an endo-beta-N-acetylglucosaminidase from pea (Pisum sativum) seeds.

An endo-beta-N-acetylglucosaminidase was purified to homogeneity from the seeds of pea (Pisum sativum). The molecular mass of the purified enzyme was estimated to be 41,669 Da by MALDI-TOF MS analysis and its isoelectric point to be 4.3 by isoelectric focusing. The enzyme was stable at pH 4-7 and at 25-50 degrees C, and had the highest activity toward Man6GlcNAc2-PA at pH around 7.0. Oligomannose type sugar chains (Man9-6GlcNAc2-PA) and a hybrid type sugar chain (GlcNAc1Man5GlcNAc2-PA) were most favored substrates followed by Man5GlcNAc2-PA, Man3GlcNAc2-PA, and GlcNAc2Man3GlcNAc2-PA, but xylose-containing sugar chains (Man4-3Xyl1GlcNAc2-PA and Man3Fuc1Xyl1GlcNAc2-PA) or a biantennary complex type sugar chain (Gal2GlcNAc2Man3GlcNAc2-PA) could not be hydrolyzed by the enzyme. The Km values of the enzyme for Man5GlcNAc2-PA, Man6GlcNAc2-PA, and Man9GlcNAc2-PA were 0.40 mM, 0.25 mM, and 0.32 mM, respectively.

Base Sequence↗
PubMed1996

Tumour pO2 can be increased markedly by mild hyperthermia.

We have studied the feasibility of improving tumour oxygenation with hyperthermia at modest temperatures which are achievable with the use of presently available clinical hyperthermia machines. FSaII tumours grown s.c. in the leg of C3H mice and R3230 AC tumours grown s.c. in the leg of Fischer rats were heated with a water bath and the tumour pO2 was determined with an Eppendorf pO2 histograph. The median pO2 in 7-8 mm diameter control FSaII tumours was 6.5 +/- 0.5 mmHg and it increased to 16.6 +/- 1.1 mmHg when the tumours were heated at 41.5 degrees C for 1 h. The median pO2 in 10 mm diameter control R3230 AC tumours was 3.7 +/- 0.3 mmHg. Heating at 42.5 degrees C for 30 min increased the median pO2 in the R3230 AC tumours to 12.2 +/- 1.8 mmHg. The pO2 in FSaII tumours measured 24 h after heating at 41.5 degrees C for 1 h was still higher than the pO2 before heating. The % frequency of pO2 values lower than 5 mmHg decreased markedly when the tumours were heated at the modest temperatures mentioned above. Modest temperature hyperthermia (MTH) may be an efficient and useful means to improve the oxygenation of human tumours.

Animals↗
PubMed1996

Increased expression of insulin-like growth factor 2 in hepatocellular carcinoma is primarily regulated at the transcriptional level.

To investigate the control mechanisms of insulin-like growth factor 2 (IGF2) gene expression, we studied 25 hepatocellular carcinomas (HCC) to compare the levels of total IGF2 mRNA and the IGF2 peptide by using in situ hybridization and immunohistochemistry, respectively. Increased expression of IGF2 mRNA and the IGF2 peptide was observed in 13 HCC. The spatial distribution and intensity of IGF2 mRNA in these 13 HCC was almost identical to that of the IGF2 peptide, which suggests that high IGF2 expression was primarily regulated at the transcriptional level. The levels of IGF2 gene expression in the 13 HCC seemed to be inversely correlated with the degree of tumor cell differentiation. Furthermore, in situ hybridization using probes specific to transcripts expressed from the IGF2 promoters P1 and P3 revealed that transcription was predominantly from P3 rather than from P1.

Adult↗
PubMed1996

[Slow axonal transport in primate experimental glaucoma].

Axonal transport abnormality has been reported to be deeply related to glaucomatous optic nerve injury. These reports mainly investigate the axonal transport blockage using the model of acute elevation of intraocular pressure in normal primates. We studied such axonal transport abnormality especially of slow flow in laser-induced glaucomatous monkey eyes by tissue autoradiography. Abnormal silver grain accumulation suggesting axonal transport damage was seen in the areas of distorted lamina cribrosa in glaucomatous eyes. Accumulation of grains was also seen in the retro-laminar optic nerve in some areas. Normal control eyes showed almost homogenous grain distribution in the pre-lamina, lamina and post-lamina areas. Areas of slightly elevated, accumulation of grains were seen around the lamina cribrosa and disc margin suggesting physiological blockage of axonal transport.

Animals↗
PubMed1996

Significance of MIB-1, PCNA indices, and p53 protein over-expression in intramedullary tumors of the spinal cord.

Due to the low incidence of intramedullary spinal cord tumors there have been few reports considering its proliferative kinetics. In this study, expression of two cell cycle related antigens (PCNA and MIB-1) were immunohistochemically examined by the percentage of positively stained cells were recorded as PCNA and MIB-1 indices. In addition, over-expression of p53 protein was also investigated in 19 cases of intrameduallary spinal cord tumors. In astrocytic tumors and ependymomas, statistically significant correlations were observed between PCNA and MIB-1 indices (R = 0.98). In hemangioblastoma cases, a similar correlation was not observed between PCNA and MIB-1 indices. The MIB-1 indices of hemangioblastoma cases were less than 1.56 while PCNA indices were more than 14.63 despite long-term survival occurred in all cases. The PCNA index in hemangioblastoma was significantly greater (p < 0.01) than all other types of tumors except for glioblastomas. Thus, interpretation of PCNA index must be made with caution in regard to the subgroup of the tumor histology. Over-expression of the p53 protein was observed only in glioblastoma cases. The MIB-1 index appears to be a useful method for predicting the outcome of all cases with intramedullary tumors of the spinal cord.

Adolescent↗
PubMed1995

Determination of tissue inhibitor of metalloproteinases-2 (TIMP-2) in experimental animals using monoclonal antibodies against TIMP-2-specific oligopeptides.

We have developed a one-step sandwich enzyme immunoassay (EIA) using monoclonal antibodies against oligopeptides of the human tissue inhibitor of metalloproteinases-2 (TIMP-2) (Fujimoto et al. (1993) Clin. Chim. Acta 220, 31). The present studies further demonstrated that the antibodies cross-react with TIMP-2 species of experimental animals including mouse, rat, guinea pig and rabbit. The detection of the TIMP-2 species in our EIA system was verified using rat TIMP-2 and the EIA was subsequently used to measure the animal TIMP-2 in the sera. Using human TIMP-2 as a standard, TIMP-2 levels in the sera of mouse, rat, guinea pig and rabbit were approximately 80, 200, 270 and 25 ng/ml, respectively.

Animals↗
PubMed1995

Differential regulation of JunD by dihydroxycholecalciferol in human chronic myelogenous leukemia cells.

1,25-Dihydroxyvitamin D3 inhibits the proliferation of the chronic myelogenous leukemia cell line RWLeu-4 but not the resistant variant, JMRD3. Although these cells exhibit no detectable differences in the vitamin D receptor, alterations in the interaction of nuclear extracts with the osteocalcin-1,25-dihydroxyvitamin D3-response element are noted. It is shown herein that the 1,25-dihydroxyvitamin D3 receptor binds to the osteocalcin-1,25-dihydroxyvitamin D3-response element along with activator protein-1 (AP-1) complexes and that the DNA binding activities of members of the Jun and Fos proto-oncogene families, which make up the AP-1 transcription factor, are differentially regulated by 1,25-dihydroxyvitamin D3. It is shown that JunD DNA binding activity is enhanced by 1,25-dihydroxyvitamin D3 during cell cycle arrest in the sensitive cells but is decreased in the resistant cells. These results suggest that the level of JunD DNA binding activity may be a critical factor in the regulation of proliferation.

Base Sequence↗