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Biomedical subjects

K Iwata

Publications and source records attributed to K Iwata.

At least 91 records · Page 5Linked to original sources
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

Effects of a novel non-steroidal anti-inflammatory drug (M-5011) on bone metabolism in rats with collagen-induced arthritis.

The effects of a novel non-steroidal anti-inflammatory drug (NSAID), d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid: M-5011, and other NSAIDs (indomethacin, zaltoprofen and tiaprofenic acid) on bone metabolism in Dark Agouti (DA) strain rats with collagen-induced arthritis were evaluated. M-5011 (1.5 and 4.5 mg/kg) and other NSAIDs (1.5 mg/kg) were administered orally once a day from day 14 to day 35 after collagen immunization. In arthritic rats, paw volume and serum levels of anti-type II collagen antibody were increased on day 21 compared to those in non-immunized rats. M-5011 (4.5 mg/kg), indomethacin and zaltoprofen tended to prevent this increase in paw volume. Elevated urinary pyridinoline and deoxypyridinoline levels were found on days 28 and 35 in arthritic rats. M-5011 (4.5 mg/kg) also tended to prevent the increase in urinary pyridinoline level on day 28, but none of the other NSAIDs affected urinary deoxypyridinoline levels. Bone mineral densities in the hindpaw and vertebrae were also decreased in arthritic rats. M-5011 and tiaprofenic acid prevented this decrease in vertebral bone mineral density. These findings indicate that M-5011 partially inhibits the generalized bone loss accompanying the development of collagen-induced arthritis in rats.

Absorptiometry, Photon↗
PubMed1998

Regulation of complement-mediated swine endothelial cell lysis by a surface-bound form of human C4b binding protein.

BACKGROUND: Human C4b-binding protein (C4bp) functions as a cofactor for factor I in the degradation of C4b and C3b and, in addition, accelerates the rate of decay of the C4b2a complex. METHODS: In this study, we constructed a surface-bound form of human C4b-binding protein (C4bp-PI) consisting of a short consensus repeat 1-8 of the alpha-chain of C4bp and a glycosyl phosphatidylinositol (GPI) of the decay-accelerating factor (CD55) and established stable swine endothelial cell (SEC) lines expressing C4bp-PI by transfection of cDNA. Amelioration of complement-mediated lysis by the transfectant molecules was tested as an in vitro hyperacute rejection model of swine to human discordant xenograft, using the lactate dehydrogenase assay. RESULTS: Flow cytometric profiles of the stable SEC lines with C4bp-PI showed a high level of expression of this molecule. The cell lysate of the SEC line with C4bp-PI showed strong cofactor activity in not only C4b but also C3b, whereas the activity of plasma C4bp to bind to C3 was very weak. Approximately 150 x 10(4) molecules of C4bp-PI per SEC blocked human complement-mediated cell lysis by approximately 75%. CONCLUSIONS: The results suggest that the surface-bound form of C4bp will be very useful in clinical xenotransplantation.

Animals↗
PubMed1998

Collagenase-3 expression is associated with advanced local invasion in human squamous cell carcinomas of the larynx.

Collagenase-3 (MMP-13) is a matrix metalloproteinase recently identified on the basis of differential expression in normal breast tissues and in breast carcinoma. To date, collagenase-3 expression has been reported only in breast carcinomas and in articular cartilage of arthritic patients; the presence and possible implication of this enzyme in the progression of other malignant tumours are unknown. In this study collagenase-3 mRNA expression has been analysed by northern blot in a series of 35 matched squamous cell carcinomas of the larynx and the corresponding adjacent non-neoplastic tissues. In addition, mRNA expression of membrane type 1-matrix metalloproteinase (MT1-MMP) and gelatinase A, two matrix metalloproteinases which have the ability to activate collagenase-3 in vitro, was also examined in the same cases. No collagenase-3 expression was detected in any of the 35 normal mucosae, but collagenase-3 mRNA was observed in 20 of the 35 carcinomas (57 per cent). Western blot analysis revealed the presence of collagenase-3 protein in those carcinomas with high levels of mRNA expression, whereas no protein was detected in the carcinomas with negative mRNA expression, or in any of the normal tissues. The protein was localized predominantly in tumour epithelial cells. Collagenase-3 expression correlated significantly with better histological differentiation of the tumours (p = 0.026), as well as with advanced local invasion (p = 0.026). Collagenase-3 upregulation was also significantly associated with MT1-MMP and gelatinase A overexpression. These findings suggest that collagenase-3 expression may contribute to the progression of a significant subset of squamous cell carcinomas of the larynx and that its coordinate overexpression with MT1-MMP and gelatinase A may have a cooperative effect in the progression of the tumours.

Adult↗
PubMed1998

Broadly reactive antibodies to hypervariable region 1 in hepatitis C virus-infected patient sera: relation to viral loads and response to interferon.

To clarify the nature of serum anti-hypervariable region 1 (HVR1) antibodies in patients infected with hepatitis C virus (HCV), we assessed the reactivity of 21 patients' sera with 42 HVR1 proteins by Western blot. HVR1 was expressed as fusion proteins with glutathione S-transferase (GST). The patients' sera reacted with variable percentages of the HVR1 proteins, and always reacted with HVR1 proteins of the different genotype. In the genotype-1b-infected patients, the percentage of genotype-1b HVR1 proteins reactive with serum correlated significantly with viral loads; the sera reactive with the higher percentages of HVR1 proteins contained the larger viral loads. In addition, it was significantly lower in the responders of interferon (IFN) therapy than in nonresponders. The competition assays indicated that multiple fractions of anti-HVR1 antibodies with different specificity in a serum reacted with different HVR1 proteins, and that, additionally, a single fraction of antibodies often reacted with more than one HVR1 protein through a similar amino acid sequence. In conclusion, serum anti-HVR1 antibodies were broadly reactive by the mechanism of both the cross-reactivity of a single fraction of anti-HVR1 antibodies with more than one HVR1 protein and the presence of multiple fractions of anti-HVR1 antibodies with different specificity in a serum. In genotype-1b-infected patients, the broad reactivity of serum anti-HVR1 antibodies correlated with viral loads and response to IFN. Further studies are necessary to elucidate the correlation among the broad reactivity of sera with multiple HVR1 proteins and clinical features of chronic hepatitis C patients.

Adult↗
PubMed1998

The relationship between deterioration and reversal of optic disc cupping in monkeys with chronic experimental high-pressure glaucoma.

PURPOSE: To investigate the correlation between the deterioration in optic disc cupping during the chronic elevation of intraocular pressure (IOP) and the reversal of cupping during a subsequent reduction in IOP in experimental glaucoma. METHODS: We examined changes in the vertical and horizontal cup to disc ratios, the rim area to disc area ratio, and the cup volume to disc area ratio in 11 monkey eyes with laser-induced glaucoma using computerized stereo-image analysis. Correlations between changes in disc parameters during a spontaneous IOP reduction and changes in disc parameters during a period of chronic IOP elevation from baseline before laser exposure (baseline) to before the IOP reduction (pre-IOP reduction) and during the period from baseline to after the reduction in IOP (post-IOP reduction) were determined by linear regression analysis. RESULTS: All disc parameters improved significantly during IOP reduction and deteriorated significantly during the periods from baseline to the pre-IOP reduction and from baseline to the post-IOP reduction. The degree of reversal in disc parameters was correlated with the deterioration from baseline to the pre-IOP reduction and from baseline to the post-IOP reduction in the vertical cup to disc ratio (r = 0.68, P = 0.0218 and r = 0.97, P < 0.0001, respectively), the horizontal cup to disc ratio (r = 0.57, P = 0.0649 and r = 0.98, P < 0.0001, respectively), the rim area to disc area ratio (r = 0.68, P = 0.0227 and r = 0.98, P < 0.0001, respectively), and the cup volume to disc area ratio (r = 0.67, P = 0.0256 and r = 0.88, P = 0.0004, respectively). CONCLUSION: The degree of deterioration in cupping from baseline before the induction of glaucoma may be an important determinant of the degree of cupping reversal during subsequent reductions in IOP in primate glaucoma.

Animals↗
PubMed1998

Hepatitis C virus infection and mutations of mannose-binding lectin gene MBL.

We assessed the genetic polymorphism of mannose-binding lectin (MBL) in 93 patients with chronic hepatitis C (45 responders and 48 nonresponders to interferon) and 218 healthy controls. Mutant allele was identified only at codon 54 (Gly-->Asp), leading to three genotypes (54 m/m, 54 W/m, and 54 W/W). Frequency of 54 m/m was significantly lower in interferon-responders (2.2%), compared to those in nonresponders (14.6%) and controls (10.6%): p < 0.05. Our results suggest that homozygous carriage of the variant allele of codon 54 of MBL may predict poor response to interferon in chronic hepatitis C patients.

Adult↗
PubMed1998

In situ detection of insulin-like growth factor II (IGF2) and H19 gene expression in hepatocellular carcinoma.

To assess the relationship between insulin-like growth factor II (IGF2) and H19 gene expression at the cellular level, we have examined the distribution of IGF2 and H19 mRNA by means of an situ hybridization in hepatic malignancies consisting of hepatocellular carcinoma (HCC), cholangiocellular carcinoma (CCC), and metastatic liver cancer (MLC). In HCC, 15 of 27 tumors (56%) and 11 of 27 tumors (41%) demonstrated increased IGF2 and H19 gene expression, respectively. Of 16 HCCs with increased expression of either IGF2 or H19, 10 tumors coexpressed both transcripts at comparable levels. Moreover, the spatiotemporal distribution and the cellular localization of the two gene transcripts were almost identical, suggesting the presence of a reciprocal relation between IGF2 and H19. In addition, 5 HCCs showed increased IGF2 expression without concomitant H19 expression, whereas 1 HCC showed increased H19 expression without IGF2 transcripts. However, 11 HCCs showed no IGF2 or H19 expression. On the other hand, neither IGF2 transcripts nor H19 transcripts were detected in 2 CCCs or 10 MLCs studied. The data suggest that IGF2 and/or H19 gene expression may be characteristic of some HCCs.

Adolescent↗
PubMed1998

Biliary cirrhosis secondary to obstruction of the common bile duct by ectopic pancreas in a cow.

A 10-year-old Japanese Black cow showed icterus with gradual emaciation for a period of 3 months. Ultrasonography demonstrated increased "echogenicity" of the entire liver, with marked dilatation of the gall-bladder. At necropsy, the common bile duct was found to be obstructed by focally thickened fibrous tissue adjacent to a flesh-like mass (9 x 4 x 4 mm) attached to the wall of the duct. The mass consisted of normal pancreatic tissue. The liver showed moderate fibrosis, with nodular regeneration of the hepatic tissue and bile duct hyperplasia. A diagnosis of biliary cirrhosis secondary to ectopic pancreas in the common bile duct was made.

Animals↗
PubMed1998

Fos protein induction in the medullary dorsal horn and first segment of the spinal cord by tooth-pulp stimulation in cats.

Electrophysiological studies using the single neuron recording technique have led to the hypothesis that nociceptive neurons in the medullary dorsal horn (MDH) and the first segment of the spinal cord (C1) encode the stimulus intensity of noxious stimuli applied to the tooth pulp. The present study utilized the Fos protein technique in combination with electrical and chemical stimulation of the tooth pulp to test this hypothesis. Upper canine tooth-pulp stimulation with intensities just above the threshold stimulus intensity for evoking the jaw-opening reflex (JOR) did not produce a clear expression of Fos protein-like immunoreactive (LI) cells in the MDH and C1 of cats. Fos protein-LI cells were mainly found in the superficial laminae (laminae I-II) of the MDH and C1 after tooth-pulp stimulation of 200% of the JOR threshold intensity. When higher intensities (400-600% of the JOR threshold intensity) or mustard oil were applied, Fos protein-LI cells were also found in laminae III-IV as well as in laminae I-II. The number of Fos protein-LI cells significantly increased when 600% of the JOR threshold intensity or mustard oil was applied. Furthermore, the rostro-caudal distribution of Fos protein-LI cells was greater following increases in stimulus intensities and the greatest after mustard oil application. These data suggest that the change in number and spatial arrangement of nociceptive neurons in the MDH and C1 reflect changes in the encoding of the stimulus intensity applied to the tooth pulp.

Animals↗
PubMed1998

Different constitution of hepatitis C virus population in peripheral blood mononuclear cells and plasma in patients with type C chronic liver disease.

We searched for the presence of the plus or minus strand of hepatitis C virus (HCV) RNA in peripheral blood mononuclear cells (PBMCs) from three patients with chronic HCV infection using the strand-specific reverse transcription and polymerase chain reaction (RT-PCR) method. To examine whether the HCV population of PBMCs differs from that of plasma, a sequence of the hypervariable region (HVR) in the E2/NS1 region was analyzed. All three patients had both plus and minus strands of HCV RNA in their PBMCs. Sequence study revealed that the HCV population in PBMCs was homogeneous in all patients, while that in plasma was composed of two main clones. One of these had the same sequence as the clones seen in PBMCs, except for one patient. Our results suggest that PBMCs represent one of the extrahepatic replication sites of HCV and that tissue tropism is expressed by some of the HCV population.

Amino Acid Sequence↗
PubMed1998

Diastereospecific kinetics of nicotine N'-oxidation in rat liver microsomes.

1. In kinetic studies, both Eadie-Hofstee plots for cis- and trans-nicotine-1'-N-oxide formation from nicotine in rat liver microsomes were linear. For the formation of cis- and trans-nicotine-1'-N-oxide, the apparent K(m) were 0.240 +/- 0.069 and 1.524 +/- 0.951 mM respectively. Corresponding Vmax were 1.52 +/- 0.48 and 1.19 +/- 0.74 nmol/mg/min respectively. 2. The formation of cis-nicotine-1'-N-oxide was greater than the formation of trans-nicotine-1'-N-oxide in rat liver microsomes and the intrinsic clearance of cis-nicotine-1'-N-oxide formation was 8.1-fold greater than that of trans-nicotine-1'-N-oxide formation. 3. The formation of both cis- and trans-nicotine-1'-N-oxide in rat liver microsomes was inhibited by the addition of 1-(1-naphthyl)-2-thiourea or by heat-treatment of microsomes. 2-Diethylaminoethyl-2, 2-diphenylvalerate (SKF525A) and carbon monoxide did not affect these activities even at high concentrations. 4. Formations of cis- and trans-nicotine-1'-N-oxide correlated significantly with each other (r = 0.862, p < 0.01). These results suggested that the same flavin-containing monooxygenase (FMO) isoform is responsible for the formation of cis- and trans-nicotine-1'-N-oxide in rat liver.

Animals↗
PubMed1998

Case report: Insulin-like growth factor II expression in hepatocellular carcinoma with alcoholic liver fibrosis accompanied by hypoglycaemia.

This case of hepatocellular carcinoma (HCC) with alcoholic liver fibrosis, which was not associated with hepatitis viruses, was accompanied by hypoglycaemia. The immunoreactive insulin level was low and other hormonal examinations were almost normal. Immunohistochemical studies showed a high level of insulin-like growth factor II (IGF2) peptide in the HCC section and the size heterogeneity of serum IGF2 investigated by western blot revealed a large form at approximately 15 kDa. These results suggest that the HCC with alcoholic liver fibrosis produced IGF2 and that the hypoglycaemia was caused by tumour-associated IGF2.

Carcinoma, Hepatocellular↗
PubMed1998

Response of healthy individuals to ninjin-yoei-to extract--enhancement of natural killer cell activity.

After administering 15 g/day of Ninjin-Yoei-To (NYT) for one week to healthy people whose NK activity had already been increased by physiological response, a further increase in NK activity was observed after two days. This increased level of NK activity continued during the administration of NYT for a one-week period. The maintaining and reinforcing effect on the immune surveillance system by NYT may be useful for prevention of carcinogenesis.

Adult↗
PubMed1998

Primary somatosensory cortical neuronal activity during monkey's detection of perceived change in tooth-pulp stimulus intensity.

To elucidate the functional properties of primary somatosensory cortical neurons for the perception of tooth-pulp sensation, neuronal activity was recorded from the primary somatosensory cortex (SI) in awake behaving monkeys. Monkeys were trained to detect changes in tooth-pulp stimulus intensity applied to the upper canine or incisor tooth pulp. Stimulus intensities applied to the tooth pulp were multiples of the threshold intensity for the jaw opening reflex (1.0 T) elicited by tooth-pulp stimulation. When monkeys pressed a button, baseline electrical pulses (V1: 0.5 T, 1.0 T, 2.0 T, or 3.0 T) were applied to the tooth pulp. After 4-8 s, a V2 stimulus (0.3 T, 0.5 T, 1.0 T, or 2.0 T) was added to V1. Percent escapes at V1 stimulus intensity of 0.5 T and 1.0 T were approximately 10%, 22% at 2.0 T, and 40% at 3.0 T (total of 1,997 trials). A total of 862 single units were recorded from the SI. Thirty-seven SI neurons responded to electrical stimulation of the tooth pulp (tooth-pulp-driven neurons; TPNs), 139 SI neurons responded to tactile stimulation of the lateral face area, 90 to upper lip and 99 to lower lip, 44 to tongue and 102 to periodontal membrane, whereas 351 SI neurons were not responsive to tactile stimulation of the orofacial regions. Thirty of 37 TPNs were recorded long enough to test with V1 stimuli ranging from 0.5 T to 3.0 T. Eleven of 30 TPNs linearly increased their firing frequency following increases in stimulus intensity (encoding TPNs), whereas 19 did not (nonencoding TPNs). Mean first spike latency of encoding TPNs was 24.8 +/- 1.7 ms (n = 11), that of nonencoding TPNs was 23.6 +/- 1.5 ms (n = 19), and that of unclassified TPNs was 24.7 +/- 3.7 ms (n = 7). TPNs were distributed in the areas 1-2, 3a, and 3b within the oral projection area and the transition zone between the face and oral projection areas of the SI. All of them received inputs from the intraoral structures, facial skin, or both. The firing frequency of eight encoding and nonencoding TPNs was correlated with detection latency at stimulus intensities of 0.5 and 1.0 T. On the other hand, when the baseline stimulus was increased to 2.0 T and 3.0 T, the discharge of most TPNs did not increase in firing frequency with the reduction in detection latency. These results indicate that the discharge rates of some SI TPNs are correlated with detection latency at near-noxious threshold and noxious stimulus intensities. These findings suggest that some TPNs are involved in the sensory-discriminative aspect of tooth-pulp sensation in the near-pain threshold and pain ranges.

Animals↗
PubMed1998

Mesencephalic projections from superficial and deep laminae of the medullary dorsal horn.

The mesencephalic projection pattern of axons arising from the medullary dorsal horn (MDH) was studied on the basis of axonal transport of Phaseolus vulgaris Leucoagglutinin (PHA-L). After large injections of PHA-L into both the superficial and deep laminae of the MDH, labeled fibers were observed in the anterior pretectal area (ATP), internal gray matter of the superior colliculus (InG), and rostral linear raphe nucleus (RLi) in the contralateral mesencephalon, and also in the ipsilateral parabrachial nucleus (PBA). Restriction of PHA-L to only the superficial laminae resulted in heavy axon labeling and varicosity in the APT and little labeling in the lateral part of the InG of the contralateral mesencephalic nuclei and the dorsal part of the ipsilateral PBA. On the other hand, after injections into the deep laminae, labeled axons were distributed mainly in the contralateral InG and RLi. Therefore, it is concluded that there are two different major pain pathways from the superficial and deep laminae of the MDH to the mesencephalic nuclei, processing nociceptive information in the trigeminal system.

Animals↗