Biomedical subjects

K Iwata

Publications and source records attributed to K Iwata.

At least 109 records · Page 6Linked to original sources

PubMed1998

Influences of long- and short-distance driving on alpha waves and natural killer cell activity.

We examined the effective amplitudes of alpha waves (using a mean frequency with a range of +/- 0.5 Hz), and activity of natural killer cells in six subjects, before and after a short-distance (43 km, 1 hr.) drive, and after a midnight (am 0:00-am 7:00 to 8:00) long-distance (550 km on average, for 7 to 8 hr.) drive. Following a long-distance drive, the activity of natural killer cells tended to decrease, and the effective amplitudes of alpha waves in the photic feedback period were greater than those observed during the rest period, showing that photic driving had occurred even under physically and mentally stressful conditions. However, after short-distance driving, no photic driving response occurred and activity of natural killer cells tended to increase, possibly related to mental concentration. Avoiding midnight long-distance driving may help prevent excessive stress and preserve high activity in natural killer cells.

Adult↗

PubMed1998

Nicotine metabolism in liver microsomes from rats with acute hepatitis or cirrhosis.

Nicotine exerts a number of physiological effects. Nicotine is absorbed through the lungs with smoking and is rapidly metabolized in humans. Although it is mainly metabolized in the liver, the effects of liver injuries on nicotine metabolism are not clear. The purpose of this study was to clarify the effects of liver injuries on nicotine metabolism. Rats were treated with D-galactosamine (GalN) or thioacetamide (TA), to induce acute hepatitis or liver cirrhosis, respectively. Serum transaminase levels were significantly elevated in model rats with both types of liver injury. Cytochrome P450 (CYP) and cytochrome b5 contents in liver microsomes were decreased significantly in TA-treated cirrhotic rats but not in GalN-treated hepatitic rats. The major metabolic pathways of nicotine, i.e. cotinine formation catalyzed by CYP and nicotine-1'-N-oxide formation catalyzed by flavin-containing monooxygenase, were investigated in these rat liver microsomes. Formation of cotinine and nicotine-1'-N-oxide from nicotine was not changed in GalN-treated hepatitic rats, in comparison with the controls, but was significantly decreased in TA-treated cirrhotic rats. By immunoblotting, decreases in CYP1A2, CYP2B2, CYP2C, and CYP2E1 protein were recognized in liver microsomes from TA-treated cirrhotic rats. It was also shown that the maximal velocity values for nicotine-1'-N-oxide formation in TA-treated cirrhotic rats were significantly decreased, compared with the controls. These results suggested that the reduction of nicotine metabolism in cirrhosis was due to decreases in CYP and flavin-containing monooxygenase protein expression levels.

Acute Disease↗

PubMed1998

Tumor oxygenation after mild-temperature hyperthermia in combination with carbogen breathing: dependence on heat dose and tumor type.

We investigated the effect of hyperthermia at 40.5-42.5 degrees C as well as the combination of hyperthermia and carbogen breathing on oxygenation in the SCK murine mammary carcinoma. In addition, the important question of how long the effect of heating on tumor oxygenation lasts was addressed in both SCK and FSaII (murine fibrosarcoma) tumors. The median pO2 in control SCK tumors was 4.4 +/- 0.2 mm Hg, and it increased to a maximum of 12.6 +/- 1.2 mm Hg when the tumors were heated at 41.5 degrees C for 1 h. Carbogen breathing increased the median pO2 of SCK tumors to 17.1 +/- 1.4 mm Hg, but after heating at 41.5 degrees C, it elevated the pO2 in SCK tumors markedly to 31.3 +/- 4.2 mm Hg. The kinetics of the return to baseline oxygenation after hyperthermia was found to vary with the type of tumor and the heat dose. The pO2 of FSaII tumors remained significantly higher than that of control tumors 24 h after heating at 41.5 degrees C for 60 min. The pO2 of SCK tumors remained elevated for up to 3 h after heating at 41.5 degrees C for 30 min, but if the tumors were heated for 60 min at this temperature, the median oxygen tension declined to the control level within 1 h after heating. It was concluded that mild-temperature hyperthermia, i.e. 41.5 degrees C, alone and in combination with carbogen breathing dramatically improves the oxygenation of these murine tumors and that the tumor type influences the duration of changes in oxygenation induced by mild-temperature hyperthermia.

Animals↗

PubMed1998

[Posttraumatic priapism in a 6-year-old boy: a case report].

A 6-year-old boy showed priapism after blunt perineal trauma. We diagnosed him with venous priapism mainly based on clinical symptoms, although we could not deny an arterial type. In fear of possible erectile dysfunction as a late complication of the venous type, we performed a shunt operation. The shunt was created between glans penis and corporacavernosa, resulting in disappearance of priapism and preservation of erectile function. We also reviewed 14 cases reported previously.

Child↗

PubMed1997

Localization of tissue inhibitor of metalloproteinases-3 in neurodegenerative retinal disease.

Tissue inhibitor of metalloproteinases-3 (TIMP-3) is one of a family of genes whose products are implicated in the regulation of remodelling of the extracellular matrix. The level of mRNA coding for TIMP-3 is increased in retinas affected by the photoreceptor degenerative disease, simplex retinitis pigmentosa (RP), and mutations in TIMP-3 are associated with an inherited form of macular dystrophy. Here we compare TIMP-3 protein expression in normal retina and in those affected by RP and by age-related macular degeneration. Immunoreactive TIMP-3 is present in normal retinal pigment epithelium, and in degenerative retinas particularly at Bruch's membrane and additionally in photoreceptor-retaining regions in simplex RP. The pattern suggests a role for TIMP-3 in normal retinal homeostasis, and, in the disease state, in the modulation of extracellular matrix metabolism and neovascularization.

Aged↗

PubMed1997

Lack of association of cytochrome P450 2E1 genetic polymorphisms with the risk of human hepatocellular carcinoma.

The iso-enzyme pattern of cytochrome P450 was shown to be related to the development of chemically induced hepatocellular carcinoma (HCC) in rats, which is accelerated by chronic alcohol ingestion. Our study was designed to investigate the association of cytochrome P450 2E1 (CYP2E1) genetic polymorphisms with the susceptibility to HCC in humans with and without chronic alcohol ingestion. We enrolled 171 male patients (108 Korean and 63 Japanese) with HCC and 31 age- and sex-matched healthy Korean subjects with no evidence of liver disease or cancer in any organ. Genotypes in the 5'-flanking region of the CYP2E1 gene were determined by restriction fragment length polymorphisms using 2 endonucleases: Pst I and Rsa I. Allelic frequencies in the CYP2E1 5'-flanking region in the Korean control population were 83.5% and 16.5% for allele c1 and c2, respectively. The frequencies of genotypes with the c2 allele (c1/c2 and c2/c2) were compared with those of genotypes without c2 (c1/c1) among HCC patients and controls, according to the pattern of alcohol consumption. There was no significant association between HCC risk and genotypes c1/c2 and c2/c2 either in all HCC patients or in HCC patients of different ethnic groups. Habitual drinkers with HCC, especially among Koreans, were more likely to carry genotype c1/c2 and c2/c2 (odds ratio = 3.0) than non-habitual drinkers (odds ratio = 1.2); however, the difference was not statistically significant. Even when patients were restricted to those without hepatitis B surface antigen and antibodies against hepatitis C virus but with a history of chronic alcohol ingestion, there was still no increased risk of HCC in those with genotypes c1/c2 and c2/c2. We conclude that there is a lack of association of the polymorphisms of CYP2E1 with the risk of HCC in humans.

Alcohol Drinking↗

PubMed1997

The CD46 transmembrane domain is required for efficient formation of measles-virus-mediated syncytium.

Two phosphatidylinositol (PI)-anchored versions of a measles virus (MV) receptor membrane cofactor protein (MCP; CD46) were generated by fusing the extracellular domain of MCP to the decay-accelerating factor (DAF; CD55) or its PI anchor. The PI-anchored forms of MCP expressed on Chinese hamster ovary cells, otherwise non-permissive to MV, conferred a smaller MV cytopathic effect than a wild-type MCP, a Ser/Thr-rich domain-deletion mutant and a cytoplasmic tail-deletion mutant of MCP. Therefore the differences in MV receptor properties between the two PI-anchored and three transmembrane forms were investigated. The PI-anchored forms were predominantly expressed on microvilli as in DAF, whereas the other transmembrane forms were found on intracellular membranes. The PI-anchored forms conferred high MV-binding capacity compared with the transmembrane versions. MV replication was, however, severely suppressed in cells expressing the PI-anchored forms, resulting in ineffective syncytium formation. In contrast, cell-to-cell fusion occurred efficiently after co-transfection of cDNA species encoding MV-H. MV-F and any version of MCP. Thus the PI-anchored forms, despite showing sufficient MV binding and cell-to-cell fusion competence together with MV-H and MV-F, mediate inefficient MV entry or replication, which causes severe suppression of the MV cytopathic effect. A biased receptor distribution on microvilli might participate in the selection of a low MV uptake pathway in the PI-anchored forms of MCP. Taken together, the transmembrane portion of MCP is a critical factor for effective virus-cell fusion and the subsequent MV replication.

Animals↗

PubMed1997

Isolation of a mouse MT2-MMP gene from a lung cDNA library and identification of its product.

We have isolated a new MT-MMP related gene of 3.3 kb from a mouse lung cDNA library using a human MT1-MMP cDNA as a probe. The deduced protein sequence shows 87% homology to human MT2-MMP and 52, 50 and 29% to MT1-MMP, MT3-MMP and MT4-MMP, respectively. Thus the gene is thought to be a mouse homologue of human MT2-MMP. A monoclonal antibody raised against a synthetic peptide recognized mouse MT2-MMP as a 70 kDa protein. Like MT1- and MT3-MMPs, mouse MT2-MMP caused activation of progelatinase A upon co-transfection into COS-1 cells.

Amino Acid Sequence↗

PubMed1997

Conformation of nucleoplasmin and its interaction with DNA-protamine complex as a simple model of fish sperm nuclei.

Nucleoplasmin was isolated from Xenopus laevis eggs and purified by an improved method using an open column. Its conformation was investigated spectrophotometrically by UV, CD and fluorescence. It was shown that alpha-helix content of nucleoplasmin was 30-40%, and one of the two tryptophan residues in nucleoplasmin located in the hydrophobic surroundings and the other in the relatively hydrophilic surroundings. The isolated nucleoplasmin was found to decondense sperm nuclei of salmon also, suggesting a possibility of the existence of nucleoplasmin-like protein in fish as well. Collapse of the protamine (salmine)-DNA complex as a simple model for fish sperm nuclei by nucleoplasmin was directly observed by measuring OD320 of aqueous protamine-DNA mixtures. This is a molecular level observation for the removal of protamine from DNA-protamine complex.

Amino Acid Sequence↗

PubMed1997

Production of interleukins 10 and 12 by peripheral blood mononuclear cells (PBMC) in chronic hepatitis C virus (HCV) infection.

We previously reported that interferon-gamma (IFN-gamma) production by PBMC in response to HCV core protein was increased in patients with type C chronic liver disease. To understand better the pathophysiology of this disease, we evaluated production of IL-10 and IL-12 by PBMC from 41 patients with chronic HCV infection, including asymptomatic HCV carriers with persistently normal serum ALT values. IL-10 is known to inhibit many effector functions of the immune system, suppressing Th1-type cell development, while IL-12 stimulates differentiation of Th1-type cells, facilitating cell-mediated immunity. IL-10 production was determined by culturing lymphocytes with concanavalin A (Con A), while IL-12 was produced by monocytes in the presence of Staphylococcus aureus Cowan 1 (SAC) with or without recombinant HCV core protein, respectively. The cytokine levels in culture supernatants were measured by ELISA. Spontaneous IL-10 production was greater in patients with chronic hepatitis (CH) (229 +/- 119 pg/ml, P < 0.01) and liver cirrhosis (LC) (185 +/- 88 pg/ml, P < 0.05) than in controls (119 +/- 27 pg/ml), while it was decreased during IFN treatment (70 +/- 25 pg/ml). Both HCV core protein and Con A enhanced IL-10 production by cells from HCV-infected patients. IL-12 was not detectable in medium alone cultures, and SAC-induced IL-12 production did not differ between various patient groups and controls. Simultaneous addition of HCV protein resulted in an increase of IL-12 production in chronic liver disease compared with SAC-alone cultures. Addition of IL-10 to the cultures equally suppressed IFN-gamma production for both controls and patient groups, but the enhancing effect of IL-12 on IFN-gamma production was significantly less in LC than in controls and other patient groups. The findings suggest that secretion of IL-10/IL-12 by cells from control individuals and various patient groups may be different, and that the cytokines might show different effects on IFN-gamma production by some cells.

Adult↗

PubMed1997

Humoral immune response to the hypervariable region of hepatitis C virus differs between genotypes 1b and 2a.

Antibody to the hypervariable region (HVR) of HCV is thought to have neutralizing activity. The HCV genotype is known to affect the clinical course of infection. The antibody response to HVR and its relationship to the virologic and clinical characteristics were investigated in 21 patients with chronic hepatitis C. HVRs amplified by polymerase chain reaction from serum HCV were expressed as glutathione S-transferase fusion proteins. From 8 to 34 clones per serum sample were obtained (375 clones total), and the anti-HVR antibody in serum was assessed by Western blot. Both the incidence of fusion proteins positive for anti-HVR antibody and the activity of antibody were significantly higher in 6 patients with genotype 2a than in 15 patients with genotype 1b. This result suggests that the quantity of humoral response to HVR affects the clinical outcome of infection with these two HCV genotypes.

Adult↗

PubMed1997

Cyclosporine therapy affects aminotransferase activity but not hepatitis C virus RNA levels in chronic hepatitis C.

Interferon (IFN) therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and is often limited by side effects. Cyclosporine A (CsA) is a potent immunosuppressant widely used in organ transplantation. We conducted a pilot study to determine whether CsA therapy could affect aminotransferase activity and hepatitis C virus RNA levels in patients with chronic hepatitis C. Cyclosporine A was administered to 10 patients (mean age of 59 years; male:female = 9:1) who did not respond to IFN therapy previously and who had elevated serum alanine aminotransferase (ALT) values for at least 6 months. All patients were positive for HCV-RNA by RT-PCR with genotype 1b. Their mean duration of hepatitis was 15 years. Oral CsA was given for 3 months in a dose that was increased at 1 month intervals from 1.5-2.0 to 2.0-3.0 and 3.0-4.0 mg/kg per day. All patients completed the treatment schedule, although two patients developed mild non-symptomatic hypertension. Serum ALT levels gradually decreased in all but one patient. The mean percentage decrease was 59.5% at the end of therapy (from 153 +/- 82 to 62 +/- 48 IU/L; P < 0.02). The ALT levels fell to the normal range in five patients, although once therapy was discontinued the enzyme levels tended to return to pretreatment levels. Serum aspartate aminotransferase and g-glutamyl transpeptidase levels similarly decreased. The serum HCV-RNA titre, determined by competitive RT-PCR, did not change in any patient throughout the study period. There were no appreciable alterations in other laboratory tests, such as serum creatinine levels and lymphocyte subsets, except for an increase in serum alkaline phosphatase levels. These findings suggest that CsA, even in a relatively low dose, reduces serum aminotransferase levels without serious side effects in patients with chronic hepatitis C, although an antiviral effect was not noted.

Administration, Oral↗

PubMed1997

Immunohistochemical evidence of insulin-like growth factor II in human small hepatocellular carcinoma with hepatitis C virus infection: relationship to fatty change in carcinoma cells.

It has recently been reported that insulin-like growth factor II (IGF-II) may play a role in the pathogenesis of hepatocellular carcinoma (HCC). We studied the relationship between the expression of IGF-II and fatty change in human small HCC using immunohistochemical staining techniques. Liver biopsy specimens were obtained from 35 patients with HCC (consisting of 15 patients with fatty change and 20 patients without fatty change). All patients had serum markers for the hepatitis C virus (HCV) and histological findings obtained from non-tumourous lesions showed liver cirrhosis or chronic active hepatitis. Immunohistochemical staining was performed using a monoclonal antibody against rat IGF-II. A positive immunoreaction was found in 69% (24/35) of HCC. Insulin-like growth factor II was immunodetected in 80% (12/15) of HCC with fatty change but only in 60% (12/20) of those without fatty change. In most cases, IGF-II was not found in hepatocytes from non-tumourous lesions. We believe this to be the first time that IGF-II has been detected immunohistochemically in small HCC derived from HCV infection. This growth factor was more frequently immunodetected in HCC with fatty change than without. As insulin is an essential factor for the metabolism of fatty acids, IGF-II may play an important role in both fatty degeneration and in the proliferation of HCC cells. Furthermore, immunohistochemical IGF-II staining may contribute to the diagnosis of HCC, particularly in early stages accompanied by fatty change.

Carcinoma, Hepatocellular↗

PubMed1997

Earlier loss of hepatitis C virus RNA in interferon therapy can predict a long-term response in chronic hepatitis C.

To distinguish responders from non-responders early in interferon (IFN) treatment would be beneficial in patients with chronic hepatitis C. Those patients unlikely to respond would be spared the cost and hazard of prolonged treatment. Forty-three chronic hepatitis C patients who had received IFN-alpha therapy (6-9 MU; six times weekly for 2 weeks followed by thrice weekly for 22 additional weeks) were randomly enrolled into the present study. Serially obtained sera were retrospectively tested for HCV-RNA by reverse transcription-polymerase chain reaction (Amplicor HCV) with a low limit detection of approximately 10(2) copies/mL. Genotypes were determined by type-specific primers. Sixteen subjects were defined as sustained responders (SR), who showed sustained loss of viraemia with normalized alanine aminotransferase values for at least 6 months of follow-up after completion of therapy. The other 27 subjects were non-responders (NR), whose viraemia persisted during follow-up. Pretreatment serum HCV-RNA levels (P < 0.0001) and the genotype (P < 0.01) were significant predictors for sustained response to IFN therapy. Hepatitis C virus RNA was detectable in only one (6%) SR and in 23 (85%) NR at the second week of therapy (P < 0.0001) and was detected in none of the SR subjects and in 18 (67%) NR at the fourth week of therapy (P < 0.0001). Pretreatment viral load was correlated with the time until loss of viraemia. Multivariate analysis revealed that loss of viraemia at the second week of therapy was the strongest predictor for a long-term response, followed by the initial viral load and loss of viraemia at the fourth week of therapy. These findings suggest that it is possible to predict a long-term response to IFN as early as at the second and fourth weeks after the start of therapy by identifying the presence or absence of HCV-RNA with a sensitive assay.

Adult↗

PubMed1997

Co-localisation of insulin-like growth factor II and the proliferation marker MIB1 in hepatocellular carcinoma cells.

AIM: To assess the effect of insulin-like growth factor II (IGF-II) on proliferation of hepatocellular carcinoma (HCC) cells. METHODS: Expression of IGF-II mRNA and protein was detected in 10 archival HCC specimens using in situ hybridisation and immunohistochemistry, respectively. Expression of the Ki-67 antigen, a proliferation marker, was determined immunohistochemically on the same sections. RESULTS: Increased expression of IGF-II mRNA and protein was detected in five of the 10 HCCs in cells located at the periphery of tumour nests. The pattern of localisation of IGF-II was almost identical with that of Ki-67 antigen. CONCLUSIONS: Most of the Ki-67 antigen positive cells co-expressed IGF-II, suggesting that IGF-II may act as an autocrine or paracrine growth factor, and may play an important role in the development of HCC.

Carcinoma, Hepatocellular↗

PubMed1997

Comparative study of the effects of indomethacin and NS-398, a selective cyclooxygenase 2 inhibitor, on duodenal bicarbonate secretion induced by luminal acidification in rats.

To clarify the mechanisms of duodenal ulcerogenic activity of non-steroidal anti-inflammatory drugs (NSAIDs), the effects of indomethacin (IND) on acid-stimulated duodenal bicarbonate secretion and histamine-induced duodenal ulcerogenic responses were studied in comparison with NS-398, a selective cyclooxygenase (COX)-2 inhibitor, in rats. IND (1 and 5 mg/kg, s.c.) significantly decreased duodenal bicarbonate secretion and potentiated duodenal lesion in a dose-dependent manner. On the other hand, NS-398 had no effect on these parameters. These findings suggest that duodenal ulcerogenicity of IND in the presence of histamine is mainly due to the inhibitory action on acid-stimulated bicarbonate secretion mediated by COX-1, but not by COX-2.

Animals↗

PubMed1997

Tissue inhibitor of metalloproteinases-3 is a component of Bruch's membrane of the eye.

Mutations in tissue inhibitor of metalloproteinases (TIMP)-3 are found in some patients with Sorsby's fundus dystrophy, a retinal degeneration characterized by abnormal deposits in Bruch's membrane and choroidal neovascularization. The purpose of this study was to localize TIMP-3 in the retina/choroid of normal human and animal eyes. Immunolabeling was performed on unfixed and fixed sections of human eyes aged 24 to 85 years and unfixed sections of baboon, chicken, cow, pig, and rat eyes using a monoclonal antibody against a human TIMP-3 synthetic peptide. The antibody produced strong immunolabeling of Bruch's membrane and drusen and weak labeling of retina blood vessels in unfixed human and baboon eyes. Unfixed chicken, cow, pig, and rat tissues showed no reactivity. After antigen retrieval, all fixed human eyes showed specific labeling of Bruch's membrane and drusen, which was strongest in eyes from elderly donors. The results indicate that TIMP-3 is an extracellular matrix component of Bruch's membrane. Thus, abnormal local function of TIMP-3 may lead to the characteristic Bruch's membrane deposits and choroidal neovascularization found in Sorsby's fundus dystrophy. Specific labeling of drusen raises the possibility that altered TIMP-3-mediated matrix remodeling may contribute to age-related degenerative changes in Bruch's membrane.

Adult↗

PubMed1997

Gelatinases and inhibitors of gelatinases in pancreatic islets and islet cell tumors.

Pancreatic islets contain trace amounts of zinc to form insulin dimer, and matrix metalloproteinases (MMPs) are single-chain zinc-containing metallo-enzymes. By immunocytochemically staining pancreatic tissue, which contained exocrine duct adenocarcinoma, normal islets were incidentally found positive for gelatinase-A (MMP-2) and gelatinase-B (MMP-9), and for tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2). Normal islets from five pancreata were exclusively stained for two each of gelatinases and TIMPs. Twenty-two islet cell tumors were also stained for pancreatic hormones, gelatinases, and TIMPs, which included insulinomas, gastrinomas, glucagonomas, pancreatic polypeptide-omas (PPomas), and nonfunctioning tumor. In general, islet cell tumors were weakly stained for gelatinases and TIMPs, compared with normal islets in the adjacent pancreatic tissue. No clear difference in staining intensity among five kinds of islet cell tumors was observed. The selective immunolocalization of gelatinases and TIMPs in islet cells and islet cell tumors may suggest possible a structure-function relationship among zinc, gelatinases-TIMPs, and pancreatic hormones.

Adenocarcinoma↗