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Biomedical subjects

K Moriya

Publications and source records attributed to K Moriya.

At least 55 records · Page 3Linked to original sources
PubMed1999

Oxidative damage to cellular and isolated DNA by metabolites of a fungicide ortho-phenylphenol.

ortho-Phenylphenol (OPP) and its sodium salt, which are used as fungicides and antibacterial agents, have been found to cause carcinomas in the urinary tract of rats. To clarify the carcinogenic mechanism of OPP, we compared the DNA damage inducing ability of an OPP metabolite, phenyl-1,4-benzoquinone (PBQ) with that of another metabolite, phenylhydroquinone (PHQ). Pulsed field gel electrophoresis showed that PBQ and PHQ induced DNA strand breakage in cultured human cells, but PBQ did it more efficiently than PHQ. Significant increases in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) were observed in cells treated with PBQ and PHQ, and the increase of 8-oxodG induced by PBQ was significantly higher than that induced by PHQ. Using 32P-5'-end-labeled DNA fragments obtained from human p53 tumor suppressor gene and c-Ha-ras-1 protooncogene, we showed that PBQ plus NADH, and also PHQ, induced DNA damage frequently at thymine residues, in the presence of Cu(II). The intensity of DNA damage by PBQ was stronger than that by PHQ, showing higher importance of PBQ than other OPP metabolites. Catalase and bathocuproine inhibited Cu(II)-mediated DNA damage by PBQ plus NADH and PHQ, suggesting that H2O2 reacts with Cu(I) to produce active species causing DNA damage. Electron spin resonance and UV-visible spectroscopic studies have demonstrated generation of semiquinone radical and superoxide from the reaction of PBQ with NADH or the Cu(II)-mediated autoxidation of PHQ. The present results suggest that these OPP metabolites cause oxidative DNA damage through H2O2 generation in cells, and the damage may lead to mutation and carcinogenesis. It is concluded that PBQ may play a more important role in the expression of OPP carcinogenicity than other OPP metabolites.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

[The natural history of renal angiomyolipoma].

PURPOSE: To make the policy of treatment with angiomyolipomas (AML) more clear, we discussed the natural history of angiomyolipomas retrospectively. PATIENTS AND METHODS: Between May 1982 and December 1997, 14 patients with AML in 18 kidneys were followed, who were 2 men in 2 kidneys and 12 women in 16 kidneys, 27 to 80 years old. No patients suffered from tuberous sclerosis. Symptoms, initial sizes and changes of the size were evaluated for these patients. RESULTS: Ten patients with AML in 14 kidneys were asymptomatic and four patients were symptomatic. But one of the 4 patients had symptoms of abdominal pain and palpable mass which were due to contralateral AML that were treated with nephrectomy, so symptoms due to small AML were seen in 3 cases (2.0 cm, 3.5 cm, 3.8 cm). Among 11 patients in 15 kidneys followed radiologically for more than 6 months, the tumors were unchanged in size in 7 kidneys, which were in all of 6 cases with unilateral solitary tumor and in 1 with bilateral multiple tumors. In other 8 kidneys the sizes of the tumors were increased, which were in the cases with multiple tumors in one kidney or in bilateral cases. Compared to the cases of unilateral solitary AML, the size of AML with multiple tumors in one kidney or in bilateral kidneys significantly increased (p < 0.01). Embolization were performed for 4 kidneys, which were in 2 cases with increased tumor in size to more than 4 cm in following period, in 1 with dull flank pain, and in 1 with the tumor more than 4 cm at diagnosis that grew to more than 5 cm. CONCLUSIONS: Unilateral solitary AML was appeared to be hard to increase in size and to have a different natural history from bilateral or multiple tumors.

Adult↗
PubMed1998

Compensatory apoptosis in preneoplastic liver of a transgenic mouse model for viral hepatocarcinogenesis.

The HBx protein of hepatitis B virus has been shown to induce hepatocellular carcinoma in transgenic mice as direct evidence for its involvement in hepatocarcinogenesis. In these transgenic mice, however, it is not clear why hepatocytes do not acquire a neoplastic phenotype by 13 months old despite the continuous growth stimulation by the HBx protein from 2 months old. In this study, we show that the accelerated proliferation of hepatocytes is counterbalanced by apoptosis, which maintains liver homeostasis. A decrease in the extent of apoptosis seems to precede the emergence of neoplasia in the transgenic mouse liver. The disappearance or block of apoptotic signals, which may be the result of additional genetic or epigenetic aberrations, may result in the preneoplastic hepatocytes becoming neoplastic.

Aging↗
PubMed1998

Precore wild-type DNA and immune complexes persist in chronic hepatitis B after seroconversion: no association between genome conversion and seroconversion.

Precore hepatitis B virus (HBV) mutants may gradually prevail during or after seroconversion (SC) from hepatitis B e antigen (HBeAg) to hepatitis B e antigen antibody (anti-HBe) status in many chronic hepatitis B (CH-B) patients. However, patients with CH-B still produce anti-HBe more than several years after SC, and the relationship between SC and genome conversion in the precore region has not been clarified. Therefore, in patients with CH-B who had a sustained loss of HBeAg and complete remission of hepatitis after SC, the precore region was sequenced in paired serum samples from 1 year before SC to 3 years after SC. Mutant precore defective HBV DNA was found in only 6 (19%) of 31 CH-B patients who had a complete remission of hepatitis after SC. Mixed-type HBV DNA (precore wild-type and mutant-type) was found in 4 (13%) patients. Wild-type HBV DNA was found in 21 (68%) CH-B patients after SC. Longer-term follow-up of 11 CH-B patients indicated that 3 of 11 patients experienced precore genome conversion 2 to 3 years after SC. E-plus DNA or e-minus DNA was semiquantitated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays before and after SC. E-plus DNA levels decreased from 10(5.56+/-1.58) to 10(2.45+/-1.61). Similarly, e-minus DNA levels declined from 10(4.25+/-1.56) to 10(1.86+/-1.37). By dot-blot assay, serum HBV DNA became negative soon after SC, as did serum HBeAg. In contrast, HBeAg-containing immune complexes were still detected after SC. Anti-HBe antibody was produced throughout SC and thereafter, as determined by a sensitive experimental assay. Therefore, we conclude that genome-conversion in the precore region is a separate event from HBeAg/anti-HBe seroconversion.

Acute Disease↗
PubMed1998

Persistent viremia after recovery from self-limited acute hepatitis B.

To define the duration of viremia in the course of acute hepatitis B, we semiquantitatively determined the levels of hepatitis B virus (HBV) DNA in the sera, using polymerase chain reaction (PCR) coupled with Southern blotting, of non-immunocompromised patients with self-limited acute hepatitis B. In the sera of 10 of 11 patients, HBV DNA, which was presumably coated with viral proteins, was detected for a long period after recovery, even at the final observation times, which ranged from 6 to 19 months after disease onset. To characterize the mode of HBV that was present in serum, we immunoprecipitated immune complexes in sera by the addition of anti-human immunoglobulin G (IgG) and determined the levels of HBV DNA separately in the supernatants and pellets. In the acute phase of hepatitis B, high levels of HBV DNA were detected both in the supernatants and pellets at comparative levels. After the convalescent phase, the amount of HBV DNA in the supernatant decreased with respect to that in the pellets. It is notable that, in most cases, serum HBV persisted as a form of immune complex even after the seroconversion to antibody to hepatitis B surface antigen (anti-HBs). These data suggest that the replication of HBV may persist in some organs, most likely in the liver or peripheral blood cells, for a long period after recovery from acute hepatitis B, and the data indicate the possible transmission of HBV from organ transplantation donors who exhibit serological markers of past infection only.

Acute Disease↗
PubMed1998

Regulation of Fas gene expression in HeLa cells as determined by modified RT-PCR.

We determined human Fas messenger RNA (mRNA) levels in HeLa cells using a 'mutagenic' reverse transcription-polymerase chain reaction, which quantitates mRNA levels using the corresponding genomic DNA as an internal control. The expression level of Fas mRNA was very low in serum-deprived quiescent HeLa cells. In conjunction with the start of cell-cycle progression upon the addition of serum to culture medium, the Fas mRNA level gradually increased, reached its peak at 36 h and returned to the basal level after 48 h. HeLa cells at 36 h exhibiting a high level of Fas mRNA expression were more susceptible to the anti-Fas antibody apoptotic signal. Thus, the regulation of Fas expression is associated with cell-cycle progression, and this method for Fas mRNA detection may be useful, particularly for the analysis of small amounts of samples.

Antibodies↗
PubMed1998

Development of glycosylated human interleukin-1alpha, neoglyco IL-1alpha, coupled with D-galactose monosaccharide: biological activities in vivo.

In our previous study, a galactose monosaccharide with C9 spacer was chemically coupled to recombinant human interleukin 1alpha (rhIL-1alpha) in order to study the effect of glycosylation on its activities, and to develop IL-1 with less deleterious effects. The glycosylated IL-la exhibited reduced activities in vitro by 10 to 10000-fold depending upon different aspects of activities addressed. The affinity to type I and II IL-1 receptors were also reduced. In this study we examined a variety of IL-1 activities in vivo, including upregulation of serum levels of IL-6, alpha1-acid glycoprotein, NOx, corticosterone, downregulation of serum level of glucose, and recovery of peripheral white blood cells (WBCs) from myelosuppression in 5-fluorouracil-treated mice. In contrast to the biological activities in vitro, these activities in vivo were uniformly reduced by only about 10 to 20-fold compared to untreated IL-1alpha.

Animals↗
PubMed1998

The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice.

Hepatitis C virus (HCV) is the main cause of chronic hepatitis worldwide. Chronic hepatitis ultimately results in the development of hepatocellular carcinoma (HCC). However, the mechanism of hepatocarcinogenesis in chronic HCV infection is still unclear. The ability of the core protein of HCV to modulate gene transcription, cell proliferation and cell death may be involved in the pathogenesis of HCC. Here, we report the development of HCC in two independent lines of mice transgenic for the HCV core gene, which develop hepatic steatosis early in life as a histological feature characteristic of chronic hepatitis C. After the age of 16 months, mice of both lines developed hepatic tumors that first appeared as adenomas containing fat droplets in the cytoplasm. Then HCC, a more poorly-differentiated neoplasia, developed from within the adenomas, presenting in a 'nodule-in-nodule' manner without cytoplasmic fat droplets; this closely resembled the histopathological characteristics of the early stage of HCC in patients with chronic hepatitis C. These results indicate that the HCV core protein has a chief role in the development of HCC, and that these transgenic mice provide good animal models for determining the molecular events in hepatocarcinogenesis with HCV infection.

Animals↗
PubMed1998

[Clinical study of long graft survival in renal transplantation recipients].

BACKGROUND: A total of 110 patients, in whom kidneys from 95 living related and 15 cadaver donor, had experienced renal transplantation between February 1985 and October 1996 in our clinic. This study was conducted to evaluate the influence of the various pre-operative factors to the graft survivals and clinical course of patients in living related renal transplantation. METHODS: In 95 recipients, 17 adult patients had long term graft survivals over 5 years including 6 recurrent or denovo nephritis without chronic allografts nephropathy. Eight failed to graft loss attributed to chronic allografts nephropathy diagnosed within 5 years. Retrospective analysis were performed to elucidate the differences of these recipients. RESULTS: Donors of long graft survival recipients were younger (49.1 +/- 12.1 v.s. 58.9 +/- 10. 2) and had a better renal function evaluated by preoperative creatinine clearance in living related donors (115.5 +/- 37.0 v.s. 79.7 +/- 22.0 1/day). Graft long survival recipients had experienced less frequencies of acute rejection within 6 months (0.53 +/- 0.62: 8 patients, 9 times) compared with chronic allografts nephropathy recipients (1.00 +/- 0.53: 7 patients, 8 times). Long graft survival recipients had better responses to the antirejection therapy. Additionally acute rejection over 6 months were experienced only in chronic allografts nephropathy recipients. Higher serum creatinine level was revealed in recipients with chronic allografts nephropathy at 1 year after transplantation (1.27 +/- 0.27 v.s. 1.88 +/- 0.42 mg/dl). CONCLUSIONS: We concluded that donor age and renal function are related to the graft long survival as background factors. Long graft survival recipients had less frequency of acute rejection and good response to the antirejection therapy. In recipients with of acute rejection and good response to the antirejection therapy. In recipients with chronic allografts nephropathy, serum cretine level had already increased gradually within 1 year.

Adult↗
PubMed1998

[Clinical evaluation of chemiluminescence immunoassay PSA (ACS-PSA) for detection of prostate cancer].

Serum prostate specific antigen (PSA) levels were measured using an ACS-PSA kit in 147 systematic biopsy cases (61 with prostate cancer (PC)) and 96 transurethral resection of prostate (TUR-P) cases (2 with PC). In the 147 biopsy cases, the sensitivity for PSA using 3.0 and 10.0 ng/ml as cut-off values was 91.8 and 90.2%, while the specificity was 9.30 and 30.2%, respectively. The sensitivity for PSAD (A) (calculated by transabdominal ultrasound) using 0.25 and 0.5 ng/ml/cm3 as cut-off values was 91.8 and 90.2%, while the specificity was 22.1 and 50.0%, respectively. These data indicated that PSAD (A) provided better information for detecting PC than PSA alone. No statistical difference was found between PSAD (A) and PSAD (R) (calculated by transrectal ultrasound) in the utility of detecting PC. PSA below 15.0 ng/ml was seen in sixteen patients with PC. Five of these sixteen patients had a PSA level of < 3.0, and they underwent prostate biopsy based on the abnormality by digital rectal examination (DRE). The other eleven patients had PSAD (A) level of > 0.3 ng/ml/cm3. In all 243 cases, PC was not found in the 49 patients (PSA < 3.0 ng/ml) or 91 patients (PSAD (A) < 0.25 ng/ml/cm3) who had no abnormal findings by DRE and transabdominal ultrasonography. These results suggested a criterion in the use of the ACS-PSA kit for the indication of prostate biopsy and TUR-P.

Aged↗
PubMed1997

ER-27319, an acridone-related compound, inhibits release of antigen-induced allergic mediators from mast cells by selective inhibition of fcepsilon receptor I-mediated activation of Syk.

Engagement of the mast cell high-affinity receptor for immunoglobulin E (IgE), FcepsilonRI, induces tyrosine phosphorylation of Syk, a non-receptor tyrosine kinase, that has been demonstrated as critical for degranulation. Herein we describe a synthetic compound, ER-27319, as a potent and selective inhibitor of antigen or anti-IgE-mediated degranulation of rodent and human mast cells. ER-27319 affected neither Lyn kinase activity nor the antigen-induced phosphorylation of the FcepsilonRI but did effectively inhibit the tyrosine phosphorylation of Syk and thus its activity. As a consequence, tyrosine phosphorylation of phospholipase C-gamma1, generation of inositol phosphates, release of arachidonic acid, and secretion of histamine and tumor necrosis factor alpha were also inhibited. ER-27319 did not inhibit the anti-CD3-induced tyrosine phosphorylation of phospholipase C-gamma1 in Jurkat T cells, demonstrating a specificity for Syk-induced signals. In contrast the tyrosine phosphorylation and activation of Syk, induced by in vitro incubation with the phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) of FcepsilonRI gamma subunit or by antigen activation of RBL-2H3 cells, was specifically inhibited by ER-27319. However, when ER-27319 was added to immunoprecipitated Syk, derived from activated cells, no effect was seen on Syk activity. ER-27319 did not inhibit the tyrosine phosphorylation of Syk induced by activation in the presence of Igbeta ITAM or the anti-IgM-induced phosphorylation of Syk in human peripheral B cells. Therefore, ER-27319 selectively interferes with the FcepsilonRI gamma phospho-ITAM activation of Syk in vitro and in intact cells. These results confirm the importance of Syk in FcepsilonRI-mediated responses in mast cells and demonstrate the mast cell selectivity and therapeutic potential of ER-27319 in the treatment of allergic disease.

Acridines↗
PubMed1997

Sialadenitis histologically resembling Sjogren syndrome in mice transgenic for hepatitis C virus envelope genes.

Hepatitis C virus (HCV), a major causative agent of non-A, non-B chronic hepatitis, is also suggested to be associated with extrahepatic manifestations such as mixed cryoglobulinemia and glomerulonephritis. Two independent lines of transgenic mice carrying the HCV envelope genes have been shown previously to express the HCV envelope proteins in organs, including the liver and salivary glands, which results in no pathological changes in the liver. Further analysis of these animals now has revealed that they develop an exocrinopathy involving the salivary and lachrymal glands. This pathology resembles Sjogren syndrome, which also is suggested to have a possible association with chronic hepatitis C. These observations suggest that HCV might be involved in the pathogenesis of sialadenitis in humans and that this transgenic mouse system would be a good animal model for the study of HCV infection.

Age Factors↗
PubMed1997

Hepatitis C virus core protein induces hepatic steatosis in transgenic mice.

Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide, which finally leads to development of hepatocellular carcinoma. Chronic hepatitis C is characterized by several histological features in the liver which discriminate it from other forms of hepatitis: bile duct damage, lymphoid follicles and steatosis (fatty change). Little is known, however, about the role of HCV or its viral proteins in the pathogenesis of hepatitis. Recently, the core protein of HCV has been suggested to have a transcriptional regulatory function, and thereby to be involved in inducing phenotypic changes in hepatocytes. To clarify whether or not the HCV core protein has an effect on pathological phenotypes in the liver, two independent transgenic mouse lines carrying the HCV core gene were established. These mice developed progressive hepatic steatosis, indicating that the HCV core protein plays a direct role in the development of hepatic steatosis, which characterizes hepatitis C. This transgenic mouse system would be a good animal model for the study of pathogenesis in human HCV infection.

Animals↗
PubMed1997

[Clinical study of gasless laparoscopic adrenalectomy in 17 cases--comparison between laparoscopic adrenalectomy with and without pneumoperitoneum].

PURPOSE: To determine the efficiency of gasless laparoscopic adrenalectomy, this procedure was compared to that with pneumoperitoneum. PATIENTS AND METHODS: Between February 1994 and December 1996, 17 gasless laparoscopic adrenalectomy were performed in 5 men and 12 women, 36 to 79 years old. Clinical diagnosis was primary aldosteronism in 8, pheocromocytoma in 2, incidentaloma in 4 and adrenal cyst in 3. When gasless laparoscopic adrenalectomy was performed, the laparoscope was inserted through the upper margin of the umbilicus by open laparotomy. To create a workable space, a 1.2 mm Kirschner wire was advanced subcutaneously below the costal arch and attached to a retractor. Operating time, estimated blood loss, changes of the end tidal CO2 concentration during operation, operative complications and postoperative course were compared to those with pneumoperitoneum in 12 cases. RESULTS: In both procedures, satisfying workable spaces were created in all cases. The mean operating time and estimated blood loss were 245 min and 201 ml without pneumoperitoneum, 317 min and 274 ml with pneumoperitoneum, respectively. The mean changes of end tidal CO2 concentration during operation were 3.2 mmHg without pneumoperitoneum and 5.1 mmHg with pneumoperitoneum. As operative complications, open operations were required in 2 cases (1 without pneumoperitoneum and another with pneumoperitoneum) to control intraoperative bleeding. They had the histories of transabdominal operations. Postoperative bleeding was observed in 2 cases (1 without pneumoperitoneum and another with pneumoperitoneum). One of them (with pneumoperitoneum) needed surgical management for hemostasis. Fever over 38 degrees C that occurred in 1 case with pneumoperitoneum appeared to be absorption fever. No differences were observed in the number of the days to the start of oral intake and for postoperative hospitalization between the two groups. CONCLUSIONS: Gasless laparoscopic adrenalectomy is available for most adrenal tumors. Suction could be used unrestrictedly and there were no hemodynamic or ventilatory effects due to pneumoperitoneum. This procedure appears to be safe and advantageous for the treatment of most adrenal tumors.

Adrenal Gland Diseases↗
PubMed1997

A comparative study of nutrition and health of mothers in Japan and the Philippines.

When comparing nutrition and health among mothers in both Japan and Philippines, it can be concluded that, in regard to nutrition, the results of the total dietary scores for mothers in divided into pregnant and after-delivery stages showed that pregnant Filipino mothers' average are lower than those of pregnant Japanese mothers. Pregnant Filipino mothers and those just after delivery to 4 months had lower average dietary scores than Filipino mothers 5 months and later after delivery. These results are thought to be an important factor in the improvement of health condition and life expectancy of Filipino mothers and their children. In Japanese mothers, such differences were not found. When comparing individual dietary scores and the rate of nutrients consumed to the optimum amounts, significant differences were found among mothers in both countries. Analysis of food diaries of mothers from both countries found that Japanese mothers had average intakes of nutrients such as energy, protein, fat, vitamin B1 and vitamin B2 and were deficient in calcium, iron and vitamin A. Filipino mothers took in average amounts of protein, calcium, iron, vitamin B2 and vitamin C and were deficient in energy, fat and vitamin B1.

Adolescent↗
PubMed1996

In vivo inhibition of hepatitis B virus gene expression by antisense phosphorothioate oligonucleotides.

While an important goal of treatment for hepatitis B is to prevent the development of hepatocellular carcinoma, there has been no effective therapy for it. Antisense oligodeoxynucleotide treatment could in principle inhibit hepatitis B virus gene expression and suppress tumor development. We used a mouse model for hepatocellular carcinoma, which is transgenic for the hepatitis B virus HBx gene, to study antisense phosphorothioate oligodeoxynucleotides. Among 2 series of sense and antisense oligodeoxynucleotides, only antisense sequences covering the initiation codon of the HBx gene effectively inhibited the expression of the HBx gene in the liver. Intraperitoneal injection of this antisense oligodeoxynucleotide thrice a week for 8 weeks resulted in the prevention of preneoplastic lesion development in the liver without inflammation in the liver or developmental disturbance of the mice. Antisense phosphorothioate oligodeoxynucleotides can inhibit the expression of a hepatitis B virus gene and may be a promising method for the prevention of hepatocellular carcinoma in hepatitis B virus infection.

Animals↗
PubMed1996

Prolonged fecal excretion of hepatitis A virus in adult patients with hepatitis A as determined by polymerase chain reaction.

In hepatitis A virus (HAV) infection, fecal excretion of the virus has been reported to cease shortly after symptoms occur. Although there have been several reports on detection of HAV in feces using polymerase chain reaction (PCR), the duration of fecal HAV shedding in human adult hepatitis A has not been well described. In the present study, we applied the reverse-transcription (RT)-PCR system to the detection of fecal HAV RNA in 10 patients with sporadic hepatitis A. The viral genomic RNA was detected in the stools from five patients after the onset of clinical symptoms. All stool samples collected within 10 days of onset of illness were HAV-RNA-positive, and the duration of positivity lasted from a few days to as long as 3 months. In four patients, HAV RNA was detected in the stool even after the serum alanine transaminase (ALT) levels had peaked, and in one patient well after ALT levels fell to normal. These results show that fecal shedding of HAV can last for months after resolution of symptoms and such patients could be a source of further spreading of the virus in the community.

Adult↗