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Biomedical subjects

H Onodera

Publications and source records attributed to H Onodera.

At least 73 records · Page 4Linked to original sources
PubMed1999

Inhibition of thyroid iodine uptake and organification in rats treated with kojic acid.

In order to elucidate the mechanisms of reduction of serum thyroid hormones caused by continuous administration of kojic acid (KA) and its thyroid tumor-promotion effects, male F344 rats were given pulverized basal diet containing 0.008%, 0.03%, 0.125%, 0.5%, or 2% KA for 4 weeks. As an untreated control group, additional rats were given basal diet alone for the same period. The thyroid 125I uptake was significantly decreased in the groups receiving 0.03% or more. In addition, significant reduction of organic formation of iodine and serum T3 and T4 levels were observed in the 2% KA group along with pronounced elevation of serum (TSH). Both absolute and relative thyroid weights were significantly increased in the groups receiving 0.5% of KA or more. Histopathologically, decreased colloid in the thyroid follicles and follicular cell hypertrophy in the thyroid were apparent at high incidences in the groups given 0.03% or more. In addition, thyroid capsular fibrosis was evident in all rats of the 2% KA group. In quantitative morphometrical analysis, the ratio of the area of follicular epithelial cells to the area of colloids was significantly increased in the groups given 0.03% KA or more. The results suggest that KA alteration of thyroid-related hormone levels in the 2% KA group are due to inhibition of iodide uptake and iodine organification in the thyroid, with tumor-promoting effects on development of thyroid proliferative lesions, probably secondary to prolonged serum TSH stimulation resulting from negative feedback through the pituitary-thyroid axis.

Animals↗
PubMed1999

Correlation of tensile strength with bursting pressure in the evaluation of intestinal anastomosis.

BACKGROUND: Although bursting pressure and tensile strength have long been measured to evaluate anastomotic techniques, it has yet to be clarified whether or not they are correlated, what implications they have, and which should be used as a gold standard. MATERIAL AND METHODS: Using an experimental model to estimate pressure and tension in the same colonic anastomosis, the following variables were measured in 48 rats between days 0 and 14: bursting pressure (BP); minimal tensile strength (MITS) necessary to break a part of the anastomosis, and maximal tensile strength (MATS) needed to disrupt the whole anastomosis. Also, circulatory wall tension (CWT) was derived from BP and the anastomotic circumference (AC), and longitudinal wall tension (LWT) from MITS and AC. These variables were compared using correlation and regression analysis. RESULTS: During the lag phase (days < or = 4) there was poor correlation between pressure-related and tension-related variables whereas highly significant correlations were noted in the subsequent fibroplastic phase (day > or = 5). It was shown by regression lines that positive MITS and MATS were expected when BP was zero. CONCLUSION: Contrary to the previous assumption, no correlation was found between BP and tensile strength in the critical postoperative period. Based on our present and previous studies, measurement of MITS is recommended to evaluate the healing of colonic anastomosis.

Anastomosis, Surgical↗
PubMed1999

Elevated plasma level of plasminogen activator inhibitor-1 (PAI-1) in patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and one of the earliest changes in inflammatory focus involves the activation of vascular endothelial cells. We determined the plasma level of plasminogen activator inhibitor-1 (PAI-1), a key regulator of fibrinolysis and cell migration, in patients with MS. The level of plasma PAI-1 was significantly higher in active MS cases when compared to stable MS and controls. Plasma concentrations of tissue plasminogen activator, transforming growth factor beta-1, and lipoprotein-a remained normal in spite of disease activity. These results suggested that PAI-1 plasma levels are associated with MS disease activity and is a good marker for MS relapse.

Adult↗
PubMed1999

Time course observation of thyroid proliferative lesions and serum levels of related hormones in rats treated with kojic acid after DHPN initiation.

Time course changes in thyroid proliferative lesions as well as related hormone levels in the blood of male F344 rats given N-bis(2-hydroxypropyl)nitrosamine (DHPN: 2800 mg/kg body weight, single s.c. injection) as an initiation treatment followed by pulverized basal diet containing 0% (Group 2), 2% (Group 3) or 4% (Group 4) kojic acid (KA) were examined at Weeks 1, 2, 4, 8 and 12. As an untreated control group (Group 1), rats were given basal diet for 13 weeks and examined in the same manner. Serum T3/T4 levels in the DHPN + 2% KA and DHPN + 4% KA groups were significantly reduced as compared with the DHPN-alone group at each time point. Serum TSH levels in both DHPN + KA groups were significantly increased at each time point in a treatment period-dependent manner from Weeks 1 to 12, and the extent of elevation was more remarkable in the DHPN + 4% KA group. At Week 2, there were no statistically significant intergroup differences in liver T4-UDP-GT activities on a milligram microsomal protein basis. Histopathologically, no thyroid proliferative lesions were observed in the untreated control group or the DHPN-alone group. However, diffuse follicular cell hypertrophy and decreased colloid in the thyroid were apparent in all rats of the DHPN + KA groups at each time point. In addition, focal follicular cell hyperplasias and adenomas of the thyroid were observed at high incidence in the DHPN + 2% KA group from Week 4 and in the DHPN + 4% KA group from Week 8. Multiplicities of focal follicular cell hyperplasias and adenomas of the thyroid in the DHPN + 2% KA group were significantly greater than those in the DHPN + 4% KA group at Week 8. In the pituitary, an increase in the number of TSH producing cells with expanded cytoplasm was apparent from Weeks 4 to 12 in both DHPN + KA groups. These results strongly suggest that thyroid proliferative lesions were induced by KA administration due to continuous serum TSH stimulation through the negative feedback mechanism of the pituitary-thyroid axis, resulting from depression of serum T3 and T4.

Adenoma↗
PubMed1999

[A case of various neurological deficits caused by multi-vitamin deficiency associated with malabsorption syndrome after pancreatomy and small bowel resection].

A 34-year-old woman presented with walking difficulty and pain in the legs 3 years after several abdominal operations for pancreatic cancer and intestinal obstruction thereafter. Corneal erosion, loss of deep sensation in the legs, polyneuropathy, myopathy, and memory disturbance were recognized. Deficiency of multiple vitamins (A, B1, B6, D, E, K) was found. The diagnoses were vitamin A-deficient corneal erosion, vitamin K-deficient bleeding abnormality (asymptomatic), and the neurological deficits caused by vitamin E, B1, B6 and D deficiency. Although the vitamin supplement started 2 years after the onset of the neurological disease, both clinical and electrophysiological recovery was seen. She was unable to walk on admission, but became able to walk after vitamin E supplement. To our knowledge, this is the first report showing multi-vitamin deficiency causing extensive neurological, ophthalmological, and hematological deficits. Recognition of this condition would prevent the progression of potentially irreversible neurological disorders in patients with malabsorption syndrome after extensive abdominal surgery.

Adult↗
PubMed1999

[A 13-week subchronic oral toxicity study of Perilla extracts in F344 rats].

A 13-week subchronic oral toxicity study of Perilla extracts in drinking water containing 0%, 2.5%, 5% and 10% extracts was performed in both sexes of F344 rats. Rats were randomly divided into 4 groups each consisting of 10 males and 10 females. No animals died during the period of administration. There were no treatment-related changes in body weight gain or in hematological or blood biochemistry values. Nor were any treatment-related histopathological changes observed in the highest dose group. These findings indicate that ingestion of 10% Perilla extracts in drinking water for 13-week does not cause any toxicological changes in rats.

Administration, Oral↗
PubMed1999

[13-week subchronic oral toxicity study of ammonium sulfate in rats].

A 13-week subchronic oral toxicity study of ammonium sulfate was performed in both sexes of F344 rats by feeding them a CRF-1 powder diet containing concentrations of 0%, 0.38%, 0.75%, 1.5%, and 3.0% of the substance. Rats were randomly divided into 5 groups each consisting of 10 males and 10 females. Male animals in the 3% group exhibited diarrhea during the administration period. No changes indicating obvious ammonium sulfate toxicity were observed in the body weights, organ weights, hematological, serum biochemical, or histopathological examinations. Based on these results, the NOEL (no-observed-effect level) of ammonium sulfate for F344 rats was judged to be 1.5% in males (886 mg/kg/day) and 3% in females (1975 mg/kg/day), and the MTD (maximally tolerated dose) for 2-year carcinogenicity studies in F344 rats was concluded to be 3.0% or more in the diet.

Ammonium Sulfate↗
PubMed1998

Pulmonary fibrosis caused by N-methyl-N-nitrosourethane inhibits lung tumorigenesis by urethane in transgenic mice carrying the human prototype c-Ha-ras gene.

Male and female transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice) and their wild littermates (non-Tg mice) received three subcutaneous injections of 0.3 mg N-methyl-N-nitrosourethane (MNUR) once every 2 weeks for the first 4 weeks followed by a single intraperitoneal injection of 1000 or 0 mg/kg urethane (UR) 2 weeks later. They were then maintained without any other treatment for a further 13 weeks and sacrificed for assessment of pulmonary pathology. Inflammatory lesions, such as macrophage infiltration, alveolar bronchiolization and/or fibrosis, were induced in both rasH2 and non-Tg mice treated with MNUR or MNUR + UR. Lung proliferative lesions were induced in 100% of the UR-treated rasH2 mice but to a significantly lesser extent in the MNUR + UR case. The incidences of lung tumors in non-Tg mice treated with UR or MNUR + UR were relatively low. Point mutations of the transgene were detected in approximately 80% of lung tumors in rasH2 mice treated with UR and MNUR + UR, but murine Ki-ras mutations were rare. No marked difference in the mutation pattern was found between the UR-treated and the MNUR + UR-treated rasH2 mice. In non-Tg mice treated with UR or MNUR + UR, point mutations of the murine c-Ki-ras gene were observed in about 50% of the lung tumors examined. The present study confirmed that rasH2 mice are very sensitive to lung tumor induction by UR and suggested that alveolar epithelial cells in the reparative stage during pulmonary fibrosis are resistant to DNA damage by this carcinogen.

Animals↗
PubMed1998

Characterization of differentially expressed genes in the bovine T lymphoma cell line.

A differential display (D.D.) analysis was made to detect differentially expressed genes in a bovine T lymphoma cell line, BTL-26, derived from the calf type of sporadic bovine lymphosarcoma. A D.D. analysis comparing BTL-26 with the bovine epithelial cell line CKT-1 and healthy bovine thymocytes yielded 24 cDNA clones. The DNA sequencing analysis followed by a homology search showed that 20 of the 24 cDNA clones had no significant homology to any sequences in DNA data base. The remaining four genes were homologous to known sequences. Northern blot hybridization among BTL-26, CKT-1 and healthy bovine thymocytes showed that a cDNA clone, BC8, was differentially expressed in BTL-26. The cloning of full-length cDNA for the BC8 clone and its DNA sequences showed that the BC8 clone is a bovine nuclear domain protein homologous to the human NDP52 gene. Northern blot analysis showed that the BC8 clone bovine NDP52 was predominantly expressed in tumor cell line BTL-26, compared with the transcripts from several bovine tissues.

Amino Acid Sequence↗
PubMed1998

Induction of midkine expression in reactive astrocytes following rat transient forebrain ischemia.

Midkine (MK), a retinoic acid-responsive gene product, is a 13-kDa heparin-binding protein with neurotropic activity. Previous studies demonstrated the expression of MK in embryonal and neonatal brains and its potent neurotropic activities in vitro. Data concerning its role in the mature central nervous system, however, are still limited. We examined the changes of MK expression in the adult rat brain following transient forebrain ischemia, by Northern blot, in situ hybridization and immunohistochemical analyses. In the control brain, MK mRNA was expressed in the cortical and hippocampal neurons. Following the ischemia, up-regulation of MK mRNA and a corresponding increase of its protein products were found in the hippocampal CA1 subfield. The maximal expression was demonstrated on day 4 after the insult. The cells expressing MK were distributed around the depleted CA1 pyramidal cells and identified as reactive astrocytes by double immunostaining. These data suggest that MK may be an insult-induced molecule which participates in the reparative processes following neuronal injury.

Animals↗
PubMed1998

Ultrastructural changes in motor endplates of the lumbrical muscles of rats induced by a microsomal Ca2+ ATPase inhibitor, 2,5-di(tert-butyl)-1,4-hydroquinone.

Female Wistar rats were treated orally for 5 days with 80 mg/kg body weight of 2,5-di(tert-butyl)-1,4-hydroquinone (DTBHQ), a microsomal Ca2+ ATPase inhibitor. Motor endplates of the lumbrical muscles were examined by light and electron microscopy. There was a decrease in body weight in the treated rats from the first day after administration, and toxic signs appeared after the third day, such as adoption of a prone position, salivation, lacrymation, and an abnormal gait and/or muscle weakness. No remarkable macroscopic or light microscopic changes were noted in the lumbrical muscles as well as other peripheral nerves of hind legs of the treated rats killed 1 day after the last DTBHQ treatment. Ultrastructurally, neurotoxicity characterized by loss of synaptic vesicles and mitochondria in the motor endplates, and by destruction of the motor terminals was detected in the lumbrical muscles of the treated rats. These results strongly indicate that DTBHQ targets the motor endplates in the rat lumbrical muscles and suggest that the resultant damage is responsible for the appearance of neurological signs, such as an abnormal gait and loss of muscle control.

Administration, Oral↗
PubMed1998

Involvement of apoptosis in the rat germ cell degeneration induced by nitrobenzene.

Nitrobenezene (NB) produces germ cell degeneration, especially of spermatocytes in rats. To examine the possible involvement of apoptosis in this process, the extent and nature of nuclear DNA fragmentation after NB dosing were assessed using both terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and DNA gel electrophoresis, in addition to conventional histological and electron microscopic procedures. Adult Sprague Dawley rats were treated with a single oral dose of NB (250 mg/kg) and euthanized subsequently at 6, 12, and 24 h and 2, 3, 5, and 7 days. The earliest morphological signs of germ cell degeneration in testes were found in pachytene spermatocytes 24 h after dosing. Electron micrographs of degenerating spermatocytes showed marked nuclear chromatin condensation at the nuclear periphery and crowding of cytoplasmic constituents, which are characteristic of apoptosis. Coincident with the appearance of such morphological changes, degenerating spermatocytes contained fragmented DNA as revealed by TUNEL. The presence of DNA laddering, a hallmark of apoptosis on gel electrophoresis, was first apparent and most prominent at 24 h, gradually becoming less detectable. No such changes were observed up to 12 h after dosing or in control animals. These results demonstrated unequivocal involvement of apoptosis in the induction of germ cell degeneration caused by NB.

Animals↗
PubMed1998

Relationship between the development of hepato-renal toxicity and cadmium accumulation in rats given minimum to large amounts of cadmium chloride in the long-term: preliminary study.

We wished to clarify the relationship between the sensitivity to induce hepato-renal toxicity and the level of cadmium (Cd) in the organs of rats exposed to minimum to large amounts of cadmium chloride (CdCl2). For this purpose, groups of female Sprague-Dawley (SD) rats, each consisting of 24 animals, were fed diet containing CdCl2 at concentrations of 0, 8, 40, 200, and 600 ppm for 2, 4, and 8 months from 5 weeks of age. All surviving rats given 600 ppm Cd were killed at 4 months because of deterioration of their general condition. Animals of this group showed anemia and decreased hematopoiesis in the bone marrow, in addition to reduction of cancellous bone in their femurs. Hepatotoxicity was observed after 2 months in the groups treated with > or = 200 ppm. By 4 months, the rats in the 600 ppm group had developed periportal liver cell necrosis. Renal toxicity characterized by degeneration of proximal tubular epithelia was apparent in the groups treated with > or = 200 ppm from 2 months, becoming more prominent in the high-dose rats at 4 months. Hepatic accumulation of Cd increased linearly with the duration of treatment. In contrast, the concentration of Cd in the renal cortex of rats treated with 600 ppm reached a plateau level of approximately 250 microg/g within the first 2 months. The renal concentration of Cd in the 200 ppm group when renal toxic lesions were first detected at 2 months ranged from 104 to 244 microg/g. No renal lesions were observed in the 40 ppm group after 8 months, despite the presence of 91-183 microg/g of Cd in the kidneys. The results thus suggest that renal toxicity would not be induced by treatment with minimum amounts of CdCl2 for periods longer than 8 months, although accumulation of Cd might gradually progress. A further 2-year feeding study of CdCl2 and Cd-polluted rice is now in progress.

Animals↗
PubMed1998

Mechanistic study on liver tumor promoting effects of piperonyl butoxide in rats.

Piperonyl butoxide, alpha-[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propyltol uene, is a widely used pesticide-synergist. Recently, results were reported indicating that piperonyl butoxide is a hepatocarcinogen in rat. Since the underlying mechanism was not elucidated, we examined the effects on rat liver cells in detail. For this purpose male F344 rats were administered piperonyl butoxide mixed in the diet at concentrations of 0 (negative control), 0.05, 0.2 or 2% for 2 days, 1, 2, and 4 weeks. As a positive control, phenobarbital was administered to rats for up to 4 weeks as a 0.1% solution in the drinking water. Increased liver weight, centrilobular hepatocellular hypertrophy due to increased smooth endoplasmic reticulum, decreased numbers and areas of connexin 32-positive spots per hepatocyte, and increased cell proliferation were observed in rats treated with 0.2 and 2% piperonyl butoxide. Similar results were obtained for 0.1% phenobarbital treated rats. Hepatocellular necrosis suggestive of hepatotoxicity was also observed in the 2% piperonyl butoxide group. These results indicate that the promoting mechanism of piperonyl butoxide in hepatocarcinogenesis is similar to that of phenobarbital, involving an ability to induce CYP isoenzymes and inhibit gap junctional intercellular communication. In addition, increased cell proliferation following hepatocellular necrosis may also play a role at high doses.

Animals↗
PubMed1998

Cytokeratin 20 mRNA in peripheral venous blood of colorectal carcinoma patients.

A highly sensitive system was previously developed by us to detect the presence of colorectal carcinoma cells in blood in the form of cytokeratin 20 (CK20) mRNA. In the present study, we used an improved version of this system to analyse the peripheral blood of 28 patients with colorectal carcinoma, five patients with non-cancerous intestinal diseases and six normal controls for the presence or absence of CK20 mRNA and to investigate the relationship between the mRNA results and prognosis. All eight patients with recurrence were positive for CK20 mRNA, as were four patients in the Dukes' C stage with either distant metastasis or dissemination. Five of the nine patients in the Dukes' C stage with neither distant metastasis nor dissemination were positive, and three of these developed recurrence within 11 months after the analysis. Only one of the seven patients in the Dukes' A or B stage was positive, and none showed recurrence during the 1-19 months of observation. None of the five patients without carcinomas or of the six normal controls was positive. Although the follow-up period is limited and the recurrences were all local at present, these results suggest that the presence of CK20 mRNA in circulation may be a useful indicator for the screening of advanced colorectal carcinoma patients with a high risk of recurrence.

Adult↗
PubMed1998

Predictive value of vascular endothelial growth factor (VEGF) in metastasis and prognosis of human colorectal cancer.

Vascular endothelial growth factor (VEGF) may affect the phenotype of cancer cells, such as growth velocity and metastatic potential, due to its probable multifunctional property including a mitogenic activity for vascular endothelial cells. The present study was designed to investigate the association of VEGF mRNA expression with progression and metastasis of human colorectal cancer. The level of VEGF mRNA expression was quantified by Northern blot hybridization in tumorous and non-tumorous tissues obtained from 60 primary colorectal cancer patients. The ratio of the former to the latter was defined as the VEGF T/N ratio, and the prognostic significance of this ratio, following surgery, in addition to the relationship to progression and metastatic potential, was evaluated. The value of the VEGF T/N ratio was significantly correlated with the depth of tumour infiltration (P=0.046), the incidence of liver metastasis (P < 0.0001) and lymph node metastasis (P=0.036). Patient prognosis was estimated by the Kaplan-Meier method and the log-rank test. When the VEGF T/N ratio was higher than 4.8 for which the chi2 value of the log-rank test was maximal, the tumour was defined as showing overexpression of VEGF mRNA. Patients with overexpression of VEGF mRNA demonstrated poorer survival than patients without overexpression of VEGF mRNA (P < 0.001). The overall estimated hazard ratio for death in patients with overexpression of VEGF mRNA was 1.94 according to a multivariate analysis (P=0.005). Thus, VEGF is associated with the progression, invasion and metastasis of colorectal cancer, and overexpression of VEGF mRNA in the primary tumour is assumed to be closely correlated with poor prognosis in colorectal cancer patients. Moreover, the VEGF T/N ratio may be used as an independent prognostic marker in colorectal cancer patients.

Adult↗
PubMed1998

Significance of local recurrence of rectal cancer as a local or disseminated disease.

BACKGROUND: The nature of 'local recurrence' of rectal cancer remains unclear. METHODS: Fifty-nine patients with locally recurrent rectal cancer who underwent extended repeat resections including total pelvic exenteration (39) and sacrectomy (43) were reviewed. Twelve patients had distant metastases before or at the time of repeat resection. RESULTS: The 5-year survival rate was 25 per cent. A second recurrence occurred in 45 patients including five of the eight 5-year survivors. Thirty-six of these recurrences had locoregional manifestations and 29 had distant metastases. Of 18 prognostic factors examined, the most significant determinant was the postoperative carcinoembryonic antigen doubling time (CEADT), followed by the preoperative CEADT, carcinoembryonic antigen (CEA) level and occurrence of distant metastases, in decreasing order. Late onset of first recurrence was also a favourable indicator. Thus, the growth rate of the tumour had a more profound impact on survival than the current extent of tumour progression. After operation the CEADT was reduced in patients with second recurrence (P = 0.05). CONCLUSION: Locally recurrent rectal cancer is a manifestation of disseminated disease spreading locoregionally and often to distant organs with a low probability of long-term cure. However, survival varies widely depending on the tumour growth rate, which is biologically predetermined and is also influenced by surgery.

Adult↗