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K Miyajima

Publications and source records attributed to K Miyajima.

At least 19 recordsLinked to original sources
PubMed2006

Preventive effects of glycaemic control on ocular complications of Spontaneously Diabetic Torii rat.

AIM: Spontaneously Diabetic Torii (SDT) rat is a new model of non-obese type 2 diabetes. SDT rats show severe ocular complications such as cataracts, tractional retinal detachment with fibrous proliferation and massive haemorrhaging in the anterior chamber. In the present study, blood glucose levels of SDT rats were controlled in order to examine whether these ocular complications are caused by hyperglycaemia. METHODS: SDT rats were treated with an insulin implant to control blood glucose. To evaluate retinal function, we used electroretinograms (ERG) and measured vascular endothelial growth factor (VEGF) concentrations within the aqueous humour. Finally, we studied retinal flat-mounts and trypsin digestion to evaluate vascular abnormalities in SDT rats. RESULTS: Forty-four-week-old SDT rats displayed an increase in VEGF concentrations within the aqueous humour and significant prolongation of the peak latencies in ERG (Sigma(OP(1)-OP(4)); Sprague-Dawley (SD): 146.2 +/- 1.06 ms; SDT: 166.3 +/- 2.38 ms; SDT + insulin: 149.2 +/- 1.83 ms). Retinal flat-mounts of SDT rats showed venous dilation and meandering vascular networks. Furthermore, acellular capillaries were observed in the retinal trypsin digestion. Insulin treatment prevented these ocular abnormalities in SDT rats. CONCLUSIONS: These findings indicate that ocular complications of SDT rats are caused by hyperglycaemia. The features of SDT rats indicate their usefulness for the future study of diabetic retinopathy.

Animals↗
PubMed2006

Effects of antibacterial agents, levofloxacin and clarithromycin, on aquatic organisms.

Contamination of surface waters by pharmaceutical chemicals is an emerging environmental problem. This study evaluated the toxic effects of the antibacterial agents levofloxacin (LVFX) and clarithromycin (CAM), which are widely used in Japan, on aquatic organisms. Ecotoxicity tests using a bacterium, alga and crustacean were conducted. Microtox test using a marine fluorescent bacterium showed that LVFX and CAM have no acute toxicity to the bacterium. From the results of the Daphnia immobilisation test, LVFX and CAM did not show acute toxicity to the crustacean. Meanwhile, an algal growth inhibition test revealed that LVFX and CAM have high toxicity to the microalga. The phytotoxicity of CAM was about 100-fold higher than that of LVFX from a comparison of EC50 (median effective concentration) value. From the Daphnia reproduction test, LVFX and CAM also showed chronic toxicity to the crustacean. Concentrations of LVFX and CAM in the aquatic environment were compared with PNEC (predicted no effect concentration) to evaluate the ecological risk. As a result, the ecological risk of LVFX is considered to be low, but that of CAM is higher, suggesting that CAM discharged into an aquatic environment after therapeutic use may affect organisms in the aquatic environment.

Animals↗
PubMed2005

Daily inhibition of postprandial hyperglycaemia with JTT-608, a novel oral antidiabetic agent, ameliorates pancreatic function in neonatally streptozotocin-treated rats.

AIM: Chronic glycaemic control, in particular, the control of postprandial hyperglycaemia, is essential for preventing the development of diabetic complications. We therefore evaluated the chronic treatment effect of a new antidiabetic agent, JTT-608 [trans-4-(methylcyclohexyl)-4-oxobutyric acid], in neonatally streptozotocin-treated rats. METHODS: The rats were maintained with liquid meal three times a day and treated orally with JTT-608 10 min before each meal for 12 weeks. Haemoglobin A1C (HbA1C) and fasting blood glucose levels were measured at 4-week intervals, and effects of JTT-608 on pancreatic function and diabetic complications were examined after dosing period. RESULTS: The postprandial hyperglycaemia was suppressed by JTT-608 administration, and both HbA1C levels and fasting blood glucose levels were reduced during the experimental period. After the treatment period of 12 weeks, JTT-608 further improved the early insulin secretion and the impaired glucose tolerance after meal loading in the diabetic rats. Also, pathological examination revealed that JTT-608 reduced the incidence of the decrease in immunoreactivity of insulin. In examination of other diabetic complications, JTT-608 ameliorated the reduced motor nerve conduction velocities observed in diabetic rats and inhibited the incidence of cataracts with diabetes. CONCLUSIONS: We conclude that a newly developed antidiabetic agent, JTT-608, improves the pancreatic function and prevents the development of diabetic complications by inhibition of daily postprandial hyperglycaemia and could be useful for the treatment of diabetic subjects with impaired insulin secretion.

Animals↗
PubMed2005

Development of on-site fish exposure system placed in water quality monitoring stations along a river.

Estrogen-like substances have been suspected to cause feminization of wild fish in rivers in Japan. To elucidate the influence of estrogen-like substances on fish in river, we have started to develop the on-site continuous fish exposure system using medaka Oryzias latipes that were placed in water quality monitoring stations along a river. Adult male medaka were exposed to the river water in a glass exposure tank placed in the monitoring stations. Flow rate of water and water temperature were controlled at 30 L/hour and 26 degrees C respectively, and a light: dark cycle was maintained 16:8 hours. A commercial diet free from phytoestrogens was fed 4 times in a day using automatic feeder. After 2-week exposure, hepatic vitellogenin concentration of each male medaka was measured. The exposure tests were repeatedly performed at both the upstream and the downstream of sewage treatment plants along the River Tama which is a representative urbanized river in Japan. At the control site Haijimabashi monitoring station, vitellogenin was not detected in male medaka. On the other hand, at the Ishihara monitoring station which is the most downstream in this test area, every male medaka were produced vitellogenin in the test performed in the spring of 2004. As the results of the water quality analysis, it could be inferred that the estrone derived from effluents of sewage treatment plants caused the feminization of male medaka. The reason why the concentrations of the estrone and the estrogenic activity using DNA recombinant yeast varied in proportion to the electric conductivity of river water measured at the water quality monitoring station. Furthermore, after continuous 2-week exposure, the vitellogenin production of male medaka was reduced similar to the decrease of the concentrations of the estrone and the estrogenic activity of river water.

Animal Feed↗
PubMed2003

p53 Mutation and MDM2 amplification in inflammatory myofibroblastic tumours.

AIMS: The pathogenic mechanism and predictive indicators of biological behaviour of inflammatory myofibroblastic tumour are poorly understood. We investigated molecular abnormalities of p53 and MDM2 in order to assess whether these play an important role in pathogenesis, and whether they also contribute to clinicopathological aggressive phenotype in inflammatory myofibroblastic tumour. METHODS AND RESULTS: We compared the immunohistochemical expression of calponin, h-caldesmon, ALK, and p53 gene mutation and MDM2 gene amplification with clinicopathological findings in 15 cases of inflammatory myofibroblastic tumour. Histologically, cellular atypia was observed in five (33.3%) out of 15 cases. Local recurrences were observed in two (14.3%) of 14 informative cases, but no distant metastasis was observed. The expression of calponin (9/14; 64%) but not h-caldesmon (0/14; 0%) was seen, which suggested myofibroblastic differentiation. ALK expression was seen in eight (53.3%) out of 15 cases, particularly in patients under 40 years old. Nuclear expression of p53 protein was recognized in only one (6.7%) of 15 cases, and polymerase chain reaction single-strand conformation polymorphism followed by direct sequencing revealed p53 gene missense mutations in two (13.3%) of 15 cases. Nuclear expression of MDM2 was seen in four (26.7%) of 15 cases, and the MDM2 gene amplification was observed in two of the four cases. CONCLUSION: Inflammatory myofibroblastic tumour shows a wide spectrum of cellular atypia and biological behaviour with p53 and MDM2 expression. However, the alterations in the p53 pathway seem not to play a major role in the pathogenesis of inflammatory myofibroblastic tumour.

Adult↗
PubMed2002

Clinicopathological prognostic factors in soft tissue leiomyosarcoma: a multivariate analysis.

AIMS: Prognostic factors affecting survival in cases of leiomyosarcoma of soft parts were investigated in this study. METHODS AND RESULTS: A retrospective study of 267 patients was carried out. This group comprised 142 females (53%) and 125 males (47%), whose ages ranged from 7 to 95 years (median 58 years). One hundred and five cases were superficially situated (arising from the skin or subcutis), while the remaining 162 cases were deeply situated (subfacial). Nineteen were cases of pleomorphic leiomyosarcoma where the diagnosis had been amended from malignant fibrous histiocytoma to leiomyosarcoma whilst under review. Of the 167 patients with follow-up data, 83 died of leiomyosarcoma. In univariate analysis, depth, tumour size (>or=50 mm), mitotic rate of >20 per 10 high-power fields (HPF), tumour necrosis of >50% and a high stage according to the most recent American Joint Committee on Cancer (AJCC) staging for soft tissue sarcoma were found to lessen significantly the rate of survival (log rank test; P < 0.05). However, in multivariate analysis (Cox's proportional hazards model), tumour size and high AJCC stage were the only factors that were correlated independently with decreased survival. CONCLUSIONS: This study indicates that the most reliable prognostic parameters are tumour size and AJCC stage in leiomyosarcoma.

Adolescent↗
PubMed2001

Calponin and h-caldesmon expression in atypical fibroxanthoma and superficial leiomyosarcoma.

To evaluate smooth muscle differentiation, myogenic markers [desmin, alpha-smooth muscle actin (SMA), and muscle-specific actin (HHF35)] have been widely used. Calponin and h-caldesmon, which are cytoskeleton-associated actin-binding proteins, have been reported to be more specific myogenic markers, especially since myofibroblasts express a small amount of h-caldesmon. Atypical fibroxanthoma (AFX) occurs in the sun-exposed skin of the elderly and follows a benign clinical course. Histologically, AFX, which is a pleomorphic spindle cell tumor and considered to be a superficial variant of malignant fibrous histiocytoma, also mimics leiomyosarcoma. AFX has been thought to differentiate along pathways with fibrohistiocytic and myofibroblastic phenotypes. AFX ( n=10), superficial leiomyosarcoma (S-LMS) ( n=17) and benign fibrous histiocytoma (BFH) ( n=17) were analyzed for myofibroblastic and smooth muscle differentiation immunohistochemically from the viewpoint of comparison. AFX and BFH showed immunoreactivities respectively for calponin (3/10, 11/17), desmin (3/10, 1/17), SMA (3/10, 13/17), and HHF35 (1/10, 5/17), but failed to express h-caldesmon (0/10, 0/17). S-LMS had a high immunoreactive rate of calponin (17/17), desmin (13/17), SMA (16/17), and HHF35 (16/17), while also expressing caldesmon (11/17). The results reveal that AFX and BFH have immunoreactivities for several myogenic markers, with myofibroblastic differentiation (calponin: +/-, h-caldesmon: -), but without the smooth muscle differentiation seen in S-LMS (calponin:+, h-caldesmon: +/-). In addition, calponin and h-caldesmon are considered to be useful markers for distinguishing AFX from S-LMS.

Adolescent↗
PubMed2001

Time-dependent promotion activity of 17beta-estradiol on uterine carcinogenesis in mice initiated with N-ethyl-N-nitrosourea.

The time-dependent promotion activity of 17beta-estradiol (E2) by initiation with N-ethyl-N-nitrosourea (ENU) on induction of mouse uterine endometrial proliferative lesions was examined. Illumination-induced persistent estrous female CD-1 mice were divided into five groups at 9 weeks of age. At 10 weeks of age, mice in all groups (n=25) were given a single intra-uterine administration of ENU (50 mg/kg), dissolved in polyethylene glycol. Animals in Groups 2 to 5 were then implanted s.c. with an E2 pellet at 9, 11, 14 and 17 weeks of age. The implants were left in place for 8 weeks and then taken out. At the termination of the experiment (week 15 after the ENU-treatment), all surviving mice were killed and the development of uterine proliferative lesions were assessed. All groups demonstrated endometrial hyperplasias and adenocarcinomas and the incidences of the latter in ENU plus E2 treated animals (Groups 2 to 5; 36, 48, 35 and 36%, respectively) were significantly higher compared to 8% for Group 1, without any variation with the age at E2 treatment. However, the incidences of adenocarcinomas plus severe hyperplasias increased from Groups 1 to 5 (28, 40, 56; P<0.05, 61; P<0.05 and 80%; P<0.01, respectively), indicating that promotion effects of E2 on induction of uterine proliferative lesions in the uterine endometrium become more pronounced with the interval after ENU initiation.

Adenocarcinoma↗
PubMed2001

Relative quantitation of p53 and MDM2 gene expression in leiomyosarcoma; real-time semi-quantitative reverse transcription-polymerase chain reaction.

To investigate the etiology of leiomyosarcoma, we examined abnormalities of p53 and its regulation in 13 cases of leiomyosarcoma using fresh tumor specimens. We estimated p53 and MDM2 mRNA level and MDM2 gene amplification using a real-time semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) based on the TaqMan fluorescence method. We also used immunohistochemistry (IHC) for p53 and MDM2 protein overexpression, polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and direct sequencing to detect p53 mutation. Eight of the 13 cases (62%) showed an overexpression of p53 protein on IHC and eight of 13 cases (62%) had p53 gene point mutations. Five of the 13 cases (38%) showed positive staining for MDM2 protein and only one case (7.7%) demonstrated MDM2 gene amplification. The relative p53 mRNA level of the tumors compared with normal tissue ranged from 1.14 to 12.19 arbitrary units (AU), and the MDM2 mRNA level ranged from 1.06 to 17.17 AU. The mRNA level in the p53-positive cases was higher than in the negative cases (positive: 7.70 AU on average; negative: 3.38 AU on average; P=0.0344). However, there was no significant correlation between the MDM2 mRNA level and other factors, such as p53 IHC, p53 mutation status, p53 mRNA level and MDM2 IHC. Our results indicate that p53 abnormalities are major events and that an increasing level of p53 mRNA is associated with an overexpression of p53 protein in leiomyosarcoma and they may play an important role in the tumorigenesis in this tumor.

Adult↗
PubMed2001

Pleomorphic leiomyosarcoma: clinicopathologic and immunohistochemical study with special emphasis on its distinction from ordinary leiomyosarcoma and malignant fibrous histiocytoma.

Pleomorphic leiomyosarcoma (PLMS) was recently described as a morphologic variant of leiomyosarcoma; however, its diagnostic criteria, as shown by morphologic features and biologic behavior, remain controversial. We describe 28 cases of pleomorphic sarcoma with pleomorphic areas in more than two thirds of the tumor and an ordinary leiomyosarcomatous fascicular area covering less than one third as PLMS. PLMS comprised 8.6% of all the leiomyosarcomas (322 cases) registered in our institute. Patients ranged in age from 31 to 89 years (average, 57.9 years). Seventeen patients (60.7%) were male and 11 were female. Tumor location was as follows: the extremities in 17 cases, the retroperitoneum or abdominal cavity in 7 cases, the chest/abdominal wall in 3 cases, and the scalp in 1 case. Histologically, all cases showed at least small foci of fascicles consisting of smooth muscle tumor cells, in addition to pleomorphic areas mimicking storiform-pleomorphic malignant fibrous histiocytoma. The border between pleomorphic and leiomyosarcomatous fascicular areas was sharp in 3 cases, gradual in 2 cases, and blending in 23 cases. Sixteen cases (57.1%) showed a typical storiform pattern, 6 cases revealed extensive stromal hyalinization, 6 cases showed a chronic inflammatory infiltrate, 2 cases had the foci of foamy xanthomatous cells, and 7 cases contained myxoid malignant fibrous histiocytoma-like areas covering less than 50% of the tumor. The tumors had a tendency to be of a morphologically higher grade (10 tumors were French Federation of Cancer Centers grade 2, 18 were grade 3). Five of 28 cases (18%) showed rhabdoid features. Immunohistochemically, all of the 28 tumors examined showed a positive reactivity for at least one smooth muscle marker (desmin, muscle-specific actin, and alpha-smooth muscle actin) in the leiomyosarcomatous fascicular areas. In the pleomorphic areas the expression of smooth muscle markers (desmin 10 of 28, muscle-specific actin 13 of 28, and alpha-smooth muscle actin 14 of 28) was significantly reduced, compared with that in leiomyosarcomatous fascicular area (desmin 18 of 28, muscle-specific actin 26 of 28, and alpha-smooth muscle actin 24 of 28). No significant difference was observed between the MIB-1 labeling index in the leiomyosarcomatous fascicular areas (26.10 on average) and that in the pleomorphic areas (26.17 on average). However, the MIB-1 labeling index in PLMS was significantly higher than that in ordinary leiomyosarcoma (n = 20, 12.86 on average) or storiform-pleomorphic malignant fibrous histiocytoma (n = 16, 16.63 on average). In 23 patients follow-up data were available with a duration of 1-239 months. Eleven patients developed metastases, and lung accounted for the most common site of metastasis (9 cases). Fifteen of 23 patients (65.2%) died of disease. Our results indicate that PLMS should be differentiated from ordinary leiomyosarcoma because of its high proliferative activities and rather aggressive biologic behavior.

Adult↗
PubMed2001

Papillary carcinoma occurring within an adenomatous goiter of the thyroid gland in Cowden's disease.

Cowden's disease is an autosomal dominant disorder characterized by multiple benign and malignant neoplastic lesions involving many organs. The presence of characteristic cutaneous lesions is crucial for the diagnosis. Thyroid disease is a major extracutaneous manifestation of this disease; however, the histologic characteristics have not been described in detail. We report a case of thyroid tumor associated with Cowden's disease. Grossly, the tumor showed a multinodular appearance, like an adenomatous goiter. Microscopically, it consisted of follicular adenomas with a trabecular pattern. Some of the nodules had a second component resembling papillary carcinoma. This was thought to be a unique histological feature not described previously, and might be specific to thyroid tumor associated with Cowden's disease.

Adenoma↗
PubMed2001

DNA methylation profiles of lung tumors.

Aberrant methylation of CpG islands in promoter regions of tumor cells is one of the major mechanisms for silencing of tumor suppressor genes. We determined the frequency of aberrant promoter methylation of the p16, adenomatous polyposis coli (APC), H-cadherin (CDH13), glutathione S-transferase P1 (GSTP1), O6-methylguanine-DNA-methyltransferase (MGMT), retinoic acid receptor beta-2 (RAR beta), E-cadherin (CDH1), and RAS association domain family 1A (RASSF1A) genes in 198 tumors consisting of small cell lung cancers [SCLCs (n = 43)], non-small cell lung cancers [NSCLCs (n = 115)], and bronchial carcinoids (n = 40). The profile of methylated genes in the two neuroendocrine tumors (SCLC and carcinoids) were very different from that of NSCLC. However, whereas the overall pattern of aberrant methylation of carcinoids was similar to that of SCLC, carcinoids had lower frequencies of methylation for some of the genes tested. There were also significant differences in the methylation profiles between the two major types of NSCLC, adenocarcinoma and squamous cell carcinoma. We performed cluster analysis and found that SCLCs clustered with other SCLCs and carcinoids but not with NSCLCs, whereas the NSCLCs tended to cluster together. Within NSCLCs, adenocarcinomas and squamous cell carcinomas clustered with their respective histological types. Finally, we compared the methylation profiles of SCLC and NSCLC tumors and their respective cell lines (n = 44). In general, methylation frequencies were higher in tumor cell lines, but these differences were seldom significant. Thus, tumor cell lines appear to be suitable models to study aberrant DNA methylation. We conclude that SCLC, carcinoids, squamous cell carcinomas, and adenocarcinomas of the lung have unique profiles of aberrant methylation. Our findings should help us understand differences in the pathogenetic mechanisms of lung cancers.

Adenomatous Polyposis Coli Protein↗
PubMed2000

Lipid A and related compounds. XXXVII. Determination of favorable binding linkages of lipid A analog to antigen moiety for synthetic vaccines.

For the determination of favorable binding linkages of lipid A analog as a synthetic immunoadjuvant to the antigen moiety for synthetic vaccines, new N-acylated L-serine-containing D-glucosamine analogs (Type A, B, C) were synthesized and their mitogenicities were examined. Among chemically synthesized compounds (6-15, 30), compound 8 for Type B exhibited the most potent mitogenicity.

Animals↗
PubMed1999

Hepatotoxicity and consequently increased cell proliferation are associated with flumequine hepatocarcinogenesis in mice.

It has been reported that flumequine (FLU) induces hepatic tumors in mice when given orally for 18 months. We investigated possible underlying mechanisms using a two-stage mouse hepatocarcinogenesis model. After initiation with a single intraperitoneal injection of 100 mg/kg body weight diethylnitrosamine (DEN) or saline, male CD-1 mice were given 4000 ppm FLU in the diet or 500 ppm phenobarbital (PB) in drinking water for 9, 19, 24 or 30 weeks. Toxicity, evidenced by centrilobular swollen and polar hepatocytes with fatty droplets, infiltration of inflammatory cells and increased numbers of mitosis in hepatocytes, was apparent in the livers of mice treated with FLU at all time points, but its severity declined towards the termination. FLU did not induce cytochrome P-450 enzymes such as 1A1, 2B1 and 3A2 as assessed immunohistochemically, while positive expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was increased in hepatocytes of both DEN + FLU and FLU groups compared with the relevant controls. In animals given PB, eosinophilic swelling of hepatocytes was prominent, and the hepatocytes showed strongly positive reactions for CYP 1A1 and 3A2. Altered cell foci were induced in the livers of FLU-treated animals both with and without DEN initiation, especially the former, and their development paralleled the degree of hepatic toxicity. These results suggest that FLU hepatocarcinogenicity in mice is dependent on hepatotoxic damage and consequently increased cell proliferation. Oxidative damage to DNA may also be a crucial factor.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Interactions of an antimicrobial peptide, magainin 2, with lipopolysaccharide-containing liposomes as a model for outer membranes of gram-negative bacteria.

F12W-magainin 2 preferentially interacted with lipopolysaccharide-containing bilayers, permeabilizing the membranes, compared with lipopolysaccharide-free phosphatidylcholine vesicles. Using this system, we demonstrated for the first time that the magainin peptide forms a helix upon binding to lipopolysaccharide. Incorporation of lipid A into phosphatidylcholine liposomes also enhanced interactions with the peptide. The presence of Mg2+, which nullifies the peptide's antibacterial activity against gram-negative bacteria, again weakened the interactions between the peptide and lipopolysaccharide-doped bilayers. This system seems to be useful for investigating the molecular details of peptide-lipopolysaccharide interactions.

Amino Acid Sequence↗
PubMed1999

Synthesis of cancer peptide antigen-lipid A analog conjugates for synthetic vaccines.

Conjugates 6 and 7 of cancer peptide antigen with N-tetradecanoyl L-serine-beta-alanine-containing D-glucosamine derivative structurally related to lipid A as an immunoadjuvant were synthesized for the development of totally synthetic vaccines against cancers. The mitogenic activities of compounds 6 and 7 were stronger than that of lipid A analog 3.

Animals↗
PubMed1999

Intravenous methylcobalamin treatment for uremic and diabetic neuropathy in chronic hemodialysis patients.

OBJECT: To study the effects of the intravenous administration of methylcobalamin, an analogue of vitamin B12, for uremic or uremic-diabetic polyneuropathy in patients who are receiving maintenance hemodialysis. An ultra-high dose of vitamin B12 has been reported to promote peripheral nerve regeneration in experimental neuropathy. METHODS: Nine patients received a 500 microg methylcobalamin injection 3 times a week for 6 months. The effects were evaluated using neuropathic pain grading and a nerve conduction study. RESULTS: Serum concentrations of vitamin B12 were ultra-high during treatment due to the lack of urinary excretion. After 6 months of treatment, the patients' pain or paresthesia had lessened, and the ulnar motor and median sensory nerve conduction velocities showed significant improvement. There were no side effects. CONCLUSION: Intravenous methycobalamin treatment is a safe and potentially beneficial therapy for neuropathy in chronic hemodialysis patients.

Action Potentials↗