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Biomedical subjects

T Oyama

Publications and source records attributed to T Oyama.

At least 127 records · Page 7Linked to original sources

Habitual and genetic factors that affect urinary background levels of biomarkers for organic solvent exposure.

Urinary hippuric acid, phenol, and o-cresol, which are biomarkers for toluene, benzene, and phenol exposures, are usually present in a significant amount in urine collected from subjects who have not been occupationally exposed to the organic solvents. With the improvement of working environments, the urinary concentrations of the biomarkers have become lower and closer to the levels of urine from unexposed subjects. It is very useful to clarify the background levels of these biomarkers and the factors which effect the background levels of the biomarkers in order to make effective use of biological monitoring under low level exposure. In the present study, the effects of life habits and the genetic polymorphisms of the metabolizing enzymes on the background levels of urinary hippuric acid, phenol and o- and p-cresol were clarified, using 351 males (means age: 38.6, range: 19-71) who were not occupationally exposed to hazardous chemical materials. Their life habits, smoking, alcohol consumption, and dietary habits were examined by means of a questionnaire. The genotypes of five metabolizing enzymes, that is, low Km aldehyde dehydrogenase (ALDH2), polymorphic N-acetyl transferase (NAT2), cytochrome P-4501A1 (CYP1A1), cytochrome P-4502E1 (CYP2E1), and glutathione-S-transferase mu (GSTM1) were determined form peripheral blood samples. The urinary hippuric acid and creatinine were analyzed by HPLC and urinary phenol, o-, p- and m-cresol were determined by GC/MS. Recoveries and the coefficients of variance of phenol, o-cresol, and p-cresol ranged from 92.7 to 107.8% and 1.3% to 6.7%, respectively. Linear relationships between the concentrations of phenol, o- and p-cresol, and their peak area ratios were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyltransferases↗

Dual effect of serotonin on formalin-induced nociception in the rat spinal cord.

To examine the role of the descending serotonergic system in the regulation of spinal nociceptive processing, the effects of serotonin (5-HT) and selective ligands for 5-HT receptor subtypes on persistent nociception were investigated. Formalin (5% formaldehyde) injected into the plantar region of the rat hindpaw induced two phases of aversive responses such as licking and biting. Intrathecal administration of selective 5-HT3 receptor antagonists, granisetron (0.1-100 pmol/rat) and ondansetron (1-1000 pmol/rat), reduced the second phase of the formalin-induced aversive responses without affecting the first one. The antinociceptive effect of granisetron (100 pmol/rat) was abolished when 5-HT was depleted from the lumbar cord by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT). In the 5,7-DHT-treated rats, intrathecal administration of 1-(m-chlorophenyl)-biguanide, a selective 5-HT3 receptor agonist, facilitated the aversive responses in the second phase whereas that of 8-OH-DPAT, a selective 5-HT1A receptor agonist, suppressed them. Intrathecal administration of 5-HT showed a dual effect on the second phase of the aversive responses in the 5,7-DHT-treated rats; 5-HT inhibited the aversive responses when administered at a low dose (0.1 nmol/rat) but facilitated them at a high dose (1 nmol/rat). In addition, the inhibitory and facilitatory effects of intrathecal 5-HT were blocked by its co-administration with NAN190, a 5-HT1A receptor antagonist, and granisetron, respectively. These results suggest that 5-HT suppresses formalin-induced nociception in the spinal cord via the 5-HT1A receptor and facilitates it via the 5-HT3 receptor.

5,7-Dihydroxytryptamine↗

Effect of Hachimi-jio-gan on scopolamine-induced memory impairment and on acetylcholine content in rat brain.

The effect of Hachimi-jio-gan (HJ) on scopolamine induced memory impairment was studied using a radial maze performance, the effect of HJ on the central cholinergic system as measured by acetylcholine (ACh) content, choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activities was also examined. HJ (0.01-1.0 g/kg, p.o.) showed no influence on the radial maze performance. However, with the administration of scopolamine (0.5 mg/kg, i.p.), the number of the correct choices decreased and the number of the error choices increased. HJ (0.1 and 0.5 g/kg, p.o.) reduced this scopolamine-induced cognitive disturbance. The effect of HJ on ACh content and enzyme activities in the brain, frontal cortex, hippocampus and striatum was also investigated. In normal rats, HJ (0.1 and 0.5 g/kg, p.o. x 7 days) significantly increased ACh content in the frontal cortex, although it did not increased ACh content in the hippocampus. In scopolamine-treated rats, ACh content decreased in the brain regions examined. HJ (0.5 g/kg, p.o.) inhibited a decrease in ACh content in the frontal cortex, and with the same dosage of HJ increased CAT activity in the frontal cortex and AChE activity in the hippocampus. These results suggest that the behavioral effects of HJ may be related to its effect on the central cholinergic system.

Acetylcholine↗

Increased levels of serum intercellular adhesion molecule-1 (ICAM-1) in patients with non-small cell lung cancer.

Serum concentrations of soluble ICAM-1 were measured by an enzyme-linked immunosorbent assay in 80 patients with non-small cell lung cancer (NSCLC). The mean serum concentration of soluble ICAM-1 in 80 patients with NSCLC was 472.8 +/- 370.8 ng ml-1 (range 75.6-3177.4 ng ml-1), whereas it was 196.8 +/- 54.6 ng ml-1 (range 128.1-276.4 ng ml-1) in 10 healthy controls. Sixty of 80 patients with NSCLC (75.0%) showed elevated concentrations (more than 306 ng ml-1, mean+2 SD in controls). The differences in mean serum concentration and positive rate between control subjects and NSCLC patients were significant (P = 0.0001). Serum ICAM-1 concentrations showed a significantly positive correlation with primary tumour size (maximum diameter) (P = 0.0209). Although the difference was not significant, the overall survival of patients with low serum ICAM-1 concentrations (< 306 ng ml-1) tended to be longer than that of patients with high concentrations (> or = 306 ng ml-1). These results suggest that serum ICAM-1 may be useful for serological diagnosis, monitoring of tumour volume or quantity in patients with NSCLC.

Adult↗

Liver transplantation for hepatocellular carcinoma: consideration from the findings on autopsy.

Extrahepatic spread of hepatocellular carcinoma was investigated in twenty autopsy cases with unresected hepatocellular carcinoma to define the appropriate patient selection criteria for liver transplantation. Diagnosis of extrahepatic spread of cancer by diagnostic imaging was not easy, and unsatisfactory prognosis after liver transplantation in patients with hepatocellular carcinoma might have been attributed to the high incidence of extrahepatic occult foci of cancer. All patients with multiple nodular, massive and diffuse tumor had extrahepatic spread of cancer. Only patients with a single nodular type tumor, no larger than 30 mm in diameter, had no extrahepatic metastasis, and these patients are the preferred candidates for liver transplantation.

Aged↗

Variant of intraductal carcinoma (with scant mucin production) is of main pancreatic duct origin: a clinicopathological study of four patients.

OBJECTIVES: To investigate the histopathological and immunohistochemical features of intraductal "nodular" tumor located in the main pancreatic duct. METHODS: Four cases were studied, and the results were compared with those in 10 cases of common ductal adenocarcinomas of the pancreas. RESULTS: The intraductal nodular carcinoma were large, more than 3 cm in diameter (range, 3-7 cm), lacked macroscopic mucin production, and presented a papillotubular adenocarcinoma. These tumors showed minimal invasion into the periductal tissue, duodenum, and choledochus. Immunohistochemically, the tumor cells were negative for anti-CEA and faintly positive for anti-CA19-9, in all except one tumor, whereas the common ductal adenocarcinomas were clearly positive for both. The postoperative course was favorable, and all three living patients remained healthy for more than 4 yr. CONCLUSION: These tumors may be variants of intraductal tumors with a more favorable prognosis.

Adenocarcinoma↗

[Results of radiotherapy combined with CDDP (BAI) plus VP-16 in the treatment of inoperable non-small cell lung cancer].

Twenty-six patients with unresectable non-small cell lung cancer were treated by chemotherapy alone or chemotherapy followed by radiotherapy from June 1988 to May 1990. CDDP (80 mg/m2) was given by bronchial arterial infusion (BAI) on day 1 in each course, VP-16 (80 mg/body) was given by drip intravenous infusion on days 1 and 2, and VP-16 (150 mg/body) was given orally on days 3 and 5. The patients were irradiated after this regimen with a single dose of 1.8-2.0 Gy, five times each week, to a volume which encompassed only the primary tumor. A total dose of 60 Gy or more was delivered. There were 10 squamous cell carcinomas, nine adenocarcinomas, five large cell carcinomas, one adenosquamous cell carcinoma and one poorly differentiated carcinoma. Median survival time (MST) was 354 days in stage III B patients and 280 days in stage IV patients. MST was 155 days in adenocarcinoma and 310 days in squamous cell carcinoma. MST was 372 days in PS 0 to 1 patients and 140 days in PS 2 patients. With chemo-radiotherapy in 17 cases resulted in no complete remissions and 10 partial remissions. The overall response rate was 58.8%. It is concluded that CDDP via BAI combined with VP-16 administration and sequential irradiation is useful to acquire a high response rate in non-small cell lung cancer. However, further studies on this modality are required.

Aged↗

[Incidence of cancer among Japanese patients with rheumatoid arthritis].

Most follow-up studies of patients with rheumatoid arthritis demonstrate no increase in the incidence of cancer apart from approximate doubling of the incidence of lymphoproliferative malignancies. A consecutive series of 1832 Japanese patients with rheumatoid arthritis seen at the center was studied to determine their cancer morbidity. Overall, 35 cancers were diagnosed in the series from 1982 through 1995 and were not significantly in excess of the expected number. No association was found between rheumatoid arthritis and subsequent development of cancer at any site, either.

Aged↗

Loss of heterozygosity at 3p in non-small cell lung cancer and its prognostic implication.

We examined 110 patients with non-small cell lung cancer who underwent consecutive pulmonary resection for loss of heterozygosity (LOH) at the short arm of chromosome 3 (3p). We performed a PCR-based microsatellite polymorphism analysis for detection of LOH. The microsatellite markers used were D3S966 (3p21.3), D3S1007 (3p21. 3-22), and D3S1228 (3p14.1-14.3). Of 98 informative cases, 3p LOH was found in 45 (46%). 3p LOH was more prevalent in squamous cell carcinoma (24/35, 69%) than in adenocarcinoma (18/52, 35%; P = 0.0019). There was no significant association between 3p LOH and sex, disease stage, or grade of differentiation. However, patients with 3p LOH tended to survive for a shorter period of time (P = 0.0631, log rank test). There was no such tendency in squamous cell carcinoma (P = 0.7513), but in adenocarcinoma, the difference of survival was significant (P = 0.0015). Cox's proportional hazards model also predicted that 3p LOH was an independent poor prognostic marker in adenocarcinoma (P = 0.0502) but not in squamous cell carcinoma or in the entire cohort (P = 0.7866 and 0.1371, respectively). LOH at 3p may help to identify non-small cell lung cancer patients with a poor prognosis, who thus need an intensive postoperative follow-up protocol or who are suitable for novel investigational therapeutic approaches. It is also suggested that the putative tumor suppressor gene at 3p may have a different role in squamous cell carcinoma and adenocarcinoma of the lung.

Adult↗

c-erbB-2 gene product directly associates with beta-catenin and plakoglobin.

Association of the c-erbB-2 oncogene product with the cadherin-catenin complex has been demonstrated in human cancer cell lines. Although beta-catenin and plakoglobin have been proven to be crucial for the association, no previous study has shown whether the interactions are direct or indirect. In the present study, the c-erbB-2 gene product was shown by far-Western blotting analysis to associate directly with both beta-catenin and plakoglobin through its cytoplasmic domain core region, which showed extensive homology with epidermal growth factor receptor. These data suggest that c-erbB-2-induced signaling is also directly liked to the cadherin-mediated cell adhesion and "invasion-suppressor" system through beta-catenin and plakoglobin in cancers.

Adenocarcinoma↗

Alpha 2-adrenoceptor-mediated inhibition of capsaicin-evoked release of glutamate from rat spinal dorsal horn slices.

It is known that the descending noradrenergic system suppresses nociceptive transmission in the spinal dorsal horn. To determine whether noradrenaline-alpha-adrenoceptor systems exert inhibitory influence on the release of glutamate from the nociceptive primary afferents, the effects of alpha-adrenoceptor agonists on the capsaicin (3 microM)-evoked release of glutamate from rat spinal dorsal horn slices were examined using an on-line continuous monitoring system for glutamate. The application of alpha 2-agonists clonidine (0.1-10 microM) and ST-91 (1 and 10 microM), respectively, decreased the capsaicin-evoked release of glutamate in a concentration-dependent manner. The partial alpha 2-agonist oxymetazoline (1 and 10 microM) produced a slight inhibition in the evoked release of glutamate. In contrast, the alpha 1-agonist phenylephrine (1 and 10 microM) did not show any significant effects on the evoked release of glutamate. The inhibitory action of 10 microM clonidine on the evoked glutamate release was antagonized by the alpha 2-antagonist yohimbine (1 microM) but not by the opioid antagonist naloxone (10 microM). These findings suggest that noradrenaline, probably released from the descending inhibitory system, reduces the release of glutamate from the capsaicin-sensitive primary afferent terminals through alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗

Change of phosphotyrosine immunoreactivity on microglia in the rat substantia nigra following striatal ischemic injury.

Using immunohistochemistry, we investigated changes in phosphotyrosine (P-Tyr) immunoreactivity on the microglia of the rat substantia nigra (SN) following striatal ischemic injury produced by transient middle cerebral artery (MCA) occlusion. Anterograde axonal degeneration in the SN due to striatal ischemic injury was detected by depletion of calcineurin immunoreactivity in that region from 1 day after operation. From 3 days to 1 month (the longest period examined in this study) after MCA occlusion, there was a significant increase in P-Tyr immunoreactivity in the SN ipsilateral to the MCA occlusion. Also, light microscopic observation showed that the microglia exhibited an increased immunoreactivity for P-Tyr and characteristic morphological changes in the ipsilateral SN. The present results indicate that a signal transducing cascade(s) associated with tyrosine phosphorylation may be involved in the activation of the microglia in the SN responding to anterograde degeneration of the striatonigral pathway.

Animals↗

Rapid and accurate method for delineating cancer lesions in laparoscopic colectomy using activated carbon injection.

The aim of our study was to evaluate the clinical efficacy of preoperative injection of activated carbon in delineation of cancer location in laparoscopic colectomy. Activated carbon particles were injected during endoscopy into the normal colonic wall surrounding cancer lesions in five cases of early colon cancer, prior to laparoscopic surgery. The carbon-stained area was clearly recognizable as a blackened patch on the serosal surface of the colon. Using the carbon-stained area as a reference point, partial colectomies were successfully performed on all five patients. The preoperative injection of activated carbon assisted in the intraoperative delineation of early colonic cancer lesions. This method is recommended for the rapid and accurate delineation of early colonic cancers in laparoscopic surgery.

Aged↗

Gastric adenoma-carcinoma sequence with special reference to p53 and Ki-ras gene alterations.

With the aim of detecting the timing of p53 and Ki-ras gene alterations in the gastric adenoma-carcinoma sequence, 19 early gastric adenocarcinomas arising from adenomas were studied. Immunohistochemically, 5 adenocarcinomas were positive for p53; 3 focally and 2 diffusely. The p53 point mutations were detected in a focal area with p53 immunoreactivity in 2 of the 5 p53-positive adenocarcinomas. This indicated that p53 point mutations may play a less crucial part in malignant conversion of adenoma to adenocarcinoma in the stomach than in the colon. No Ki-ras gene mutations at codons 12 and 13 were detected in any lesion. These results suggest that the adenoma-carcinoma sequence in the stomach has a different mechanism from that in the colon.

Adenocarcinoma↗

Striatal cells containing the Ca(2+)-binding protein calretinin (protein 10) in ischemia-induced neuronal injury.

The present study concerns the vulnerability of striatal interneurons immunopositive for the Ca(2+)-binding protein calretinin to ischemic neuronal injury. An immunohistochemical study was carried out on the striata of rats which had undergone transient middle cerebral artery occlusion. Two weeks after the ischemia, there was a marked reduction in the number of calretinin-positive neurons in the ipsilateral ischemic lesion, although the striatal interneurons positive for parvalbumin, which are a neuronal population distinct from the calretinin-immunoreactive cells in the striatum, were spared in the insulted areas. The present data indicate that the striatal calretinin-positive neurons are less resistant to transient ischemia, suggesting that there may exist vulnerability differences among the striatal interneurons in ischemia-induced neuronal injury.

Animals↗

The anti-proliferative effect of proliferating cell nuclear antigen-specific antisense oligonucleotides on human gastric cancer cell lines.

The proliferating cell nuclear antigen (PCNA) is a nuclear protein that leads DNA synthesis by the DNA polymerase delta. As the PCNA gene is strongly expressed in invasive gastric cancer cells with high proliferative activity, PCNA is suspected of playing an important role in the proliferation and advancement of gastric cancer. Thus, the effects of antisense oligonucleotides specific for PCNA mRNA were examined in seven gastric cancer cell lines. It was found that treatment with antisense oligonucleotides at concentrations of 10-40 microM dose-dependently inhibited the growth of all cell lines; however, random sequence oligonucleotides did not modify the proliferation of any type of cells. These results indicate that PCNA is essential for cell proliferation in gastric cancer cells, and that the growth inhibitory effect results from the inhibition of PCNA gene expression. Therefore, PCNA-specific antisense oligonucleotides may be effective in the treatment of gastric cancer.

Base Sequence↗