Studies on rabies encephalitis by means of fluorescent antibody staining.
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Animals↗
Biomedical subjects
S Otani
Publications and source records attributed to S Otani.
[Experimental rabies with special reference to pathology of suckling mice].
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Animals↗
Increased biological potency of hexafluorinated analogs of 1,25-dihydroxyvitamin D3 on bovine parathyroid cells.
1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is known to be involved in regulating the proliferation of parathyroid cells and PTH synthesis through reactions involving its nuclear receptor. We evaluated the effects of 1,25-(OH)2D3 and its hexafluorinated analog, 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3 (26,27-F6-1,25-(OH)2D3), on parathyroid cells. The 1,25-(OH)2D3 and 26,27-F6-1,25-(OH)2D3 each inhibited [3H]thymidine incorporation and ornithine decarboxylase (ODC) activity, which is important in cell proliferation, in primary cultured bovine parathyroid cells. The inhibitory effect of 26,27-F6-1,25-(OH)2D3 on PTH secretion from parathyroid cells was significantly more potent than that of 1,25-(OH)2D3 between 10(-11) M and 10(-8) M. Study of 26,27-F6-1,25-(OH)2D3 metabolism in parathyroid cells in vitro elucidated its slower degradation than that of 1,25-(OH)2D3. After 48 h of incubation with [1beta-3H]26,27-F6-1,25-(OH)2D3, two HPLC peaks, one for [1beta-3H]26,27-F6-1,25-(OH)2D3, and a second larger peak for [1beta-3H]26,27-F6-1,23(S),25-(OH)3D3, were detected. No metabolites were detected after the same period of incubation with 1,25-(OH)2[26,27-3H]D3. We observed that 26,27-F6-1,23(S),25-(OH)3D3 was as potent as 1,25-(OH)2D3 in inhibiting the proliferation of parathyroid cells. Data suggest that the greater biological activity of 26,27-F6-1,25-(OH)2D3 is explained by its slower metabolisms and by the retention of the biological potency of 26,27-F6-1,25-(OH)2D3 even after 23(S)-hydroxylation.
Animals↗
Epidemiologic study of glenohumeral osteoarthritis with plain radiography.
We analyzed the incidence and cause of glenohumeral osteoarthritis including its early stage with plain radiographs. In Kishiwada City Hospital we treated 4035 patients with orthopaedic complications in 1995. A total of 345 patients (390 shoulders) had shoulder diseases. The patients with primary glenohumeral osteoarthritis were 2 men and 14 women (18 shoulders) aged 60 to 86 years (mean 71.9 years), and 2 cases were secondary osteoarthritis. In 2 cases (3 shoulders) of severe osteoarthritis other joints were also affected. Only 4 (25%) of the patients with primary glenohumeral osteoarthritis had osteoarthritic changes only in the glenohumeral joint. The incidence of primary glenohumeral osteoarthritis was 0.4% in the patients with orthopaedic complications and 4.6% in the patients who had shoulder diseases. Women were more likely to have primary glenohumeral osteoarthritis than men, and patients older than 60 years of age were more likely to have it than younger patients.
Adolescent↗
Long-term potentiation and evidence for novel synaptic association in CA1 stratum oriens of rat hippocampus.
In CA1 stratum oriens of hippocampal slices, a robust long-term potentiation (LTP) induced by tetanic stimulation (20 pulses at 100 Hz, 10 trains delivered at 0.1 Hz) was accompanied by a slowly developing potentiation in a second, untetanized pathway. N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (D-APV, 50 or 100 microM) reduced the homosynaptic LTP by 80% but failed to affect heterosynaptic LTP. The metabotropic receptor antagonist DL-2-amino-3-phosphonopropionic acid DL-AP3, 300 microM) or (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM), applied with DL-APV, further reduced homosynaptic LTP and blocked heterosynaptic LTP. The inhibitor of Ca(2+)-induced Ca2+ release dantrolene (20 microM), also applied with DL-APV, blocked both components of LTP. Importantly, when low-frequency test stimulation (0.017 Hz) to the untetanized, heterosynaptic pathway was interrupted for 30 min after homosynaptic tetanization, heterosynaptic LTP did not develop. These results demonstrate homosynaptic and heterosynaptic LTP inductions in stratum oriens of the area CA1 and suggest that the heterosynaptic LTP is induced by NMDA-independent, novel associative processes between tetanized and untetanized pathways.
Animals↗
Effect of hyperthermia and protein kinase C inhibitors on DNA synthesis and cell proliferation on Ehrlich ascites tumour cells in vitro.
Effect of hyperthermia and/or protein kinase inhibitors on DNA synthesis and cell proliferation was investigated in Ehrlich ascites tumour cells in vitro. Both H-7 and H-8, potent inhibitors of protein kinase C, suppressed DNA synthesis significantly, but HA1004, an inhibitor of cAMP- and cGMP-dependent protein kinase, did not. Hyperthermia increased greatly the suppressive activity of H-7 and H-8 but not that of HA1004. H-7 also inhibited cell growth. These results suggest that the inhibition of protein kinase C enhances the suppression of DNA synthesis and the proliferation of tumour cells by hyperthermia.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Elevation in putrescine level and spermidine/spermine N1-acetyltransferase activity coincide with tumor development in 1, 2-dimethylhydrazine-induced rat colon.
Spermidine/spermine N1-acetyltransferase (SSAT), rate-limiting enzyme of polyamine interconversion, has been demonstrated to play an important role in malignant transformation of cells. We examined the involvement of altered polyamine metabolism in the colonic carcinogenesis, using 1,2-dimethylhydrazine (DMH)-induced rat colon tumor model. Following findings were obtained: i) Ornithine decarboxylase demonstrated high activity from the early phase in colon mucosa, and increased significantly in tumors. ii) Spermidine and spermine levels gradually elevated in DMH-treated mucosa, while putrescine increased significantly in tumor tissues. iii) SSAT activity increased gradually in DMH-treated colon mucosa, which preceded elevation of tissue putrescine level, and coincided with tumor development. In conclusion, elevation of putrescine level and induction of SSAT activity are suggested to have a close association in colonic carcinogenesis.
1,2-Dimethylhydrazine↗
Relationship of polyamine metabolism to degree of malignancy of human hepatocellular carcinoma.
We investigated polyamine metabolism in hepatocellular carcinoma (HCC) with respect to tumor volume doubling time, degree of differentiation, and prevalence of portal invasion and intrahepatic metastasis. Ornithine decarboxylase (ODC) activity and the spermidine/spermine ratio were correlated with tumor volume doubling time. ODC activity was higher in moderately and poorly differentiated HCC than in well-differentiated HCC. The prevalence of portal invasion and intrehapatic metastasis was higher in patients with high ODC activities. We conclude that polyamine metabolism in HCC estimates the degree of malignancy.
Adult↗
Cytotoxicity of docosahexaenoic acid and eicosapentaenoic acid in tumor cells and the dependence on binding to serum proteins and incorporation into intracellular lipids.
Docosahexaenoic acid (DHA) inhibited the DNA synthesis in Ehrlich ascites tumor cells more markedly than eicosapentaenoic acid (EPA), which was more inhibitory than oleic-, linoleic-, linolenic-, and arachidonic acids. Their activities augmented according to the increase of number of double bonds in the molecule. To correlate the cytotoxicity with lipid syntheses in the cells, distribution of EPA and DHA incorporated into cellular lipids was assessed. EPA was incorporated into triglycerides (TG) and DHA into phosphatidylcholine (PC). These synthesis into TG and PC etc., which shattered from cytotoxicity, may be involved in tumor-cellular protecting actions against EPA or DHA. EPA and DHA involved in cytotoxicity exhibition are their free acid forms. Thus, as an anticancer reaction, intracellular accumulation in the free acid form of DHA was more marked than that of EPA.
Animals↗
Relationship between ornithine decarboxylase gene abnormalities and human hepatocarcinogenesis.
BACKGROUND/AIMS: Ornithine decarboxylase is essential for cell growth. Its activity was high in human hepatocellular carcinoma tissues and was highest in poorly differentiated tumors. METHODOLOGY: To find if there are tumor-specific ornithine decarboxylases, we examined the ornithine decarboxylase cDNA sequences of 91 clones prepared from hepatoma tissue and non-cancerous tissue of resected liver specimens from 15 patients with hepatocellular carcinoma. RESULTS: Ornithine decarboxylase gene mutations were more frequently detected in the hepatoma tissue. The incidence of mutation in hepatoma tissue was related to dedifferentiation. Mutation in regions rich in proline, glutamic acid, serine, and threonine were detected in moderately and poorly differentiated hepatocellular carcinoma only. CONCLUSIONS: Our findings suggested that the sequence of ornithine decarboxylase in hepatocellular carcinoma often is different from that in normal liver and that mutation of its gene is related to the progression of hepatocellular carcinoma.
Adult↗
The role of polyamines in growth factor induced DNA synthesis in cultured rat hepatocytes.
BACKGROUND/AIMS: Hepatocyte growth factor and transforming growth factor-alpha are growth factors with important roles in hepatocyte proliferation. The polyamines, putrescine, spermidine, and spermine are widely distributed in many different cells and play an essential role in cell growth and differentiation. The present study examined the role of polyamine in this growth promoting factor-induced hepatocyte proliferation, in primary cultured rat hepatocytes. METHODOLOGY: Hepatocytes were isolated from rats by the collagenase perfusion method. Ornithine decarboxylase and S-adenosylmethionine decarboxylase activities were measured as the release of 14CO2 from L-[-14C]ornithine and S-adenosyl-L-[carboxyl14C]methionine, respectively. The concentration of polyamine was analyzed by high performance liquid chromatography. RESULTS: When transforming growth factor-alpha and hepatocyte growth factor were added to the hepatocyte culture simultaneously, ornithine decarboxylase activity, S-adenosylmethionine decarboxylase activity, polyamine concentration and DNA synthesis increased additively. The increase in DNA synthesis caused by transforming growth factor-alpha, hepatocyte growth factor, or both was completely inhibited by alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone). The inhibition was reversed by exogenous spermidine or spermine, but not by putrescine. CONCLUSIONS: Increased spermidine or spermine levels are essential for hepatocyte proliferation in cultured rat hepatocytes.
Animals↗
Human erythrocyte polyamine levels after portal vein embolization.
BACKGROUND/AIMS: Polyamine levels in erythrocytes are related to liver regeneration and could be used as an index of liver regeneration after partial hepatectomy. We investigated liver regeneration after portal vein embolization according to the changes of erythrocyte polyamine levels. METHODOLOGY: Levels of polyamines (putrescine, spermidine, and spermine) in erythrocytes were assayed by high-pressure liquid chromatography for 13 patients with hepatocellular carcinoma after portal vein embolization and 16 patients (8 from group reported earlier) after right bisegmentectomy of the liver for hepatocellular carcinoma. In the first group, embolization preceded surgery by 3 weeks. RESULTS: The mean total polyamine level in erythrocytes and the levels of spermidine and spermine were significantly higher at day 7 after embolization, decreasing later. Spermidine and spermine increased by day 7 after partial hepatectomy, decreasing later. Their mean increase was smaller and more gradual when embolization was done before resection than without embolization. CONCLUSIONS: Embolization causes regeneration of the non-embolized portion of the liver, and embolization before liver resection allows regenerative activities of the liver remaining after resection to be lower than without the embolization.
Adult↗
Abnormal cell morphology and cytotoxic effect are induced by 6-0-palmitol-ascorbate-2-0-phosphate, but not by ascorbic acid or hyperthermia alone.
A new derivative of ascorbic acid (AsA), 6-0-palmitoyl-ascorbate 2-0-phosphate (Asc2P6Pal) was developed to enhance the antitumor activity of AsA. When Ehrlich ascites tumor cells were treated with 50 microM Asc2P6Pal at 37 degrees C or 42 degrees C for 1 h and then cultured for 20 h, most of cells exhibited some morphological abnormalities, including exudation of intracellular granules together with other contents on the cell membrane surface, resulting in cell fragmentation. The abnormal features were further enhanced by a long term culture for 96 h and heat treatment at 42 degrees C. In contrast, no abnormality was detected for untreated cells or cells treated with AsA (free acid) at 37 degrees C or 42 degrees C. Cells cultured for 96 h after the treatment suffered from inhibition of DNA synthesis and proliferation. This inhibition was markedly enhanced by combination with the hyperthermic treatment at 42 degrees C, but not for a short-term culture of 20 h after the treatment. No effects were seen upon similar treatment with AsA. The abnormal cells produced during culture for 20 h after the treatment were evaluated to be viable, because they failed to be stained with trypan blue and retained most of the DNA synthesizing ability of Asc2P6Pal-untreated cells. However, they appeared and died after a continuous 76 h of culture (96 h).
Animals↗
Ornithine decarboxylase activity in the non-cancerous hepatic tissue of patients with hepatocellular carcinoma.
BACKGROUND/AIMS: Hepatocellular carcinoma may develop in patients with chronic hepatitis and cirrhosis. Active hepatitis is an important etiologic factor in the development of hepatocellular carcinoma. We measured ornithine decarboxylase activity, an important enzyme during cell proliferation, in non-cancerous hepatic tissue in patients with hepatocellular carcinoma. METHODOLOGY: Thirty-four patients who underwent liver resection for hepatocellular carcinoma were the subjects of this study. Hepatitis B surface antigen was detected in 7 patients (HBV group) and hepatitis C virus antibody was detected in 27 patients (HCV group). Tissue ornithine decarboxylase activity was measured. Histologic severity in active hepatitis (activity score) and degree of fibrosis (staging score) were determined. RESULTS: Ornithine decarboxylase activity was significantly higher in the HCV group than in the HBV and control groups. In all patients, ornithine decarboxylase activity correlated directly with the histologic activity score and the histologic staging score. In the HCV group, ornithine decarboxylase activity correlated with the histologic activity score. CONCLUSIONS: Ornithine decarboxylase activity in non-cancerous hepatic tissue correlated with the severity of active hepatitis and degree of fibrosis. In patients with hepatitis C virus, active hepatitis with increased ornithine decarboxylase activity is an important factor in the development of hepatocellular carcinoma.
Adult↗
Induction of apoptosis in CTLL-2 cells by protocatechualdehyde.
The purpose of this study was to investigate the possible molecular mechanisms of the antiproliferative effect induced by protocatechualdehyde (PA, a dihydroxybenzene derivative). The viability of cytotoxic T cells (CfLL-2) stimulated by IL2 was significantly inhibited at 0.12 mM PA. This inhibitory effect was associated with the induction of apoptosis detected by DNA fragmentation assay. DNA ladder appeared at 0.12 mM PA and the intensity of DNA ladder was visible at 0.3 mM PA. PA inhibited the Ib2-dependent tyrosine phosphorylation of 91, 80 and 55 KDa proteins, but did not affect IL2-dependent serine/threonine phosphorylation of proteins. The levels of bcl-2 protein and mRNA were suppressed by PA. An alteration in bax protein expression on the apoptosis process in CTLL-2 cells was not observed. However, caspase-3 activity was increased by PA. Our results demonstrate that PA inhibited cell proliferation and induced apoptosis in CTLL-2 cells. It is concluded that PA is a potent anti-proliferative agent and is expected to be a promising candidate for novel therapeutics.
Apoptosis↗
Excerpts from "Pathology of the breast".
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Adenocarcinoma, Scirrhous↗
Large, sessile mucosal polyps of the colon: the problem of repeatedly negative biopsies.
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Biopsy↗