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Biomedical subjects

J Ogata

Publications and source records attributed to J Ogata.

At least 55 records · Page 3Linked to original sources
PubMed1996

Modulation of platelet-activating factor synthesis by recombinant interferon-alpha in human renal cell carcinoma.

Platelet-activating factor (PAF), a potent phospholipid chemical mediator of inflammation, is involved in multiple cellular functions. Since PAF has a strong effect on platelet aggregation and on the enhancement of capillary permeability, it is possible that this factor plays an important role in tumor progression. In human renal cell carcinoma (RCC), it has recently been reported that immunotherapy with interferon (IFN) is effective for the prevention of tumor recurrence and progression. To evaluate the role of PAF and the effect of interferon-alpha (IFN-alpha) on PAF production in RCC, we measured PAF content and the activity of choline phosphotransferase (CPT), an enzyme involved in the de novo biosynthesis of PAF, in RCC specimens obtained from 30 patients who had undergone radical nephrectomy for RCC, and in specimens of normal renal cortex and normal renal medulla. PAF was present in both RCC and the normal renal tissues. Although CPT activity in RCC was similar to that in normal renal cortex, CPT activity in the normal medulla was significantly higher than that in RCC and the normal cortex. No correlation was found between CPT activity and the pathological findings in RCC. Although there was no difference in CPT activity in normal renal tissues between patients treated preoperatively with IFN-alpha and those untreated, CPT activity in RCC was significantly reduced in patients who had received IFN-alpha compared with those who had not. These findings suggest that IFN-alpha may modulate the production of PAF in RCC patients.

Antineoplastic Agents↗
PubMed1996

Heterogeneity in the appearance and distribution of macrophage subsets and their possible involvement in hypertensive vascular lesions in rats.

In hypertensive vascular lesions, various pathologic changes are exhibited. To clarify the mechanisms responsible for this diversity of vascular lesions, we immunohistochemically examined hypertensive vascular lesions in stroke-prone spontaneously hypertensive rats with reference to the distribution of macrophage subsets. The brain, kidney, heart, and aorta were dissected from stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats at 8, 12, 16, and 20 weeks of age. Immunohistochemistry was performed with antibodies against the macrophage markers ED1, ED2, and OX42, the MHC class II antigen marker OX6, the T-lymphocyte markers CD4, CD5, and CD8, and other markers, such as alpha-smooth muscle actin, proliferating cell nuclear antigen, and von Willebrand factor. Fibrinoid necrosis was dominant in the brain, and fibrocellular proliferative lesions were dominant in the kidney. Immunohistochemically, the decreased intensity of alpha-smooth muscle actin immunostaining preceded the formation of vascular lesions. Although preexisting ED2-positive perivascular resident macrophages completely disappeared in fibrinoid necrosis, MHC class II-negative and ED1-positive macrophages were scattered around the lesion and showed phagocytosis in the brain, which indicates that macrophages in fibrinoid necrosis had extravasated and acted only as scavengers. In the kidney, there was extensive accumulation of MHC class II-positive and ED1-positive macrophages with T lymphocytes along the affected arteries. These inflammatory cells seemed to be supplied through the perivascular interstitial space, not through the endothelium, and the accumulation of these cells preceded the development of fibrocellular proliferative lesions. In the heart and aorta, macrophage accumulation was either absent or slight, and vascular lesions were rarely observed. These findings suggest that heterogeneity in the time course of macrophage infiltration and in the distribution of macrophage subsets among the vascular trees of various organs seems to be correlated with the diversity of hypertensive vascular lesions. Differences in the routes that supply macrophages and their functions may determine the pathologic changes in the vascular lesions.

Animals↗
PubMed1995

Allele-specific methylation and expression of an imprinted U2af1-rs1 (SP2) gene.

The mouse U2af1-rs1(SP2) gene, which was cloned by a two-dimensional genome scanning method, is expressed exclusively from the paternally inherited chromosome. This gene has significant similarity to U2AF and located in chromosome 11, of which maternal duplication/paternal deficiency results in a small body. In this report, we cloned genomic U2af1-rs1(SP2) and found its promoter was methylated in a maternal-allele-specific manner. This allelic methylation was not established in parental gametes, but established between 1.5 d.p.c. and 12.5 d.p.c. on the contrary, the allele-specific expression occurred in the two-cell stage when transcription initiates. Absence of the methylation of the upstream region in this stage indicates that methylation is not necessary for inactivation of the expression.

Alleles↗
PubMed1995

Tyrosine kinase inhibitors inhibit multiple steps of the cell cycle of vascular smooth muscle cells.

Protein tyrosine kinase (PTK) inhibitors have been reported to inhibit proliferation of vascular smooth muscle cells (SMC). To elucidate the mode of this inhibition, the effects on the cell cycle of cultured vascular SMC of three PTK inhibitors with different modes of action (methyl 2,5-dihydroxycinnamate, genistein, and herbimycin A) were studied. Rat aortic SMC were synchronized to the G0 phase of the cell cycle and then released to proceed through the cell cycle by the addition of platelet-derived growth factor (PDGF), and [3H]thymidine incorporation into DNA was measured. The three PTK inhibitors all inhibited PDGF-induced DNA synthesis in a dose-dependent fashion, with IC50 values of 4.7 +/- 1.4 microM for methyl 2,5-dihydroxycinnamate, 6.7 +/- 2.5 microM for genistein, and 0.17 +/- 0.07 microM for herbimycin A. Time course studies suggested that the agents inhibited early G1 phase but not the G0-G1 transition. the lack of effect on the G0-G1 transition was also supported by the finding that the agents did not inhibit the ligand-induced autophosphorylation of PDGF receptor nor the induction of c-fos mRNA at concentrations which were sufficient to inhibit DNA synthesis. PTK inhibitors inhibited progression of the S phase when they were added to SMC that had been arrested at the G1-S border with hydroxyurea. Methyl 2,5-dihydroxycinnamate also blocked the M phase when it was added to SMC cultured in the presence of 10% fetal calf serum, while genistein and herbimycin A did not inhibit the M phase under the same experimental conditions. In accordance with our previous observation, methyl 2,5-dihydroxycinnamate impaired microtubule networks and formation of the mitotic spindle during the M phase. Our findings indicated that PTK inhibitors inhibit multiple steps of the vascular SMC cell cycle.

Animals↗
PubMed1995

Combined intraarterial cisplatin infusion and radiation therapy for invasive bladder cancer.

Combined intraarterial cisplatin infusion and radiation therapy were performed as the initial treatment for 23 patients (mean age: 70 years) with invasive bladder cancers (T2 in 17, T3 in 6) who were suitable for total cystectomy. Of these patients, five who had multiple invasive cancers without laterality had their intrapelvic hemodynamics altered by embolizing a contralateral internal iliac artery. Cisplatin (50 mg) was infused into the internal iliac artery through a subcutaneous reservoir twice a week over three weeks while concurrent radiation therapy with 30 Gy, delivered in 15 fractions, was performed. Additional cisplatin infusions were given in six patients. After this combined therapy, total cystectomy and ileal conduit was performed in six patients and transurethral resection of bladder tumor (TURBT) in 17. Two of the patients who underwent total cystectomy were found to exhibit a complete response. Therefore, the overall response rate was 87%, including 13 complete responses and seven partial responses. The complete response rates in patients with clinical stage T2 and T3 disease were 53 and 67%, respectively. The complete response rate was slightly higher in patients with a non-papillary cancer than in those with a papillary one. Toxic reactions included a decrease in bladder capacity in two patients and severe diarrhea due to methicillin-resistant Staphylococcus aureus colitis in one. Other forms of toxicity, including nausea, vomiting, neurotoxicity in the gluteal region, nephrotoxicity and myelosuppression, were tolerable. All but one of the patients are alive.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Effects of aging and chronic hypertension on cerebral blood flow and cerebrovascular CO2 reactivity in the rat.

We measured regional cerebral blood flow (rCBF) in young and old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats by a minimally invasive microsphere technique. Blood flows to the cerebrum, diencephalon, mesencephalon, cerebellum and pons-medulla during normocapnia were determined. To test the ability of the vessels to dilate, rCBF was also measured during hypercapnia. Reactivity to CO2 was calculated as delta rCBF/delta paCO2. In the old SHR, blood flow to the pons-medulla (88 +/- 8 ml/min/100 g, mean +/- SEM) was markedly lower than that in the young SHR (107 +/- 4 ml/min/100 g, p < 0.05), whereas the difference of those values in the old and young WKY rats was slight (0.05 < p < 0.1). There were no differences in the values of blood flow to the cerebrum, diencephalon, mesencephalon or cerebellum between the young and old rats in both species. Cerebrovascular CO2 reactivity was markedly impaired in the old SHR (p < 0.05) compared to that in the young SHR, but the difference in reactivity in the WKY rats was not significant. The results indicate that blood flow to the pons-medulla is reduced in association with age, particularly in the hypertensive animals, and that the ability of the cerebral vessels to dilate is impaired homogeneously by the combination of chronic hypertension and aging.

Aging↗
PubMed1995

Arteriovenous fistula around the ventriculoperitoneal shunt system in a patient with a dural arteriovenous malformation of the posterior fossa. Case report.

A dural arteriovenous malformation (AVM) of the posterior fossa can produce persistent tinnitus, convulsions, and dementia. Successful therapeutic embolization may result in a complete cure, but in some cases, patients do not respond to the treatment. The authors report a patient with a dural AVM of the posterior fossa that did not respond to repeated intravascular treatments, but resulted in an arteriovenous shunt in the scalp around the ventriculoperitoneal shunt system. Although several hypotheses have been proposed on the pathogenesis of dural AVMs, the underlying mechanisms remain unknown. The rare complication we encountered may shed some light on the pathogenesis of dural AVMs.

Arteriovenous Fistula↗
PubMed1995

Combined intraarterial cisplatin infusion and radiation therapy for invasive bladder cancer.

Combined intraarterial cisplatin infusion and radiation therapy were performed as the initial treatment for 23 patients (mean age: 70 years) with invasive bladder cancers (T2 in 17, T3 in 6) who were suitable for total cystectomy. Of these patients, five who had multiple invasive cancers without laterality had their intrapelvic hemodynamics altered by embolizing a contralateral internal iliac artery. Cisplatin (50 mg) was infused into the internal iliac artery through a subcutaneous reservoir twice a week over three weeks while concurrent radiation therapy with 30 Gy, delivered in 15 fractions, was performed. Additional cisplatin infusions were given in six patients. After this combined therapy, total cystectomy and ileal conduit was performed in six patients and transurethral resection of bladder tumor (TURBT) in 17. Two of the patients who underwent total cystectomy were found to exhibit a complete response. Therefore, the overall response rate was 87%, including 13 complete responses and seven partial responses. The complete response rates in patients with clinical stage T2 and T3 disease were 53 and 67%, respectively. The complete response rate was slightly higher in patients with a non-papillary cancer than in those with a papillary one. Toxic reactions included a decrease in bladder capacity in two patients and severe diarrhea due to methicillin-resistant Staphylococcus aureus colitis in one. Other forms of toxicity, including nausea, vomiting, neurotoxicity in the gluteal region, nephrotoxicity and myelosuppression, were tolerable. All but one of the patients are alive. This patient died of distant metastasis and seven other patients had a local recurrence of bladder cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Reversal by a dihydropyridine derivative of non-P-glycoprotein-mediated multidrug resistance in etoposide-resistant human prostatic cancer cell line.

PURPOSE: We have isolated etoposide-resistant prostatic cancer cell lines, P/VP10 and P/VP20, to investigate the multidrug resistance (MDR) mechanism and to find MDR reversal agents. MATERIALS AND METHODS: We examined expression of MDR-related genes and screened reversal agents of MDR in P/VP20 cells. RESULTS: These cells demonstrated a non-P-glycoprotein (P-gp)-mediated MDR phenotype with overexpression of MDR-associated protein (MRP) mRNA due to MRP DNA amplification. A 1,4-dihydropyridine derivative, bis(4-pyridylmethyl)4-[2-(3-methyl-5,6- dihydro-1,4-dithiinyl)]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicar boxylate (NIK250), was found to overcome MDR in P/VP20 cells. CONCLUSIONS: NIK250 might be useful in reversing MDR, which often develops during chemotherapy of advanced or hormone-resistant prostatic cancer.

Cell Line↗
PubMed1994

Position-independent, high-level, and correct regional expression of the rat aldolase C gene in the central nervous system of transgenic mice.

Aldolase C is mainly expressed in the central nervous system (CNS). To clarify the regulatory mechanisms for the CNS-specific expression, transgenic mice were created using two constructs of the rat aldolase C gene. A fusion gene comprising the 5' regulatory region of the aldolase C gene was expressed in a CNS-specific manner. However, the expression levels and the cellular localization of the gene varied among transgenic mice. The other construct, including both 5' and 3' regulatory regions of the gene, showed position-independent and high-level expression as well as the correct regional distribution in the CNS. These results indicate that the 13-kb sequence of the rat aldolase C gene contains sufficient information for faithful expression of the gene.

Animals↗
PubMed1994

Gene expression of monocyte chemoattractant protein-1 in human monocytes is regulated by cell density through protein tyrosine kinase and protein kinase C.

The present study investigated the signal transduction pathways leading to the gene expression for monocyte chemoattractant protein-1 (MCP-1) in human monocytes. By Northern blot analysis, MCP-1 mRNA was undetectable in freshly isolated monocytes, but was induced and reached a maximal level at 4 h during culture. The level of accumulated mRNA altered with cell density of the monocytes and was highest at a density of 1 x 10(6) cells/ml. Nuclear run-on assay demonstrated that this cell density-dependent expression of MCP-1 mRNA was regulated at the transcriptional level, and protein tyrosine kinase (PTK) inhibitors, genistein and herbimycin A, completely abrogated this gene transcription. Immunoblot analysis for phosphotyrosine in whole cell lysates demonstrated gradual increases in tyrosine phosphorylation of 55-, 60-, and 70-kDa proteins during culture. Cell density regulated tyrosine phosphorylation of 70-kDa protein in parallel with alterations in MCP-1 mRNA expression. The protein kinase C (PKC) inhibitor H-7 also abrogated the gene transcription and suppressed tyrosine phosphorylation of 70-kDa protein, whereas HA1004, a structural analogue of H-7, did not. These results suggest that MCP-1 gene expression in cultured monocytes is regulated by the cell density at the transcriptional level and that the signaling pathways leading to the gene transcription are mediated through PTK and PKC. It is also suggested that PKC activity plays a critical role in tyrosine phosphorylation of 70-kDa protein, which may mediate signals regulating the cell density-dependent expression of the MCP-1 gene.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Changes in morphology of elastin fibers during development of the tunica intima of monkey aorta.

The normal development of elastin fibers in the thoracic aorta was studied in fetal, young, and adult monkeys. Tissue was examined by scanning electron microscopy (SEM) after NaOH treatment and by transmission electron microscopy (TEM). The NaOH treatment of fixed tissues effectively removed collagen fibers and enabled three-dimensional visualization of the elastin fibers. In intact fetal aortae, the internal elastic lamina (IEL) was situated immediately beneath the endothelium. This IEL consisted of superficial, longitudinally arranged bundles of elastin fibrils and an underlying solid sheet containing round fenestrations. In neonates, diffuse intimal thickening was observed. In the young and young-adult monkeys, the aortae exhibited intimal thickening with slender but split IEL. One of the most important findings of this study was that elastin fibers in the intimal thickening, as well as smooth muscle cells, ran in a longitudinal fashion. This was in contrast with the elastic laminae of the media which were mainly oriented circumferentially. Subendothelial elastin fibers in this intimal thickening combined with longitudinally arranged microfibrils which formed close associations with endothelial stress fibers. In some adult monkey aortae with well-developed intimal thickening, a complex meshwork of slender elastin fibers was also found beneath the endothelium. The development of the intimal elastin fibers is discussed in relation to hemodynamic forces.

Actin Cytoskeleton↗
PubMed1994

Metabolic and non-metabolic cerebrovasomotor mechanisms operational during hypertensive states of different origin in rats.

We attempted to elucidate the vasomotor mechanisms regulating the cerebral circulation of rats under arterial hypertensive states of different origin. Sudden cold exposure elicited a cerebrovasodilator response mediated primarily by an enhanced cerebral metabolic state. The response was not modified by the concomitantly enhanced cerebrovascular sympathetic action. Central inhibition of the baroreceptor reflex, as achieved by chemical inhibition of the caudal ventrolateral medulla, disinhibited a non-metabolic cerebrovasodilator mechanism. However, its action was masked by a concomitantly enhanced sympathetic vasoconstrictor action. Another type of cerebrovasodilator response, also of non-metabolic origin, was elicited by chemical stimulation of the defence area within the periaqueductal grey matter. Thus, the cerebrovasomotor mechanisms are diversely activated so as to cope adequately with the individual conditions imposed on the animals.

Animals↗