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Biomedical subjects

J Ogata

Publications and source records attributed to J Ogata.

At least 73 records · Page 4Linked to original sources
PubMed1994

Interferon as adjunctive treatment for non-metastatic renal cell carcinoma.

OBJECTIVE: To investigate the effect of recombinant alpha 2b-interferon therapy on natural killer (NK) activity and antibody-dependent cell-mediated cytotoxicity (ADCC) in the peripheral blood in patients with renal cell carcinoma who had undergone radical nephrectomy. PATIENTS AND METHODS: Between January 1988 and June 1989, 20 patients (14 men and six women, mean age 59 years, range 43-80) received interferon (IFN) therapy following radical nephrectomy for renal cell carcinoma. Thirteen patients had stage I disease, one had stage II and six had stage III; none had metastases. RESULTS: There was a significant increase in NK activity at 5 and 7 months after starting IFN therapy but there was no increase in ADCC. CONCLUSIONS: Low doses of IFN administered long-term increased NK activity in patients with renal cell carcinoma. This finding should be helpful in designating protocols for randomized studies of post-operative IFN administration as adjuvant therapy.

Adult↗
PubMed1994

Mechanisms of cerebral artery thrombosis: a histopathological analysis on eight necropsy cases.

The mechanisms of thrombus formation in atherosclerotic cerebral arteries are still controversial, although intraplaque haemorrhage and rupture of the atheromatous plaques have been proposed. A histopathological analysis of segments of the thrombosed large intracranial arteries was carried out on eight patients who died within 28 days after brain infarction. The study revealed occlusive thrombi in six and mural thrombi in two, developing mostly at the site of greatest stenosis or just distal to it. The histological characteristics of the thrombosed arteries were plaque rupture in three, intramural haemorrhage in one, ulceration in one, and thrombosis in the absence of plaque rupture or intramural haemorrhage in three. Occlusive emboli distal to the site of cerebral artery thrombosis (intracranial artery-to-artery thromboembolism) were observed in two. The following conclusions were drawn from the study: 1) plaque rupture or intraplaque haemorrhage is not a sine qua non for cerebral artery thrombosis; 2) occlusions occur at the site of greatest luminal compromise or just distal to it, and 3) non-occlusive mural thrombosis can occur in the absence of plaque rupture and eventually lead to local occlusion or distal embolisation.

Aged↗
PubMed1994

Neointima formation after vascular stent implantation. Spatial and chronological distribution of smooth muscle cell proliferation and phenotypic modulation.

Intravascular stents have proved useful as angioplasty devices, but intimal hyperplasia after stent implantation remains an unsolved problem. In the present study, we analyzed the spatial and chronological distribution of proliferation and phenotypes of smooth muscle cells (SMCs) in rabbit aortas during the process of neointima formation after stent implantation (Gianturco's Z type) by immunohistochemistry for proliferating cell nuclear antigen (PCNA) and myosin heavy chain isoforms (SM1, SM2, and SMemb). Stent implantation induced regional injury in the arterial wall. Medial SMCs then began to proliferate adjacent to the injured SMCs, maximally on day 4 (PCNA index in the media: 3.9 +/- 3.4% [mean +/- SD]), and were modulated to the embryonic phenotype (SMemb-positive and SM2-negative). They migrated into the intima and proliferated most frequently on day 7 (PCNA index in the intima: 20.3 +/- 5.5%) and subsequently led to fibrocellular neointima formation at 2 weeks and later. At 1 month after implantation and later, SMC proliferation was rare, and the phenotype of intimal SMCs was gradually returning to the adult type (SMemb-negative and SM2-positive). Thus, this stent implantation model demonstrates that the regional effect on arterial wall by stenting leads to neointima formation through transient and regional proliferation and migration of SMCs and their phenotypic modulations.

Animals↗
PubMed1994

Protein tyrosine kinase inhibitors inhibit chemotaxis of vascular smooth muscle cells.

The effects of protein tyrosine kinase inhibitors on platelet-derived growth factor (PDGF)-induced chemotaxis in cultured rat aortic smooth muscle cells (SMCs) were investigated to elucidate the role of tyrosine phosphorylation in the chemotaxis of vascular SMCs. Two tyrosine kinase inhibitors, methyl 2,5-dihydroxycinnamate and genistein, inhibited PDGF-induced chemotaxis, the IC50 being 5 and 150 mumol/L, respectively. Methyl cinnamate and genistein partly inhibited the adhesion of SMC to collagen-coated dishes. A chemotaxis assay using double-well culture dishes revealed that both agents also inhibited cell migration after adhesion. H-7, a C kinase inhibitor, did not inhibit either chemotaxis or SMC adhesion at 100 mumol/L. Western blot analysis using anti-phosphotyrosine revealed that the tyrosine kinase inhibitors inhibited the tyrosine phosphorylation of at least two proteins of molecular weight 85 and 95 kD under our experimental conditions. An immunocytochemical study revealed that these inhibitors eliminated tyrosine phosphorylation along the cell margins; these agents also inhibited the reorganization of microtubules and stress fibers, both of which are involved in directional cell locomotion. These findings suggest that tyrosine kinases may play an important role in SMC chemotaxis.

Animals↗
PubMed1994

Atheromatous embolism in the brain: a clinicopathologic analysis of 15 autopsy cases.

We report 15 autopsy cases with cerebral atheromatous embolism (14 men and one woman, 57 to 76 years of age) and analyze their pathologic features. Cardiovascular surgery or catheterization triggered the atheromatous embolism in the brain in six cases (aortocoronary bypass, two; emergency aortocoronary bypass after percutaneous transluminal coronary angioplasty, one; graft implantation for thoracic aortic aneurysm, two; coronary angiography, one). The events that had triggered embolism were not clear in the remaining nine cases. Pathologic examination of the brains revealed that nine cases had single or multiple cortical hemorrhagic infarcts corresponding to the border zones between two main cerebral arterial territories. Many of the leptomeningeal arteries located in the subarachnoid spaces of cortical sulci and surfaces adjacent to the infarcts were occluded by atheromatous emboli composed mostly of cholesterol crystals. The internal diameters of the occluded arteries ranged from 50 to 300 microns. Arterial territorial infarcts were present in six cases, three of which had thromboemboli containing various amounts of cholesterol crystals occluding the major arteries or their large branches supplying the infarcted areas, which were pale in two cases and hemorrhagic in one. The other three cases had hemorrhagic infarcts in which atheromatous emboli were present only in the small leptomeningeal arteries and were composed mostly of cholesterol crystals. Atheromatous embolism in the brain frequently causes border-zone infarcts by occlusion of the terminal cortical branches, and sometimes causes arterial territorial infarcts if the emboli are associated with fibrin and sufficiently large to occlude the larger arteries.

Aged↗
PubMed1994

Bidirectional regulation of smooth muscle cell proliferation by IFN-gamma.

We studied the effects of interferon gamma (IFN-gamma), a T-cell lymphokine, on the proliferation and chemotaxis of vascular smooth muscle cells (SMC). Recombinant human IFN-gamma dose-dependently inhibited the proliferation of SMC cultured in the presence of 20% fetal calf-serum. It also inhibited PDGF-induced chemotaxis of SMC. Similar concentrations of IFN-gamma induced DNA-synthesis of SMC cultured in mitogen-depleted medium for 5 days. The inhibition and the stimulation of SMC proliferation were accompanied by concomitant decrease and increase in the number of PDGF receptors. Our study indicated that IFN-gamma is a bidirectional regulator of SMC proliferation.

Cell Division↗
PubMed1994

[Bilateral spermatocele developed after vasectomy: a case report].

A rare case of bilateral spermatocele developed 17 years after vasectomy was presented. A forty-seven year old man visited to our hospital with a chief complaint of swelling of bilateral intrascrotal contents. Sonographic findings demonstrated multilocular lesions of the bilateral intrascrotal contents. Operative procedure revealed bilateral cysts originating from the caput of the epididymis. Bilateral epididymectomy were performed. It was diagnosed as spermatocele because of demonstration of spermatozoa in the cystic fluid. We concluded that bilateral spermatocele has been induced by prolonged increased pressure of the intraepididymal duct following vasectomy 17 years ago.

Humans↗
PubMed1994

[Urogenital sinus cyst in a child. A case report].

A rare case of urogenital sinus cyst in a child is reported. A 10-month-old boy was referred to our hospital under the diagnosis of acute epididymitis. IVP showed left hydronephrosis and round filling defect in the bladder. Ultrasonography and CT scan demonstrated a retrovesical cystic lesion. Right vesiculography under general anesthesia revealed a midline cystic lesion. Fenestration between the prostatic urethra and cystic lesion was performed by TUR-velmontanum. However, that cystic lesion did not disappeared. Our case seems to be the youngest case of urogenital sinus cyst reported in the Japanese literature.

Cysts↗
PubMed1994

Decreased beta-amyloid and increased abnormal Tau deposition in the brain of aged patients with leprosy.

We examined the brains of 37 leprosy patients (mean age, 76.3 +/- 7.8 years), 5 patients with Alzheimer-type dementia (mean age, 79.0 +/- 9.5 years), and 23 age-matched non-dementia controls (mean age, 77.6 +/- 5.4 years). The frequency of beta-amyloid (A beta)-positive cases was lower (27.0%) in leprosy patients (n = 37) than in controls (47.8%; P = 0.05, Z = 1.49). When senile plaque subtypes were examined, type III (classical) plaques were significantly fewer (P < 0.05) in leprosy subjects compared with controls. Interestingly, neurofibrillary tangles in the temporal cortex were much more frequent in leprosy patients than in controls (P < 0.05). However, hippocampal CA3 pyramidal neurons in leprosy patients were well preserved. These data indicate that 1) leprosy patients have a low risk of A beta deposition but a high risk of abnormal tau deposition, 2) abnormal tau deposition is unrelated to A beta deposition in leprosy, and 3) neuronal loss is unrelated to abnormal tau deposition. It is not clear at present whether the result is related to the disease process itself, antileprosy treatment, environmental factors, or the genetic background in leprosy patients.

Aged↗
PubMed1993

Protein kinase C-mediated inhibition of cyclin A expression in human vascular endothelial cells.

Proliferation of cultured human vascular endothelial cells may be negatively regulated by the protein kinase C (PKC) pathway, because phorbol 12-myristate, 13-acetate (PMA) inhibits DNA synthesis and cell population doubling in PKC-retaining cells, but not in cells depleted of PKC by a long-term exposure to PMA. We investigated the mechanism through which PKC arrests the cell cycle with regard to cyclin A, which has been reported to play a key role in G1/S progression activating CDK2. Cyclin A mRNA was elevated from late G1 in accordance with the protein expression, which reached the maximal level during the S phase. PMA added at late G1 potently reduced the levels of cyclin A mRNA and the protein in concentration-dependent manners parallel to its effect on the proliferation. However, it failed to inhibit the expression in PKC-depleted cells. The mRNA reduction by PMA was due to inhibition of the transcription. The PMA effects were mimicked by multiple doses of 1,2-dioctanoylglycerol. These findings suggest that PKC inhibits G1/S progression through suppression of cyclin A gene transcription in endothelial cells.

Blotting, Western↗
PubMed1993

Protein kinase C-mediated inhibition of vascular smooth muscle cell proliferation: the isoforms that may mediate G1/S inhibition.

The role of protein kinase C (PKC) in the regulation of vascular smooth muscle cell proliferation was studied using not only phorbol ester but also diacylglycerol, with regard to the molecular species of PKC. Phorbol 12,13-dibutyrate (PDBu) and 1,2-dioctanoylglycerol (DOG) both potently inhibited serum-stimulated DNA synthesis and cell population doubling. The PDBu effect on DNA synthesis was maximal when applied at late G1. Neither PDBu nor DOG inhibited DNA synthesis in cells incubated with phorbol 12-myristate 13-acetate (PMA) for 24 h, which down-regulates PKC. Moreover, long exposure to PMA shortened the G1 period and the cell population doubling time. Therefore, a PKC isoform(s) that can be activated by phorbol ester and down-regulated by long exposure to PMA should be involved in the G1/S inhibition. A PKC enzyme assay of the soluble proteins extracted from late G1 cells and fractionated by anion exchange and hydroxylapatite chromatography showed that the activity eluting with PKC-alpha predominated, whereas that eluting with PKC-zeta was detectable. The former was dependent on Ca2+ and phorbol ester but the latter was not. PKC-zeta appeared to be expressed as two subspecies of M(r) 70 and 80 kDa. In cells incubated with PMA for 24 h, the activity eluting with PKC-alpha was completely abolished, whereas the significant activity eluting with PKC-zeta (70 kDa) remained. On the other hand, a relatively low, Ca(2+)-independent activity eluted with PKC-epsilon from the particulate fraction. This was reduced by long exposure to PMA, although not completely. Therefore, PKC-alpha and -epsilon may be the most probable mediators of the G1/S inhibition.

Animals↗
PubMed1993

Human neonatal and adult vascular smooth muscle cells in culture.

Neonatal vascular smooth muscle cells (SMC) in culture have been demonstrated to be quite different from adult SMC and to be similar to intimal SMC in animal models. To characterize human neonatal vascular SMC in culture, cultures of arterial SMC were prepared by an explant method from the subclavian arteries of autopsied patients (10 adults and 6 neonates). The morphology and growth characteristics of these cells were compared. All cells were positively immunostained with HHF 35, a monoclonal antibody specific for muscle actin. Electron microscopically, both adult and neonatal SMC were of synthetic phenotype. SMC from neonates had a short population doubling time (PDT, 28.6 +/- 7.5 hr) and high saturation density (SD, 37.5 +/- 11.9 x 10(4) cells/cm2). They did not show hill and valley growth patterns. Among the SMC cultured from adult media, two subtypes were distinguished, based on their growth characteristics. Classical adult SMC (7 of 10 cases) grew in hill and valley patterns with long PDT and low SD values (61.7 +/- 28.8 hr, 6.5 +/- 1.9 x 10(4) cells/cm2, respectively). The second subtype (3 of 10 cases), neonatal-type adult SMC, had PDT and SD values (22.9 +/- 4.0 hr, 31.3 +/- 14.7 x 10(4) cells/cm2, respectively) similar to those of neonatal SMC. Intimal SMC became senescent in early phases of subculture. To test for the possible participation of autocrine growth factors in the heterogeneity of the growth patterns, Northern blot analysis was conducted for PDGF-A, TGF-beta, c-myc, and c-fos mRNA in three types of SMC. There was no significant difference in these mRNA levels between the SMC. We demonstrated that human neonatal vascular SMC in culture are quite different in their growth characteristics from classical adult SMC in culture and that neonatal-type SMC can be isolated from adult media.

Adult↗
PubMed1993

Reduction of drug accumulation in cisplatin-resistant variants of human prostatic cancer PC-3 cell line.

We have isolated cis-diamminedichloroplatinum (II) (CDDP)-resistant variants, P/CDP4 and P/CDP5, from human prostatic cancer PC-3 cells after a stepwise exposure to CDDP. P/CDP4 and P/CDP5 showed 11-fold and 23-fold higher resistance to CDDP than did PC-3. P/CDP5 was cross-resistant to carboplatin, mitomycin C, etoposide, m-AMSA, bleomycin and UV irradiation. Alkaline elution of DNA showed an increased amount of DNA interstrand cross-links in PC-3 but not in P/CDP5 when PC-3 and P/CDP5 were cultured with CDDP. Flameless atomic absorption spectrophotometry revealed that intracellular accumulation of CDDP in P/CDP4 and P/CDP5 was decreased to 18 to 34% and 9 to 18% of that of PC-3, respectively, when PC-3 and its CDDP-resistant counterparts were incubated with 5 and 10 micrograms./ml. of CDDP for 24 hours. These data suggest that decreased drug accumulation is involved in the development of CDDP-resistance in the PC-3 cell line.

Cisplatin↗
PubMed1993

Effects of thiols on prostaglandin synthesis in bovine bladder epithelium.

The regulation of prostaglandin (PG) synthesis was characterized in microsomes of bovine bladder epithelium. Coenzyme A (CoA) and its metabolite cysteamine drastically decreased total PG synthesis. Furthermore, CoA inhibited solubilized cyclooxygenase which was precipitated by anti-cyclooxygenase antibody. Reduced glutathione (GSH) slightly increased total PG production and changed the pattern of PG synthesis. Other thiols, cysteine and ergothioneine, did not change total PG production. None of the thiols stimulated the incorporation of arachidonic acid into the phospholipid fraction. These findings suggest that CoA may directly regulate cyclooxygenase activity and GSH may subsequently change the pattern of PG production in bovine bladder epithelium.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Changes of rat urinary bladder during acute phase of spinal cord injury.

Spinal cord injury (SCI) at Th13 was induced in female Wistar rats, and changes in the urinary bladder were examined during the acute phase of SCI. Wet weights of the spinal bladders increased twofold over controls by 7 days after SCI. Intravesical volumes increased sixfold over control values by day 3, and then decreased 7 days after the injury. Maximal pressure within the bladder decreased in all spinal rats compared with controls. Smooth muscle cells were isolated from the urinary bladder, and their total protein and DNA content were measured by multiparametric cytofluorometry. DNA content of isolated smooth muscle cells decreased by day 3 and remained 7 days after the spinal injury. Total protein content of isolated smooth muscle cells was decreased 1 day after and increased 7 days after the spinal injury, just when spinal reflex of the bladder recovered. These findings suggest that hypertrophy of smooth muscle cells in urinary bladder is related to the activity of peripheral autonomic nerve and that smooth muscle cells already begin to hypertrophy during the spinal shock period to adjust themselves to the new state, that is, the spinal bladder.

Acute Disease↗
PubMed1993

Parasympathetic cerebrovasodilator center of the facial nerve.

Functional studies have yet to be undertaken to establish which brain region subserves the parasympathetic regulation of the cerebral circulation. Using 31 anesthetized rats with precluded cervical sympathetic trunks, we therefore attempted to perform chemical stimulation of the greater petrosal nerve (GPN) cell group, which is a subgroup of the superior salivatory nucleus and sends off axons largely to the parasympathetic pterygopalatine ganglion via the GPN component of the facial nerve. The cerebrocortical blood flow was monitored with a laser-Doppler flowmeter. Unilateral stimulation of the GPN cell group by microinjection of L-glutamate reduced the ipsilateral cerebrocortical vascular resistance, maximally by 16.4 +/- 4.1% (mean +/- SD, n = 61). The response was not mediated by the classic muscarinic receptors of the cerebral vessel wall. However, pharmacological blockade of the peripheral parasympathetic ganglia and acute and chronic bilateral removal of the parasympathetic postganglionic fibers originating in the pterygopalatine ganglion abolished the response. The present data thus provide functional evidence that the GPN cell group may constitute a parasympathetic cerebrovasodilator center.

Animals↗
PubMed1993

Smooth muscle cell proliferation and localization of macrophages and T cells in the occlusive intracranial major arteries in moyamoya disease.

BACKGROUND AND PURPOSE: Stenosis or occlusion due to fibrocellular intimal thickening in the intracranial major arteries is thought to be the primary lesion in moyamoya disease, but its etiology and pathogenesis are unknown. The present study was designed to analyze cellular components of the lesions and their pathological process. METHODS: Stenotic or occlusive intracranial arterial lesions were collected from six autopsied patients who died of moyamoya disease. The cellular components were analyzed by immunohistochemical staining using cell-type-specific monoclonal antibodies. The sections were also immunostained for proliferating cell nuclear antigen (PCNA) to detect proliferating cells and for two different types of intermediate filaments, desmin and vimentin, to evaluate phenotypes of the intimal smooth muscle cells. RESULTS: The thickened intima was composed predominantly of smooth muscle cells with an admixture of some macrophages and T cells. Macrophages and T cells were scattered in the superficial layer of the intimal thickening, and these were occasionally associated with organization of fibrin thrombi. Proliferating smooth muscle cells, indicated by PCNA-positive nuclei and muscle actin-positive cytoplasm, were found in the thickened intima in four patients. Immunohistochemical staining for intermediate filaments revealed intimal smooth muscle cells showing positive staining for vimentin and negative staining for desmin, compatible with the phenotype of synthetic smooth muscle cells. CONCLUSIONS: The present study provides evidence that smooth muscle cells are proliferating in the occlusive lesions in intracranial major arteries in moyamoya disease. The colocalization of inflammatory cells and PCNA-positive cells suggests that inflammatory stimuli may induce proliferative response of smooth muscle and contribute to the formation of the intracranial occlusive lesions in moyamoya disease.

Adolescent↗