Biomedical subjects

M Oka

Publications and source records attributed to M Oka.

At least 217 records · Page 12Linked to original sources

PubMed1998

Synthesis and muscarinic activity of a series of quinolines and naphthalenes with a 1-azabicyclo[3.3.0]octane moiety.

In order to discover a medicine effective against Alzheimer's disease, we synthesized a series of quinoline derivatives having a characteristic 1-azabicyclo[3.3.0]octane amine ring, and performed pharmacological evaluation of them. Acetylcholine esterase inhibitory activities of these derivatives were unexpectedly weak. Tests for central nervous muscarinic cholinergic receptor binding affinity indicated that these compounds had higher affinities to muscarinic M1 receptors than to M2 receptors. A series of naphthalene derivatives substituted with the 1-azabicyclo[3.3.0]octane ring were also synthesized and muscarinic M1 and M2 receptor binding affinity determined. These compounds had much higher affinity for M1 receptors than the quinoline derivatives, and 1-[N-(1-azabicyclo[3.3.0]octan-5-yl)methyl-N-methylamino]-4-nitronaph tha lene showed the highest affinity and selectivity. The ability of this compound to improve cognitive function was assessed using the passive avoidance test in scopolamine-induced mice.

Animals↗

PubMed1998

A case of invasive lobular carcinoma of the breast.

A 43-year-old woman presented to our department with left breast lump, measuring 10 mm x 10mm x 6mm. On physical examination and mammography, the lump was suspected to be due to mastopathy, but malignancy could not be excluded based on ultrasonography. Excisional biopsy showed that it was an invasive lobular carcinoma. A modified radical mastectomy was performed after obtaining informed consent. She remained disease-free seven years after surgery.

Adult↗

PubMed1998

Source of reactive oxygen species in anti-Thy1 nephritis.

In proliferative glomerulonephritis, both macrophages and mesangial cells generate reactive oxygen species (ROS), contributing to the development of glomerular injury. We have attempted to determine which cell produces ROS during anti-Thy1 nephritis (ATN) in rats. The generation of ROS was studied using luminol amplified chemiluminescence (GCL) on isolated glomeruli. Immunohistochemical studies used avidin-biotin complex (ABC) to label macrophages and mesangial cells. Immediately after ATN induction, mesangiolysis and infiltration with ED-1 positive cells (referred to as macrophage) was noted with a peak at day 1. After day 4, mesangial proliferation appeared with a decrease of the ED-1 positive cells and a prominent increase of PCNA positive cells (regarded as mesangial cells). In the early phase of ATN, GCL, reflecting ROS generation, increased along with the appearance of ED-1 positive cells. GCL subsequently decreased as mesangial cells increased. This suggested that macrophage were the principal participants in ROS generation in the early phase of ATN although mesangial cells cannot be completely disregarded in the generation of ROS and development of glomerular injury.

Animals↗

PubMed1998

[Imaging of myocardial perfusion and metabolism with positron emission tomography].

Positron emission tomography (PET) has been providing new information in the diagnosis and the pathophysiological assessment of heart diseases. The PET tracers commonly used in Japan are 13N-ammonia, 18F-fluorodeoxyglucose (FDG) for imaging of myocardial perfusion and metabolism, respectively. Measurement of regional myocardial blood flow by 13N-ammonia dynamic PET scan and a compartment model analysis is applied to the functional estimation of coronary stenotic lesions and the detection of perfusion abnormalities in hypertrophic heart diseases, familial hyperchlesterolemia and other diseases with possible microvascular lesions. 18F-FDG is commonly used to differentiate ischemic but viable tissue from myocardial scar in coronary artery disease and also used to detect cardiac tumor and the cardiac involvement in sarcoidosis. In addition to these two tracers, 11C-acetate is now expected to provide the clinical analysis of pathophysiology of heart failure by estimating the efficiency of energy conversion of the heart into external work.

Acetates↗

PubMed1998

[E 4021, a cGMP phosphodiesterase inhibitor, is a selective pulmonary vasodilator in chronically hypoxic pulmonary hypertensive rats].

To test whether a potent cGMP-specific phosphodiesterase inhibitor, E 4021, is a selective pulmonary vasodilator in pulmonary hypertension, we studied its acute hemodynamic effects in conscious, chronically hypoxic pulmonary hypertensive rats. Chronically hypoxic pulmonary hypertension was induced by keeping adult Sprague-Dawley rats in a hypobaric chamber for 3 weeks. Two days after catheterization. E 4021 was injected intravenously at doses of 3, 10, 30, 100, 300, and 1,000 micrograms/kg at 10-min intervals. E 4021 caused significant decreases in mean pulmonary arterial pressure of 11 +/- 5, 12 +/- 6, and 18 +/- 5% at doses of 100, 300, and 1,000 micrograms/kg, respectively. In contrast to its depressor effect on mean pulmonary arterial pressure, E 4021 decreased mean systemic arterial pressure significantly (by 9 +/- 2%) at a dose of 1,000 micrograms/kg only. Heart rate and cardiac output were unchanged after the administration of E 4021. Tissue cGMP-specific phosphodiesterase activity was markedly higher in lung than in aorta. These results indicate that E 4021 is a relatively selective pulmonary vasodilator in chronically hypoxic pulmonary hypertensive rats. We conclude E 4021 may be useful for the treatment of pulmonary hypertension.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1998

[Novel mechanisms for increasing Ca2+ sensitivity of contractile apparatus in smooth muscle].

Smooth muscle contraction is primarily regulated not only by changes in cytosolic Ca2+ concentrations ([Ca2+]i) but also by changes in the force/[Ca2+]i ratio. The use of membrane-permeabilization technique facilitated demonstration of an increase in the level of force at constant [Ca2+]i (Ca2+ sensitization). It was clarified that Rho-associated kinase (Rho-kinase) is a novel mediator of Ca2+ sensitization of the smooth muscle contraction, by introducing the recombinant catalytic domain of Rho-kinase into the cytosol of vascular smooth muscle permeabilized with beta-escin. This review article focuses on novel mechanisms, by which activation of receptor-coupled G-protein(s) increases Ca2+ sensitivity of the contractile apparatus in smooth muscle: Rho-kinase and protein kinase C.

Animals↗

PubMed1998

[Combined hepatic resection and removal of portal vein tumor thrombi].

Portal thrombectomy with extended hepatectomy for extensively progressive primary liver cancer (Vp 3), in which the tumor thrombus has spread beyond the first portal branches, will make other non-surgical treatments possible and improve patients quality of life. We have performed extensive resections in 15 cases of such Vp 3 liver cancer. One patient with huge HCC involving retrohepatic IVC underwent in situ extended left hepatectomy without reconstruction of IVC, resulting in postoperative renal failure because of thrombosis in the bilateral renal veins, but 14 other patients' postoperative courses were uneventful. Ten of 14 patients relapsed within one year, but these patients underwent non-surgical treatments, resulting in improvement in the quality of life. The 1-, and 3-year survival rates were 55.6% and 32.5%, respectively.

Adult↗

PubMed1998

Nerve regeneration over a 20-mm gap through a nerve conduit containing blood vessels in rats: the influence of interstump distance on nerve regeneration.

BACKGROUND: The present study was conducted in rats to investigate whether a tube with additional intrachamber vascularization could permit axons to extend over a distance greater than 10 mm, which appears to be the maximum axon regeneration distance for rat sciatic nerve axons through a normal empty tube. METHODS: A sural vessel-containing tube (VCT) was designed and interposed between transected sciatic nerve stumps in the thigh, leaving a 20-mm interneural gap. RESULTS: Twelve weeks after tubulation, six out of nine rats showed successful nerve regeneration and re-innervation of the soleus muscle using the VCT. At 24 weeks, intrachamber nerve regeneration and re-innervation of the soleus and pedal adductor muscles were electrophysiologically and histologically confirmed in all rats. However, no neural tissue was observed within any ligated sural vessel-containing tube (LVCT) or empty unmodified tube (ET) with a 20-mm interneural gap. When nerves regenerated in the VCT with a 20-mm gap were compared with those regenerated in a VCT with a 10-mm gap 12 and 24 weeks after surgery, the results produced by the VCT with a 20-mm gap were inferior to those after use of the VCT with a 10-mm gap, except for motor nerve conduction velocity at 24 weeks. CONCLUSIONS: The value recovered to almost identical levels (about 50-60% normal) in both groups.

Animals↗

PubMed1997

Human canalicular multispecific organic anion transporter (cMOAT) is expressed in human lung, gastric, and colorectal cancer cells.

Human canalicular multispecific organic anion transporter (cMOAT), a glutathione conjugate membrane transporter, has been isolated from cisplatin-resistant cancer cells and is distributed mainly in normal liver. We analyzed the expression of human cMOAT in 14 lung, 11 gastric, and 9 colorectal non-drug-selected human cancer cells, two multidrug-resistant cells, and one cisplatin-resistant cells, using quantitative RT-PCR and newly developed anti-human cMOAT antibody. All cell lines analyzed here expressed human cMOAT at the level of mRNA and protein, and some of them expressed higher levels of human cMOAT than the cisplatin-resistant cells. The two multidrug-resistant cell lines co-expressed human cMOAT gene and both or either of MRP and MDR1 genes. Immunostaining showed that human cMOAT was predominantly localized to the cytoplasm of these single cells. Our results indicate that human cMOAT is expressed in various human cancer cells including drug-resistant cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Effect of a novel cognition enhancer NS-105 on learned helplessness in rats: possible involvement of GABA(B) receptor up-regulation after repeated treatment.

We have previously found that a cognition enhancer [(+)-5-oxo-D-prolinepiperidinamide monohydrate] (NS-105) reversed the inhibition of cyclic AMP formation induced by the GABA(B) receptor agonist baclofen. The GABA(B) receptor has been implicated in the pathophysiology of depressive illness. The present experiment was designed to evaluate the antidepressant activity of NS-105 in the forced swimming and learned helplessness tests in rats. NS-105 (1-100 mg/kg, p.o.) significantly decreased immobility time in the forced swimming test, an effect similar to that of desipramine. Repeated administration of NS-105 also reversed the failure to escape in the shuttle-box test of rats previously exposed to inescapable footshock. Biochemical data showed that repeated administration of NS-105 increased the number of GABA(B) receptors in rat cerebral cortex without affecting the binding properties of beta-adrenoceptors and 5-HT2 receptors. In contrast to other antidepressants, NS-105 did not inhibit monoamine uptake in vitro, nor did it change monoamine concentrations in brain tissues or extracellular fluids. These findings suggest that NS-105, which lacks an effect on monoaminergic systems, has potent antidepressant activity, which may involve up-regulation of GABA(B) receptors after repeated administration.

Animals↗

PubMed1997

CYFRA 21-1 is a useful marker for esophageal squamous cell carcinoma.

BACKGROUND: CYFRA 21-1 measures soluble cytokeratin-19 fragments in serum and is a useful marker for lung carcinoma, especially squamous cell carcinoma (SCC). The authors conducted this study to determine the significance of CYFRA 21-1 in patients with esophageal SCC. METHODS: Expression and production of cytokeratin-19 in the authors' six established esophageal SCC cell lines were determined by immunocytochemical staining and enzyme-linked immunoadsorbent assay, respectively. The correlation between serum CYFRA 21-1 levels and expression of cytokeratin-19 in human tumors was investigated by immunohistochemical staining. The correlation between serum CYFRA 21-1 levels and clinicopathologic factors was examined in 48 patients with esophageal SCC, as were SCC antigen and carcinoembryonic antigen (CEA). RESULTS: Of the 6 cell lines, 5 lines expressed cytokeratin-19 in their cytoplasm and produced soluble cytokeratin-19 fragments. Twenty-three of 48 patients had elevated CYFRA 21-1 levels (>3.5 ng/mL), whereas none of the reference group (consisting of healthy volunteers or patients with benign disease) showed positive levels. The specificity, sensitivity, and accuracy of CYFRA 21-1 were 100%, 47.9%, and 66.7%, respectively. CYFRA 21-1 showed significantly higher sensitivity and accuracy than SCC antigen or CEA (P < 0.05). Univariate analysis revealed that CYFRA 21-1 levels correlated with disease progression (including tumor size, tumor depth, and pTNM stage), resectability, and curability. There was a significant association between the level of CYFRA 21-1 and its intensity of immunohistochemical staining in vitro as well as in vivo. CONCLUSIONS: CYFRA 21-1 appears to be a useful marker for human squamous cell carcinoma of the esophagus.

Adult↗

PubMed1997

Involvement of metabotropic glutamate receptors in Gi- and Gs-dependent modulation of adenylate cyclase activity induced by a novel cognition enhancer NS-105 in rat brain.

The effect of a novel cognition enhancer [(+)-5-oxo-D-prolinepiperidinamide monohydrate] (NS-105) on cAMP formation was investigated in both slices and membranes of the rat cerebral cortex. NS-105 (10(-8)-10(-6) M) inhibited forskolin-stimulated cAMP formation in membranes, however, the compound significantly enhanced the cAMP formation in pertussis toxin-pre-treated membranes, an action that was abolished by cholera toxin. In contrast, in digitonin-permeabilized membranes, NS-105 had no influence on Mn2+-stimulated cAMP formation. Both of the inhibitory and facilitatory actions of NS-105 on cAMP formation were mimicked by a metabotropic glutamate receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and an adrenergic alpha2 agonist UK-14,304, and blocked by a mGluR antagonist 2-amino-3-phosphonopropanoate but not by an alpha2 antagonist yohimbine. In cortical slices, NS-105 (10(-8)-10(-7) M) inhibited forskolin-stimulated cAMP accumulation but enhanced isoproterenol-stimulated cAMP accumulation, as did by a GABA(B) agonist (-)baclofen. On the other hand, (-)baclofen, while it significantly inhibited cAMP accumulation in slices, did no longer inhibit cAMP accumulation, when treated with NS-105 (10(-8)-10(-5) M). Similarly, (-)baclofen-induced inhibition of the cAMP accumulation was reversed by 1S,3R-ACPD and UK-14,304. NS-105 (10(-6)) increased [35S]GTPgammaS binding in the intact but not digitonin-permeabilized cortical membranes, as produced by UK-14,304, although the compound (10(-9)-10(-3) M) had no influence on various neurotransmitter receptor bindings, including alpha2 receptors. These results suggest that NS-105 modulates adenylate cyclase activity by stimulating mGluRs which might coupled to both Gi/Go and Gs.

Adenylate Cyclase Toxin↗

PubMed1997

Differentially expressed MHC class II-associated invariant chain in rat stomach pyloric mucosa with N-methyl-N-nitro-nitrosoguanidine exposure.

Administration of N-methyl-N'-nitro-N-nitrosoguanidine, a glandular stomach carcinogen, at the concentration of 100 microg/ml in drinking water for 8 days induced the appearance of a MHC class II-associated invariant chain in the target organ of stomach pyloric mucosa of male Lewis rats. The up-regulation of the MHC class II-associated invariant chain was revealed by fluorescent differential display analysis, reverse transcription-PCR, Northern blot, and histochemical staining. The appearance of MHC class II and MHC class I was also demonstrated by reverse transcription-PCR and Northern blot. The results suggest the involvement of MHC-controlled immune reactions in chemically-induced stomach carcinogenesis.

Animals↗

PubMed1997

Serotonin increases Na(+)-dependent Ca2+ efflux from bovine adrenal chromaffin cells in culture.

The effect of serotonin (5-hydroxytryptamine, 5-HT) on Ca2+ mobilization in bovine adrenal chromaffin cells in culture was examined. 5-HT (10(-5) M) did not increase secretion of catecholamine, uptake of 45Ca2+ and levels of intracellular free Ca2+ ([Ca/+]i). However, 5-HT (10(-8)-10(-5) M) stimulated the efflux of 45Ca2+ from cultured bovine adrenal chromaffin cells in a concentration-dependent manner. Its stimulatory effect on 45Ca2+ efflux was inhibited by cyproheptadine (a 5-HT1A and 5-HT2 receptor antagonist) or mianserin (a 5-HT2 receptor antagonist). The increase in 5-HT-stimulated 45Ca2+ efflux was dependent on extracellular Na+ concentration, but not extracellular Ca2+ concentration. These results indicate that stimulation of the 5-HT receptors induces extracellular Na(+)-dependent Ca2+ efflux from bovine adrenal chromaffin cells in culture, probably by acceleration of Na+/Ca2+ exchange.

Adrenal Glands↗

PubMed1997

Substratum-dependent and region-specific control of attachment and proliferation of gastrointestinal epithelial cells in primary serum-free culture.

A system for the primary serum-free culture of fetal rat gastrointestinal epithelial cells was used to examine the role of the extracellular matrix (ECM) in the attachment and proliferation of these epithelial cells. Forestomach epithelial cells (FSEC) were able to attach to and proliferate on plastic dishes without a substratum, while glandular stomach epithelial cells (GSEC) and duodenal epithelial cells (DEC) were unable to do so. The presence of a substratum promoted the attachment and proliferation of these epithelial cells. The effects of various components of the ECM differed depending on the type of cell. FSEC attached most efficiently to a substratum of fibronectin, while GSEC did so to laminin. DEC attached more efficiently to type I collagen and fibronectin than to any other substratum. FSEC proliferated most rapidly on laminin, while GSEC and DEC did so on collagen gels. These substrata induced the most efficient attachment and proliferation of FSEC, and they were effective in promoting the attachment and proliferation of GSEC and DEC in decreasing order of efficiency, indicating the existence of a head-to-tail gradient in the response of epithelial cells to substrata. The expression of c-myc mRNA in these cells differed depending upon the substratum on which they were cultured and the mRNA level was well correlated with the extent of the cell proliferation, indicating that the cell proliferation is mediated by c-myc gene expression, which is regulated by cell-ECM interactions. The results of the present study demonstrate that proliferation of gastrointestinal epithelial cells is regulated region-specifically not only by soluble factors but also by insoluble components of the ECM.

Animals↗

PubMed1997

Histologic comparison of tibial articular surfaces against rigid materials and artificial articular cartilage.

After endoprosthetic replacement of the femoral head, marked pathologic changes of the acetabulum, such as penetration and ulceration, often occur. These changes are caused by the rigid material surface properties of the prosthesis and the lack of damping effects. In this study, we compared the time-dependent changes of tibial articular surfaces with three kinds of femoral implant under loading conditions in dogs. Marked pathologic changes of the menisci and tibial articular cartilage were observed from 8 weeks after implantation with hard material implants, whereas the tibial joint surface against an artificial articular cartilage was still intact 24 weeks postoperatively. These results showed clearly that marked pathologic changes of the articular cartilage against rigid materials occurred and were caused by the surface properties of the counterfaces and high friction coefficients of ceramic and metal materials used.

Animals↗

PubMed1997

Pelvic exenteration for the treatment of gynecological malignancies.

Twenty-three patients undergoing pelvic exenteration for primary and recurrent gynecological malignancies from 1976 to 1994 are reported. Fifteen patients underwent total pelvic exenteration, 3 underwent anterior exenteration, and 5 underwent a posterior procedure. Eight patients had exenteration as their primary treatment (primary group), and 15 underwent exenteration as secondary treatment (recurrent group). In the primary group, two patients developed recurrence and died of it at 6 and 20 months after operation. Five patients are still being followed up and are alive without disease. Four of these 5 patients have survived more than 5 years. In the recurrent group, 12 patients were followed up and three died of complications during the early years. Seven patients died of cancer with the mean survival time of 16.6 months. The mean age, average operating time, and mean blood loss in the primary and recurrent groups were 57 vs. 53 years, 8 hours and 20 min vs. 8 hours and 10 min, and 4,120 vs. 4,190 ml, respectively. The overall cumulative 5-year survival rate was 34.7%, being 68.6% in the primary group and 16.7% in the recurrent group. It is noteworthy that the 5-year survival rate was 51.3% in the patients who had surgical margins free of disease. In conclusion, pelvic exenteration should be considered an acceptable therapeutic option when appropriately selected.

Adult↗

PubMed1997

A novel cognition enhancer NS-105 modulates adenylate cyclase activity through metabotropic glutamate receptors in primary neuronal culture.

The effect of (+)-5-oxo-D-prolinepiperidinamide monohydrate (NS-105), a novel cognition enhancer, on adenylate cyclase activity was investigated in cultured neurons of the mouse cerebral cortex. NS-105 (10(-7) and 10(-6) M) inhibited forskolin-stimulated cyclic AMP formation, an action that was dependent on pertussis toxin-sensitive G proteins. Conversely, in pertussis toxin-pretreated neurons, NS-105 (10(-7)-10(-5) M) significantly enhanced the forskolin-stimulated cyclic AMP formation, and this action was completely reversed by cholera toxin. A metabotropic glutamate receptor agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S, 3R-ACPD) produced similar bi-directional actions on the cyclic AMP formation. Both of these inhibitory and facilitatory actions of NS-105 and 1S, 3R-ACPD were blocked by L(+)-2-amino-3-phosphopropinoic acid (L-AP3). NS-105 (10(-6) M) and 1S, 3R-ACPD (10(-4) M) significantly enhanced isoproterenol- and adenosine-stimulated cyclic AMP formation. The enhancement of such Gs-coupled receptor agonists-stimulated cyclic AMP formation was also produced by quisqualate but not by L(+)-2-amino-4-phosphonobutanoate (L-AP4). The phosphoinositides hydrolysis was enhanced by 1S, 3R-ACPD (10(-4) M) but not by NS-105 (10(-6) M), however, 1S, 3R-ACPD-induced increase in phosphoinositides turnover was attenuated by NS-105. These findings suggest that NS-105 stimulates metabotropic glutamate receptor subclasses that are coupled both negatively and positively to adenylate cyclase, but it acts as an antagonist at the receptor subclasses that are linked to phosphoinositides hydrolysis.

Adenylate Cyclase Toxin↗