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Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 307 records · Page 17Linked to original sources
PubMed1993

Interaction between a phorbol ester and dopamine DA1 receptors on vascular smooth muscle.

The interaction between dopamine DA1 receptors and a phorbol ester was studied to elucidate the role of protein kinase C in the response of this receptor. The in vitro binding of [3H]Sch 23390 to DA1 receptor sites on vascular smooth muscle cells was saturable. The extent of [3H]Sch 23390 binding to phorbol ester-treated cells was increased without any change in the dissociation constant. The production of adenosine 3',5'-cyclic monophosphate (cAMP) in response to DA1 receptor stimulation was enhanced by preincubation of vascular smooth muscle cells with the phorbol ester for 4 h. However, no enhancement was observed when the medium used for preincubation was supplemented with a protein kinase C inhibitor. Direct stimulation of stimulatory guanine nucleotide-binding regulatory protein with 5-guanylylimidodiphosphate and direct stimulation of adenylate cyclase with forskolin produced no significant differences in cyclase levels between phorbol ester-treated and untreated cells. These results suggest that activation of protein kinase C triggers an increase in the membrane expression of DA1 receptors, thereby enhancing receptor-coupled cAMP generation.

Adenylyl Cyclases↗
PubMed1993

Natriuretic peptides inhibit mesangial cell production of endothelin induced by arginine vasopressin.

The present study examined the effects of atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP, respectively) on endothelin-1 (ET-1) secretion after stimulation with arginine vasopressin (AVP), using cultured rat glomerular mesangial cells. AVP stimulated immunoreactive (ir) ET-1 secretion in a concentration-dependent manner via a receptor-mediated process. Rat ANP-(1-28) and rat BNP-45 potently inhibited this stimulated secretion in a concentration-dependent manner. Inhibition by ANP and BNP of AVP-stimulated ET-1 secretion was paralleled by an increase in the medium level of guanosine 3',5'-cyclic monophosphate (cGMP). The addition of a cGMP analogue, 8-bromo-cGMP, reduced the stimulated ET-1 secretion. CNP was much less effective than rat ANP-(1-28) or rat BNP-45 with respect to inhibiting irET-1 secretion and increasing cGMP levels. High-performance liquid chromatography indicated that the major component of irET-1 in the culture medium corresponds to ET-1-(1-21). These findings indicate that AVP stimulates ET-1 secretion in cultured rat mesangial cells and that rat ANP and BNP inhibit this stimulated secretion, probably through a cGMP-dependent process.

Animals↗
PubMed1993

Heparin regulates endothelin production through endothelium-derived nitric oxide in human endothelial cells.

Heparin shows blood pressure lowering effect in hypertensive patients and animal models. The present study examined the effect of heparin on vasoconstrictor endothelin-1 (ET-1) production in cultured human umbilical vein endothelial cells (ECs) to elucidate the mechanism of antihypertensive effect of heparin. Heparin suppressed both basal and thrombin-stimulated ET-1 mRNA expression paralleled with a decrease in ET-1 peptide release in a dose-dependent manner. Heparin concomitantly enhanced nitric oxide (NO) formation measured by NO2/NO3 levels and cGMP production in ECs. These enhancements were more marked when ECs were stimulated by thrombin. However, these heparin's effects were blunted in the presence of endothelium-derived nitric oxide (EDNO) synthesizing inhibitor NG-monomethyl L-arginine. Therefore, these results suggest that suppression of ET-1 production by heparin is EDNO mediated.

Analysis of Variance↗
PubMed1993

Primary Sjögren's syndrome with subcortical dementia.

A 48-year-old man with primary Sjögren's syndrome (P-SS) developed subcortical dementia, characterized by forgetfulness, poor attention and concentration, slowness of thought process, difficulty to manipulate acquired knowledge, introversive and hostile personality change and inactivity. These were improved by corticosteroid treatment. Magnetic resonance imaging (MRI) revealed small lesions in the subcortical and periventricular white matter. An electroencephalogram (EEG) revealed short runs of theta activities in bilateral parietal areas. Latency of P300 shortened in accordance with clinical improvement. These findings suggest that the cognitive and neuropsychiatric manifestations in P-SS are included in a spectrum of organic brain dysfunction and are treatable.

Brain↗
PubMed1993

Clinical characteristics and hearing recovery in perilymphatic fistulas of different etiologies.

Clinical features and hearing recovery were compared between three types of perilymphatic fistula groups; surgically confirmed (PLF-conf, n = 16), suspected (PLF-susp, n = 24) and traumatic (trauma-PLF, n = 11). Initial average hearing level was best in the PLF-susp group (50.9 dBHL), followed by the trauma-PLF (55.7 dBHL) and PLF-conf (59.7 dBHL) groups, though the difference was not significant (ANOVA, p > 0.05). Of 51 patients, 27 cases were operated on and fistula was confirmed in 19 ears (70.4%). Conservative treatment, including bed rest and medication, was given to all patients. After the treatment, meaningful hearing recovery was obtained only at 1 kHz in the PLF-conf group (paired t-test, p < 0.05). However, significant recovery was seen at all frequency ranges (0.125-8 kHz) in the PLF-susp group (average, 16.8 dB; p < 0.01), while hearing improvement was intermediate for the trauma-PLF group. The initial hearing level and the period until the start of treatment strongly correlated with the final hearing level. Although 27 patients (47%) complained of dizziness, the prognosis for vertigo is excellent as noted by other authors. It was concluded that if conservative treatment is started early for PLF patients with mild hearing loss, hearing recovery can be ensured.

Adult↗
PubMed1993

Effects of sodium and chloride ions on blood pressure in deoxycorticosterone acetate-treated rats.

The effects of sodium (Na+) and chloride ions (Cl-) on blood pressure were studied in rats treated with deoxycorticosterone acetate (DOCA). Four groups were prepared, each consisting of male Wistar rats that underwent heminephrectomy and administration of DOCA: the control group was maintained with tap water, the NaCl group with tap water containing 1% sodium chloride, the NaCit group with tap water containing 1.67% sodium citrate (including an equivalent dose of Na+ to 1% NaCl), and the ChoCl group with tap water containing 1.15% choline chloride (including an equivalent dose of Cl- to 1% NaCl). The time-course of systolic blood pressure showed only slight change in blood pressure in the control and ChoCl groups, and in the NaCl and NaCit groups. The rotational correlation time, an index of the fluidity of erythrocyte membrane, with spin-labeling of 16-doxyl-stearic acid, was significantly (p < 0.05) higher in the NaCl and NaCit groups than in the control group, indicating an increase in the membrane fluidity, i.e., membrane fragility. The sodium, potassium ions-activated adenosine triphosphatase (Na+,K(+)-ATPase) activity of the erythrocyte membrane was decreased to 22% (P < 0.01) and 24% (P < 0.01) in the NaCl and NaCit groups, respectively, compared with the control groups; this activity was decreased to 43% in the ChoCl group (P < 0.05). The Ca(2+)-ATPase activity showed similar changes. In contrast, there were no marked differences in the erythrocyte electrolyte level between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Successful treatment with salazosulfapyridine in cases sister and brother with ankylosing spondylitis].

Cases of half sister and brother with ankylosing spondylitis (AS) in whom drug therapy with salazosulfapyridine (SASP) showed excellent effect were reported. A 31 year-old female and her 28 year-old brother visited the out-patient clinic because of low back pain which lasted for the past 14 and 9 years, respectively. HLA examination revealed positive B27 antigen, X-ray and CT examination clarified sacroiliitis (grade III) in both patients. The diagnosis of AS was made and drug therapy with several non-steroidal anti-inflammatory drugs was started, but had little effects in both patients. After combination therapy with 2 g/day of SASP and 20 mg/day of tenoxicam, both clinical and laboratory abnormalities disappeared within a month. It is well known that AS has hereditary characteristic, nevertheless there were only a couple of case reports which showed familial occurrence of AS and there was no report showing the effectiveness of SASP for the drug therapy of AS in Japan. The patients reported here were the first cases with AS occurred in sister and brother in Japan. We emphasized SASP might be a drug which is useful for the treatment of AS.

Adult↗
PubMed1993

Stimulation of nerve growth factor synthesis/secretion in mouse astroglial cells by coenzymes.

We examined the effect of coenzymes such as PQQ, pyrroloquinoline quinone; TOPA, 3-(2,4,5-trihydroxyphenyl)-DL-alanine, and lipoic acid on nerve growth factor (NGF) synthesis in mouse astroglial cells, BALB c/3T3 cells, and WS-1 cells in culture. These coenzymes had a stimulating effect on NGF synthesis without causing cytotoxicity. Especially PQQ showed the strongest activity of promoting NGF synthesis in astroglial cells, whereas lipoic acid had the strongest effect on BALB c/3T3 cells. The activity may not due to the catechol ring or 1,4-benzoquinone ring, but due to the oxidative or reductive activity. These results suggest that these coenzymes may play a role in NGF synthesis and neuronal survival through the stimulating effect of the NGF synthesis in brain and such compounds are good candidates as NGF inducers.

3T3 Cells↗
PubMed1993

[Pseudo-false aneurysm of the left ventricle perforated into the right ventricle--a case report].

A case of pseudo-false aneurysm of the left ventricle perforated into the right ventricle was reported. The patient was 60-year-old male with acute inferior myocardial infarction. Echocardiography showed a thin wall cavity on the apex of the right ventricle. Communication between the left ventricle and the right ventricle was detected on pulsed Doppler echocardiography. Surgery revealed a pseudo-false aneurysm in the free wall of the right ventricle communicating to both ventricles. We emphasize the importance of preoperative morphological and hemodynamic evaluation with Doppler echocardiography in the case of post-myocardial infarction ventricular septal perforation.

Heart Aneurysm↗
PubMed1993

[An autopsy case report of hemolytic uremic syndrome after allogeneic bone marrow transplantation].

A 27-year-old male with acute lymphoblastic leukemia (L2) received allogeneic bone marrow transplantation on June, 7 1990. He was conditioned with cyclophosphamide, Ara-C and total body irradiation. GVHD prophylaxis consisted of cyclosporin and short term methotrexate. He was diagnosed as having hemolytic uremic syndrome (HUS) on the basis of microangiopathic hemolytic anemia, thrombocytopenia and renal dysfunction on day 224. Cyclosporin was discontinued and FFP was transfused and plasma exchange was performed. He died of heart failure and sepsis on day 582. Autopsy confirmed the findings of HUS.

Adult↗
PubMed1993

[Case report of metastatic cutaneous angiosarcoma causing bilateral pneumothorax].

The patient was a 72-year-old man who underwent operation for bilateral pneumothorax due to rupture of cystic lung lesions. Two months after the operation, intrathoracic bleeding redeveloped. The patient developed a tumor on his head. Pathological examination of the scalp lesion revealed cutaneous angiosarcoma. A biopsy of thickened pleura showed that the bleeding was due to pleural metastatic angiosarcoma of the skin. The multiple cystic lesions were considered to be metastases of angiosarcoma. We conclude that pneumothorax or hemothorax in the elderly should be differentiated from malignant metastatic lung tumor. Cystic lung lesions should be considered as possible metastatic angiosarcoma from the skin.

Aged↗
PubMed1992

Hydroxyl radical production by H2O2 plus Cu,Zn-superoxide dismutase reflects the activity of free copper released from the oxidatively damaged enzyme.

To elaborate the catalytic activity of Cu2+ of Cu,Zn-superoxide dismutase (SOD) in the generation of hydroxyl radical (.OH) from H2O2, we investigated the mechanism of inactivation of alpha 1-protease inhibitor (alpha 1-PI), mediated by H2O2 and Cu,Zn-SOD. When alpha 1-PI was incubated with 500 units/ml Cu,Zn-SOD and 1.0 mM H2O2, 60% of anti-elastase activity of alpha 1-PI was lost within 90 min. ESR spin trapping using 5,5-dimethyl-1-pyrroline N-oxide showed that free .OH was indeed generated in the reaction of Cu,Zn-SOD/H2O2; this was substantiated by the almost complete eradication of .OH by either ethanol or dimethyl sulfoxide accompanied by the generation of carbon-centered radicals. .OH production and alpha 1-PI inactivation in the H2O2/SOD system became apparent at 30 min or later. Dimethyl sulfoxide and 5,5-dimethyl-1-pyrroline N-oxide protected inactivation of alpha 1-PI significantly in this system, indicating that alpha 1-PI inactivation was mediated by .OH. SOD activity decreased rapidly during the reaction with H2O2 for the initial 30 min. Time-dependent changes in the ESR signal of SOD showed the destruction of ligands for Cu2+ in SOD by H2O2 within this initial period. Thus we conclude that inactivation of alpha 1-PI is mediated in the H2O2/Cu,Zn-SOD system via the generation of .OH by free Cu2+ released from oxidatively damaged SOD.

Cyclic N-Oxides↗
PubMed1992

Mitogen-induced tyrosine phosphorylation of 41 kDa and 43 kDa proteins. Potential role in integrating multiple mitogenic signalling pathways.

We have examined the possible involvement of pertussis toxin (PT)-sensitive GTP-binding protein and protein kinase C (PKC) in mitogen-induced tyrosine phosphorylation of the 41 kDa and 43 kDa cytosol proteins using PT-pretreated (inactivation of PT-sensitive GTP-binding protein) or phorbol 12-myristate 13-acetate (PMA)-pretreated (depletion of PKC) mouse fibroblasts. The effects of the inactivation of PT-sensitive GTP-binding protein and the depletion of PKC on mitogen-stimulated tyrosine phosphorylation of the proteins were similar and varied significantly and systematically in response to growth factors. The important finding was that such inhibitory effects of PT-sensitive GTP-binding protein inactivation and PKC depletion on protein tyrosine phosphorylation induced by each mitogen always correlated well with their inhibitory effects on each mitogen-stimulated DNA synthesis. Although the extent of platelet-derived-growth-factor-induced phosphorylation of the proteins was decreased to approx. 50% in PT- and PMA-pretreated cells compared with native cells, protein phosphorylation itself was not affected and occurred at identical sites on each protein in native, PT- and PMA-pretreated cells. These results suggest that: (1) 41 kDa and 43 kDa proteins are located downstream of PT-sensitive GTP-binding protein and PKC in the mitogenic signalling pathways of growth factors, (2) protein phosphorylation occurs via a cascade of events which includes the activation of the receptor tyrosine kinases, PKC and other unidentified kinase(s) which directly participate(s) in the phosphorylation of the 41 kDa and 43 kDa proteins, and (3) their phosphorylation may play an important role in integrating multiple mitogenic signalling pathways.

3T3 Cells↗
PubMed1992

Biphasic activation of two mitogen-activated protein kinases during the cell cycle in mammalian cells.

We studied mitogen-activated protein kinase (MAPK) activities during the cell cycle of Chinese hamster ovary (CHO) cells using site-specific antibodies against extracellular signal-regulated kinase-1, a 44-kDa MAPK (Boulton, T.G., Yancopoulos, G.D., Gregory, J.S., Slauer, C., Moomaw, C., Hsu, J., and Cobb, M.H. (1990) Science 249, 64-67). These antibodies detected two distinct MAPKs (44- and 42-kDa MAPKs) in CHO cells. CHO cells were arrested at metaphase in the M phase by treatment with nocodazole, and activities of MAPKs were analyzed at specific time points after release from arrest. Immune complex kinase assay and renaturation and phosphorylation assay in substrate-containing gel revealed that both 44- and 42-kDa MAPKs had activities in the G1 through S and G2/M phases and were activated biphasically, in the G1 phase and around the M phase. MAPKs were inactivated in metaphase-arrested cells. The amount of MAPKs did not change significantly in the cell cycle. In the G1, S, and G2/M phases, MAPKs were phosphorylated on both tyrosine and threonine residues and dephosphorylated in metaphase-arrested cells. Our data suggest that MAPKs may play some role in the cell cycle other than G0/G1 transition.

Amino Acid Sequence↗
PubMed1992

Hepatocyte growth factor rapidly induces the tyrosine phosphorylation of 41-kDa and 43-kDa proteins in mouse keratinocytes.

We have examined the hepatocyte growth factor (HGF)-mediated changes in protein-tyrosine phosphorylation in mouse keratinocytes (PAM-212) and canine kidney epithelial cells (MDCK). In PAM-212 cells HGF and epidermal growth factor, both of which stimulated the DNA synthesis, rapidly induced the tyrosine phosphorylation of two 41-kDa and two 43-kDa proteins: increased tyrosine phosphorylation of those proteins has been commonly observed when quiescent fibroblasts are stimulated with a variety of mitogenic agents. In contrast, HGF did not stimulate the DNA synthesis but induced cell dissociation in MDCK cells; under this condition, increased tyrosine phosphorylation of the 41-kDa and 43-kDa protein was not observed. A possible role of the increased tyrosine phosphorylation of 41-kDa and 43-kDa protein in the signaling pathway of HGF is discussed.

Amino Acids↗
PubMed1992

Generation of hydroxyl radical from linoleic acid hydroperoxide in the presence of epinephrine and iron.

When linoleic acid hydroperoxide was reacted with ferrous iron, the electron spin resonance signals characteristic of the spin adduct of 5,5-dimethyl-1-pyrroline-N-oxide and the hydroxyl radical were detected. Although the signals were not detected with the hydroperoxide and ferric iron, they were actually found if epinephrine was added, indicating that the hydroxyl radical could be generated from the hydroperoxide upon reduction of the latter with ferrous iron formed by epinephrine. The possible generation of the hydroxyl radical from lipid peroxides in vivo was discussed from the viewpoint of pathogenesis of lipid peroxide-related diseases.

Cyclic N-Oxides↗
PubMed1992

Metabolism of 15N-ammonia in patients with cirrhosis: a three-compartmental analysis.

Urinary 15N-ammonia and 15N-urea were measured by gas chromatography-mass spectrometry after the intravenous administration of 15N-ammonia (0.2 mumol/kg/hr) to 6 volunteers and 11 patients with cirrhosis. Urinary 15N-nitrogen excretion as ammonia and urea was measured during the 210-min infusion period, and urea synthesis and ammonia conversion to amino acids were analyzed with a three-compartment model using the nonlinear least-squares method. The rate of urea synthesis in control subjects was 14.1 +/- 1.2 mg/kg/hr (mean +/- S.E.M.), and in cirrhotic patients it was 11.0 +/- 3.2 mg/kg/hr. The cirrhotic group was divided into those with compensated cirrhosis (Child class A patients) and those with decompensated cirrhosis (Child classes B and C patients), and the rates of urea synthesis for these groups were 14.5 +/- 1.5 and 8.9 +/- 1.6 mg/kg/hr, respectively. The difference between decompensated cirrhotic patients and control subjects was statistically significant (p less than 0.001). The percentage of ammonia reutilization of a given dose of 15N-ammonia was 75.9% +/- 2.4% in compensated cirrhotic patients and 82.9% +/- 3.6% in decompensated cirrhotic patients (p less than 0.05). Fasting venous ammonia levels correlated inversely with urea synthesis (p less than 0.001) and correlated positively with ammonia reutilization (p less than 0.05). These results are consistent with a decreased capacity to synthesize urea and an increased capacity to convert ammonia to amino acids in chronic liver failure.

Aged↗