Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 163 records · Page 9Linked to original sources

PubMed1998

Polylysine-induced rapid Ca2+ release from cardiac sarcoplasmic reticulum.

The rapid kinetics of polylysine-induced Ca2+ release from cardiac sarcoplasmic reticulum (SR) was assessed in combination with its effect on ryanodine binding. SR vesicles were isolated from canine cardiac SR. The time course of SR Ca2+ release was continuously monitored by a stopped-flow apparatus, and [3H]ryanodine binding was done by using the filtration method. The initial rate of polylysine-induced Ca2+ release from cardiac SR revealed different concentration dependence from those observed in skeletal SR. The initial rate peaked at 0.11 microM, followed by a decrease at higher concentrations in skeletal SR, whereas it increased to 3.7 microM in cardiac SR. The [3H]ryanodine binding was also stimulated by polylysine with an identical parallelism with Ca2+ release in terms of polylysine concentration dependence. Thus we demonstrated that the cardiac SR Ca2+ release channel is sensitive to activation by polylysine and that there is a difference in the concentration dependence of polylysine-induced activation of cardiac and skeletal SR Ca2+ release channels.

Animals↗

PubMed1998

Effects of balanced vasodilator, flosequinan, on aortic impedance in failing heart.

An arteriovenous vasodilator, flosequinan, has been shown to be effective for the treatment of acute heart failure. However, little is known as to its effect on aortic impedance, which is known to be a proper and precise expression of left ventricular (LV) afterload. To evaluate the acute cardiovascular effect of flosequinan in failing heart, we administered flosequinan intravenously to seven dogs with cardiac failure produced by an infusion of carbon powder (20-50 microm in diameter) into left main trunks of coronary artery. The LV-pump function was severely impaired after intracoronary injection of carbon powder, as evidenced by the findings that cardiac output, circumferential shortening velocity (mean Vcf), and peak +dP/dt of LV pressure were all decreased, associated with a significant increase in LV end-diastolic pressure. Flosequinan (0.9 mg/kg, i.v.) increased cardiac output by 28%, mean Vcf by 44%, and peak +dP/dt by 24%, whereas it decreased total systemic resistance by 32%, time constant of LV pressure decay by 22%, and LV end-diastolic pressure by 18%. Moreover, flosequinan substantially decreased the pulsatile components of LV afterload (i.e., characteristic impedance by 11% and arterial wave reflection coefficient by 45%). Thus flosequinan exerted not only positive inotropic but also positive lusitropic effects, in association with a significant reduction of both pulsatile and steady components of LV afterload, contributing to an improvement of LV-pump function in acute cardiac failure.

Animals↗

PubMed1998

Effects of hypertonic saline and dextran 70 on cardiac contractility after hemorrhagic shock.

OBJECTIVE: The effects of a bolus of 7.5% NaCl-6% dextran 70 (HSD) on cardiac contractility were evaluated in anesthetized sheep with hemorrhagic shock. BACKGROUND: HSD has been shown to be effective at resuscitation in cases of hypovolemia caused by hemorrhage. Common hemodynamic findings after the injection of HSD in hemorrhagic shock are the restoration of cardiac output, increased blood pressure, and improvement of peripheral circulation. Some mechanisms by which HSD maintains circulation in hemorrhagic shock have been proposed: rapid shift of fluid from intracellular to extracellular space, improved peripheral perfusion, and increased cardiac contractility. Conflicting data exist, however, regarding the positive effect of HSD on cardiac contractility after hemorrhagic shock. METHODS: Hemorrhagic shock was induced by shedding mean blood volume of 31.4 mL/kg, and mean blood pressure was maintained at 50 mm Hg for 30 minutes. The HSD group (n = 6) received HSD (4 mL/kg), and the saline group (n = 6) received normal saline (40 mL/kg) after shock. Cardiac functions were measured in both groups using the left ventricular end-systolic pressure-volume relationship and preload recruitable stroke work during the experimental period: before shock, immediately after the resuscitation, and 2 hours after resuscitation. RESULTS: Hemodynamic parameters in both groups demonstrated similar changes throughout the experimental period without significant difference between the two groups. Not only the slopes of end-systolic pressure-volume relationship and preload recruitable stroke work but also their placements did not result in any significant differences between the groups. CONCLUSION: HSD seems to be an effective resuscitation fluid after hemorrhagic shock because the volume required to maintain circulation is smaller than that of normal saline. Our data, however, show that HSD does not enhance cardiac contractility after hemorrhagic shock.

Animals↗

PubMed1998

New evidence that the Tyr-157 and Tyr-159 residues of staphylococcal exfoliative toxin B are essential for its toxicity.

To determine the active site of exfoliative toxin B (sETB) of Staphylococcus aureus, the etb gene was cloned from an S. aureus SU strain obtained from a patient with impetigo. We prepared a frame shift mutant protein from a recombinant plasmid with a BglII linker inserted into the Tyr-155 codon of the ETB gene (pETB/BglIIL). The recombinant mutant protein (ETB/BglIIL) obtained from Escherichia coli containing pETB/BgIIIL showed no toxicity in neonatal mice and no agglutination activity. The 20-kDa ETB/BglIIL contained 185 amino acid residues. Site-directed mutagenesis was used to introduce mutations at either Tyr-155, Tyr-157, Tyr-159, or Tyr-162. Substitution of any of the Tyr residues decreased exfoliative activity compared with that of native sETB (4,000 EU/ml). Substitution of Tyr-155 with a Phe (ETBYN155) decreased activity 5-fold (800 EU/ml). Substitution of Tyr-157 with Leu (ETB/Y157) decreased activity 80-fold (50 EU/ml) and decreased agglutination titer 5-fold compared with that of native sETB (400,000). Substitution of Tyr-159 with Leu (ETB/Y159)decreased activity 4-fold (1,000 EU/ml). When both Tyr-157 and Tyr-159 were mutated (ETB/Y157-159), both toxicity and antigenicity were completely lost. On an immunodiffusion test, ETBNY157 showed a faint precipitation line, but ETB/BglIIL and ETB/Y157-159 had no activity, showing that the Tyr-157 and Tyr-159 residues are essential for the toxicity and antigenicity of ETB.

Amino Acid Sequence↗

PubMed1998

[Effect of shikonin and alkannin on hydroxyl radical generation system concerned with iron ion].

The effects of shikonnin (SK) and its optical isomer alkannin (AK) on the hydroxyl radical (HO.) generation system including iron ions were evaluated using the spin trap method by ESR spectroscopy. 5,5-Dimethyl-1-pyrroline-1-oxide (DMPO) was used as a spin trap agent and HO. was generated by a reaction between an iron ion and hydrogen peroxide, which is called Fenton reaction system. SK inhibited the HO. spin adduct (DMPO-OH) yielded in a dose-dependent manner. In this effect no difference was observed between SK and AK. When different concentrations of DMPO were used for the confirmation of its competitive reaction, no difference was also observed in the concentration of SK required to reduce the amount of the DMPO-OH by 50% (ID50). These findings suggested that the inhibitory effect of SK against the thus yielded DMPO-OH was not generated by the scavenging for HO., but by the inhibition on the Fenton reaction system. The mechanism of the inhibition on this system may be based on the formation of a complex between SK and the iron ion. The molar ratio of SK to the iron ion in the complex was considered 2 to 1 (2:1), because the concentrations of the observed ID50 and the used iron ion exhibited the same value. In addition, the same result was also obtained from the study using spectroscopic analysis.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

Cloning of genomic DNA of Rhizopus niveus lipase and expression in the yeast Saccharomyces cerevisiae.

Genomic DNA encoding Lipase I was cloned from Rhizopus niveus strain IFO4759. For expression of this gene in S. cerevisiae, DBY746 was transformed with YEp352PLipS, which had the cloned lipase gene under the control of a PGK promoter. This strain secreted the lipase at a high level (350 U/ml). The strain ND-12B was produced by a mating of DBY746, harboring YEp352PLipS, and NA74-3A, and dissection of asci. This new strain secreted the lipase up to 530 U/ml. Moreover, the lipase was produced most effectively in a medium containing Bacto-yeast extract, soy-peptide, and sucrose.

Blotting, Western↗

PubMed1998

Primitive neuroectodermal tumor in the spinal epidural space--case report.

A 4-year-old boy presented with a rare case of an epidural tumor causing compression of the thoracic spinal cord manifesting as rapid worsening of gait disturbance. The tumor was grossly totally resected, and radiotherapy and chemotherapy were subsequently administered. The histological diagnosis was primitive neuroectodermal tumor. He has been free of recurrence for more than 6 years. Early tumor resection followed by chemotherapy and irradiation is recommended for patients with primitive neuroectodermal tumor and unstable symptoms.

Chemotherapy, Adjuvant↗

PubMed1998

[A case of relapsing polychondritis with IgA nephropathy].

We report a case of a 37-year-old man with relapsing polychondritis and IgA nephropathy. He visited our hospital with high fever and the swelling of his ears and eyelids. His symptoms and the results of the biopsy of his right auricle fulfilled the Damiani's criteria. Laboratory examination on admission showed an increase of serum IgA level, a presence of immune complex, remarkable hematuria (grade III) and proteinuria (grade II). Most of his symptoms were improved by the administration of antibiotic and NSAIDs, however, urinary findings still remained unchanged. The biopsy of his right kidney led to a diagnosis of IgA nephropathy (group II). Although relapsing polychondritis is known to associate rarely with renal involvement, it is very rare to associate with IgA nephropathy. This case indicates that immune disorders including IgA nephropathy should be investigated in patients with relapsing polychondritis.

Adult↗

PubMed1998

Mesencephalic projections from superficial and deep laminae of the medullary dorsal horn.

The mesencephalic projection pattern of axons arising from the medullary dorsal horn (MDH) was studied on the basis of axonal transport of Phaseolus vulgaris Leucoagglutinin (PHA-L). After large injections of PHA-L into both the superficial and deep laminae of the MDH, labeled fibers were observed in the anterior pretectal area (ATP), internal gray matter of the superior colliculus (InG), and rostral linear raphe nucleus (RLi) in the contralateral mesencephalon, and also in the ipsilateral parabrachial nucleus (PBA). Restriction of PHA-L to only the superficial laminae resulted in heavy axon labeling and varicosity in the APT and little labeling in the lateral part of the InG of the contralateral mesencephalic nuclei and the dorsal part of the ipsilateral PBA. On the other hand, after injections into the deep laminae, labeled axons were distributed mainly in the contralateral InG and RLi. Therefore, it is concluded that there are two different major pain pathways from the superficial and deep laminae of the MDH to the mesencephalic nuclei, processing nociceptive information in the trigeminal system.

Animals↗

PubMed1998

Changes in muscle sympathetic nerve activity and effect of breathing maneuvers during microgravity induced by parabolic flight in humans.

UNLABELLED: This study aimed to clarify how muscle sympathetic nerve activity (MSNA) in humans, which plays an important role in blood pressure control against gravity, is altered under microgravity (microG) conditions, and how the MSNA change is modified by breathing maneuvers. Ten subjects seated themselves in a jet aircraft with their knees extended. MSNA was recorded microneurographically from the left tibial nerve with simultaneous monitoring of ECG, blood pressure, respiration, and intrathoracic blood volume estimated by the impedance method during parabolic flight in a jet aircraft. In half of the parabolas, their respiration was controlled at 0.25 Hz by a metronome. RESULTS: MSNA was enhanced under hypergravity just before microG entry, and immediately suppressed by microG induced by parabolic flight. The suppression was more marked with controlled than with uncontrolled respiration (51.6 +/- 7.2 vs 82.8 +/- 2.5%, mean +/- SE, 1G=100%). MSNA changes during microG correlated significantly to changes in blood pressure and intrathoracic blood volume. The blood pressure fall 10 to 15 sec after microG entry was less prominent with controlled than with uncontrolled respiration. We conclude that changes in arterial blood pressure and intrathoracic blood volume modulate MSNA during microG induced by parabolic flight, depending largely on breathing maneuvers.

Adult↗

PubMed1998

[A case of bilateral infraoptic course of ACA associated with multiple cerebral artery aneurysms].

Infraoptic course of anterior cerebral artery (ACA) is a rare cerebral vascular anomaly frequently associated with intracranial aneurysm. A 58-year-old woman suffered, subarachnoid hemorrhage due to aneurysmal rupture. Carotid angiography revealed multiple aneurysms and bilateral infraoptic course of ACA. Usual A1 segments were not visualized on both sides. These findings were also confirmed by craniotomy. Only 46 cases have been reported including ours. In this paper, we reviewed previously reported cases and the cause of aneurysm formation was discussed.

Cerebral Arteries↗

PubMed1998

[Gamma-heavy chain disease associated with MALT lymphoma of the duodenum].

We report a case of a 63-year-old woman with gamma heavy chain disease (HCD) associated with mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum. She was suffering from drug-resistant tonsillitis with high fever. Examination on admission showed leukocytopenia and thrombocytopenia. Bone marrow aspirate revealed granulocytosis and a hypocellular marrow with no increase in plasma cells or atypical lymphocytes. Serum electrophoresis disclosed, in addition to hypogamma-globulinemia, an abnormal band due to the presence of gamma HCD protein. This abnormal protein was a molecular weight of approximately 40 kd as determined by Western blots technique, and belonged to the IgG1 subclass as determined by ELISA with monoclonal antibodies against IgG. An endoscopic examination of the patient's duodenum found a small tumorous lesion, which was confirmed pathologically to be MALT lymphoma. HCD is known to be associated with lymphoproliferative diseases. In this case, gamma HCD had developed as a secondary complication of MALT lymphoma. gamma HCD associated with MALT lymphoma of the duodenum is rare in the literature.

Biomarkers↗

PubMed1997

Effect of a protein phosphatase inhibitor, okadaic acid, on thrombomodulin expression in cultured human umbilical vein endothelial cells.

We examined the effects of okadaic acid, a potent specific inhibitor of protein phosphatases 1 and 2A, on the expression of thrombomodulin (TM), a cell surface anti-thrombotic glycoprotein, on cultured human umbilical endothelial cells. Okadaic acid (2.5-10 nM) significantly increased TM antigen levels in parallel with its cofactor activity for thrombin-dependent protein C activation. Incubation of cells with 10 nM okadaic acid for 18 h induced an approximately 240% up-regulation of TM antigen levels that was accompanied by an increase in TM mRNA levels. Co-incubation of cells with okadaic acid and dibutyryl cyclic AMP further increased TM antigen levels. Furthermore, the effect of cAMP on TM expression was augmented by the pretreatment of cells with 10 nM okadaic acid for 18 h. These results provide evidence for the involvement of protein phosphatase in the cellular regulatory mechanisms for TM expression, which is distinct from that by cAMP.

Blotting, Northern↗

PubMed1997

Altered cardiac mechanism and sarcoplasmic reticulum function in pressure overload-induced cardiac hypertrophy in rats.

Cardiac sarcoplasmic reticulum (SR) sequesters Ca2+ and plays a crucial role in the regulation of intracellular Ca2+. Its functional properties are central to the excitation-contraction (E-C) cycle of cardiac muscle. In this study, we examined the hypothesis that alterations in SR function occur during the development of hypertrophy of the left ventricle (LV) induced in rats by pressure overload secondary to abdominal aortic coarctation. Ten days, 4 and 8 weeks after the operation, hemodynamic parameters were measured using a catheter-tip manometer. The SR vesicles of hypertrophic LV (group A) and sham-operated LV (group S) at each stage were used to study Ca2+ release and uptake, and to characterize the ryanodine receptor. Moderate hypertrophy was observed in group A even at the earliest stage. Systolic LV pressure and peak +dP/dt were significantly increased in group A. There were no significant change in diastolic LV pressure in either group at any stage. Hemodynamic data indicated that LV function in group A was enhanced during the development of the hypertrophy. The amount of Ca2+ release and uptake, and the number of ryanodine binding sites on the SR were higher in group A than in group S at both early and middle stages. However, 8 weeks after the operation, SR activity was normal, even though cardiac function was still augmented. Our results indicated that LV hypertrophy induced by pressure overload is associated with altered intracellular Ca2+ regulation, as reflected by the increased Ca2+ release and uptake functions of the SR and the quantitative change in the number of ryanodine receptors during the early stages of the development of hypertrophy. Therefore, alterations in the SR Ca2+ transport capacity could account, at least in part, for the alterations in E-C coupling seen in hypertrophy.

Adaptation, Physiological↗

PubMed1997

Effect of aortic impedance on preload-afterload mismatch in canine hearts in situ.

The aim was to examine the influence of the independent increase of aortic wall characteristics from vascular resistance on global left ventricular (LV) function in intact hearts. In 11 anesthetized dogs, aortic stiffness was increased by a constriction of the thoracic aorta using a stiff tube, and then, in nine dogs, total systemic resistance (TSR) was increased by an infusion of angiotensin II. During the above procedures, aortic input impedance and LV dimension were measured. Aortic input impedance spectra revealed the steady increase in the moduli at high frequencies by aortic constriction, indicating the increase in aortic stiffness. At the stage of increased aortic characteristic impedance (Zc) (134% of control) without a change in TSR, both LV end-diastolic diameter (LVEDD, 99%, p < 0.01 and stroke volume (SV, 95%, p < 0.01) decreased significantly without a change in LV end-systolic diameter (LVESD). During the increase in TSR produced by angiotensin II (128% of control) without a change in Zc, LVEDD tended to increase and LVESD significantly increased (103%, p < 0.01) associated with a decrease in SV (94%, p < 0.01). LV systolic mean wall stress was increased by angiotensin II (118%, p < 0.01), whereas it was unchanged by aortic constriction. In conclusion, the isolated increase in aortic stiffness without a change in TSR was associated with a reduction in LV preload and SV.

Animals↗

PubMed1997

1 alpha,25-dihydroxyvitamin D3 induces very low density lipoprotein receptor mRNA expression in HL-60 cells in association with monocytic differentiation.

Expression of VLDL receptor mRNA during differentiation of HL-60 cells was investigated by Northern analysis. The expression induced in 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3)-treated cells was 3 times that in untreated cells, while LDL receptor mRNA expression was unchanged. VLDL receptor mRNA levels were not changed in macrophages caused to differentiate from HL-60 cells by treatment with phorbol 12-myristate 13-acetate (PMA). Treatment of sarcoma cells which possess the vitamin D receptor (MG-63 cell line) with 1 alpha,25(OH)2D3 did not affect VLDL receptor mRNA levels. Therefore, 1 alpha,25(OH)2D3 induces VLDL receptor mRNA in HL-60 cells through differentiation-dependent mechanisms.

Calcitriol↗

PubMed1997

Quantification of singlet oxygen from hematoporphyrin derivative by electron spin resonance.

The mechanism of the generation and the quantitative analysis of singlet oxygen (1O2) formed by the exposure of a hematoporphyrin derivative (HpD) to light was re-evaluated by electron spin resonance (ESR) combined with 2,2,6,6,-tetramethyl-4-piperidine (TMPD). The change from TMPD to 2,2,6,6,-tetramethyl-4-piperidine-N-oxide (TAN) has been reported to depend on singlet oxygen. However, we confirmed that this reagent also react with superoxide anion (O2-) and hydroxyl radicals (OH). Therefore, the reactions between TMPD and 1O2, O2- and OH were re-examined using a kinetic approach. We found that the generation of TAN was proportional to the concentration of TMPD and HpD, as well as to the duration and strength of the illumination. The generation of TAN was not inhibited by dimethyl-sulfoxide (DMSO) or superoxide dismutase (SOD). The reaction rate between TMPD and 1O2 was determined to be 5.0 x 10(-7) M min-1. The generation of 1O2 from HpD was 2.7 x 10(-7) M min-1 under our conditions. The competitive reaction observed between 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and TMPD for O2- or OH shows that TMPD reacts with both forms of active oxygen, but gave no ESR signal. The second-order reaction rate constant of TMPD between O2- and OH was calculated as 73 M-1 s-1 and 1.5 x 10(9) M-1 s-1, respectively. The photochemical generation of 1O2 from methylene blue, another sensitizer, was also demonstrated by this method. These results show that ESR signal of TAN can be used for the highly selective monitoring of 1O2.

Cyclic N-Oxides↗

PubMed1997

Endothelin production in cultured vascular smooth muscle cells--modulation by the atrial, brain, and C-type natriuretic peptide system.

We examined the regulatory mechanisms of endothelin-1 (ET-1) production in cultured rat vascular smooth muscle cells (VSMC) with a special focus on the roles of protein kinase C (PKC)- and cyclic guanosine-3',5'-monophosphate (GMP)-mediated signaling systems. Effects of atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP) on angiotensin II (Ang II)-, and arginine vasopressin (AVP)-induced production of ET-1 were examined in cultured rat aortic VSMC. Ang II and AVP stimulated ET-1 production in a concentration-dependent manner through angiotensin subtype 1 (AT1) and vasopressin subtype 1 (V1) receptors, respectively. The stimulatory effects of Ang II and AVP were markedly abolished in PKC-depleted cells. Rat ANP (1-28), rat BNP-45, and rat CNP-22 potently inhibited Ang II- and AVP-stimulated ET-1 production in a concentration-dependent manner, respectively. The inhibitory effect by CNP on ET-1 production was paralleled by an increase in the cellular level of cyclic GMR.8-Bromo cyclic GMP reduced the stimulated ET-1 production by Ang II and AVP. These results indicate that Ang II and AVP stimulate ET-1 production in cultured rat VSMC through AT1 and V1 receptors by a mechanism probably involving activation of PKC, and that ANP, BNP, and CNP inhibit this stimulated production through a cyclic GMP-dependent process.

Angiotensin II↗