Search PubMed⌕ Search

Biomedical subjects

S Komori

Publications and source records attributed to S Komori.

At least 109 records · Page 6Linked to original sources

Caffeine and carbachol act on common Ca2+ stores to release Ca2+ in guinea-pig ileal smooth muscle.

To characterize intracellular Ca2+ stores, the Ca(2+)-releasing effects of caffeine, carbachol and inositol 1,4,5-trisphosphate (IP3) were compared by measuring the drug-induced tension development in beta-escin-skinned longitudinal smooth muscle of guinea-pig ileum. Caffeine (20 mM), carbachol (10 or 100 microM) or IP3 (40 microM), applied after loading Ca2+ within intracellular stores, produced a transient rise in tension in a Ca(2+)-free solution. This change in tension occurred in response to release of Ca2+ from the stores. The effect of either caffeine or carbachol was markedly reduced or abolished after preceding application of the other drug. IP3 was without effect when applied subsequently to caffeine. The effects of carbachol and IP3 were abolished after combined treatment with ryanodine (30 microM) and caffeine (20 mM) which causes functional removal of caffeine-releasable Ca2+ stores, but not after combined treatment with ryanodine (30 microM) and carbachol (10 microM). The results suggest that caffeine, carbachol and IP3 all act on common Ca2+ stores to release Ca2+.

Animals↗

A report on the perinatal diagnosis of 4 cases of cardiac tumors.

Since 1973, we have identified 4 cardiac tumors by ultrasonography in fetal or early postnatal life. Tuberous sclerosis was diagnosed in three infants whose mother was also affected. The first infant died from acute cardiac failure after birth, and the second required cardiac surgery. The third infant had a cardiac tumor and a focal seizure at the age of 8 months. The cardiac tumor disappeared at the age of 2 years. The fourth cardiac rhabdomyoma may be the only sign of tuberous sclerosis.

Diagnosis, Differential↗

Effects of bidisomide (SC-40230), a new class I antiarrhythmic agent, on ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats; comparison with mexiletine and disopyramide.

We investigated the antiarrhythmic effects of bidisomide (SC-40230), a new class I antiarrhythmic drug, in early-phase ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats. The effects of bidisomide were compared with those of mexiletine (MXT) and disopyramide (DSP), established class I antiarrhythmic drugs. Drugs were administered intravenously, 5 min before induction of coronary occlusion. Bidisomide (5 mg/kg) reduced the number of premature ventricular complexes and the incidence of ventricular tachycardia and ventricular fibrillation similarly to MXT and DSP in rats with ventricular arrhythmias induced by coronary artery occlusion. In rats with ventricular arrhythmias induced by coronary artery reperfusion following a 5-min coronary occlusion, the antiarrhythmic effects of 5 mg/kg of bidisomide were similar to those of the same doses of MXT and DSP. All three drugs significantly slowed the heart rate. Our results suggest that bidisomide may effectively reduce the severity of life-threatening ventricular arrhythmias that occur during acute coronary syndrome.

Animals↗

Fetal loss in the first trimester after demonstration of cardiac activity: relation of cytogenetic and ultrasound findings.

A retrospective comparison of cytogenetic and ultrasound findings in first trimester spontaneous fetal loss after demonstration of cardiac activity was made. The crown-rump length (CRL) was measured twice for each fetus resulting in spontaneous abortion: (i) CRL was measured in the viable state while demonstrating cardiac activity, and the growth deviation was expressed as the measured/expected CRL ratio (M/E CRL ratio); (ii) in the same fetus, CRL was measured after confirmation of fetal death, and designated as the post-mortem CRL. The chorionic tissues of these abortuses were karyotyped. The CRL of fetuses which resulted in normal deliveries were also measured as controls. As a result, 16 of 24 abortuses displayed an abnormal chromosomal analysis (67%). The mean M/E CRL ratio of still-viable fetuses was smaller than that of control fetuses (0.74 +/- 0.20 versus 0.98 +/- 0.13 respectively, P < 0.01). The differences in ratio between karyotypically normal and abnormal abortuses were not statistically significant. The post-mortem CRL of dead fetuses was > 20 mm in four of five monosomy X, two of three 21-trisomy, one of three triploidy and none of eight embryos with normal karyotype and five other trisomies. In conclusion, our study demonstrated that the M/E CRL ratio could be used as a predictor of spontaneous abortions, although it does not discriminate abnormal karyotypes from normal ones. The embryos with a post-mortem CRL more than 20 mm have a higher likelihood of suffering monosomy X or 21-trisomy. The ultrasonographic findings might offer a cytogenetic clue as to a possible cause to the developmental arrest.

Abortion, Spontaneous↗

Direct production of the Fab fragment derived from the sperm immobilizing antibody using polymerase chain reaction and cDNA expression vectors.

PROBLEM: Sperm immobilizing antibodies cause infertility mainly through complement dependent sperm immobilization. To analyze any effect of sperm immobilizing antibody on fertilization, we had already established cell lines that secrete IgM monoclonal antibody (MAb H6-3C4) and IgG monoclonal antibody (MAb EnBCMGS). The latter was a class-switched recombinant IgG antibody that shares the same variable region as MAb H6-3C4. The biological effects of the IgG antibody were also reported previously to eliminate sperm immobilizing or sperm agglutinating activities. However, the method of chemical digestion of IgG had some disadvantage to prepare the purified Fab fragment stably and in large quantities. This time we report a unique method to obtain the recombinant Fab fragments (Fab EnBCMGS) using polymerase chain reaction (PCR) and cDNA expression vectors. METHOD: Two kinds of PCR primers were designed to make a truncated heavy chain (Fd) gene of MAb EnBCMGS. The amplified Fd gene and light chain gene were ligated into cDNA expression vectors and then transfected into mammalian cells. RESULTS: Expression of the Fd gene and light chain gene were confirmed by Northern blotting. Secretion of the recombinant Fab fragment from mammalian cells was also confirmed by Western blotting. The Fab fragment showed biological activity as is expected by FACS analysis. CONCLUSION: This method enables the stable production of genuine Fab fragments of IgG in mammalian cells without any chemical treatment that may be time consuming and affect the quality of the Fab fragments.

Amino Acid Sequence↗

Possible involvement of a small G-protein sensitive to exoenzyme C3 of Clostridium botulinum in the regulation of myofilament Ca2+ sensitivity in beta-escin skinned smooth muscle of guinea pig ileum.

The effects of exoenzyme C3 of Clostridium botulinum on Ca(2+)- and drug-induced tension developments were investigated in beta-escin skinned smooth muscle of guinea pig ileum to test the involvement of a small G-protein in the regulation of myofilament Ca2+ sensitivity. C3 is known to ADP-ribosylate the rho p21 family of small G-proteins. Treatment with C3 (0.35 microgram/ml, for 30 min) shifted the pCa-tension curve rightward along the Ca2+ concentration axis, indicating a decrease in Ca2+ sensitivity of the contractile elements. The inhibitory effect of C3 was not preserved after treatment with GDP beta S (1 mM), an antagonist of GTP for the binding to G-proteins. Stimulation of muscarinic receptors with carbachol (CCh, 100 microM) shifted the pCa-tension curve leftward, indicating Ca2+ sensitization of tension development. The Ca(2+)-sensitizing effect of CCh was not observed after C3 treatment. When GTP gamma S (10 microM), an activator of G-proteins, was applied at a plateau of tension development produced by a moderate concentration of Ca2+, further increase in tension was elicited and the effect of GTP gamma S was inhibited by C3 treatment. The results suggest the possible involvement of a rho p21-like small G-protein in the regulation of Ca2+ sensitivity of smooth muscle myofilaments.

Animals↗

Regression of hypertrophic osteopathy following removal of intrathoracic neoplasia derived from vagus nerve in a dog.

Surgical removal of an intrathoracic tumor derived from a vagus nerve was undergone in a dog with hypertrophic osteopathy. The tumor was pathologically diagnosed as malignant schwanoma. Soft tissue swelling, lameness, and itchiness in four limbs disappeared within 7 days after surgery. The proliferated periosteal osteophytes of the four limbs was progressively reduced with time by follow-up radiography on the 58th day after surgery. On the 710th day after surgery, these osteophytes were greatly decreased as osteopathy, malignant schwanoma.

Animals↗

Sedative effect of medetomidine and its reversal by atipamezole in house musk shrews (Suncus murinus).

This study was undertaken to evaluate the sedative effect of medetomidine, an alpha 2-adrenoceptor agonist, and the counteractive effect of atipamezole, an antagonist to medetomidine, in house musk shrews (Suncus murinus). Two hundred, 300, 400, or 600 micrograms/kg of medetomidine was intraperitoneal injected into 89 house musk shrews. A sedative effect was produced in one to two minutes after injection. The dose-dependent prolongation of the sedative duration and the dose-dependent appearance of a hypothermic effect were demonstrated. With 200 micrograms/kg of medetomidine, the sedative effect obtained was not adequate in some of the animals. With 300 micrograms/kg and above, a stable sedative state was induced in all the animals. The duration of sedation in the house musk shrews was much longer (p < 0.01) in males than in females. This suggested the higher susceptibility of male house musk shrews to this drug. The sedative effect and hypothermia obtained with 400 micrograms/kg of medetomidine were completely counteracted by more than 2.0 mg/kg of atipamezole. With 0.5 and 1.0 mg/kg of atipamezole, only a partial antagonistic action was produced. Transient vomiting appeared in 4.5% of the house musk shrews at approximately one minute after injection of medetomidine. This side-effect had occurred before the sedative effect was obtained, and was not serious enough to be a problem. None of the 89 house musk shrews died in this experiment. The above results show that the combination of medetomidine and atipamezole is a highly effective and safe anesthetic treatment which permits easy handling of house musk shrews.

Adrenergic alpha-Antagonists↗

Effects of bathing in hot water on portal hemodynamics in healthy subjects and in patients with compensated liver cirrhosis.

Bathing in hot water induces vasodilatation of the peripheral vessels and alteration of blood distribution. Using a Doppler flowmeter, we evaluated the effect of bathing in hot water on portal hemodynamics. Eight controls and 8 patients with compensated liver cirrhosis remained immersed in hot water at 42 degrees C for 5 minutes. Portal flow significantly decreased from 811 +/- 141 (ml/min) at the baseline to 530 +/- 98 in the controls and from 855 +/- 308 to 642 +/- 208 in cirrhotics immediately after bathing. This decrease (25%) in cirrhotics was significantly less than that (35%) in controls because vessel diameter did not decrease as rapidly as it did in controls. Portal flow after 30 minutes returned to the baseline values in controls but remained low in cirrhotics. These findings suggest that cirrhotics have a lower hemodynamic response to bathing in hot water compared with that in controls.

Adult↗

[Clinical significance of ultrasonographic screening for Down syndrome in the second trimester].

OBJECTIVE: This study was undertaken to evaluate the clinical significance of ultrasonographic screening for the detection of Down syndrome in the second trimester of pregnancy of Japanese women. MATERIALS AND METHODS: BPD (biparietal diameter), FL (femur length), BPD/FL ratio and M/E FL (measured/expected femur length) ratio were measured in 734 normal second-trimester fetuses and 13 consecutive Down syndrome fetuses undergoing genetic amniocentesis mainly for advanced maternal age. RESULTS: Two fetuses with Down syndrome had small BPD, three fetuses had a short femur length, four fetuses had a high BPD/FL ratio and four fetuses had a low M/E FL ratio. A cutoff value of 1.5SD below the mean value for the normal populations for BPD and FL, that of above 1.5SD for BPD/FL ratio, and that of 0.91 or less for M/E FL ratio yielded a sensitivity of 15.4, 23.1, 30.8 and 30.8% and false positive rates of 2.7, 6.0, 5.7 and 11.4%, respectively. CONCLUSION: The ultrasonographic measurements of femur length for the screening of Down syndrome in the Japanese population revealed the low discriminative ability reported in recent studies conducted in Western countries. Further investigation would be necessary to apply it as the routine screening method for Down syndrome in clinical practice.

Adult↗

Identification and characterization of a sperm peptide antigen recognized by a monoclonal antisperm autoantibody derived from a vasectomized mouse.

A monoclonal autoantibody (MAb) to mouse sperm was established from a vasectomized mouse. The MAb, termed 4A11, reacted exclusively to mouse and rat live sperm tail, without any cross-reaction with sperm of other mammalian species or any somatic organ tissues in the mouse. MAb 4A11 significantly inhibited in vitro fertilization of mouse ova. Western blotting showed a single band of 67 kDa as the corresponding antigen protein of MAb 4A11. By screening a mouse testis cDNA library with MAb 4A11, one positive clone (964bp) was obtained. DNA sequence of the clone showed no homology with any previously reported mammalian genes, but showed 54% homology with a bacterial gene of sucrose-specific phosphotransferase enzyme II. The rabbit antisera raised to the recombinant protein of the 4A11 cDNA gene showed reaction to mouse, rat, hamster and guinea-pig sperm.

Amino Acid Sequence↗

Ca2+ inhibition of inositol trisphosphate-induced Ca2+ release in single smooth muscle cells of guinea-pig small intestine.

1. Single smooth muscle cells from the longitudinal muscle layer of guinea-pig small intestine were voltage clamped using patch pipettes in the whole-cell mode. 2. When D-myo-inositol 1,4,5-trisphosphate (InsP3) was released at intervals, by photolysis of 'caged' InsP3 within the cell, increases in [Ca2+]i in many cells, as judged from Ca(2+)-activated K(+)-current, were all-or-none; release of InsP3 before a critical interval had elapsed, which was quite stable for an individual cell, resulted in no response. After Ca(2+)-induced Ca2+ release had been evoked by depolarization, the InsP3 response was inhibited. Oscillations in [Ca2+]i evoked by muscarinic receptor activation were unaffected by Ruthenium Red; during these oscillations exogenous InsP3 was not effective close to, or shortly after, peak [Ca2+]i but was effective at other times. 3. Reproducible release of Ca2+ and elevation of [Ca2+]i could be produced by brief (up to 0.5 s) pressure applications of 10 mM caffeine at intervals of 10 s or greater but caffeine itself rarely evoked oscillations in [Ca2+]i. Responses to flash release of InsP3 were reduced after caffeine-induced responses and recovery of caffeine-induced Ca2+ release was faster than recovery of InsP3-induced Ca2+ release. 4. The results support the idea that InsP3-induced Ca(2+)-store release can be inhibited by a certain level of [Ca2+]i at a time when Ca2+ stores have refilled and can be released by caffeine; they also support the suggestion that during oscillations of [Ca2+]i evoked by muscarinic receptor activation, Ca2+ inhibition of InsP3-induced Ca2+ release at some critical level of [Ca2+]i allows Ca2+ stores to refill and leads to a fall in [Ca2+]i so contributing to the oscillations which are observed.

Animals↗

Identification and characterization of a 27 kDa acrosome protein of human sperm defined by a monoclonal antibody with fertilization-blocking effect.

A monoclonal antibody, MAb 1G1, possessing a strong fertilization-blocking activity was prepared by immunizing a BALB/c mouse with capacitated human sperm in order to study the molecular nature of sperm antigens relevant to fertilization. MAb 1G1 inhibited human sperm penetration into zona-free hamster eggs. It reacted to the apical portion of acrosome-reacted human sperm, but did not react to live sperm before the acrosome reaction as demonstrated by immunofluorescence staining. In paraffin-embedded testis sections, the round spermatids, spermatocytes and spermatozoa were stained with MAb 1G1, but the spermatogonia were not stained. Neither Sertoli cells, Leydig cells nor other somatic tissues were stained. The sperm of Japanese monkey, bull, boar, hamster and mouse were not stained. Therefore, the staining of sperm was species specific. The antigen corresponding to MAb 1G1 showed a band at 27 kDa by immunoblotting. The reactivity of the antigenic component was not destroyed by periodic acid treatment. From the results obtained, it was postulated that the antigenic molecule might be a polypeptide. These results indicated that this MAb might be a useful tool for studying the mechanism of human sperm-egg fertilization and the development of a contraceptive vaccine.

Acrosome↗

Mechanical and current responses to neurotensin in the smooth muscle of guinea-pig intestine.

1. The effects of neurotensin (NT) on the mechanical activity of the smooth muscle and membrane currents of enzymatically-dispersed single smooth muscle cells of guinea-pig intestine were investigated by the isometric tension recording method and the whole-cell patch clamp technique, respectively. 2. NT (0.3-670 nM) produced an initial relaxation followed by a contraction in segment preparations of the jejunum and ileum. Atropine (0.2 microM) abolished the contraction. In 30% of ileal segments, NT produced a slowly-developed contraction in the presence of atropine. The atropine-resistant contraction was insensitive to tetrodotoxin (TTX, 0.2 microM). The relaxant effect of NT was unaffected by TTX (0.2 microM) and guanethidine (2 microM), but markedly reduced or abolished by apamin (67 nM). 3. In segment preparations of the colon and rectum, NT produced a biphasic response, similar to that in the small intestine, or a triphasic one (relaxation, contraction and relaxation). The contractile effect of NT was affected neither by atropine (0.2 microM) nor by TTX (0.2 microM). The first relaxation in response to NT was similar in pharmacological properties to that in the small intestine. 4. Responses to NT in longitudinal muscle strips were similar to those in segment preparations. The taenia caecum responded to NT with a contraction alone and the effect was unaffected by atropine (0.2 microM) and TTX (0.2 microM). 5. NT had little or no effect on the mechanical activity in the circular muscle of the small intestine. In the circular muscle of the large intestine, NT had a weak inhibitory effect on the spontaneous activity which was followed by a small rise in muscle tone. Apamin (67 nM) converted the biphasic response to a contraction. 6. In cells dialysed with a KCl-based solution under voltage clamp at 0 mV, NT (5 microM) produced a brief, outward current in a very small fraction of cells (4 out of 40 cells). When cells were dialysed with a CsCl-based solution under voltage clamp at -50 or -60 mV, no current response to NT (5 microM) was observed in all 37 cells, but NT increased inward Ca2+ currents evoked upon depolarization. 7. From these results, it appears that there is a regional difference in the mode of action of NT to contract and relax the smooth muscle of guinea-pig intestine, and NT acts on its receptors on the smooth muscle to enhance activation of voltage-dependent Ca2+ channels, which underlies the slow contraction in the longitudinal muscle of the intestine.

Adenosine Triphosphate↗

The protective effect of preconditioning on reperfusion-induced arrhythmia is lost by treatment with superoxide dismutase.

The purpose of this study was to investigate the relation between free radicals and the effect of preconditioning on reperfusion arrhythmias using the isolated working rat heart model. Rats were divided into 3 groups: control, preconditioned without superoxide dismutase (SOD) and preconditioned with SOD (n = 8 each group). The incidence of reperfusion-induced ventricular fibrillation (Vf) in the preconditioned without SOD group was reduced from 100% to 13% (p < 0.005 vs control). This protective effect of preconditioning was not observed in the SOD-treated group (incidence of Vf increased from 13% to 75%, p < 0.025). The protective effect of preconditioning on reperfusion arrhythmias is related to the presence of oxygen free radicals which occur during the reperfusion period of the preconditioning phase.

Animals↗

Effects of NS-2, a new class 1 antiarrhythmic agent, and AFD-19, its active metabolite, on ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats: comparison with disopyramide and mexiletine.

We studied the antiarrhythmic effects of NS-2 (4-diisobutylamino-1,1-diphenyl-1-butanol maleate) and AFD-19 (active metabolite of NS-2) on early stage ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized male rats. These effects were compared with those of disopyramide and mexiletine. Drugs were intravenously administered either before or after coronary occlusion. When administered 5 min before occlusion, 3 mg/kg of NS-2 and AFD-19 exhibited equivalent anti-arrhythmic activity to that of 5 mg/kg of disopyramide and mexiletine, as assessed by reductions in the number of premature ventricular complexes and in the incidences of ventricular tachycardia and ventricular fibrillation. In a dose of 5 mg/kg, the antiarrhythmic effects of NS-2 and AFD-19 were more pronounced. When administered 5 min after coronary artery occlusion, only NS-2 and AFD-19 (in doses of 5 mg/kg) had significant antiarrhythmic effects. None of the drugs influenced the severe ventricular arrhythmias induced by reperfusion when administered 1 min before reperfusion. In conclusion, NS-2 might be effective in reducing the severity of the life-threatening ventricular arrhythmias that occur during acute myocardial infarction.

Amino Alcohols↗

Effect of trimebutine on contractile responses in skinned ileal smooth muscle.

The effects of trimebutine on Ca2+ release and modulation of Ca2+ sensitivity of contractile elements induced by carbachol (CCh) were investigated using a tension measuring method in beta-escin-treated skinned smooth muscle of the longitudinal muscle layer of guinea pig ileum. Trimebutine (10-100 microM) concentration-dependently inhibited tension development brought about by Ca2+ release from intracellular stores induced by CCh (10 microM), but did not affect those induced by inositol 1,4,5-trisphosphate (IP3, 25 microM) or caffeine (5 mM). The inhibitory effect was reversible. Trimebutine (100 microM) neither altered the Ca2+ sensitivity of the contractile elements nor affected the effects of GTP gamma S (50 microM) and CCh (100 microM) in potentiating Ca2+ sensitivity of the contractile elements after the Ca2+ storage function had been eliminated by A23187. These results suggest that trimebutine inhibits CCh-induced Ca2+ release by acting at some point during the coupling of muscarinic receptors through a G-protein to phospholipase C and thus reducing the accumulation of IP3.

Animals↗

Two separate mechanisms of T cell clonal anergy to Mls-1.

T cell tolerance to superantigen can be mediated by clonal anergy in which Ag-specific mature T cells are physically present but are not able to mount an immune response. We induced T cell unresponsiveness to minor lymphocyte stimulations locus antigen (Mls)-1a in mice transgenic for TCR V beta 8.1 in three different systems: 1) injection of Mls-1a spleen cells, 2) mating with Mls-1a mice, and 3) bone marrow (BM) chimeras in which Mls-1a is present only on nonhematopoietic cells. CD4+8-V beta 8.1+ cells from all these groups did not proliferate in response to irradiated spleen cells from Mls-1a mice. We compared the response of these cells by T cell/stimulator cell conjugate formation, Ca2+ mobilization, and proliferation assays. The mechanisms underlying the unresponsiveness of these T cells appear to differ. CD4+8-V beta 8.1+ cells from Mls-1a spleen cell-injected mice mobilized cytoplasmic Ca2+ but proliferated at a reduced level in response to cross-linking with anti-TCR mAb. However, these cells formed conjugates, mobilized Ca2+, and proliferated in response to Mls-1a when activated B cells were used as stimulators, although they produced reduced levels of IL-2. In Mls-1a/b V beta 8.1 transgenic mice, a subset in CD4+8-V beta 8.1+ cells did not mobilize cytoplasmic Ca2+ after TCR cross-linking. Their conjugate formation, Ca2+ mobilization, or proliferation in response to Mls-1a on activated B cells was undetectable. Finally, CD4+8-V beta 8.1+ cells from the BM chimeras proliferated to TCR cross-linking at a partially reduced level and formed conjugates, mobilized Ca2+, and proliferated in response to Mls-1a on activated B cells. These features suggest that the mechanisms underlying the maintenance of anergy in Mls-1a spleen cell-injected mice are distinct from those in Mls-1a mice.

Animals↗