Biomedical subjects

M Matsuo

Publications and source records attributed to M Matsuo.

At least 19 recordsLinked to original sources

PubMed1992

Vitamin E: inhibition of retinol-induced hemolysis and membrane-stabilizing behavior.

For the elucidation of the mechanism of membrane stabilization by vitamin E, the effects of alpha-tocopherol and its model compounds on either retinol-induced hemolysis of rabbit erythrocytes or the permeability and fluidity of liposomal membranes have been studied. Retinol-induced rabbit erythrocyte hemolysis has been found not to be caused by the oxidative disruption of erythrocyte membrane lipids initiated by retinol oxidation, but rather to arise from physical damage of the membrane micelle induced by penetration of retinol molecules. In suppressing hemolysis, alpha-tocopherol was more effective than other naturally occurring tocopherols. alpha-Tocopheryl acetate, nicotinate, and 6-deoxy-alpha-tocopherol were more effective than alpha-tocopherol itself. The inhibitory effects of alpha-tocopherol model compounds having side chains with at least two isoprene units or a long straight chain instead of the isoprenoid side chain were similar to those of alpha-tocopherol. These data suggest that for protection of membranes against retinol-induced damage, the hydroxyl group of alpha-tocopherol is not critical, but rather the chroman ring, three methyl groups on the aromatic ring, and the long side chain are necessary. To verify the mechanism of the inhibitory effect on hemolysis, not only the effect of vitamin E and its model compounds on the membrane permeability and fluidity, but also the mobility of alpha-tocopherol molecule in membranes has been investigated using bilayer liposomes as the model membranes. Addition of alpha-tocopherol to membranes produced a greater decrease in the permeability and fluidity of rat liver phosphatidylcholine liposomes compared with egg yolk phosphatidylcholine liposomes. In dipalmitoylphosphatidylcholine liposomes, however, alpha-tocopherol was less effective, that is, the more unsaturated the lipids, the more they interact with alpha-tocopherol. 2,2,5,7,8-Pentamethyl-6-chromanol with no isoprenoid side chain and phytol without the chromanol moiety had no effect. The measurement of 13C NMR relaxation times revealed that the mobility of methyl groups on the aromatic ring of alpha-tocopherol in membranes is significantly restricted. In contrast, the methyl groups at positions 4'a and 8'a on the isoprenoid side chain have high degrees of motional freedom in the lipid core of membranes. Furthermore, it was found that alpha-tocopherol in membranes interacts with chromate ions added as potassium chromate outside the membranes, resulting in an increase in membrane fluidity. These results are compatible with those of the inhibitory effect on retinol-induced erythrocyte hemolysis. On the basis of the results obtained here, a possible mechanism for membrane stabilization by vitamin E is proposed.

Animals↗

PubMed1992

Studies on neurokinin antagonists. 2. Design and structure-activity relationships of novel tripeptide substance P antagonists, N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N1-formyl-D-tryptophyl]-N- methyl-N-(phenylmethyl)-L-phenylalaninamide and its related compounds.

Continuing studies on the chemical modification of the previously reported novel tripeptide SP antagonist, N alpha-[N alpha-[N alpha- (tert-butyloxycarbonyl)glutaminyl]-N1-formyl-D-tryptophyl]phenylalanine benzyl ester [Boc-Gln-D-Trp-(CHO)-Phe-OBzl (1)], are described herein. We initially investigated the stability of 1 in guinea pig plasma and liver homogenate to elucidate the most labile part in the structure. It was consequently revealed that the benzyl ester part was easily hydrolyzed to produce the inactive acid analog. Thus we searched for a benzyl ester surrogate that would be more resistant to hydrolytic enzymes. This approach found an isosteric amide structure, N-methyl-N-(phenylmethyl)amide, suitable in terms of potency and stability. Subsequent modification of the amino terminal into N alpha-acetyl-L-threonine led to the most potent compound, N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N1-formyl-D-tryptophyl]-N- methyl-N-(phenylmethyl)-L-phenylalaninamide [Ac-Thr-D-Trp(CHO)-Phe-NMeBzl (5a, FR113680)]. This compound 5a potently blocked 3H-SP binding to guinea pig lung membranes with IC50 of (5.8 +/- 0.78) x 10(-9) M. In vitro, 5a inhibited SP-induced contraction of isolated guinea pig trachea strips with IC50 of 2.3 x 10(-6) M and caused no contraction when used alone in this preparation up to 3.2 x 10(-5) M. In addition 5a exhibited no effect on the contraction induced by histamine or acetylcholine. Intriguingly, it was demonstrated in vivo that 5a suppressed the SP-induced bronchoconstriction and airway edema in guinea pigs with ED50 of 0.42 mg/kg and 0.66 mg/kg, respectively, when administered intravenously.

Acetylcholine↗

PubMed1992

Age-related alterations in antioxidant capacity and lipid peroxidation in brain, liver, and lung homogenates of normal and vitamin E-deficient rats.

Age-related alterations in both antioxidant capacity and lipid peroxidation in the cerebrum, lung and liver homogenates of normal and vitamin E-deficient rats were investigated. The antioxidant capacity, which includes superoxide dismutase, catalase and glutathione peroxidase activities and vitamin E (alpha-tocopherol) concentration, was relatively stable throughout the lifespan. It was observed, however, that catalase and glutathione peroxidase activities in livers of old rats decreased and that vitamin E concentration in lung and liver increased with age. In vitamin E-deficient animals, catalase activity in liver increased and glutathione peroxidase activity in liver and lung decreased. Lipid peroxidation was monitored by use of three different indices, i.e. the thiobarbituric acid (TBA) value, oxygen absorption and conjugated-diene formation. In the absence of any initiator, neither oxygen absorption into tissue homogenates nor conjugated-diene formation in lipid extracts from the homogenates occurred. The TBA value of each cerebrum homogenate incubated under air or an oxygen atmosphere was larger than that of the corresponding unincubated cerebrum homogenate. From comparison between the TBA value and oxygen absorption, this increase in the TBA value was suggested to be due to some reactions other than lipid peroxidation. Although tissue homogenates examined contained TBA-reacting materials, no lipid peroxidation seems to arise during incubation of them. No age-related alterations in the TBA value and oxygen absorption in rat tissue homogenates were observed. Vitamin E deficiency had no effect on the TBA values of cerebrum and lung homogenates, while it seemed to increase the TBA values of liver homogenates. Vitamin E deficiency had no effect on oxygen absorption in these tissue homogenates. The induction period of initiator-induced conjugated-diene formation in lipid extracts from liver and lung homogenates from normal and vitamin E-deficient rats tended to be extended with age. Vitamin E deficiency decreased the induction period of initiator-induced conjugated-diene formation. As a result, the length of the induction period was found to be proportional to vitamin E concentration in lipid extracts. The overall antioxidant capacity of rat tissues appears to be maintained without large variation during ageing. Decreases in the capacity of some antioxidant factors may be compensated by increases in the capacity of other factors.

Aging↗

PubMed1992

Congenital protein C deficiency and myocardial infarction:concomitant factor VII hyperactivity may play a role in the onset of arterial thrombosis.

A 29-year-old man with congenital protein C deficiency and acute myocardial infarction is reported. Four hours after the onset of chest pain, he was treated intravenously with tissue-type plasminogen activator. Subsequent coronary angiography revealed only slight stenosis of the left anterior descending coronary artery without any atherosclerosis. The propositus, his brother, and his mother, showed low levels of both protein C activity and antigen, while plasma thrombomodulin levels were normal. His grandfather had died from acute myocardial infarction at 38 years of age. We investigated several other risk factors for arterial thrombosis, including factor VII, fibrinogen, heparin cofactor II, lipoprotein (a), and anticardiolipin antibodies. No other haemostatic abnormalities apart from factor VII hyperactivity were detected in this family. To study the effects of protein C and factor VII on procoagulant activity, prothrombin time was measured after the addition of activated protein C and factor VII to protein C-deficient plasma. The prothrombin time ratio decreased along with an increase in the factor VII level. It also decreased with a decrease in the activated protein C level. These findings indicated that the procoagulant activity of factor VII was enhanced by low protein C levels, suggesting that concomitant factor VII hyperactivity may cause acute myocardial infarction in patients with protein C deficiency.

Adult↗

PubMed1992

Factor VII hyperactivity in chronic dialysis patients.

To study factor VII (F VII) hyperactivity in chronic dialysis patients, we measured the plasma levels of F VII activity (F VII c) and antigen (F VII Ag), prothrombin activation fragments 1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), and thrombomodulin in 28 patients on hemodialysis. Marked elevation of F VII c was found in long-term dialysis patients (185 +/- 30%). This hyperactivity was accompanied by both elevation of the F VII Ag level (153 +/- 28%) and enhanced activation of F VII zymogen, expressed as the F VII c/F VII Ag ratio (1.23 +/- 0.23), but pseudocholinesterase activity was decreased. The 6 patients with ischemic heart disease had slightly higher F VII c (200 +/- 25%) than those without ischemic heart disease (181 +/- 30%), although the difference was not significant. Increased F VII c was accompanied by factor Xa hyperactivity (a high plasma F1 + 2 level) in the long-term dialysis patients, but there was no significant elevation of plasma TAT levels when compared with controls matched for age, sex, and the presence or absence of diabetes mellitus. Plasma TAT levels were significantly correlated with plasma thrombomodulin levels, suggesting that thrombin generation in blood as a result of hemodialysis could induce systemic endothelial cell injury.

Aged↗

PubMed1992

Prophylactic antithrombin III administration during pregnancy immediately reduces the thrombin hyperactivity of congenital antithrombin III deficiency by forming thrombin-antithrombin III complexes.

We examined the changes of haemostatic molecular markers after antithrombin III (AT III) administration in a 22-year-old woman with congenital AT III deficiency in the third trimester of pregnancy who did not have thrombosis. Various markers including fibrinopeptide A (FPA), thrombin-antithrombin III complex (TAT), prothrombin fragment F1 + 2 (F1 + 2), plasmin-alpha 2antiplasmin, D-dimer, beta-thromboglobulin, and platelet factor 4 were measured before and just after 3,000 U of AT III concentrate, which was given three times per week from the 34 week of pregnancy until delivery. Just after AT III administration, F1 + 2 and FPA levels decreased on most occasions, while TAT sometimes increased. Plasma FPA levels were markedly decreased on all 8 occasions when the plasma FPA levels was above 2.0 ng/ml before AT III administration. Plasma FPA levels were always greater than or equal to 6.4 ng/ml before AT III administration on the 4 occasions when TAT increased to above 115%. The changes of plasma F1 + 2 levels were significantly correlated with the AT III level. These results suggest that prophylactic AT III administration in the third trimester immediately inactivates intravascular thrombin to form TAT and reduce the plasma FPA level. Thus, the transient TAT elevation following AT III administration may not only be due to extraction of thrombin from the fibrin clots of thrombi but also to intravascular thrombin which is not attached to thrombi. FPA is the best molecular marker for thrombin hyperactivity and it should be monitored in AT III-deficient pregnant women in the third trimester.

Adult↗

PubMed1992

Studies on neurokinin antagonists. 1. The design of novel tripeptides possessing the glutaminyl-D-tryptophylphenylalanine sequence as substance P antagonists.

To discover a novel and low molecular weight substance P (SP) antagonist we postulated that the essential binding domain of peptide ligands was only a small portion in the whole structure. On the basis of this assumption, we selected the known octapeptide SP antagonist D-Pro-Gln-Gln-D-Trp-Phe-D-Trp-D-Trp-Phe-NH2 (1) as a lead and synthesized its fragment tripeptides which were evaluated for their activity to block 3H-SP binding on guinea pig lung membranes. The protected tripeptide N alpha-[N alpha-[N alpha-(tert-butyloxycarbonyl)-L-glutaminyl]-N1-formyl-D-tryptophyl]- L-phenylalanine benzyl ester [Boc-Gln-D-Trp(CHO)-Phe-OBzl (4a)], corresponding to the Gln-D-Trp-Phe part of 1, exhibited 7-fold potent inhibitory activity in comparison with 1. Studies on structure-activity relationships revealed that the D-tryptophan, L-phenylalanine, and benzyl ester were quite important to maintain the high binding affinity. It was also indicated that 4a antagonized the SP-induced contraction of isolated guinea pig trachea strips (IC50 = 4.7 x 10(-6) M).

Amino Acid Sequence↗

PubMed1992

Rapid quantitative evaluation of plasma D-dimer levels in thrombotic states using an automated latex photometric immunoassay.

To evaluate a recently developed latex photometric immunoassay (LPIA) that which can measure 40 samples quantitatively within 30 minutes, we measured D-dimer levels in blood samples obtained from patients with disseminated intravascular coagulation (DIC). Linearity of D-dimer determination was shown over the range from 0.5 to 36 micrograms/ml, and recovery studies demonstrated 94 to 108% recovery. The intra-assay and inter-assay coefficients of variation ranged from 0.6 to 11.3% at plasma D-dimer levels of 0.54 to 30.1 micrograms/ml. No interference by lipids, bilirubin, haemoglobin, rheumatoid factor, or gamma-globulin was noted. The normal D-dimer range was less than 0.5 microgram/ml in healthy ambulatory subjects, while the level in elderly subjects with atherosclerosis (14%) or in immobilized subjects (38%) was well above this limit. There was a strong correlation between plasma and serum D-dimer levels (r = 0.993). D-dimer levels measured by this LPIA showed a good correlation with those determined using two kinds of ELISA. The LPIA D-dimer levels were elevated in some subjects with diseases predisposing to DIC, but remained below 10.0 micrograms/ml. On the other hand, the LPIA D-dimer levels in DIC subjects were almost always above 10.0 microgramS/ml. Our study showed that a hypercoagulable state should be suspected when the LPIA D-dimer level is greater than 0.5 microgram/ml and that DIC should be diagnosed when the level is greater than 10.0 micrograms/ml in the presence of an appropriate underlying disease. This LPIA system can rapidly evaluate the presence of a hypercoagulable state as accurately as any ELISA, and thus seems potentially valuable for both emergency and routine laboratory use.

Adult↗

PubMed1992

Trypsin inhibitors from bottle gourd (Lagenaria leucantha Rusby var. Depressa Makino) seeds. Purification and amino acid sequences.

Two almost identical trypsin isoinhibitors, LLDTI-I and LLDTI-II, from bottle gourd (Lagenaria leucantha Rusby var. Depressa Makino) seeds were purified by acetone precipitation, gel filtration and reversed phase chromatography. LLDTI-I and LLDTI-II consist of 30 and 29 amino acid residues, respectively, and have identical sequences, except that LLDTI-I has one additional pyroglutamic acid residue at N-terminus. Both proteins are strong inhibitors of bovine trypsin, with Ki values of 2.4.10(-10) M (LLDTI-I) and 9.6.10(-11) M (LLDTI-II). Amino acid sequences are as follows: [sequence: see text]

Amino Acid Sequence↗

PubMed1992

Amplification of ten deletion-rich exons of the dystrophin gene by polymerase chain reaction shows deletions in 36 of 90 Japanese families with Duchenne muscular dystrophy.

We analyzed DNA samples taken from 95 Duchenne muscular dystrophy (DMD) patients belonging to 90 different families in Japan using the polymerase chain reaction. Ten different regions at the 5' end or in the central region of the dystrophin cDNA gene that were previously shown to be prone to deletion were selected for amplification and analysis. Patients in 36 of the 90 families (40%) had deletions in at least one of these segments of the gene. Identical deletions were detected in the dystrophin gene of patients from the same family. The deletions were heterogeneous in size and location. One patient had deletions in 7 of the 10 amplified regions, while 19 patients from 18 families had a deletion in only one of the regions studied. Deletions at the 5' end were generally larger and more heterogeneous than those in the central region of the gene. One third of deletions had their proximal end breakpoints between exons 44 and 45. This region seems to be particularly vulnerable to gene breakage in DMD patients.

Asian People↗

PubMed1992

Partial deletion of a dystrophin gene leads to exon skipping and to loss of an intra-exon hairpin structure from the predicted mRNA precursor.

In dystrophin Kobe exon 19 of the dystrophin gene is skipped during the process of mRNA precursor splicing even though the splice sites are unchanged (Matsuo et al. J. Clin. Invest. 87:2127-2131,1991). In the predicted secondary structure of the mRNA precursor, exon 19 of dystrophin Kobe is paired with intron sequences, whereas a large part of exon sequence from wild type is paired with itself and folded into a large hairpin structure. As all of 22 additional dystrophin exons analyzed also form intra-exon hairpin structures, these structures may be considered essential components of exons. We suggest that the abolishment of a hairpin structure in the truncated exon of dystrophin Kobe might prevent the splicing machinery from recognizing the splice sites and induce exon skipping.

Base Composition↗

PubMed1992

Paraganglioma of the posterior mediastinum: value of magnetic resonance imaging.

A case of paraganglioma arising in the posterior mediastinum in a 29-year-old man diagnosed by magnetic resonance imaging is reported. Excision of mediastinal paraganglioma is often hazardous because of its rich vascular supply and tendency to involve surrounding structures. Magnetic resonance imaging is valuable for the preoperative diagnosis of this vascular tumor as well as for determination of its resectability and appropriate surgical procedure.

Adult↗

PubMed1992

Lifespan shortening of the nematode Caenorhabditis elegans under higher concentrations of oxygen.

The effects of higher concentrations of atmospheric oxygen on the lifespans of wild type and a temperature-sensitive zyg-9(b244) mutant of the nematode Caenorhabditis elegans were examined. Their mean and maximum lifespans decreased with increasing oxygen concentration. The mean and maximum lifespans of the wild type under 60, 75, and 90% oxygen shrunk by 17 and 10, 31 and 31, and 40 and 41%, respectively, as compared with those under 21% oxygen (normal air). The mean and maximum lifespan of the zyg-9(b244) mutant under 60 and 90% oxygen shrunk by 18 and 22%, and 38 and 39%, respectively, as compared with those under 21% oxygen. The Gompertz analysis of the survival data of the wild type revealed that the exponential Gompertz component, the rate of acceleration of mortality, increased with increasing oxygen concentration: i.e. the ageing was accelerated under higher concentrations of oxygen. Oxygen acts as a lifespan determinant of the nematode. When the animals were exposed to a high concentration of oxygen at the early phase of lifespan, the oxygen-induced lifespan shortening was not observed. This means that oxygen-induced damage leading to lifespan shortening is repaired under 21% oxygen and that the oxygen-induced lifespan shortening does not result from any alteration in development and/or mutation.

Aging↗

PubMed1992

Mode of relaxing action of FK336, a new antianginal agent, in rabbit aorta.

1. FK336 (10(-6)-10(-4) M) inhibited contractile responses to norepinephrine (NE), KCl and Ca2+ in isolated rabbit aortas. 2. Relaxing effect of FK336 on KCl-response was inhibited by nitroglycerin (NG), but not by nifedipine or verapamil. 3. FK336 inhibited residual NE response and a subsequent Ca2+ response in Ca(2+)-free medium. FK336 did not affect the inositol monophosphate level. 4. Relaxing effect of FK336 on NE response was inhibited by methylene blue, NG, K(+)-channel inhibitors and acetylcholine (ACh), and potentiated by M&B 22,948 and theophylline. 8-Br cGMP and dibutyl cAMP had no effect. 5. FK336 increased cGMP level in rat aorta. 6. Potentiation of isoproterenol-relaxation by FK336 was inhibited by methylene blue. 7. The inhibitory effect of ACh on FK336-relaxation was eliminated by endothelium removal, nordihydroquaiaretic acid and guinacrine, but not by indomethacin. These treatments themselves did not affect FK336-relaxation. 8. The mode of vasorelaxing action of FK336 is discussed.

Acetylcholine↗

PubMed1992

T cell activation and T cell receptor variable region gene usage in measles.

T cell activation and T cell receptor variable (V) regions were studied with monoclonal antibodies in peripheral blood lymphocytes from 22 patients with measles. Increased (greater than 5%) activated T cells (HLA-DR+ CD3+ cells) were noted in 14 of the 22 patients. Elevations of V beta 5+ and V beta 8+ T cells were observed in two and four patients, respectively, and appeared to be associated with T cell activation. The duration of fever was significantly prolonged in those with increased (greater than 10%) activated T cells (p less than 0.01). These results suggest that T cell activation and the preferential expansion of V beta 8+ and V beta 5+ T cells are associated with the pathogenic process of measles.

Adolescent↗

PubMed1992

FR 113680: a novel tripeptide substance P antagonist with NK1 receptor selectivity.

1. We have discovered a novel tripeptide substance P (SP) antagonist, FR 113680 [N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N'-formyl-D- tryptophyl]-N-methyl-N-phenylmethyl-L-phenylalaninamide]. In binding experiments, FR 113680 inhibited [3H]-SP binding to guinea-pig lung membranes (NK1) in a competitive manner but had not effect on [3H]-SP binding to rat cerebral cortical membranes (NK1), [3H]-neurokinin A ([3H]-NKA) binding to rat duodenum smooth muscle membranes (NK2) and [3H]-eledoisin (Ele) binding to rat cerebral cortical membranes (NK3). 2. In bioassay experiments, FR 113680 dose-dependently inhibited SP-induced guinea-pig ileum contraction (NK1), but did not inhibit either NKA-induced rat vas deferens contraction (NK2) or neurokinin B (NKB)-induced contraction of rat portal vein (NK3). According to Schild plot analysis, the inhibitory effect of FR 113680 on SP-induced guinea-pig ileum contraction is competitive and the pA2 value is 7.53. 3. The inactivity of FR 113680 on NK1 receptors in rat compared to guinea-pig may represent species-specific forms of the NK1 receptor. 4. These findings suggest that FR 113680 interacts selectively with the NK1 neurokinin receptor.

Animals↗

PubMed1992

Pharmacological profile of a high affinity dipeptide NK1 receptor antagonist, FK888.

1. In our search for compounds that inhibit the binding of [3H]-substance P (SP) to guinea-pig lung membranes, the dipeptide SP antagonist, FK888, was developed by chemical modification of the parent compound, (D-Pro4, D-Trp7,9,10, Phe11)SP4-11. 2. In a [3H]-SP binding assay using guinea-pig lung membranes and rat brain cortical synaptic membranes, FK888 displaced [3H]-SP binding with a Ki value of 0.69 +/- 0.13 nM and 0.45 +/- 0.17 microM, respectively, in a competitive manner. 3. FK888 inhibited the contraction of guinea-pig isolated ileum induced by SP in the presence of atropine and indomethacin (a NK1 receptor bioassay) with a pA2 value of 9.29 (8.60-9.98). 4. FK888 inhibited contractions of rat vas deferens by NKA (a NK2 receptor bioassay) and of rat portal vein by NKB (a NK3 receptor bioassay) at concentrations at least 10,000 times greater than that required to inhibit contractions of guinea-pig ileum. 5. FK888 also inhibited SP-induced airway oedema in guinea-pig after both intravenous and oral administration. 6. These data demonstrate that FK888 is a potent and selective NK1 antagonist which is active both in vitro and in vivo.

Administration, Oral↗

PubMed1992

Characteristics of vasoinhibitory action of FK 453 (a pyrazolo-pyridine derivative), a new antihypertensive agent with diuretic action in isolated rabbit aorta.

The vasoinhibitory effect of FK 453 was examined in isolated rabbit aorta. FK 453 inhibited contractile responses to norepinephrine, angiotensin-I and KCl. Pretreatment of the tissue with FK 453 failed to affect the relaxing effect of verapamil on the KCl response and the inhibitory effect of prazosin on the phenylephrine response. FK 453 inhibited both the residual norepinephrine response and the subsequent Ca2+ response in a Ca(2+)-free medium containing EGTA and nifedipine. The inhibitory effect of a combined treatment with either FK 453 plus nitroglycerin or FK 453 plus theophylline, but not with FK 453 plus M & B 22,948 (2-o-propoxyphenyl-8-azapurine-6-one; May & Baker), was much greater than that of any single treatment. Pretreatment with FK 453 also potentiated relaxing effects of nitroglycerin and isoproterenol on the PGF2 alpha response. The effect of a combined treatment with FK 453 plus theophylline, but not with FK 453 plus M & B 22,948, was much greater than that of any single treatment. FK 453 also inhibited the activity of phosphodiesterase from canine aorta to convert cyclic [3H]-GMP and cyclic [3H]-AMP to 5'-GMP and 5'-AMP, respectively. These results suggest that the inhibitory action of FK 453 is not due to inhibition of voltage-operated Ca2+ channels or alpha-adrenoceptors, but due to increase in cyclic GMP level.

Angiotensin I↗