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Biomedical subjects

M Okabe

Publications and source records attributed to M Okabe.

At least 343 records · Page 19Linked to original sources

Comparative platelet anti-aggregant activity of D-cysteinolic acid analogues.

D-Cysteinolic acid (1) analogues with an S-C-C-N skeleton showed increased platelet anti-aggregant activity in the following order: 2-aminoethanesulfonic acids, thiazolidines, 2-aminoethanethiols and 2-aminoethyl disulfides. Methyl substitutions at the 2-position potentiated the activity. Of these analogues, bis [(R)-2-aminopropyl] disulfide was the most potent inhibitor of platelet aggregation, with about 600-fold the activity of (1).

Animals↗

Induction of angiotensin-converting enzyme inhibitory activity by acid-limited proteolysis of glyceraldehyde 3-phosphate dehydrogenase.

Angiotensin-converting enzyme (ACE) inhibitors were excised from glyceraldehyde 3-phosphate dehydrogenase (GAPDH) preparations of tuna and porcine muscles by heating at 120 degrees C for 5 min in 1 M AcOH-20 mM HCl. The inhibitors were then purified by successive chromatographies. The final product from tuna was identified as Pro-Thr-His-Ile-Lys-Trp-Gly-Asp, which was the ACE inhibitor obtained from tuna muscle [Kohama et al. (1988) Biochem. Biophys. Res. Commun. 155, 332-337]. The porcine ACE inhibitor was found to be Pro-Ala-Asn-Ile-Lys-Trp-Gly-Asp, which was identical to the porcine muscle GAPDH peptide 79-86. These results strongly suggested that the ACE inhibitory octapeptides derived from GAPDH proteins by acid-limited proteolysis at Asp-Pro and Asp-Ala peptide bonds.

Amino Acid Sequence↗

Mutagenesis of human granulocyte colony stimulating factor.

To define the structure-function relationship, we have made a number of mutants of human granulocyte colony-stimulating factor (hG-CSF) by in vitro mutagenesis. The results indicate that most of the mutations located in the internal and C-terminal regions of the molecule abolished the activity, whereas the mutants without N-terminal 4, 5, 7, or 11 amino acids retained the activity. N-terminal amino acids were also altered by cassette mutagenesis using a synthetic oligonucleotide mixture. Among them, KW2228, in which Thr-1, Leu-3, Gly-4, Pro-5 and Cys-17 were respectively substituted with Ala, Thr, Tyr, Arg and Ser, showed more potent granulopoietic activity than that of intact hG-CSF both in vitro and in vivo.

Amino Acid Sequence↗

Glucosamine enhanced sperm-egg binding but inhibited sperm-egg fusion in mouse.

In order to study the sperm-egg recognition mechanism on the surface of the plasma membrane, zonae were removed from mouse eggs by exposure to acidic conditions. Sperm binding to denuded eggs was then observed in the presence of various sugars. Among several carbohydrates tested, only glucosamine (GlcN) was found to increase the number of sperm bound to eggs while inhibiting sperm-egg fusion. The inhibition was reversible; when denuded eggs were transferred to a GlcN free medium, a high rate of polyspermy was observed.

Animals↗

Activation of Chlamydomonas rhodopsin in vivo does not require isomerization of retinal.

The unicellular eukaryote Chlamydomonas reinhardtii is a phototactic alga that swims toward or away from light, using rhodopsin as the photopigment. The activity of retinal analogues was tested in the mutant FN68, which has high phototactic sensitivity only after incubation with retinal or analogues of retinal. Analogues prevented from isomerizing about the 7-ene, 9-ene, 11-ene, 13-ene, or 15-ene (C = N+H) bonds retained full activity. Also, bleaching, protonation of the N, and a stable geometrically altered chromophore are not required for full activity. An attractive hypothesis is that charge redistribution in the excited state of retinal directly triggers the activity of rhodopsin.

Chlamydomonas↗

bcr rearrangement and C-abl gene expression in Ph1-positive hybrid acute leukemia with simultaneous proliferation of lymphoid and myeloid blasts.

bcr gene rearrangement and c-abl gene expression were analyzed in a patient with Philadelphia chromosome (Ph1)-positive hybrid acute leukemia with simultaneous proliferation of lymphoid and myeloid blasts. These data were compared with those from a patient with chronic myelogenous leukemia (CML) in mixed crisis. The leukemic cells of both patients showed immuno-phenotypic profiles such as non-T, non-B common ALL with some MPO-positive leukemic cells and rearranged JH genes. On analysis of molecular events associated with the Ph1 chromosome, the leukemic cells of a patient with CML in mixed crisis showed bcr rearrangement and an 8.5-kb bcr-abl chimeric mRNA, but those of a patient with Ph1-positive hybrid acute leukemia showed no 8.5-kb bcr-abl mRNA, as previously reported in a number of Ph1-positive acute lymphoblastic leukemia (ALL) cases. These results revealed that the molecular event found in Ph1-positive ALL is not only restricted to lymphoid lineage but may play an important role in the proliferation of the myeloid lineage.

Adult↗

Flow cytometric analysis of mouse sperm using monoclonal anti-sperm antibody OBF13.

The variable reactivity of OBF13 monoclonal antibody to mouse sperm was studied using a fluorescein activated cell sorter. Sperm from cauda epididymis were incubated with ionophore A23187, subjected to indirect immunostaining and analyzed by a cell sorter. Three peaks showing different fluorescence intensities were observed. These peaks contained (i) not stained (N), (ii) acrosomal cap or anterior region stained (A) and (iii) head stained (H) sperm, respectively. H type sperm showed more intense integral fluorescence than A type sperm. It was also noted that the H type were observed when cauda epididymal sperm were incubated with A23187, but not among non-incubated, or A23187 treated caput epididymal sperm. When sperm were pre-categorized as "dead" or "alive" by propidium iodide staining, no A type were observed in the "live" population. These results suggest that the sperm exhibiting the OBF13 antigen in the acrosome region lost their viability before they accomplished a "true" acrosome reaction.

Acrosome↗

A transarterial approach of electrical ablation of atrioventricular junction in a dog model: comparison of the effects between high and low energy shocks.

To analyze the effectiveness of a transarterial catheter technique for electrical ablation of the atrioventricular junction, 30 mongrel dogs were studied by means of synchronized electrical shock between the catheter adjacent to the noncoronary cusp and a metal plate behind the dog's back using a standard cardioversion unit. These dogs were classified into two groups according to the energy delivered. The high energy group received more than 100 joules (group A) and the low energy group received from 20 to 60 joules (group B). Complete atrioventricular block was induced by a single shock in all dogs. In group A, ventricular premature beats appeared in all dogs; ventricular fibrillation and ventricular tachycardia appeared immediately in half (6/12) after electrical ablation. No ventricular dysrhythmias occurred in group B. Temporary right ventricular pacing was also performed in 10 out of 12 dogs in group A after electrical ablation. In contrast only one dog required pacing in group B. The cycle length of the subsidiary pacemaker rhythm was essentially identical in both groups. The QRS duration of the subsidiary pacemaker rhythm in group A was significantly longer in group B (P less than 0.01). The extent of myocardial damage induced by electrical ablation in group B was more localized than those in group A. However, the histological lesion representing the granulation tissue with necrosis and slight chronic inflammatory cell infiltration, was identical between both groups A and B. It was concluded that this technique of low energy electrical ablation of the atrioventricular junction adjacent to the noncoronary cusp via a transarterial approach was useful in producing an experimental model of chronic complete AV block.

Animals↗

Studies on pharmacological activation of human serum immunoglobulin G by chemical modification and active subfragments. VIII. Effect of carboxamide-methylated light chain (Fr.I-L) on leukocyte functions.

Human serum immunoglobulin G light chain (Fr.I-L), which was reduced and carboxamide-methylated, showed no effect on formyl-methionyl-leucyl-phenylalanine (FMLP)-induced chemotaxis nor on phagocytosis of yeasts when directly added to guinea pig polymorphonuclear leukocytes (PMNs). However, intravenously administered Fr.I-L inhibited emigration of leukocytes into the peritoneal cavity and promoted phagocytosis of yeasts in a yeast-induced peritonitis model in mice. Moreover, Fr.I-L reduced FMLP-induced chemiluminescence (CL) from PMNs. These facts indicated that the anti-inflammatory action of Fr.I-L was caused by inhibiting emigration of leukocytes into the injured site and scavenging superoxide radicals from the cells.

Animals↗

Enhancement of heparin-binding ability of fibronectin by S-carboxamide-methylation.

Human plasma fibronectin (FN) was reduced and carboxamidemethylated, and its binding ability to several matrices was analyzed in vitro. The binding of S-carboxamidemethyl (Cam)-FN to heparin-Sepharose was not influenced by either 4 M urea, 0.5 M NaCl or 0.5% heparin, but was disrupted by the coexistence of urea and NaCl or heparin. S-Cam-FN, compared with intact FN, obviously had a more potent ability to bind heparin, while it had little or no binding ability to gelatin, fibrin and thrombin-stimulated platelets. A conformational change of S-Cam-FN by heparin-binding has been proposed as a possible mechanism from the result of circular dichroic spectrum measurement.

Binding Sites↗

The inhibitory effect of bis[2-[(E)-2-octenoylamino]ethyl] disulfide on the cyclooxygenase pathway.

Bis[2-[(E)-2-octenoylamino]ethyl] disulfide (compd. I-3) inhibited collagen- and arachidonic acid-induced rat platelet aggregation, although not adenosine 5'-diphosphate (ADP)-induced rat platelet aggregation. Based on these results, we then investigated the inhibitory effect of compd. I-3 on thromboxane B2 formation from arachidonic acid in rat platelets, and prostaglandin I2 formation in rat aortae. Compound I-3 inhibited both thromboxane B2 and prostaglandin I2 formation, suggesting that it has an inhibitory effect on cyclooxygenase. The inhibitory effect of compd. I-3 was confirmed in experiments using a crude preparation of sheep seminal vesicle microsomal prostaglandin synthetase. These findings suggested that compd. I-3 has an inhibitory effect on cyclooxygenase activity, like nonsteroidal anti-inflammatory drugs.

Animals↗

[A case of epilepsy with myoclonoic absences].

A case of epilepsy with myoclonic absences is reported. A boy, 3 years and 8 months old, had the first attack at the age of 1 year and 8 months. He was mentally retarded, but had no evidence of organic brain damages. He had been said to have "absence" at another hospital for 2 years until he was referred to our hospital. The attack was characterized clinically by sudden loss of consciousness accompanied with rhythmical massive myoclonias. The ictal EEGs showed synchronous diffuse 3 c/s spike-wave discharges. There was a strict and constant relation between spike-wave discharges and the myoclonia. The polygraphy recording (EEG and EMG of various muscles) was very helpful for the diagnosis of epilepsy with myoclonic absences. We think that epilepsy with myoclonic absences should be considered in any case of "absence" with concomitant 3 c/s spike-wave discharges which is resistant to appropriate treatment, or is accompanied with mental retardation.

Child, Preschool↗

[Treatment of prosthetic valve endocarditis--analysis of eleven cases].

A retrospective examination was made of eleven patients that developed prosthetic valve endocarditis (PVE) during the period from January 1960 to December 1987. Infection occurred in one patient within 60 days after surgery and in 10 thereafter. Causative organism was found in 6 patients. As organism, Staphylococcus species were noted in 4 patients and Peptstreptococcus was noted in one patient and Aspergyllus was noted in one patient. Three of eleven patients received medical treatment only and the other 8 patients were received surgical treatment. Mortality rate was 67% in medical group and 29% in surgical group. Two patients with medical treatment died of cerebral infarction about 40 days after the onset of PVE. In surgical group one patient died of uncontrollable Aspergillus infection and the other one died of dyspnea. No survivors who was treated surgically have developed reinfection or relapse of infection but four of them developed perivalvular leakage and needed reoperation. Absolute removal and closure of the valve ring abscess and reconstruction of defect should be considered for those needed surgical treatment to prevent reinfection and relapse developing.

Adolescent↗

[Successful removal of ball thrombus in the left atrium].

Two cases of left atrial ball thrombus associated with severe mitral stenosis in which echocardiography provided the clue to the diagnosis preoperatively were reported. First case was a 58 years old man who was admitted because of dyspnea and frequent syncopal attacks. An echocardiographic examination revealed a tight mitral stenosis and a floating ball thrombus in the left atrium. Under the extracorporeal circulation, the ball thrombus, 30 X 40 mm in size, weight 20 g was taken out. The other case was a 51 years old woman who had undergone surgery for closed mitral commissurotomy 14 years ago. She had a episode of syncope attack and a sudden loss of consciousness. The removed thrombus was 20 X 26 mm in size and weighed 5 g. Their cut surfaces showed an laminated structure in both cases. These mitral valves were replaced by Björk-Shiley prosthetic valves.

Echocardiography↗

Isolation of angiotensin-converting enzyme inhibitor from tuna muscle.

A novel inhibitor of angiotensin-converting enzyme (ACE) has been discovered and isolated in a pure form from acid extract of tuna muscle by successive column chromatographies and HPLC. The final preparation showed IC50 values of 1 microM and 2 microM for ACEs from bovine and rabbit lungs, respectively. The amino acid sequence of the inhibitor has been established as Pro-Thr-His-Ile-Lys-Trp-Gly-Asp by the Edman procedure and carboxypeptidase digestion.

Amino Acid Sequence↗

Suppression of gastric ulcer induced by stress and HCL-ethanol by intravenously administered metallothionein-II.

A metallothionein isoform metallothionein-II was isolated from the livers of zinc acetate-treated rats. Metallothionein-II, which showed a single band on polyacrylamide gel electrophoresis, was subjected to two kinds of anti-ulcer screening systems. It was shown that intravenously administered metallothionein-II suppressed the formation of rat water-immersion stress- and HCl-ethanol-induced gastric ulcer significantly. The effect may partly be derived from the zinc contained in the metallothionein-II. However, the effect of metallothionein-II was much stronger than that of an equivalent mole of zinc. Apparently, metallothionein-II had an anti-ulcerogenic activity not based on the effect of intrinsic zinc.

Acetates↗

Electron microscopic study of the biopsied cardiac muscle in Duchenne muscular dystrophy.

Cardiac muscular biopsies were performed on 4 patients with Duchenne muscular dystrophy (DMD). None of the patients had cardiac symptoms and all of them exhibited normal electro- and echocardiographic findings. Electron microscopic examination of cardiac muscles from 4 patients with DMD disclosed proliferation of the mitochondria, changes in the cristae, abnormalities of the Z-bands, dilatation of the sarcoplasmic reticulum, deposition of glycogen, and changes in the nuclei. The most striking finding in these patients was that the residual bodies were increased and were observed mainly in the perinuclear region. These ultrastructural features suggest that an extreme exhaustion had already been present in myocardial tissue of the patients prior to the onset of cardiac symptoms.

Adolescent↗