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Biomedical subjects

H Manabe

Publications and source records attributed to H Manabe.

At least 37 records · Page 2Linked to original sources

[Experimental study on liquefaction of intracranial hematoma: usefulness of tissue-plasminogen activator (t-PA), a hematolytic agent, and its combination].

In stereotaxic aspiration of intracerebral hematoma and extensive removal, or cisternal drainage for subarachnoid hematoma, rapid and safe liquefaction and removal of clots are important and urgent measures to be taken. We performed a pharmacological experimental study on the efficacy, administration method, and toxicity of various hematolytic agents, especially tissue-Plasminogen Activator (t-PA). The following findings were obtained. 1) The amount, hardness, and histological findings concerning the remaining hematoma differed markedly according to which hematolytic agents were used. 2) The local effects of each hematolytic agent continued for about 4-8 hours but markedly decreased thereafter. 3) The hematolysis rate following single administration (6 hours after the blood collection) was 88.9% with t-PA + Elase (Fibrinolysin + Deoxyribonuclease), 85.4% with t-PA, 84.6% with t-PA + Urokinase, 80.2% with t-PA + Urokinase + Elase, 27.55 with Elase + Urokinase, 24.6% with Elase + Urokinase + Heparin, 17.2% with Heparin + Urokinase, 16.4% with Urokinase, 13.2% with Elase + Heparin, 12.6% with Elase, 9.3% with Heparin, and 10.1% with the control (Saline). Locally administered t-PA had remarkably greater hematolytic effects than Urokinase on the hematoma (p less than 0.001). 4) The hematolysis rate after 24 hours of repeated administration of small doses at 8-hour intervals was 100% with t-PA + Urokinase + Elase, 94.2% with t-PA, 93.8% with t-PA + Urokinase, 50.9% with Elase + Urokinase, 46.6% with Elase + Urokinase + Heparin, 33.7% with Urokinase, and 4.8% with the control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Structure of the major O-glycosidic oligosaccharide of monkey erythrocyte glycophorin.

Sialic acids and the major O-glycosidic oligosaccharide of glycophorin MK from monkey (Japanese monkey, Macaca fuscata) erythrocyte membranes were characterized. N-Glycolylneuraminic acid (Neu5Gc) was found as the major sialic acid, which was confirmed by gas-liquid chromatography-mass spectrometry as the trimethylsilyl methyl ester. Three O-glycosidic oligosaccharide units were obtained from a tryptic glycopeptide that contained all of the carbohydrate units in glycophorin MK by mild alkaline borohydride/borotritide treatment. Carbohydrate analyses of the oligosaccharides revealed that they were composed of Neu5Gc, galactose and N-acetylgalactosaminitol in the molar ratios of 1:1:1 (trisaccharide), 2:1:1 (tetrasaccharide) and 3:1:1 (pentasaccharide). The content of oligosaccharide units was estimated to be 1:12:5 for penta-, tetra- and trisaccharide, respectively, based on the yields, the molecular weight, and the number of oligosaccharide attachment sites in the amino-acid sequence. The tetrasaccharide was the major oligosaccharide and its structure was proposed to be Neu5Gc alpha 2-3Gal beta 1-3[Neu5Gc alpha 2-6]GalNAcol.

Animals

Sodium nuclear magnetic resonance imaging of acute cardiac rejection in heterotopic heart transplantation.

Nuclear magnetic resonance (NMR) imaging was used to measure tissue sodium-23 in the myocardium undergoing cardiac rejection. In six dogs, the donor heart was heterotopically transplanted into the recipient's chest cavity. The dogs were then killed and sodium-23 images of the excised hearts were obtained using a high field (1.5 Tesla) NMR imaging system. Proton NMR imaging of each excised heart was also performed and T1, T2 relaxation times were calculated. Subsequently, these data were correlated with pathological findings of mild, moderate and severe rejection. The correlation coefficients between the rejection score and the T1, T2 relaxation times and sodium NMR signal intensity were 0.79, 0.70 and 0.84, respectively. Severely rejected areas of the myocardium were visualised by increased sodium NMR signals. These findings suggest that an increase of sodium NMR intensity is mainly caused by an increase of intracellular sodium content due to irreversible myocardial necrosis. Sodium NMR allows evaluation of the location and extent of rejection of myocardium after heart transplantation.

Animals

The immunopotentiating property of lipophilic muramyl dipeptide and its molecular state in liposomal membranes: plaque-forming cell responses and ESR studies.

The immunopotentiating property of spin-labeled lipophilic muramyl dipeptide (SL-MDP) in liposomes was studied as to the plaque-forming cell (PFC) response to glycophorin, as an antigen, in membranes. The effect of SL-MDP depended on the densities of both SL-MDP itself and the antigen. The addition of the optimal amount of SL-MDP to liposomes containing a low density (0.016 mol%) of the antigen increased the PFC response by three times, whereas the presence of SL-MDP in optimal antigen density (0.032 0.127 mol%) membranes was rather inhibitory. In these liposomes, the amounts and molecular states of SL-MDP were determined from ESR spectra and are discussed in connection with its immunopotentiating property.

Acetylmuramyl-Alanyl-Isoglutamine

Effect of host lattice on antigenicity of glycophorin in membranes.

The influence of the host lattice on the antigenicity of glycophorin in membranes was confirmed by complement-dependent immune lysis of liposomes with two rabbit antisera, which were prepared by immunization with either human red blood cells or isolated glycophorin A. The immune lysis by either antiserum depended on the kind of phospholipid in the liposomes. Anti-glycophorin antiserum more strongly recognized glycophorin in egg-lecithin membranes than in dipalmitoyl-lecithin membranes, as did anti-red blood cell antiserum. Cholesterol in the liposomal membranes influenced the antigenicity of glycophorin. The relationship between the state of glycophorin in membranes and recognition by antibody is discussed.

Antigen-Antibody Reactions

[Protective effects of nicorandil against catecholamine induced myocardial damage under hypoxia].

Direct myocardial protective effects of Nicorandil (NR) against hypoxic injury were evaluated using an in vitro model of isolated, adult rat myocytes. Ca++-tolerant, trypan blue negative, viable cells were suspended for 1 hour in a hypoxic (Po2 20 mmHg) Eagle's MEM culture medium. Myocytes were then divided into 4 groups and incubated for 3 hours either without (control) or with norepinephrine (NE) (10(-6)M), NR (10(-4)M) or NE+NR. Cell viability ratio (trypan blue staining method) and intracellular ATP contents were measured as indexes of cell damage. NE significantly decreased the cell viability ratio compared to that in control after 1 to 3 hours. Addition of NR prevented the reduction in viability ratio produced by NE. NR markedly attenuated intracellular ATP reduction induced by NE after 1 hour incubation. These results suggest that NR has potent direct effects against hypoxia-induced cell injury in the presence of catecholamines.

Adenosine Triphosphate

[Development and evaluation of ventricular assist blood pump to salvage patients with profound heart failure].

One of the most important characteristics of a ventricular assist device (VAD) is good antithrombogenicity such that the circulating blood does not clot on the surface even when the bypass flow through the device is reduced at the time of weaning-off. A pneumatic and diaphragm-type VAD with excellent antithrombogenicity was developed for clinical use. The pump is made of Japanese-made segmented polyether polyurethane and the maximum output is 7.0 L/min. If the bypass flow was maintained above 2.0 L/min during early postoperative period, thrombus formation was rarely observed even when the flow rate decreased afterwards in chronic animal experiments using 30 goats. Experimental analyses suggested that a biolization mechanism of the material surface covered by absorbed plasma protein might play a major role in the establishment of antithrombogenicity of the pump. No mechanical failure, thrombosis, calcification, and complication in experimental animals occurred when the VAD manufactured under our good quality control system was driven adequately. These results proved that the VAD could be used reliably for at least 3 months. In conclusion, the VAD is safely applicable to clinical cases and contributes to treatments of profound heart failure patients.

Acute Disease

[Surgical management of pulmonary metastasis from carcinoma of the uterine cervix].

The present study was designed to evaluate the efficacy of surgical management of pulmonary metastasis from carcinoma of the uterine cervix. We saw 609 cases of carcinoma of the uterine cervix from 1979 to 1987, and during the same period also saw 110 cases of recurrent carcinoma of the uterine cervix. Fourteen of these 110 cases were identified as having pulmonary metastasis, and in 11 of 14 cases the recurrent tumors were limited to the lung. Seven of these 11 cases underwent pulmonary resection. Six of the 7 survived more than 2 years after pulmonary resection. Among them, 1 patient has survived more than 4 years, and 1 patient more than 8 years. The tumor cells were thought to metastasize to the lung through the vertebral venous plexus (Batson's plexus) which was suggested as a metastatic route by Thomford et al. in their report on recurrent colon cancer. As a result of this study, if the recurrent tumor is clinically limited to the lung in patients with recurrent carcinoma of the uterine cervix, they should be treated by surgical resection of the pulmonary tumor.

Adenocarcinoma

[Experimental studies of prolonged circulatory maintenance with a left ventricular assistance in cardiac arrested goats].

Recently, various types of left ventricular assist systems (LVAS) have become available to treat the patients in profound heart failures beyond the limit of the effects of IABP. However, the occurrence of an intractable severe bi-ventricular failure, ventricular fibrillation (VF) or cardiac arrest during the time with left ventricular assistance became a more serious problem. Since during the usage of these assist devices, pulmonary venous return will decrease, consequently, LVAS will not be able to maintain sufficient systemic circulation over a extended duration. This study was intended to develop a method of prolonged circulatory maintenance only with a LVAS in cardiac arrested goats until the time when heart transplantation will be performed. In this study, our LVAS was implanted between the left atrium and the aorta in twelve goats in which the hearts were fibrillated. We have followed the principle of circulatory maintenance only with our LVAS in cardiac arrest based on the pressure gradient between the right and left atria and at the same time the pump suction effect through the lungs. The results showed that when pulmonary vascular resistances (PVRs) were kept within normal ranges (less than 15,000 dynes.sec.cm-5), systemic circulations were well maintained only with LVAS as long as RAPs were kept in 14-18 mmHg. Under these conditions, the systemic circulatory flows have fluctuated between 80-140 ml/kg/min depending on the animals demands. The mean arterial pressures were kept above 80 mmHg and the goats have shown quite normal behaviors. However, in goats which showed the presence of pleural effusions and ascites were found to be more difficult to maintain prolonged normal circulation. In our study, the maintenance of total serum protein level above 6.0 g/dl was found to be essential to prevent the development of both pleural effusions and ascites . The authors have achieved the longest survival goat for a duration of 38 days after implantation with our LVAS. We have concluded that when PVRs may be kept in normal ranges, our LVAS can maintain normal systemic circulation even in arrested hearts for a prolonged duration during which time heart transplantation or total artificial heart replacement can be performed.

Animals

[Relationship between directions of cerebellar retractions and cochlear and vestibular nerve injuries].

It is said that lateral-to-medial retraction of the cerebellar hemisphere is hazardous because, by this retraction, avulsion injury of the cochlear nerve and internal auditory artery may be caused. Caudal-to-rostral retraction of the cerebellar hemisphere is, therefore, recommended in operations in the CP angle such as microvascular decompression procedures. From the results of our present study, however, it can be said caudal-to-rostral retraction can easily cause vestibular nerve damage. However, rostral-to-caudal retraction may damage the cochlear nerve just as lateral-to-medial retraction does. These differences of the eighth nerve injuries according to directions of cerebellar retractions are explicable from the fact that the vestibule and vestibular nerve are located posterior to the cochlea and cochlear nerve. Most of dysequilibrium appearing after manipulations in the CP angle may be due to vestibular nerve damage-avulsion of the vestibular nerve and its accompanying vessels from the vestibular apparatus.

Action Potentials

[Pulmonary dirofilariasis found unexpectedly during thymectomy].

A 56-year-old woman in Kitakyushu City was operated on after diagnosis of mediastinal tumor with myasthenia gravis. Besides the thymoma, a small nodule was palpated in the lower lobe of the left lung and biopsied. A segmented worm was found in sections of this granulomatous nodule. A cross section of the degenerated worm (400 X 310 micron) showed a 3-layered tegument and internal cuticular ridges with high lateral chords. The muscle layer consisted of high and polymyarian muscles. Based on these characteristics, this worm was identified as an immature dog heartworm, Dirofilaria immitis. The recent sharp increase of dirofilariasis cases reported in Japan is discussed.

Dirofilariasis

Assessment of severity of cardiac rejection in heterotopic heart transplantation using indium-111 antimyosin and magnetic resonance imaging.

Seven canine donor hearts in which atrial septal defect and tricuspid regurgitation had previously been produced were heterotopically transplanted into the recipients' chest cavities. Indium-111 antimyosin myocardial imaging of the excised heart was performed using a scinticamera. Magnetic resonance imaging was also performed and the T2 relaxation time calculated. Subsequently, these data were correlated with pathological findings, which indicated the degree of rejection. Indium-111 antimyosin uptake was high in moderate and severe rejection, but the T2 relaxation time was prolonged even in mild rejection. Thus indium-111 antimyosin uptake was specific, and the T2 relaxation time was sensitive, for detecting the severity and extent of cardiac rejection. Although ex vivo experimental results have been reported, these new methods allow characterisation and accurate evaluation of myocardial tissue undergoing cardiac rejection.

Animals

Oxatomide inhibits the release of chemical mediators from human lung tissues and from granulocytes.

The effects of oxatomide on the release of histamine and leukotriene C4 (LTC4) from human lung fragments and granulocytes were examined and the findings compared with the effects of the antiallergic drugs ketotifen, azelastine and tranilast. Oxatomide inhibited the release of both histamine and LTC4 from human lung fragments in cases of passive sensitization with human IgE myeloma serum upon anti-epsilon stimulation. IC50 values for the release of LTC4 from human lung fragments were as follows: oxatomide, 2.35 x 10(-5) M; azelastine, 27.2 x 10(-5) M; ketotifen, 52.1 x 10(-5) M; tranilast, 62.9 x 10(-5) M. Oxatomide also inhibited the release of both histamine and LTC4 from human mixed leukocytes stimulated by the calcium ionophore A23187. IC50 values for the release of LTC4 from human mixed leukocytes were as follows: oxatomide, 1.67 x 10(-5) M; azelastine, 3.65 x 10(-5) M; ketotifen, 12.2 x 10(-5) M; tranilast, 15.1 x 10(-5) M. The effects of oxatomide on the release of LTC4 from purified human neutrophils and eosinophils were also given attention. Oxatomide inhibited the release of LTC4 from eosinophils more effectively than from neutrophils and mixed leukocytes. As there is evidence that eosinophils play an important role in the development of late asthmatic responses and/or in the aggravation of asthma, oxatomide is expected to be an effective treatment for such conditions.

Dose-Response Relationship, Drug

Biochemical mechanism of release of atrial natriuretic polypeptide.

To define transmembrane and intracellular mechanisms of production and release of atrial natriuretic polypeptide (ANP) in the absence of mechanical atrial stretch, we studied the direct effects of physiological stimuli on isolated adult rat atrial myocytes maintained under tissue culture. Although stimulation of beta-adrenergic receptors on the surface of atrial myocytes by isoproterenol did not affect ANP release, adrenergic alpha-1 receptor stimulation by methoxamine enhanced ANP release with reciprocal intracellular ANP reduction. When muscarinic receptors were stimulated by acetylcholine, ANP release was accelerated and intracellular ANP reduced. The activation of the phosphatidylinositol system, which is a common pathway for muscarinic and alpha-1 adrenergic receptor stimulation, was thus considered to regulate ANP release, but not ANP production.

Acetylcholine

Antiinflammatory and antiallergic effects of a novel metabolite of Nocardiopsis sp. as a potent protein kinase C inhibitor from microbial origin.

The antiallergic and antiinflammatory effects of the new protein kinase C and calmodulin inhibitor K-252a (8R, 9S, 11S)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11- epoxy-1H,8H,11H-2,7b,11a-triazadibenzo [a,g]cycl oocta [cde] trinden-1-one) were investigated in animal models, and the following results were obtained: 1. Oral administration of K-252a, ketotifen or oxatomide showed a dose-dependent inhibition on 48 h homologous passive cutaneous anaphylaxis in rats and anaphylactic bronchoconstriction in passively sensitized guinea pigs. 2. K-252a (1-100 mg/kg p.o.) exerted a dose-dependent protection against platelet-activating factor (PAF)-induced mortality in mice. This protective effect of K-252a was sustained for 7 h. 3. K-252a (1-100 mg/kg p.o.), as well as dexamethasone (1 mg/kg s.c.), showed remarkable inhibitory effects on rat paw edema induced by carrageenin, zymosan, PAF, and antigen-antibody reaction (passive Arthus reaction) and on the croton oil-induced rat ear edema. On the other hand, indomethacin (10 mg/kg p.o.) significantly inhibited carrageenin-induced edema, but did not inhibit edema induced by other phlogistic agents. Based on these results it is suggested that K-252a, by oral administration, has antiallergic and antiinflammatory effects.

Anaphylaxis