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Biomedical subjects

H Manabe

Publications and source records attributed to H Manabe.

At least 91 records · Page 5Linked to original sources

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↗

Alkali-labile oligosaccharide units of a sialoglycoprotein from rabbit erythrocyte membranes.

Two glycoproteins (apparent molecular weights 120,000 and 70,000) were extracted from rabbit erythrocyte membranes, and only one (Mr 120,000), which is a sialoglycoprotein, contained O-glycosidically linked sugar chains. Alkali-labile oligosaccharide units of the sialoglycoprotein were released as reduced oligosaccharides by NaOH-NaB3H4 treatment, and then purified by gel filtration on a Bio-Gel P-4 column followed by ion-exchange chromatography. From the results of methylation analysis, mass spectrometry and chromium trioxide oxidation, the main oligosaccharide unit was determined to be a linear trisaccharide (85% by weight), NeuNGc alpha(2----3)Gal beta(1----3)GalNAcol. In addition, small amounts of a tetrasaccharide (11% by weight) and a disaccharide (4% by weight) were found, which were determined to have the following structures, NeuNGc alpha(2----3)Gal beta(1----3)[NeuNGc alpha(2----6)] GalNAcol and Gal-GalNAcol, respectively.

Animals↗

[A human case of pulmonary dirofilariasis suspected to be lung cancer].

A 50-year-old man in Kitakyushu City visited a hospital for evaluation of an opacity in a routine chest X-ray film. After examinations by bronchoscopy and chest roentgenography, a clear coin lesion was found in the middle lobe of the right lung and was suspected to be a lung cancer. A right thoracotomy was performed to remove it. The lesion (10.6 X 9.8 mm) was a well-defined ellipsoid granuloma due to a foreign body with a central zone of necrosis surrounded entirely by a fibrous wall. In a cross section of the dissected granuloma two degenerated worm-like structures were revealed. The sections of the worm (216-240 X 296 mu m at the greatest diameter) had at least a 3-layered cuticle and prominent internal longitudinal cuticular ridges but no external cuticular ridges. The lateral chords were as high as the muscle layer which consisted of abundant somatic muscle (more than 30 muscle cells/quadrant). Judging from these morphological characteristics, the pulmonary granulomatosis was diagnosed to be due to an immature dog heartworm, Dirofilaria immitis. This identification was further supported by results from immunological methods. The present case is the 56th human case of dirofilariasis (the 39th as a pulmonary case only) in Japan.

Diagnostic Errors↗

Identification of cardiac rejection in heterotopic heart transplantation using 111In-antimyosin.

It is important in heart transplantation to evaluate precisely the extent and location of cardiac rejection. At present, right ventricular endomyocardial biopsy has been used as the gold standard, however, establishment of noninvasive, simple, and easy diagnostic procedure is desired. The canine donor heart, in which atrial septal defect and tricuspid regurgitation had been produced beforehand, was heterotopically transplanted into the recipient's chest cavity. In seven dogs, two to three mCi of 111In-antimyosin was injected intravenously upon cardiac rejection before the heart was excised. 111In-antimyosin myocardial imaging was then performed using a gamma camera. In the same slice, a histopathological rejection score was calculated and divided into mild, moderate or severe injection. The uptake of 111In-antimyosin was significantly higher in moderate and severe rejected myocardium, since this agent produced a specific and selective localization and concentration in areas of myocardial damage. Therefore, this new technique allows the evaluation of therapeutic intervention upon cardiac rejection and may replace right ventricular endomyocardial biopsy.

Animals↗

Identification of cardiac rejection with magnetic resonance imaging in heterotopic heart transplantation model.

It is important to evaluate the severity and extent of cardiac rejection in heart transplantations. Eight heterotopic heart transplantations using mongrel dogs were performed, and grated magnetic resonance imaging (MRI) of the donor hearts was carried out. High signal intensity was obtained in the rejected myocardium at the time of cardiac rejection, especially from the right ventricular wall to the intraventricular septal wall compared with the left ventricular posterolateral wall. In addition, MRI was performed in the excised heart. High signal intensity was also observed in the same region of the excised donor hearts. The histopathological rejection scores were well in agreement with prolonged T1 and T2 relaxation times; severe and mild rejection of the myocardium were distinguished by the T1 and T2 relaxation times. Our results suggest that MRI is able to visualize the transplanted myocardium undergoing rejection and that the right ventricular wall is more sensitive to cardiac rejection than the left. MRI may allow noninvasive evaluation of the severity and extent of cardiac rejection.

Animals↗

Cardiac transplantation in dogs: evaluation with gated MRI and Gd-DTPA contrast enhancement.

It is important to evaluate the severity and extent of cardiac rejection in heart transplantation. Six heterotopic heart transplantation models in the peritoneal cavity were prepared with 12 adult mongrel dogs and in vivo imaging of the donor heart was performed using gated magnetic resonance imaging, (MRI) and Gd-DTPA contrast enhancement. In cardiac rejection, high signal intensity was obtained in the rejected myocardium, especially from the right ventricular wall to the intraventricular septal wall. The rejected myocardium was clearly visualized after administration of Gd-DTPA (0.5 mmol/kg body weight) via the femoral vein in all donor hearts. The mean ratios of signal intensity calculated from the rejected and normal myocardium were also increased from 25% to 42% after administration of Gd-DTPA. On the other hand, in the cases with no rejection, whole myocardium was visualized homogeneously before and after Gd-DTPA and there was no high signal intensity. Thus, our method has the potential of assessing the extent and severity of cardiac rejection using gated MRI and Gd-DTPA contrast enhancement.

Animals↗

Varicella-zoster virus infections during pregnancy: hypothesis concerning the mechanisms of congenital malformations.

An analysis of the data on 52 infants whose mothers had contracted varicella during pregnancy revealed that 27 had congenital malformations ascribed to the maternal varicella infections, while another 25 developed herpes zoster in the early postnatal period. Most of the mothers whose infants had congenital malformations had contracted varicella within the first 20 weeks of gestation, whereas most of the mothers whose infants developed herpes zoster had varicella after 21 weeks of gestation. The clinical features of the various congenital malformations and dysfunctions after maternal varicella were diverse; however, there were peculiar segmental manifestations of anomalies of the skin, the peripheral nervous, the autonomic nervous, and the musculoskeletal systems, all of which receive common innervations from the same levels of the spinal cord. Most other dysfunctions may be ascribed to an encephalitis. Therefore, the mechanism of congenital malformations caused by varicella-zoster virus seems to be due not to fetal varicella but to the development of herpes zoster in utero and to an encephalitis associated with herpes zoster. At least one infant had congenital malformations that were due to maternal herpes zoster infection.

Congenital Abnormalities↗

Micellar formation of spin-labeled fatty acyl derivatives of lipophilic muramyl dipeptides and their incorporation into liposomal membranes.

A lipophilic muramyl dipeptide (MDP) with a nitroxide moiety in its acyl chain (SL-MDP) and its N-methyl derivative (SL-methyl MDP) were synthesized. The SL-MDPs formed micelles (cmc, 0.1-0.3 mM). The ESR spectra of the SL-MDPs in phosphatidylcholine (PC) liposomes at 25 degrees C consisted of an anisotropic signal and three sharp lines, indicating that both SL-MDPs partitioned between membranes and aqueous phase. The amounts of the SL-MDPs in membranes depended on the phospholipid species and the cholesterol (Chol) content, but no appreciable difference was observed between SL-MDPs. The SL-MDPs partitioned well at 25 degrees C into egg yolk PC liposomes but not into pure dipalmitoylphosphatidylcholine (DPPC), suggesting that the incorporation may be related to the membrane fluidity. Chol enhanced the incorporation into both phospholipids. The mobilities of the SL-MDPs in the membranes were less than that of the corresponding spin-labeled fatty acid. Comparison of the mobilities among SL-MDPs, spin-labeled ganglioside and spin-labeled galactosylceramide showed that the hydrophilicity of the polar group may influence the immobilization of their acyl chains.

Acetylmuramyl-Alanyl-Isoglutamine↗