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Biomedical subjects

I Okada

Publications and source records attributed to I Okada.

At least 37 records · Page 2Linked to original sources

Beta-blocker treatment of dilated cardiomyopathy. Beneficial effect of carteolol in mice.

BACKGROUND: The effects of carteolol, a nonselective beta-adrenergic receptor blocker with intrinsic sympathomimetic activity, were compared with those of metoprolol in a murine model of viral myocarditis and dilated cardiomyopathy caused by encephalomyocarditis virus. METHODS AND RESULTS: In the acute experiment, BALB/c and DBA/2 mice were inoculated with encephalomyocarditis virus. BALB/c mice were then given carteolol at 1 (n = 10), 10 (n = 10), 30 (n = 11), or 100 mg/kg (n = 9) daily, and DBA/2 mice were given carteolol at 1 (n = 9) or 10 mg/kg (n = 9) daily starting the day of inoculation. Controls were given distilled water (n = 23 for BALB/c mice and n = 8 for DBA/2 mice). BALB/c mice were killed on day 7, and DBA/2 mice were killed on day 14. In the subacute experiment, DBA/2 mice were inoculated with the virus and then given carteolol at 1 (n = 12) or 10 mg/kg (n = 16), or distilled water (n = 27) daily, starting on day 14. Mice were killed on day 28. Virus replication, murine survival, heart weight to body weight ratio, and histopathological findings were similar in each group in the acute and subacute experiments. In the chronic experiment, DBA/2 mice were inoculated with the virus and were then given carteolol at 1 (n = 13) or 10 mg/kg (n = 9), metoprolol at 30 mg/kg (n = 9), or distilled water (n = 31) daily, starting on day 14. Mice were killed on day 104. Heart weight to body weight ratio and histopathological scores were significantly lower in mice given carteolol than in the infected control group. Furthermore, left ventricular cavity dimension, left ventricular wall thickness, and myocardial fiber diameter of the left ventricle were significantly reduced in mice given carteolol compared with the control group. Metoprolol did not cause any significant changes compared with the control group. CONCLUSIONS: This study suggests that carteolol prevents the development of myocardial lesions similar to those in dilated cardiomyopathy after myocarditis in the chronic stage.

Adrenergic beta-Antagonists↗

Pathogenesis of myocardial injury in myocarditis and cardiomyopathy.

The pathogenesis of myocardial cell injury in myocarditis and cardiomyopathy was investigated. The presence of viral genomes in the murine heart in experimental coxsackievirus B3 myocarditis was studied by Northern blotting analysis using a 32P-labeled cDNA probe from the 5' end sequence. The strongest signal of positive autoradiograms was always at about 7.4 kilobases, corresponding to the size of the complete genome of the virus. Successive infections with coxsackievirus and encephalomyocarditis (EMC) virus infection showed simultaneous acute myocarditis and healed myocarditis, and the results suggest that successive virus infections cause additional myocardial damage, and develop lesions similar to chronic myocarditis or dilated cardiomyopathy. Anti-heart auto-antibody, induced during EMC virus infection, reacted predominantly with myosin. Indium-111 antimyosin scintigraphy showed positive in some of the patients with cardiomyopathy, and the uptake was inversely correlated with left ventricular function. When mice were injected with antimyosin antibody, mouse immunoglobulin G was detected in hearts in the chronic stage of EMC virus myocarditis, in myocytes surrounding fibrosis and calcification, suggesting deposition of antimyosin antibody. Although further study is necessary to clarify the mechanism of uptake of antimyosin in cardiomyopathy, antimyosin antibody may accumulate in viable myocytes with ongoing degeneration as well as in necrosis.

Animals↗

The effect of cyclosporine on the immunopathogenesis of viral myocarditis in mice.

The effect of cyclosporine on the immunopathogenesis of viral myocarditis was studied using a murine viral myocarditis model. Mice in the treated group had a higher mortality rate compared with those of the infected control group before day 15 (47/67 vs. 14/31, p less than 0.05). On day 7, treated mice showed higher titers of anti-heart autoantibody than the control group (12 +/- 7 vs 4 +/- 2, p less than 0.05), but no significant difference was seen on day 14 (28 +/- 15 vs. 39 +/- 34). Histologic lesions, lymphocyte subsets in the peripheral blood and heart in situ, the neutralizing antibody, and virus concentrations in the heart showed no significant differences between these groups. This study suggests that with the use of cyclosporine the production of anti-heart autoantibody was enhanced in the early stages of viral myocarditis in mice, and was associated with higher mortality rate.

Animals↗

Genetic resistance to a Marek's disease transplantable tumor cell line in chicken lines selected for different immunological characters.

The tumor incidence and mortality of Marek's disease (MD) were determined for 471 progeny from four pairs of lines two-way selected for different immunological characters: graft versus host reaction (GVHR) competence, IgG levels, antibody response to rabbit serum albumin (RSA), and anaphylactic shock to BSA. All chicks were inoculated at 1 wk of age with 1 to 2 x 10(6) viable cells of a MD lymphoblastoid cell line, MDCC-MSB1-41C (41 C). Tumor incidence differed significantly between the high (H) and low (L) lines of each GVHR-, IgG-, RSA-, or BSA-selected group. There were also significant differences in mortality rates between H and L lines of all selected groups. The IgG-H, BSA-H, and RSA-H lines were more resistant than their respective L lines. The H line of the GVHR-selected lines was more susceptible than the L line. Tumor regression could be detected only in the IgG- and RSA-selected lines. No definite correlation could be found between genetic resistance to 41C and genetic resistance to MD virus.

Anaphylaxis↗

Hearing screening in health examination services for young children at health centers in Japan.

The infant hearing screening program (IHSP) was devised for the early discovery of severe to profound hearing impairments in children. The program has been planned for use in the ordinary health examination services (with a follow-up program) for young children in health centers. The IHSP consists of a three-part test battery: a high-risk register for deafness, a developmental test of auditory function, and an auditory behavioral test. From 1977 to 1983, 22,443 young children were screened in four health centers in Osaka City. Ten of these children were identified as having serious hearing loss. Five of these 10 children were below 11 months of age. The incidence of children with severe to profound hearing impairment was inferred to be approximately 0.04% in the general population of young children. Certain problems occurred in the IHSP, and included a high level of over-referrals. However, the IHSP was considered to be a useful screening method for the early detection of severe hearing impairments when used in general health check-ups in health centers.

Child Health Services↗

The viral genome in experimental murine Coxsackievirus B3 myocarditis: a Northern blotting analysis.

The presence of viral genomes in the murine heart in experimental coxsackievirus B3 myocarditis was investigated by Northern blotting analysis. Four-week-old C3H/He mice were inoculated with coxsackievirus B3. After sacrifice, the hearts were divided into 3 parts. Total RNA was extracted from one part of the heart. The other two parts were used for investigation of histopathology and of virus titer by plaque assay. The 32P-labeled cDNA probe was derived from the 5' end sequence of the coxsackievirus B3 genome. Northern blot autoradiograms of heart RNA were positive for viral RNA until day 7 and negative after day 10 and in control (uninfected) hearts. Positive autoradiograms always had the strongest signal at about 7.4 kilobase, corresponding to the size of the complete genome of the virus. The viral genomes were detected earlier than the appearance of the histopathologic changes in the murine heart. This type analysis of the viral genome in the murine myocardium may be useful in evaluating the effects of specific drugs on experimental viral myocarditis at the level of the viral genome.

Animals↗

[Magnetic resonance angiography using a magnetic resonance flow tagging technique].

A direct bolus imaging method, which was developed for flow quantitation, was applied to the cervical regions of four normal volunteers to perform magnetic resonance angiography. A transverse section of 10 mm thickness was selectively excited to tag blood flow in the supraclavicular region and a projected image of the tagged bolus viewed in terms of anteroposterior direction was obtained after the echo time (TE). Like cine magnetic resonance imaging, multiple images representing four to 16 cardiac phases were obtained with repeated excitations. With a relatively long TE, ranging from 50 to 200 msec, we advanced tagged blood farther downstream, so as to elongate the visualized bolus along the vessel. Within the visualized bolus, the outer layer close to the vessel wall, where the blood flow velocity was slow, stretched like long tails behind the central part of the bolus producing arrow-head shapes, and the tails were assumed to represent the vascular structure. Bilateral common carotid and vertebral arteries were visualized in each image size approximately 5 cm obtained at the systolic phase. Since prolonged TE yielded less signal intensity, the bolus was not clearly visualized when TE was longer than 100 msec. The cine display of images with multiple cardiac phases produced good evaluations of dynamic changes of pulsatile flow, and this method is expected to be a useful diagnostic tool which combines the capability of flow quantitation with non-invasive angiography. The accuracy of this method in delineating a stenotic lesion was also evaluated using phantom with steady flow, since it is one of the most important capabilities of a clinically used angiographic method.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Myocardial uptake of antimyosin monoclonal antibody in a murine model of viral myocarditis.

The myocardial uptake of 125I- and 131I-antimyosin monoclonal antibody Fab in experimental myocarditis in BALB/c mice induced by encephalomyocarditis virus was studied. The biodistribution of 125I-antimyosin demonstrated that the highest ratio of radioactivity appears in the heart of infected mice on day 14 (the ratio of percent dose per gram for the organ to percent dose per milliliter for blood; 9.75 +/- 2.79 vs. 1.27 +/- 0.78 at 24 hours in inoculated mice vs. control mice). There was no statistically significant difference between the mean activity ratios of tissues other than the heart in control and inoculated mice. The uptake ratio for the heart increased significantly 3 days after virus inoculation and reached a maximum on day 14 when myocardial lesions were most extensive and prominent. The uptake ratio decreased significantly, but it still remained high compared with controls on day 28 when cellular infiltration had decreased and fibrosis was evident. The scintigraphic images obtained with 131I-antimyosin monoclonal antibody clearly demonstrated that visualization of the heart in experimental myocarditis was possible 24 hours after administration of radiotracer, and localized activity was still observed in the 48-hour image. We conclude that antimyosin monoclonal antibodies localize selectively in the heart from the acute to subacute stage of viral myocarditis. These findings indicate that antimyosin scintigraphy is a reliable noninvasive method for the evaluation of patients suspected of having myocarditis.

Animals↗

[Clinical trial of 111In-antimyosin antibody imaging: (2). Imaging of myocardial infarction and myocarditis].

A new scintigraphic method to detect myocardial necrosis has been developed using antimyosin monoclonal antibody F ab labeled with indium-111 (111In-antimyosin). We investigated 111In-antimyosin scintigraphy in 35 patients with myocardial infarction, 5 patients with myocarditis and 3 patients with angina pectoris. 111In-antimyosin F ab was administered iv and antimyosin images were recorded by planar and single photon emission computed tomography (SPECT) 48-72 hrs after injection. Planar images showed discrete localization of 111In-antimyosin in 26 of 27 patients within 16 days after the onset of acute myocardial infarction in 14 of whom creatine kinase, glutamic oxaloacetic transaminase and lactic dehydrogenase had already normalized. In addition, positive scans were also obtained in 4 of 8 patients 1 to 9 months after the onset of the disease. Three patients with acute myocarditis (two of whom were biopsy-proven) had positive scans 2 and 4 weeks after the onset of the disease. Although mechanism of persistent positive anti-myosin images in the chronic stage remains to be clarified, 111In-antimyosin scintigraphy holds potential promise as a noninvasive method for the detection of myocardial injury.

Adult↗

Immunocompetences and Marek's disease resistance in three pairs of chicken lines selected for different immunological characters.

Three pairs of chicken lines selected for high (H) and low (L) graft vs. host reaction (GVHR) competences, serum immunoglobulin G (IgG) levels, and antibody responses to Leucocytozoon caulleryi were examined for their immunocompetences and Marek's disease (MD) resistance. The GVHR-H and GVHR-L lines were further divided into two sublines according to their major histocompatibility B genotype. Immune responses to sheep erythrocytes (SRBC), bovine serum albumin (BSA), and a lipopolysaccharide (LPS) were compared between the high and low lines of each pair of selected lines. Significant differences were found in responses to SRBC and LPS in IgG-selected lines and in response to BSA in Leucocytozoon-selected lines. In all three instances antibody titers of the H line were higher than those of the L line. The GVHR competence expressed by the splenomegaly index (SI) was also significantly different between the H and L lines of all three selected-line pairs. The SI values in the GVHR-selected and IgG-selected lines were higher in the H line than in the L line, whereas those in the Leucocytozoon-selected lines were lower in the H line. Differences in MD incidence and in MD mortality were found between the GVHR-selected B11B11 subline and the IgG-selected lines. In both instances the L line was more resistant to MD than the H line.

Animals↗

Parabiosis between avian embryos selected for high and low competences of the graft-versus-host reaction.

Parabiosis of chicken embryos was conducted to determine if changes in immunological competences could occur by parabiosis between lines of chickens selected for high (H) and low (L) graft-versus-host reaction (GVHR). Eggs of the B9B9 genotype from the H line (H-B9B9) were parabiosed to eggs of the B11B11 from the L line (L-B11B11) and also the H-B11B11 were parabiosed to the L-B9B9. There were significant differences in hatchability between the line-genotype groups. The percentage of blood chimerism of parabionts showed also significant genetic differences. Chimerism was the highest in the H-B11B11 birds and the lowest in the L-B11B11. All chimeric parabionts showed immunological tolerance and almost all nonchimeric parabionts did not. Immunological competence was measured by splenomegaly index (SI) based on GVHR. The SI value of parabionts changed in the direction of the SI value of the partner. The SI value of chimeric parabionts differed significantly from those of nonchimeric parabionts and controls. Antibody response to bovine serum albumin was tested only for the H-B11B11. Antibody titers of parabionts were significantly lower than those of controls.

Animals↗

Comparison of the major histocompatibility antigen on Marek's disease-derived cell lines detected by membrane fluorescent antibody, cytotoxicity, and lymphoagglutination tests.

The reactivity of 13 antisera specific for the major histocompatibility antigen (MHA) of the B complex against cells in 6 cell lines (MDCC-JP1, JP2, HP1, HP2, RP1, and MSB1), derived from Marek's disease (MD) lymphoma, was compared by using membrane fluorescent antibody, cytotoxicity, and lymphoagglutination tests. The membrane fluorescent antibody test was found to be the most sensitive method for detecting the MHA of the B complex on the MD cell lines. After absorption of these antisera with the homologous erythrocytes, the reactivities of the absorbed sera to the homologous erythrocytes and the MD line cells were reduced or lost altogether. However, after absorbing the antisera reactive for MD cell lines with the respective cell line, the reactivities of the absorbed sera to the line cells were not detected at all when examined by the above tests. However, the reactivities of these absorbed sera to the homologous erythrocytes could still be observed when examined by a hemagglutination test. These results indicate that the antisera contain at least two kinds of antibody (against Class I and Class IV antigens), and the three different tests used here are detecting the Class I antigens of MHA on the MD line cells.

Agglutination Tests↗

Ecology of non-O 1 Vibrio cholerae in Toyama Prefecture.

The ecology of non-O 1 Vibrio cholerae and Vibrio mimicus as causes of cholera-like diarrhea or seafood-associated gastroenteritis has been investigated in Toyama Prefecture since 1980. The relationship between biological or serological characteristics of the isolates and their enteropathogenicity is discussed. Overall isolation rates from river water, sea water, and fish were 24.0, 59.5, and 33.7%, respectively, the isolation frequency being, in general, extremely high in the summer season, although the organisms were detected all year around in the case of sea water. Most isolates from river water were unable to grow on plates of TCBS agar to which colistin was added at a concentration of 1 microgram/ml (CL-TCBS). These strains quickly fermented cellobiose. O-51 and O-70 were the two most frequently detected serogroups among them and they did not show enteropathogenicity in the rabbit ileal loop ( RIL ) test. On the other hand, almost all isolates from sea water and fish as well as those from human diarrhea cases were able to grow on CL-TCBS, but were unable to ferment cellobiose quickly. O-36, O-10, O-6, O-8, O-39, and O-26 were the dominant serogroups of these isolates, and some of them showed enteropathogenicity in the RIL test. Six out of 98 isolates from river water, 14 out of 116 from sea water, and 19 out of 112 from fish were classified as Vibrio mimicus . All of these strains were able to grow on CL-TCBS and quickly fermented mannose but not cellobiose. O-41 was the most common serogroup among them and some of these strains showed enteropathogenicity in the RIL test. Production of a cholera-like enterotoxin among the isolates in Toyama Prefecture, if any, seemed to be poor.

Animals↗