[Six families of familial cardiomyopathy].
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Biomedical subjects
Publications and source records attributed to S Onodera.
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The hepatitis B virus (HBV) core antigen was purified by mild procedures, including hydroxyapatite column chromatography, with care taken to avoid the degradation of the particles. Circular dichroism (CD) of the HBV core particles in saline showed low intensities of negative ellipticities in the region dominated by amide bond absorption. Acid treatment of the particles induced a remarkable change in the CD spectrum, with the appearance of a positive extremum at about 208 nm. The amino acid composition and the COOH-terminal residue of the isolated core polypeptide (Mr 21,000-21,500) were shown to be essentially the same as those of the polypeptide deduced from the nucleotide sequences which had been proposed for the HBV core antigen by other laboratories. We failed to detect any NH2-terminal dansyl-derivatives from the core polypeptide by the dansyl-Edman method. We also showed by the method of fluorescein polarization that the core polypeptide conjugated with fluorescein isothiocyanate has an affinity for serum albumin. This may indicate a state of disassembled or non-assembled core polypeptide in sera.
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The ultrastructure of the nucleocapsid component of human hepatitis B virus (core particle) was studied by negative staining-carbon film technique. Using this method an improved image of core particles was obtained in respect of resolution and contrast. Two-dimensional crystalline arrays of core particles were formed in vitro. Under these arrays the distance between the particle centers was 28.3 nm, corresponding to the capsid diameter, when analyzed through optical diffraction patterns. Positively stained images of these arrays revealed that core particles contain an electron-dense center of nucleoid-like area about 21 nm in diameter. The capsid surface rarely exhibited small capsomeres, ie, small spheres or ring-like structures measuring 4.0-4.2 nm. From the dimension of these structures and the analysis by Markham's rotational technique, it was suggested that each of these capsomeres is an individual subunit (monomer) and 180 of these subunits build up the core particle capsid according to the icosahedral symmetry (T = 3), but not clustering into distinct morphological features.
After injections of horseradish peroxidase (HRP) into various parts of the superior colliculus (SC) in 14 cats, retrogradely labeled neurons were found in parts of all deep cerebellar nuclei. The present study demonstrated that there are three main origins of the cerebellotectal projections in regard to the locations of the cell bodies: (1) the caudal half approximately of the fastigial nucleus (NM) including the subnucleus medialis parvocellularis (SMP), (2) the ventral and lateral parts of the posterior interpositus nucleus (NIP), and (3) the ventral part of the dentate nucleus (NL) including the subnucleus lateralis parvocellularis (SLP). The pathways and terminations of these projections have also been shown autoradiographically. Thus, fibers from NM crossed within the cerebellum and terminated in the intermediate and deep gray layers of the bilateral SC. Fibers from NIP and NL passed within the superior cerebellar peduncle, which crossed in the tegmentum ("decussation" of the peduncle) and ended in the two layers of the contralateral SC. In addition, some cerebellofugal fibers were found to terminate in the nuclei interstitialis of Cajal and Darkschewitsch, as well as in parts of pretectum and thalamus. The tecto-ponto-(and olivo-) cerebellotectal loop (cf. Kawamura 1980) has been established morphologically and it is briefly commented on in correlation with the propagation of the teleceptive (optic and acoustic) impulses.
Highly purified and homogenous hepatitis B core particles were obtained from an autopsy liver. The core particles consisted mainly of an electrophoretically single major polypeptide with a molecular weight of 20,000 daltons. When antigenic conversion from hepatitis B core antigen (HBcAg) to hepatitis B e antigen was achieved by treating these core particles by sonication or by passing them through an anti-HBc IgG-conjugated Sepharose 4B column, no appreciable changes were found in the above protein composition. The same antigenic conversion was also achieved by centrifugation of core particles in CsCl, which revealed the process of morphological disintegration accompanied by antigenic conversion. These observations may support the hypothesis that HBcAg resides on a protein conformation which consists of a polypeptide sharing HBe antigenicity.
IgG immune deposits in glomerular lesions were found in 62% of 4-week-old mice born from anti-DNA antibody positive mothers but not in the mice born from anti-DNA antibody negative ones. In the former mice anti-DNA antibody producing cells could not be detected in spite of the presence of antibody. These results indicate that maternal anti-DNA antibody might be responsible for the development of glomerular lesions in the offsprings. Renal lesions, however, was not observed in the 2- to 3-month-old mice indicating that permanent lesions were not induced by this transient maternal antibody.
In order to evaluate the effect of handgrip on left ventricular dynamics, cineventriculography was performed in 16 patients with heart disease and 5 normal subjects at 30% of maximal voluntary contraction. No patient had ventriculographic evidence of asynergy or valve regurgitation. During exercise, left-ventricular end-diastolic volume (LVEDV) insignificantly increased, left ventricular end-systolic volume (LVESV) decreased, and hence stroke volume (SV) and ejection fraction (EF) rose in the normal group, while in the patient group a similar change in LVEDV was associated with increased LVESV, resulting in unchanged SV and decreased EF. It is notable that during exercise LVEDV increased in both groups, despite a shortened diastolic filling period. Mean velocity of fiber shortening (mean VCF) increased in the normal group and remained unchanged in the patient group. The changes in mean VCF during exercise were correlated with the alterations in SV and EF (r=0.46, p less than 0.05 and r=0.90, p less than 0.001), respectively). These data signify that an increased afterload induced by handgrip leads to an enhanced left ventricular myocardial contraction in addition to an increase in preload in the normal group, while the Frank-Starling mechanism is mainly utilized in the patient group.
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Mild detergent treatment (0.1% Sarkosyl-0.1% beta-mercaptoethanol) of Dane particle-rich fraction from human serum resulted in the release of core particles together with HBe antigen activity when examined by the reversed passive haemagglutination method. Furthermore, when the core particles isolated by the above procedure were exposed to stronger detergent (1% Sarkosyl-0.1% beta-mercaptoethanol), additional HBe antigen activity was released only from intact core particles with DNA polymerase activity and not from empty core particles.
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Passive hemagglutination (PHA) and hemolysis (PHL) tests using chromium chloride-treated sheep red blood cells were developed to detect and measure the anti-DNA antibodies. Sonication of native DNA was found to prevent the incidence of non-specific agglutination. Sheep red cells were coated with double-stranded DNA (dsDNA) which had been sonicated and treated with nuclease S1 to digest the single-stranded regions in the DNA. The specificities for dsDNA-coated cells were checked by inhibition studies in PHA test and plaque assay. In clinical studies fairly close correlations were found between the antibodies to DNA and the activity of the disease in patients with systemic lupus erythematosus (SLE). Complement-fixing antibodies were detected in most of SLE patients with active lupus nephritis, but rarely in those in remission. Anticomplementary activity seemed to be negligible in PHL test. These tests are simple and may be useful to the diagnosis and the management of SLE.
Peripheral blood lymphocytes of 16 patients with secretory type of multiple myeloma and 5 with nonmyelomatous monoclonal gammopathy were investigated for the surface immunoglobulins on the cell by immunofluorescence. A low pH shock of cells before staining was applied to dissociate the passively absorbed immunoglobulins present on the cell surface. Increases of B lymphocytes bearing surface immunoglobulins which have the same light chains as those of monoclonal immunoglobulins produced by the plasma cells were found in 5 of 11 common secretory myeloma patients and in all of 6 Bence-Jones myeloma patients. Ratios of cells bearing light chains of kappa- and lambda-types (kappa/lambda) appeared abnormal in almost all with an exception of only 3 cases of myeloma patients, even in the cases where the number of Ig bearing cells did not increase. Increases of possible monoclonal B cells bearing IgG, in addition to IgA cells, were observed in some patients with IgA myeloma. Increases of B cells bearing certain heavy chains were also observed in all 5 patients with Bence-Jones myeloma during the course of disease. No abnormalities of B cells bearing surface immunoglobulin were found in nonmyelomatous monoclonal gammopathy. These results suggest that proliferation of monoclonal B lymphocytes, which may be progenitors to the malignant plasma cells, occurs in a majority of myeloma patients, but not in nonmyelomatous monoclonal gammopathy.
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