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Biomedical subjects

S Kubo

Publications and source records attributed to S Kubo.

At least 433 records · Page 24Linked to original sources

A new hereditary single band variant of the Gc system.

A new single band variant (Gc Ar) or the Gc subtypes not identical with the known Gc variants has been detected in the plasma of a healthy blood donor by isoelectric focusing. Using this technique the variant is represented by a single band which has a similar isoelectric point to the Gc 1C2 anodal band. It is well known that the single band Gc phenotypes remain unaltered after neuraminidase treatment. Nevertheless, the new single band variant (Gc Ar) is altered after neuraminidase treatment as is Gc 2A3. After neuraminidase treatment, the Gc Ar band is affected and moved to the nearby position of the Gc 2 band. Investigation of the proband's family shows that the variant occurs combined with the common alleles Gc 1F, Gc 1S and that it has an autosomal dominant inheritance.

Alleles↗

Left ventricular diastolic function of spontaneously hypertensive rats and its relationship to structural components of the left ventricle.

Left ventricular (LV) diastolic function was investigated in three different age groups (15, 28 and 50 weeks) of paired spontaneously hypertensive (SHR) and normotensive (WKY) rats under pentobarbital anaesthesia. A time constant of LV pressure decay, represented by T, was used as an index of LV relaxation. We assessed the relationship between haemodynamic parameters and LV structural components as quantified by microspectrophotometry (MSP), using multivariate analysis. T was significantly prolonged in the 28 and 50 week old SHR compared with their normotensive counterparts (P less than 0.05 and P less than 0.01, respectively). T was prolonged by volume loading but was not affected with afterload elevation by angiotensin infusion in all age groups of the SHR and WKY. LV wall thickness was greater in the SHR at all ages and was positively correlated with T (r = 0.42, P less than 0.05). A significant correlation was found between the increase in cardiac muscle fibre and collagen, the decrease in elastin and glycoprotein, and T on multivariate analysis (r = 0.53, P less than 0.05). We conclude that LV relaxation of SHR is disturbed from a relatively young age (28 weeks), for which we consider myocardial hypertrophy and LV structural changes found by MSP as being responsible.

Animals↗

Messenger RNA structure participating in the initiation of synthesis of cucumber mosaic virus coat protein.

The sequence of the 5'-terminal 106 nucleotides of cucumber mosaic virus (strain Y) RNA 4, the mRNA coding for viral coat protein, has been determined. The first AUG was located at 77 nucleotides from the 5'-terminus and was confirmed to be an initiation codon by analysis of the N-terminal amino acid sequence of the protein. The nucleotide sequence (positions 77-106) beyond the AUG codon predicted the sequence of ten amino acids corresponding to the N-terminal region of the protein, which exactly matched the determined amino acid sequence containing an acetyl methionine as the N-terminal amino acid. The distance of the initiation codon AUG from the cap structure was 76 nucleotides and the longest among the mRNAs for coat protein of plant viruses so far reported (9-36 nucleotides). This noncoding region is rich in U residues (40%) and the number of G residues (21 nucleotides) is the largest among these mRNAs (usually 1 or 2 residues). A possible secondary structure is postulated for the region, which might be implicated in efficient translation of the RNA 4 in vivo.

Amino Acid Sequence↗

The structural relation between the antigenic determinants to monoclonal antibodies and binding sites to rat brain synaptosomes and GT1b ganglioside in Clostridium botulinum type C neurotoxin.

The inhibition of the binding of 125I-labeled Clostridium botulinum type C neurotoxin to synaptosomes by unlabeled toxin indicated that there were two kinds of receptors on the synaptosomal membrane. The dissociation constants (Kd) were calculated as 79 pM and 35 nM from the concentration of unlabeled toxin that induced half-displacement of bound 125I-toxin. These values agree satisfactorily with the values obtained from direct binding experiments (Agui, T, Syuto, B., Oguma, K., Iida, H., & Kubo, S. (1983) J. Biochem. 94, 521-527). The inhibition of the binding of 125I-toxin to synaptosomes and N-acetylneuraminyl(alpha 2-3)galactosyl(beta 1-3)N-acetylgalactosaminyl(beta 1-4) [N-acetylneuraminyl(alpha 2-8) N-acetylneuraminyl(alpha 2-3)]galactosyl(beta 1-4)glucosyl(beta 1-1)ceramide (GT1b) by unlabeled heavy chain indicated that heavy chain facilitates the binding of toxin to synaptosomes and GT1b. The synaptosomal and heavy chain complex Kd values were estimated as 12 nM and 24 microM. Monoclonal antibodies C-9 and CA-12 recognized the binding sites to GT1b and synaptosomes, respectively. Antigenic determinants against the two antibodies are presumably partially overlapping, and the overlapping area seems to be essential to the reaction between toxin and C-9 antibody.

Animals↗

Purification and characterization of neurotoxin produced by Clostridium botulinum type C 6813.

The toxin produced by Clostridium botulinum type C 6813 (C-6813) was purified 1,009-fold from the culture supernatant in an overall yield of 30%. The specific toxicity was 1.1 X 10(7) mouse minimum lethal doses per mg of protein. The toxin had a molecular weight of 144,000, composed of the light and heavy chains with molecular weights of 52,000 and 92,000, respectively, linked by one or two disulfide bond(s). The purified C-6813 toxin heavy and light chains reacted strongly with anti-type D heavy chain immunoglobulin G and anti-type C1 light chain immunoglobulin G, respectively. The amino acid compositions of C-6813 toxin heavy and light chains were more similar to those of type D heavy chain and type C1 light chain than to those of type C1 heavy chain and type D light chain, respectively. These results suggest that in the toxin produced by the type C strain at least two subtypes exist.

Amino Acids↗

Intrathymic T cell differentiation in radiation bone marrow chimeras and its role in T cell emigration to the spleen. An immunohistochemical study.

Immunohistochemical studies were made on the regeneration of T cells of host- and donor-type in the thymus and spleen of radiation bone marrow chimeras by using B10- and B10.BR-Thy-1 congenic mice. Both the thymic cortex and the medulla were first repopulated with thymocytes of irradiated host origin, restoring the normal histologic appearance by days 11 to 14, regardless of the H-2 compatibility between the donor and the host. In Thy-1 congenic chimeras, thymocytes of donor bone marrow origin, less than 100 cells in one thymic lobe, were first recognized at day 7, when the thymus involuted to the smallest size after the irradiation. The thymocytes of donor-type then proliferated exponentially, showing a slightly faster rate when higher doses of bone marrow cells were used for reconstitution, reaching a level of 100 million by day 17 and completely replacing the cortical thymocytes of host origin by day 21. The replacement of cortical thymocytes started from the subcapsular layer in a sporadic manner. The replacement of medullary thymocytes from host- to donor-type occurred gradually between days 21 and 35, after the replacement in the cortex was completed. In the spleen, about 1 million survived cells were recovered at day 3 after the irradiation, and approximately 60% of them were shown to be host-type T cells that were observed in the white pulp areas. The host-type T cells in the spleen increased gradually after day 10, due to the influx of host-type T cells from the regenerating thymus. Thus a pronounced increase of T cells of host-type was immunohistochemically observed in the splenic white pulp between days 21 and 28, when thymocytes of host-type were present mainly in the thymic medulla. These host-type T cells were shown to persist in the spleen for a long time, as long as 420 days after the treatment. Phenotypically, they were predominantly Lyt-1+2+ when examined at day 28, but 5 mo later, they were about 50% Lyt-1+2+ and 50% Lyt-1+2-. Donor-type T cells in the spleen began to appear at about day 14 in chimeras that were transplanted with a larger dose of bone marrow cells, whereas this was slightly delayed in those grafted with a smaller dose of bone marrow cells, starting at about day 28.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Hepatectomy after transcatheter arterial embolization (TAE) for hepatocellular carcinomas].

Subjects of this study were 26 patients with hepatocellular carcinoma who underwent hepatectomy after TAE. They did not develop serious complications due to TAE. A suitable interval between TAE and the planned hepatectomy was about one month, based on AFP levels and the recovery of liver functions. Hepatic arteriography after TAE was useful to observe changes of the blood flow into the liver and the carcinoma, as well as to find intrahepatic metastases. It is also necessary for making final decisions on the strategy of the hepatectomy. The effects of TAE greatly depended on patterns of arterial blood feeding. When the tumor was less than 5 cm in diameter, had a capsule, and was fed by a single artery the necrotic rate was high. TAE was effective in intrahepatic metastases 0.5 cm or more in diameter, which were detectable by hepatic arteriography. TAE had little effect on intrahepatic metastases less than 0.5 cm in diameter, on intracapsular or extracapsular invasion, or on tumor embolus. For tumor embolus in the portal vein, since TAE and hepatectomy give poor results, other methods should be considered.

Adult↗

Comparison of Clostridium botulinum toxins type D and C1 in molecular property, antigenicity and binding ability to rat-brain synaptosomes.

Botulinum type D neurotoxin was purified 950-fold from the culture supernatant with an overall yield of 32%. The purified toxin had a specific toxicity of 5.8 X 10(7) mouse minimal lethal dose per mg of protein and a relative molecular mass of 140000. The purified toxin had a di-chain structure consisting of heavy and light chains with relative molecular masses of 85000 and 55000, respectively, linked by one disulfide bond. These subunits had different amino acid compositions and antigenicities. A similarity in molecular constructions and amino acid compositions was observed between type D and type C1 toxins as well as between their subunits. Among the seven kinds of monoclonal antibodies against type D toxin, six reacted with the heavy chain of type D toxin, while one of the six also reacted with the heavy chain of type C1 toxin and neutralized the toxicities of the two toxins. The other one of monoclonal antibodies reacted with the light chains of both toxins. This evidence indicates that both toxins have common antigenic sites on their heavy and light chains and that the antigenic site on the heavy chain may contribute to the neutralization of both toxins by antibody. The binding of type D toxin to rat brain synaptosomes was examined by use of 125I-labelled type D toxin. The binding was competitively inhibited not only by unlabelled type D and C1 toxins, but also by the heavy chains of both toxins, however, it was not inhibited by the light chain of type D toxin. These results suggest that the toxin receptors on synaptosomal membrane are common for type D and C1 toxins, and that the heavy chain contributes to the binding of toxin to synaptosomes and the structure of the binding sites on the heavy chains of both toxins is quite similar.

Amino Acids↗