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Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 1,405 records · Page 78Linked to original sources

Molecular cloning of translocations involving chromosome 15 and the immunoglobulin C alpha gene from chromosome 12 in two murine plasmacytomas.

Expression of IgA by plasmacytomas occurs as a result of a DNA rearrangement that brings the variable region gene, VH, a few kilobases 5' to the constant region gene, C alpha. In this study, we show that the allelic nonexpressed C alpha gene also is rearranged in most plasmacytomas. Cloning, restriction mapping, heteroduplex analyses, and sequence analyses of the nonproductively rearrange C alpha genes from two plasmacytomas, M603 and M167, have demonstrated that the nonproductive rearrangement occurs within the alpha switching region, S alpha. In each case, the same DNA sequence has been joined to the 5' side of C alpha and we have termed this DNA "NIRD" (for nonimmunoglobulin rearranged DNA). Southern blotting analyses of genomic DNAs from various IgG-, IgM-, or IgA-producing plasmacytomas suggest that NIRD is rearranged in almost all plasmacytomas. However, NIRD rearranges to the S alpha region only in IgA-producing cells, not in IgM or IgG producers. Cytogenetic evidence has shown that T(12;15) translocations are common in murine plasmacytomas. Immunoglobulin heavy chain genes are located on chromosome 12, and the translocation breakpoint in plasmacytomas occurs near the immunoglobulin genes. NIRD has been mapped to chromosome 15 by Southern blotting analysis of mouse-hamster cell lines, suggesting that the nonproductively rearranged C alpha clones represent the T(12;15) translocations identified cytogenetically. Therefore, we have identified a region of DNA on chromosome 15 that is commonly rearranged in transformed mouse lymphocytes. We speculate on the significance of NIRD in neoplastic transformation of mouse lymphocytes.

Animals↗

Familial occurrence of cerebellar hemangioblastomas--analysis of five families.

Characteristic features of familial cases of cerebellar hemangioblastoma were analyzed on the basis of 54 patients, 32 male and 22 female. In this group there were 7 cases from five affected families. The overall recurrence rate was 33.3% among patients who had been followed for more than 4 years after total removal of the tumor. Recurrence was more common in the familial cases (50%). The average age at the onset of symptoms was younger (23.4 years) in familial cases than in nonfamilial cases (36.2 years) and tended to be even younger (18.9 years) in the second generation of familial cases. These findings suggest that the integration of primitive vasoformative tissues is disturbed more severely in familial cases of cerebellar hemangioblastoma.

Adolescent↗

Synthetic-dynamic theory of drug abuse: a revisit with empirical data.

A revised version of the synthetic-dynamic theory of drug abuse is presented. A partial test of the validity of the theory is implemented through a drug survey taken in November 1979 involving 14,594 students in Mecklenburg County, North Carolina. Utilizing multiple regression analysis, 50.08% (R = .708) of the total variation in student drug involvement is explained by four components operating jointly. An examination of individual standardized regression coefficients indicates that the drug attitude component accounts for the largest change in the dependent variable, followed by the environmental, the socialization, and (responsible for the least change) the personal discontent components. On the basis of these findings, the implications for future drug education models and prevention policies are examined.

Adolescent↗

Feeder area approach: an impact evaluation of a prevention project on student drug abuse.

To determine the impact of a primary prevention project at the community level, a feeder area approach has been implemented for a period of 2 years. The operational objective of the approach has been to concentrate most of the prevention agency's programs in one small area rather than scattering its resources throughout the country at large. It has been assumed that the country as a whole is too large a unit to have a measurable impact in a short period of time. The feeder area chosen therefore is used as an experimental group while the rest of the country is viewed as a control group in a natural social setting. Through countrywide drug surveys implemented before and after the project, it has been determined that there is a significant reduction in the current users of various drugs in the selected feeder area when compared to the rest of the country.

Adolescent↗

Antibody and MHC genes.

The striking homology relationships, both in sequence and in general organizational features, among the genes encoding antibodies, transplantation antigens and beta 2-microglobulin suggest that these genes are members of a supergene family. It will be interesting to determine whether any of the regulatory strategies displayed by the antibody gene families will also be employed by the MHC gene families. Indeed, the recombinant DNA approach has given us profound insights into the organization and expression of antibody genes. These same techniques are now beginning to unravel the mysteries of the MHC complex. It is clear that the future will require a much closer collaboration between molecular biologists, cellular immunologists, and immunogeneticists to obtain the appropriate reagents and cell lines necessary to expand our understanding of the molecular biology and enzymology of gene expression in these fascinating systems.

Animals↗

Reduced erythrocyte membrane protein methylation in sickle cell anemia.

The methylation of erythrocyte membrane components in sickle cell anemia has been studied and found to differ considerably from that of normal erythrocytes. When sickle erythrocytes were incubated under physiological conditions (pH = 7.4, 37 degrees C) in the presence of L-[methyl-3H]methionine or S-adenosyl-L-[methyl-3H] methionine, a 50% decrease in the protein-carboxyl methylation was observed compared to the normal erythrocyte. This reduction in degree of methylation was reflected in all of the major methylated protein bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Since this methylation is catalyzed by the cytosolic protein methylase II (S-adenosylmethionine:protein-carboxyl O-methyltransferase, EC 2.1.1.24), the in vitro substrate capability of sickle erythrocyte ghosts and pH 11 treated ghosts were tested by incubation with purified protein methylase II and S-adenosyl-L-[methyl-14C]methionine. Both types of sickle cell ghost preparations showed the same 50% decrease in methylation as was seen in the intact cells. Since it was also shown that the protein methylase II and methyl acceptor membrane protein levels in the sickle erythrocytes are the same as the normal control, the data suggest that the observed reduced methylation may be due to an altered membrane conformation. The methylation of phospholipid was also studied and found to be decreased in sickle cell erythrocytes. However, this methylation was extremely minor in comparison to protein-carboxyl methylation which represents the bulk of the membrane methylation.

Anemia, Sickle Cell↗

Preparation of cell-size unilamellar liposomes with high captured volume and defined size distribution.

Cell-size unilamellar vesicles were made by removing solvents from microscopic chloroform spherules containing smaller water droplets within. The average diameter of the vesicles in a typical preparation was 9.2 mum, comparable to that of human erythrocytes (7 mum). The standard deviation of the size distribution was 3.0 mum. The unilamellarity and bilayer unit membrane of vesicles were demonstrated by transmission electron microscopy. Materials so far successfully incorporated into vesicles include glucose, sucrose, Arsenazo III and Ponceau S dyes, thymidine triphosphate, methotrexate, agarose, collagen, ferritin, polyadenylic aid, DNA, and whole bacteria. The captured volume per milligram of lipids (up to 144 microliter/mg) was almost an order of magnitude greater than the highest value reported in the literature to date (up to 15.6 microliter/mg) (Szoka, F.C. and Papahadjopoulos, D. (1978) Proc. Natl. Acad, Sci. U.S.A. 75, 4194-4198).

Chloroform↗

Effect of methylation on the stability of cytochrome c of Saccharomyces cerevisiae in vivo.

The in vivo stability of methylated and unmethylated cytochrome c in Saccharomyces cerevisiae was studied by pulse-labeling the hemoproteins with [methyl-3H]-methionine and/or [2-14C]methionine and following the fate of these proteins under anaerobiosis and in the presence of cycloleucine. These two conditions will respectively block further cytochrome c synthesis and inhibit methylation by lowering the cellular S-adenosyl-L-methionine pool and, thus, permit an unambiguous interpretation of the data. The results showed that the rate of degradation of unmethylated cytochrome c was constant throughout the chase period, while methylated cytochrome c degradation was seen only in the later part of cold chase. At the end of the chase period (40 h), the extent of degradation of the unmethylated species was three times higher than the methylated species. This indicated that the methylation of cytochrome c has a protective effects against the intracellular proteolytic enzyme attack on itself. Furthermore, this protective effect was considerably reduced in the petite mutant, which lacks high affinity cytochrome c binding sites, functional cytochrome c reductase, and oxidase, and possesses a less integrated and organized mitochondrial membrane. These results led us to the conclusion that the mechanism of methylated cytochrome c stabilization is best explained by a higher efficacy of binding to the mitochondria.

Cytochrome c Group↗

Antibody diversity: somatic hypermutation of rearranged VH genes.

The immune response to phosphorylcholine in BALB/c mice has been well characterized. Amino acid sequence analyses of heavy-chain variable (VH) regions from 19 myeloma and hybridoma immunoglobulins binding phosphorylcholine show that 10 are identical (the prototype T15 VH sequence) and 9 are distinct variants differing by one to eight residues. A T15 VH DNA probe was used to isolate four closely related members of the T15 VH gene family, including one encoding the T15 VH sequence, from a sperm genomic library. A comparison of the protein and germline VH sequences suggested that most of the immune response to phosphorylcholine is derived from the T15 germline VH gene segment. The variant heavy chains from the M167 and M603 alpha immunoglobulins differ in their VH protein sequences from T15 by eight and three residues, respectively. We analyzed the somatic variability in and around the coding regions of these two variant VH genes by comparing them with the corresponding regions of the appropriate germline gene segments. The somatic variation has three properties: it is extensive and is found in flanking as well as coding sequences (for example, at least 44 substitutions for the M167 sequence and 10 substitutions for the M603 sequence); in the coding regions, it includes many silent as well as replacement substitutions; and it is focal in nature and centered around the rearranged VH genes. Although the mutations extend into the neighboring upstream and downstream flanking sequences, sequences approximately 5 kb upstream and downstream from the VH genes show no substitutions. Moreover, the associated heavy-chain constant genes (C alpha) from both variant alpha genes are unaltered, indicating that a closely linked and coexpressed gene is unmutated. We conclude that this somatic variation is generated by a special hypermutational mechanism highly localized in its site of execution and highly restricted in its time of operation during B-cell development.

Animals↗

Microsome-dependent methylation of erythrocyte proteins by dimethylnitrosamine.

The precarcinogen, N-[methyl-14C]dimethylnitrosamine, rat liver microsomes and NADPH were incubated in the presence of intact human erythrocytes. Uptake of radioactivity into erythrocytes was time-dependent and analysis of an acid hydrolysate of the erythrocyte proteins showed several radioactive peaks which were identified as 3-N-methyl- and 1-N-methyl-histidine, S-methyl-cysteine. Since no binding occurs in the absence of microsomes, the alkylating species from dimethylnitrosamine metabolism can clearly penetrate the erythrocyte plasma membrane.

Amino Acids↗