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S Kim

Publications and source records attributed to S Kim.

At least 1,315 records · Page 73Linked to original sources
PubMed1987

Multivesicular liposomes containing cytarabine for slow-release Sc administration.

Sc administration of cytarabine entrapped in multivesicular liposomes to BDF1 mice resulted in slow first-order release from skin, with a half-life of 4 days. The half-life was 10 minutes for unencapsulated free drug. A single-dose sc treatment of BDF1 mice, inoculated iv with 10(5) L1210 leukemia cells 24 hours previously, resulted in long-term survivors over a wide dose range. This study demonstrates that encapsulation of cytarabine in multivesicular liposomes results in slow release from skin and that a single sc dose is often curative for mice with systemic leukemia.

Animals↗
PubMed1986

Studies on myelin-basic-protein methylation during mouse brain development.

The synthesis and methylation in vivo of myelin basic protein (MBP) during the mouse brain development has been investigated. When mice ranging in age from 13 to 60 days were injected intracerebrally with L-[methyl-3H]methionine, the incorporation of radioactivity into MBP isolated from youngest brain was found to be the highest and declined progressively in mature brains. This pattern of radioactivity incorporation was inversely correlated with the total amount of MBP in the brains, suggesting a higher ratio of MBP methylation to synthesis in younger brain. To differentiate the relative rate of protein synthesis and methylation, animals were given intracerebral injections of a L-[methyl-3H]methionine and L-[35S]methionine mixture and the ratio of 3H/35S (methylation index) was determined. The ratios in the isolated MBP fractions were higher than those of 'acid extracts' and 'breakthrough' fractions, with a maximal ratio in the youngest brain. This high ratio was well correlated with the higher protein methylase I (PMI) activity in younger brains. The MBP fractions were further separated on SDS/polyacrylamide-gel electrophoresis into several species with apparent Mr ranging from 32,400 to 14,500. The results indicated that each protein species accumulated at a characteristic rate as a function of age. The high-Mr (32,400) species was predominant in younger brain, whereas the smaller MBP was the major species in older brain tissue. The importance of this developmental pattern of MBP synthesis and methylation is discussed in relation to PMI activity.

Aging↗
PubMed1986

Myelin basic protein inhibits histone-specific protein methylase I.

Bovine brain myelin basic protein, free of associated proteolytic activity, was found to be a specific inhibitor of histone-specific protein methylase I (S-adenosyl-L-methionine:protein-L-arginine N-methyltransferase, EC 2.1.1.23) purified from bovine brain. 50% of the methyl group incorporation into the histone substrate catalyzed by the methylase I was inhibited by myelin basic protein at a concentration of 0.326 mM. However, neither of the peptide fragments (residues 1-116 and residues 117-170) generated by the chemical cleavage of myelin basic protein at the tryptophan residue retained the inhibitory activity for histone-specific protein methylase I. Proteins such as gamma-globulin, bovine serum albumin, bovine pancreatic ribonuclease and polyarginine did not exhibit significant inhibitory activity toward the enzyme. The Ki value for myelin basic protein was estimated to be 3.42 X 10(-5) M for histone-specific protein methylase I and the nature of the inhibition was uncompetitive toward histone substrate.

Amino Acids↗
PubMed1986

Identification of sequences in a yeast histone promoter involved in periodic transcription.

Sequences between a pair of divergently transcribed histone genes in Saccharomyces cerevisiae are able to confer periodic transcription during the cell cycle. This conclusion contrasts to our previous hypothesis that an ars (autonomously replicating sequence) 3' to this locus is a transcription timer for yeast histone genes. The promoter sequences required for periodic expression have been localized by deletion analysis, and isolated elements have been analyzed by insertion into a heterologous promoter. Two cell-cycle-specific promoter functions have been identified. One function activates transcription in a cell-cycle-dependent manner. The other periodically represses transcription. Negative regulation may be the predominant form of cell-cycle control, because removal of the repressing function results in constitutive expression of the histone genes.

Base Sequence↗
PubMed1986

Site specificity of histone H4 methylation by wheat germ protein-arginine N-methyltransferase.

CNBr treatment of calf thymus [methyl-14C]histone H4, methylated in vitro with S-adenosyl-L-[methyl-14C]methionine by a highly histone-specific wheat germ protein methylase I (S-adenosyl-L-methionine:protein-L-arginine N-methyltransferase, EC 2.1.1.23), produced two peptide fragments corresponding to residues 1-83 and 84-102, with the former being radioactive. Two-dimensional peptide mapping of the chymotryptic and tryptic digest of [methyl-14C]histone H4 and analysis of the chymotryptic digest on HPLC have shown that only a single peptide is radiolabeled. In order to define the exact site of methylation (arginine residue), the radioactive peptide from the chymotryptic digest of [methyl-14C]histone H4 was further purified on HPLC by linear and then isocratic elution. The purified chymotryptic peptide was then digested with trypsin and purified on HPLC, and its amino acid composition was determined on HPLC. These results indicate that the peptide corresponding to residues 24-35 of histone H4 is radiolabeled. Since this peptide contains a single arginine residue at position 35, we have concluded that the enzyme is specific not only to the protein substrate but also to the methylation site.

Animals↗
PubMed1986

Studies on naturally occurring proteinous inhibitor for transmethylation reactions.

An inhibitor for S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases has been purified from rat liver particulate fraction to apparent homogeneity, as judged by high-performance liquid chromatography, two-dimensional paper electrophoresis and isoelectric focusing chromatography. This inhibitor molecule, which is composed of 27 amino acid residues with an additional fluorescent chromophore, is rich in glycine, contains no basic amino acid, and has an isoelectric point (pI) of 3.70. A single absorption peak was observed at 248 nm in acidic as well as in neutral media, while two peaks were detected in alkaline medium at 206 nm and 248 nm. The former peak was found to be quite labile. The fluorescent spectra with excitation peak at 285 nm and emission peak at 358 nm are greatly influenced by the pH, being the highest in alkaline medium. The purified inhibitor inhibits all the AdoMet-dependent methyltransferases examined.

Animals↗
PubMed1986

Studies on the distribution of O6-methylguanine-DNA methyltransferase in rat.

O6-Methylguanine-DNA methyltransferase, a DNA repair enzyme which transfers the methyl group of O6-methylguanine residue to a cysteinyl residue in the methyltransferase itself, was examined in rat organs by quantifying the S-methylcysteine formed in the methyl acceptor protein. Among the various organs examined, the spleen exhibited the highest enzyme specific activity followed by the thymus, liver, lung and testis. Brain had the lowest activity. The patterns of subcellular distribution of the methyltransferase in spleen and liver were different: while 75-80% of the activity was present in the nuclear fraction of the spleen, 54% of the activity in the liver was found in the nuclei and 35% in the cytosolic fraction. Forty-five and thirty-five percent of the total nuclear enzyme activity could be extracted with 1 M and 2 M NaCl solutions, respectively, indicating that the repair enzyme is not tightly bound to the nuclear matrix. When isolated nuclei were incubated with [methyl-3H]DNA substrate and subsequently fractionated into histone and non-histone protein fractions, over 90% of the radioactivity was coeluted on a Bio-Rex 70 column with the non-histone fraction and only a negligible amount of radioactivity was found to be associated with the histone fraction. The molecular mass of the [methyl-3H]methyltransferase in the non-histone fraction was determined to be 23,000, and its pI value was found to be 6.6 by two-dimensional polyacrylamide gel electrophoresis.

Animals↗
PubMed1986

Myelin basic protein-specific protein methylase I activity in shiverer mutant mouse brain.

Myelin basic protein (MBP)-specific protein-arginine N-methyltransferase (protein methylase I) activity in homozygous shiverer (shi/shi) mutant mouse brain is significantly higher than in the normal littermate brain at the onset of myelination. While the enzyme activity (expressed as pmol of S-adenosyl-L-[methyl-14C]methionine used/min/mg enzyme protein) increases coincidently during the period of myelination in the normal brain (15-18 days of age), it decreases significantly in the mutant brain during this period of time. These results are in contrast to those found with another dysmyelinating mutant, jimpy (jp/Y) mice, in which the enzyme activity in the mutant brains is similar to that in the normal animals but remains unchanged during the myelination process. There is no difference in the weight and protein concentration of the normal and shiverer mutant brains with corresponding ages, and the histone-specific protein methylase I activity is also unaffected in the shiverer brain.

Animals↗
PubMed1986

A new HPLC analytical method for o-hydroxyhippuric acid in uremic serum.

o-Hydroxyhippuric acid (HHA) is formed in liver during the process of detoxication of salicylic acid which arises from either salicylic-containing dietary vegetables or hydrolysis of aspirin. Recently, HHA has also been shown as one of the so-called 'uremic toxins'. By derivatization of HHA with o-phthaldialdehyde (OPA), the resulting fluorescent product can easily be measured with the limit of measurement somewhere below 3 pmol on high performance liquid chromatography. Using the method described, an approximately 85% recovery of added HHA in human sera was obtained. This analytical system is now being employed to determine the concentration of HHA in human sera of uremic patients. Determination of HHA content in human uremic patients is very important, since uremia is associated with defective binding of many acidic drugs to serum protein(s) and HHA replaces these drugs by tightly binding to these proteins. This could potentially affect the therapeutic effectiveness of various pharmacologic agents.

Chromatography, High Pressure Liquid↗
PubMed1986

O6-methylguanine methyltransferase increases before S phase in normal human cells but does not increase in hypermutable Bloom's syndrome cells.

The regulation of the O6-methylguanine methyltransferase was examined during cell proliferation in hypermutable Bloom's syndrome fibroblasts and normal human skin fibroblasts. During synchronous growth following serum stimulation normal human cells enhanced methyltransferase activity 2.4-fold in the absence of exogenous damage as a normal regulatory event during the cell cycle. Methyltransferase activity was increased prior to the induction of DNA replication and of DNA polymerase and was diminished when each replicative activity was maximal. In contrast, although methyltransferase levels in quiescent cells are equivalent, hypermutable Bloom's syndrome cells did not increase methyltransferase at any interval in the cell cycle.

Bloom Syndrome↗