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Biomedical subjects

M Yoo

Publications and source records attributed to M Yoo.

25 records · Page 2Linked to original sources
PubMed1993

The human cytochrome b5 gene and two of its pseudogenes are located on chromosomes 18q23, 14q31-32.1 and 20p11.2, respectively.

Using very high stringency hybridization conditions for the Southern blot hybridization analysis of hamster-human cell hybrid DNA, we were able to map the human cytochrome b5 gene and two of its pseudogenes (psgb(5)1 and psgb(5)2) unambiguously to chromosomes 18, 14, and 20. These localizations were confirmed and extended to 18q23, 14q31-32.1, and 20p11.2 by using a combination of nonisotopic in situ hybridization of chromosomal spreads and the polymerase chain reaction analysis of DNA samples isolated from somatic cell hybrids retaining deletions or translocations of chromosome 18.

Animals↗
PubMed1991

Multiple forms of mouse 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase and differential expression in gonads, adrenal glands, liver, and kidneys of both sexes.

Observations of patients deficient in the steroidogenic enzyme 3 beta-hydroxy-delta 5-steroid dehydrogenase/isomerase (3 beta HSD) have suggested the presence of distinct 3 beta HSD structural gene(s) that are expressed at peripheral sites, possibly the liver. We now report the isolation of cDNA clones representing three forms of 3 beta HSD from mouse Leydig cell and liver libraries. The three forms share significant identify but differ from each other by 5-10% within their coding regions. RNA that hybridizes to radiolabeled 3 beta HSD probes is present in the gonads, adrenal glands, liver, and kidneys of both sexes. Ribonuclease protection analysis using antisense probes derived from each of the three forms demonstrates that one form, 3 beta HSD I, is restricted to steroidogenic tissues. Two other forms, 3 beta HSD II and III, are expressed in liver and kidney but are not detected in steroidogenic tissues. A polyclonal antibody raised against the human placental form of 3 beta HSD recognizes a 42-kDa protein in gonadal and adrenal tissue and a 45-kDa protein in liver. The antibody recognizes a 42-kDa protein in kidney only weakly. 3 beta HSD enzyme activity is present in testicular, adrenal, hepatic, and renal tissue, with adrenal tissue possessing the highest specific activity. When expressed as total 3 beta HSD activity for whole organ mass, activity is greatest in the liver. The results demonstrate that the mouse liver is a significant site of 3 beta HSD activity and demonstrate the existence of multiple 3 beta HSD structural genes in the mouse.

Adrenal Glands↗
PubMed1989

The characterization of three types of partially processed mRNA and two pseudogenes for human liver cytochrome b5.

We have isolated cDNA clones corresponding to partially processed human liver cytochrome b5 mRNAs. All the clones contained poly(A) sequences, and one clone had a shorter 3' non-translated sequence, indicating the use of an alternative poly(A) addition signal. In addition, all the clones contained the coding information for amino acids 87-134; however, there were two types of intron junction adjacent to the coding sequence. Detailed analysis of the Type I clones showed that the Type II intron sequence was contained within the Type I sequence, but approximately 1000 bp 5' of the Type I intron-exon junction showed alternative splicing within this intron. In addition, we have isolated two pseudogenes which lack introns, suggesting the retroviral insertion of human liver cytochrome b5 mRNA sequences into the human genome.

Amino Acid Sequence↗
PubMed1988

The complete nucleotide sequence of human liver cytochrome b5 mRNA.

We have isolated and sequenced a cDNA clone corresponding to human liver cytochrome b5 mRNA. The 760 base pair (bp) sequence contains the complete coding and 3' non-translated regions plus 52 bp of 5' non-translated sequence. The derived amino acid sequence showed that the previous assignment of several amino acids was in error. In addition, the sequence of the previously unknown COOH hydrophobic region has been obtained.

Amino Acid Sequence↗
PubMedDate not supplied

The effect of DA-8159, a novel PDE5 inhibitor, on erectile function in the rat model of hypercholesterolemic erectile dysfunction.

This study examined the effects of a new phosphodiesterase type 5 inhibitor, DA-8159, on erectile function associated with hypercholesterolemia. First of all, in order to investigate whether chronic administration of DA-8159 prevents the development of erectile dysfunction associated with hypercholesterolemia, male SD rats were divided into four groups (normal control, hypercholesterolemic control, DA-8159 5 or 20 mg/kg/day). Over a 5-month period, the animals were fed a 2% cholesterol diet and administered DA-8159 orally once a day. After 5 months, the electrostimulation-induced penile erection and the vascular function using acetylcholine-induced vasodilation with endothelium-intact aortic rings were examined. Furthermore, the plasma lipid profiles, endothelin and N(G),N(G)-dimethylarginine (asymmetrical dimethylarginine, ADMA) concentrations were measured. In order to investigate the acute treatment effect of DA-8159 on the erectile function in an established hypercholesterolemic model, additional animals were given a 2% cholesterol diet for 5 months without DA-8159. At the end of 5 months, the rats were divided into three groups (hypercholesterolemic control, DA-8159 0.3 or 1 mg/kg). DA-8159 was administered intravenously 1 min prior to the intracavernous pressure (ICP) measurement. In a chronic treatment study, while the hypercholesterolemic control showed a significantly lower erectile function, vascular reactivity, and increased plasma cholesterol, endothelin and ADMA concentration, the chronic DA-8159 treatment clearly restored the erectile responses by electric stimulation, preserved the potential of thoracic aortic relaxation in a dose-dependent manner, and significantly decreased the plasma endothelin and ADMA concentrations. In an acute treatment study, DA-8159 induced a dose- and frequency-dependent increase in ICP. The ICP/BP ratio and the corresponding AUC values, and the detumescence time were also significantly increased compared to the hypercholesterolemic control. These results suggest that DA-8159 is beneficial for erectile dysfunction in a rat hypercholesterolemic model and provided a rationale for the potential use of DA-8159 for treating erectile dysfunction secondary to hypercholesterolemia.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMedDate not supplied

Role of human cytochrome P450 3A4 in the metabolism of DA-8159, a new erectogenic.

The purpose of this paper was to characterize cytochrome P450 (CYP) enzymes involved in N-dealkylation of a new oral erectogenic, DA-8159 to DA-8164, a major circulating active metabolite, in human liver microsomes and to investigate the inhibitory potential of DA-8159 on CYP enzymes. CYP3A4 was identified as the major enzyme responsible for DA-8159 N-dealkylation to DA-8164 based on correlation analysis and specific CYP inhibitor and antibody-mediated inhibition study in human liver microsomes, and DA-8159 metabolism in cDNA expressed CYP enzymes. There is the possibility of drug-drug interactions when prescribing DA-8159 concomitantly with known inhibitors or inducers of CYP3A4. DA-8159 was found to be only a very weak inhibitor of eight major CYPs (1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4), the largest inhibition occurring against CYP2D6 (IC5o 67.7 microM) in human liver microsomes. Drug-drug interactions would not be predicted on the basis of DA-8159 inhibiting the metabolism of coadministered drugs.

Cells, Cultured↗