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Biomedical subjects

M Yoo

Publications and source records attributed to M Yoo.

At least 19 recordsLinked to original sources
PubMed2003

DA-8159, a new PDE5 Iihibitor, induces penile erection in conscious and acute spinal cord injured rabbits.

OBJECTIVES: DA-8159 is a pyrazolopyrimidinone derivative showing potent and selective phosphodiesterase 5 (PDE5) inhibition. In the previous study, DA-8159 induced a dose-dependent increase in the intracavernous pressure (ICP) in anaesthetized dogs. The aim of this study was to investigate the effects of DA-8159 on penile erection in conscious and acute spinal cord injured (ASCI) rabbits. METHODS: DA-8159 was given orally (0.3 to 10mg/kg) to normal rabbits and ASCI rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion. The erection was evaluated in a time-course manner by measuring the length of the uncovered penile mucosa in the absence or presence of intravenous sodium nitroprusside (SNP), a nitric oxide (NO) donor. RESULTS: DA-8159 induced a dose-dependent penile erection in both the conscious and ASCI rabbits. The efficacy of DA-8159 was potentiated and the effective doses were significantly decreased by an intravenous injection of SNP. Potentiation of the effect by a nitric oxide donor implies that DA-8159 can enhance the erectile activity during sexual arousal. CONCLUSION: These results demonstrate that DA-8159 may be a useful treatment option for erectile dysfunction in patients with or without a spinal cord injury, but further evaluation of the effects of DA-8159 on humans must be performed.

Administration, Oral↗
PubMed2001

Thymic cyst: is a correct preoperative diagnosis possible? Report of a case and review of the literature.

UNLABELLED: A case of a giant cervico-mediastinal cyst of thymic origin in an 8-year-old child is presented. The cyst was asymptomatic except for deformity due to its size. In spite of several diagnostic approaches like ultrasonography, computed tomography, cyst puncture with biochemical analysis of cyst content and direct contrast injection and radiography after emptying of the cyst, the ultimate diagnosis as to the origin of the cyst was not disclosed until after operation and histopathological examination of the operative specimen. On a more general basis the diagnostic possibilities and pitfalls are discussed. CONCLUSION: a correct preoperative diagnosis of a thymus cyst is difficult and in many instances impossible even when all diagnostic measures at hand are utilized, including radiographic methods, computed tomography, magnetic resonance imaging, ultrasonography and biochemical examination of cyst aspirate and estimation of tumour markers in cyst fluid and serum.

Biopsy↗
PubMed2001

Pregnancy-associated plasma protein-A accounts for the insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4) proteolytic activity in human pregnancy serum and enhances the mitogenic activity of IGF by degrading IGFBP-4 in vitro.

Pregnancy-associated plasma protein-A (PAPP-A) has been identified as the insulin-like growth factor (IGF)-dependent IGF-binding protein-4 (IGFBP-4) protease produced by human fibroblasts. Recently, we found that serum proteases induced during human pregnancy cleaved IGFBP-4 in both an IGF-II-dependent and an IGF-II-independent fashion. This study sought to determine whether PAPP-A is the predominant IGFBP-4 protease in human pregnancy serum (PS) and to assess the in vitro role of serum PAPP-A. Immunoprecipitation with PAPP-A antibody effectively depleted PAPP-A from the PS and completely abolished both IGF-II-dependent and IGF-II-independent IGFBP-4 proteolytic activity in PS. Direct addition of PAPP-A antibody to PS completely blocked IGFBP-4 proteolysis and partially blocked IGFBP-5 proteolysis, but had no effect on IGFBP-3 proteolysis. To evaluate the role of serum PAPP-A, we tested whether PAPP-A in PS modulated the inhibitory activity of IGFBP-4 on IGF-II-induced cell proliferation in human osteosarcoma MG63 cells. The wild-type IGFBP-4 (WTBP-4; 200 ng/mL) failed to inhibit proliferation of the cells treated with PS (0.1% or 0.3%) alone or in combination with IGF-II (40 ng/mL), whereas the inhibitory effect of WTBP-4 was observed in the cells treated with nonpregnancy serum alone or in combination with IGF-II (P < 0.05). In contrast to WTBP-4, a protease-resistant IGFBP-4 was able to inhibit proliferation of the cells treated with PS alone or in combination with IGF-II (P < 0.05). In the presence of PAPP-A neutralizing antibody, the inhibitory effect of WTBP-4 on proliferation of the cells treated with IGF-II and PS was restored. In summary, these data demonstrate 1) that PAPP-A represents the predominant IGFBP-4 protease in PS; 2) that PAPP-A may in part contribute to IGFBP-5, but not IGFBP-3, proteolytic activity in PS; and 3) that PAPP-A enhances the bioactivity of IGFs in vitro by degrading IGFBP-4.

Cell Division↗
PubMed2000

The DNA replication-related element (DRE)-DRE-binding factor (DREF) system may be involved in the expression of the Drosophila melanogaster TBP gene.

The TATA box binding protein (TBP) is a general transcription factor required for initiation by all three eukaryotic RNA polymerases. Previously, we found that the promoter region of the Drosophila melanogaster TBP gene contains three sequences similar to the DNA replication-related element (DRE) (5'-TATCGATA). In the present study, we found that the DRE-like sequences are also present in the promoter of the Drosophila virilis TBP gene, suggesting a role for these sequences in TBP expression. Band mobility shift assays revealed that oligonucleotides containing sequences similar to the DRE of D. melanogaster TBP gene promoter form specific complexes with a factor in a Kc cell nuclear extract and with recombinant DRE-binding factor (DREF). Furthermore, these complexes were either supershifted or diminished by monoclonal antibodies to DREF. Transient luciferase assays demonstrated that induction of mutations in two DRE-related sequences at positions -223 and -63 resulted in an extensive reduction of promoter activity. Thus, the DRE-DREF system appears to be involved in the expression of the D. melanogaster TBP gene.

Animals↗
PubMed2000

Factors influencing the protein binding of a new phosphodiesterase V inhibitor, DA-8159, using an equilibrium dialysis technique.

Various factors influencing the protein binding of DA-8159 to 4% human serum albumin (HSA) were evaluated using an equilibrium dialysis technique at an initial DA-8159 concentration of 5 microg/mL. It took approximately 8 h incubation to reach an equilibrium between 4% HSA and an isotonic phosphate buffer of pH 7.4 containing 3% of dextran ('the buffer') using a Spectra/Por 2 membrane (mol. wt. cut-off: 12,000--14,000) in a water bath shaker kept at 37 degrees C and at a rate of 50 oscillations per min. The extent of binding was dependent on DA-8159 concentrations, HSA concentrations, incubation temperature, buffer pH, and alpha-1-acid glycoprotein (AAG) concentrations. The binding of DA-8159 in heparinized human plasma (93.9%) was significantly higher than in rats (81.4%), rabbits (80.4%), and dogs (82.2%), and this could be due to differences in AAG concentrations in plasma.

Animals↗
PubMed2000

Erectogenic effect of the selective phosphodiesterase type 5 inhibitor, DA-8159.

DA-8159, a new phosphodiesterase 5 inhibitor, was assessed for its erectogenic potential by a penile erection test in rats, the relaxation of isolated rabbit corpus cavernosum (CC), and estimation of the intracavernous pressure (ICP) in the anesthetized dog. Oral administration of DA-8159 (0.3 to 1 mg/kg) increased the number of erections in rats with increasing dosage, with the highest penile erection index at 10 mg/kg. DA-8159 induced the relaxation of phenylephrine (PHE)-induced contractions in the rabbit CC and decreased the IC50 of the nitric oxide donor sodium nitroprusside (SNP) in a dose-dependent fashion. In pentobarbital-anesthetized dogs, the intravenous administration of DA-8159 (1 approximately 300 g/kg) potentiated the increase in ICP induced by the intracavernosal SNP in a dose-related manner. These findings suggest that DA-8159 has significant therapeutic potential in the treatment of erectile dysfunction.

Animals↗
PubMed2000

A systemic administration of NMDA induces immediate early gene pip92 in the hippocampus.

In the mammalian CNS, aspartate and glutamate are major excitatory amino acids, and their receptors are believed to mediate a wide range of physiological and pathological processes, including neurotransmission, plasticity, excitotoxicity, and various forms of neurodegeneration. The immediate early gene pip92 has been identified in serum-stimulated BALB/c 3T3 fibroblasts, activated T lymphocytes treated with cycloheximide, and fibroblast growth factor-stimulated hippocampal cells during neuronal differentiation. In this study we have demonstrated that pip92 is expressed in the mouse brain after a single intraperitoneal injection of NMDA. The distribution of pip92 mRNA levels in the NMDA-treated mouse brain was investigated using in situ RT-PCR. The region-specific activation of pip92 in the CNS was observed 3 h after NMDA injection, and high levels of pip92 mRNA were detected in the hippocampal dentate gyrus and piriform cortex regions. In addition, the activation of pip92 by NMDA was mediated by activation of mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK) and p38 kinase, but not extracellular signal-regulated kinase (ERK) in the mouse hippocampus and immortalized rat hippocampal progenitor cells. This study suggests that pip92 is likely to play an important role in neuronal cell death induced by excitotoxic NMDA injury in the CNS.

Animals↗
PubMed2000

Studies on human pregnancy-induced insulin-like growth factor (IGF)-binding protein-4 proteases in serum: determination of IGF-II dependency and localization of cleavage site.

Insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4), a consistent inhibitor of IGF action, is subject to proteolytic cleavage by the IGF-II-dependent IGFBP-4 protease. However, regulation of the IGF-II-dependent IGFBP-4 protease in vivo is not known. As IGFBP proteases are known to be triggered during pregnancy, we systematically evaluated the changes in IGFBP-4 proteolysis by serum collected throughout human pregnancy. Results from in vitro protease assays using recombinant IGFBP-4 revealed that IGFBP-4 proteolysis determined in both the presence and absence of exogenous IGF-II significantly increased during the first and second trimesters and reached a plateau by the third trimester. However, in the absence of IGF-II, IGFBP-4 proteolysis by pregnancy serum was only observed after prolonged incubation. IGF-II dose dependently increased IGFBP-4 proteolysis by pregnancy serum, with maximal stimulation observed at a concentration of 0.7 mol/L relative to IGFBP-4. In contrast, IGF-II at an equimolar dose had little effect on proteolysis of recombinant human IGFBP-3, whereas excess IGF-II reproducibly inhibited recombinant human IGFBP-3 proteolysis by pregnancy serum. Although IGF-II enhanced IGFBP-4 proteolysis, results from N-terminal sequence and mass spectrometric analyses of IGFBP-4 proteolytic fragments demonstrate that the cleavage site (Met135-Lys136) in human IGFBP-4 was not altered by IGF-II. Deletion of the residues 121-141 containing this cleavage site blocked IGFBP-4 proteolysis. These findings demonstrate that the increase in IGFBP-4 proteolysis during pregnancy was accounted for mainly by the IGF-II-dependent IGFBP-4 proteolysis. Because IGFBP-4 is a potent inhibitor of IGF actions, it can be speculated that the pregnancy-induced IGFBP-4 proteases may play an important role in regulating fetal growth.

Adult↗
PubMed2000

Sequence analysis and tissue specific expression of human HOXA7.

A 3071-bp fragment containing the human HOXA7 gene was sequenced. It contained two exons, one intron, and two polyadenylation signals (AATAAA) at positions 1844 and 2923. The exon encoded 230 aa residues, while the hexapeptide, homeodomain, and C-terminal acidic domains were detected. When the total sequences were compared with those of murine Hoxa-7, the 5' untranslated region (UTR), exon I, intron, exon II, and 3' UTR exhibited 99, 92, 65, 85, and 72% homology, respectively. Through Northern analysis, about a 1.9-kb transcript was detected in the fetal kidney. Minor transcripts of 1.5 and 1.1-kb were also detected in the fetal liver as well as in the kidney. In the case of adult tissues, most of the tissues tested (lung, liver, skeletal muscle, kidney, pancreas, and placenta), except brain tissue, expressed a 5.3 kb transcript with various intensities. Our results here suggested that not only Abd-B type Hox genes, but the ones in paralogous groups I-VIII could generate multiple transcripts. The characterization of these tissue-specific and stage-specific alternative transcripts would help to understand the regulatory function of the HOXA7 gene during development, and possibly the pathology of human disease caused by Hox genes.

3' Untranslated Regions↗
PubMed2000

Pharmacokinetics, stability, and blood partition of DA-8159, a new phosphodiesterase V inhibitor.

The pharmacokinetics of DA-8159, a new phosphodiesterase V inhibitor, after 1 min intravenous, 30 mg/kg, and oral, 30 mg/kg, administration of the drug to rats, the stability of DA-8159 in various pH solutions ranging from 1 to 13, and human and rat plasma and urine, and the blood partition of DA-8159 between plasma and blood cells of rabbit were evaluated. After intravenous administration, DA-8159 was eliminated fast with the mean total body clearance of 126 ml/min/kg, and was almost completely metabolized in rats; 5.98% of intravenous dose of DA-8159 were excreted unchanged in 24-hr urine. The extent of absolute oral bioavailibility of DA-8159 was approximately 25%. The apparent volume of distribution at steady state was considerably large, 15048 ml/kg, suggesting that DA-8159 has a good affinity to rat tissues. DA-8159 was relatively stable in various pH solutions, and human and rat plasma and urine for up to 48 h incubation in a water-bath shaker kept at 37 degrees C and at a rate of 50 oscillations per min. DA-8159 reached equilibrium fast (within 30 sec mixing manually) between plasma and blood cells of rabbit blood and the plasma-to-blood cell concentration ratios were independent of initial blood concentrations of DA-8159, 1, 5, and 10 microg/ml, when the rabbit whole blood was incubated for up to 120 min; the ratios were in the range of 0.662-0.812. There was no in vitro 'blood storage effect' in the plasma concentration of DA-8159.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1999

Two homologous cytochrome b5s are expressed in both neurons and glial cells of the rat brain.

To avoid the possibility of blood contamination and of gene rearrangement during library construction we isolated total RNA directly from cultured rat embryonic neuronal cells and glioma C6 cells to be used as template for RT-PCR. By using specific primers for both membrane-bound b5 and soluble b5, DNA bands of appropriate size were clearly amplified indicating that both neurons and glial cells expressed b5s, although soluble b5 seemed to be less expressed in these cells. Nucleotide sequence of the internal exon for soluble b5 was reinvestigated and confirmed to be 58 bp containing genetic codons for His-Ser-Ala-Leu and stop.

Alternative Splicing↗
PubMed1999

Effect of DA-6034, a derivative of flavonoid, on experimental animal models of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034, 7-carboxymethyloxy-3', 4', 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD: two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3 to approximately 3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 mg/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.

Acetic Acid↗
PubMed1997

Identification of two homologous cytochrome b5s in rat brain.

Two kinds of PCR products were isolated from adult rat brain. The smaller product matched up to liver b5 mRNA completely. However, the larger one contained an additional 58 bp inserted between amino acids 96 and 97. This insertion was previously unknown and corresponded to in-frame codons for his-ser-ala-leu and the early stop. It is assumed that these two forms arise from a primary transcript by differential mRNA processing. This finding strongly suggests that there are two homologous b5s expressed in rat brain.

Amino Acid Sequence↗
PubMed1997

Identification of cytochrome P450 2E1 in rat brain.

We have isolated cDNA fragments that were originated from P450 2E1 in rat brain by PCR analysis. Their size matched up to what we expected based on the reported sequence of rat liver P450 2E1 mRNA. Internal structure of the longest first-round PCR products were investigated by Southern blot analysis and "nested" PCR. Their results confirmed that PCR products actually originated from P450 2E1 mRNA in rat brain. RT-PCR was also carried out using P450 2E1 specific primers and the size of the product was exactly as we expected for P450 2E1. These experimental evidences should clarify the presence of P450 2E1 in rat brain.

Animals↗
PubMed1996

A clinical and histopathological study of 22 patients with membranous lipodystrophy.

Membranous lipodystrophy, an uncommon disorder, was described by Nasu et al. in 1973 as a form of regressive degeneration or localized destruction of the adipose tissue. Clinical features of the lesions with membranous fat necrosis are variable and the condition can only be diagnosed histopathologically. These peculiar changes in fat tissue have been associated with many local and systemic diseases including lupus erythematosus, diabetes mellitus, erythema nodosum, stasis dermatitis, morphoea and trauma, but occasionally no underlying disease is found. Even though various hypotheses concerning the pathogenesis of membranous lipodystrophy have been proposed, the exact causes are still in dispute. We reviewed 22 patients having membranous lipodystrophy confirmed by biopsy and discuss the pathogenetic mechanisms which have been suggested by many authors.

Adipose Tissue↗
PubMed1995

The isolation and characterization of the human cytochrome b5 gene.

From a series of lambda and cosmid libraries, we isolated DNA sequences corresponding to the complete coding region for the human cytochrome b5 (CYB5) gene. The overall gene organization was the same as the bovine and rabbit CYB5 genes. One cosmid clone containing exon I plus the 5' flanking region was extensively characterized. From this clone we obtained 2000 bp of 5' flanking sequence, containing several distinctive GC rich regions, potential trans-acting factor binding sites and a 74 bp direct repeat. A series of deletion constructs were made in the pGL2 luciferase vector and then used to transfect HepG2 and K562 cells. The data obtained suggest the presence of two promotors and one silencer region in the analyzed 5' sequence.

Animals↗