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Biomedical subjects

J S Han

Publications and source records attributed to J S Han.

At least 37 records · Page 2Linked to original sources
PubMed2001

Changes in brain content of nociceptin/orphanin FQ and endomorphin 2 in a rat model of neuropathic pain.

Orphanin FQ (OFQ) and endomorphins (EM) are newly characterized members of opioid peptide family. OFQ has been shown to antagonize morphine analgesia at supraspinal level, whereas endomorphins are highly selective endogenous ligands for mu receptor, showing analgesic effect at both spinal and supraspinal level. OFQ and EM-2 (EM2) immunoreactivity (ir) was measured by radioimmunoassay in nociception-related brain areas of rats subjected to L5/L6 spinal nerve ligation, using sham operated rats as control. It was found that: (1) the content of EM2-ir of spinal nerve ligated rats showed a significant increase (778%) in periaqueductal gray (PAG), and a significant decrease (43%) in striatum, compared with the control group. (2) a significant increase of the content of OFQ-ir was found in amygdala (+841%) and PAG (+459%), respectively in spinal nerve ligated rats. High pressure liquid chromatography showed that the EM2-ir and OFQ-ir were both heterogeneous with the major part eluting at the position of EM2 and OFQ standard, respectively. These results suggest that spinal nerve ligation induces significant changes in the content of EM2-ir and OFQ-ir in some discrete brain areas, which may play a role in nociceptive modulation.

Amygdala↗
PubMed2001

Multimerization of phosphorylated and non-phosphorylated ArcA is necessary for the response regulator function of the Arc two-component signal transduction system.

To adapt to anaerobic conditions, Escherichia coli operates the Arc two-component signal transduction system, consisting of a sensor kinase, ArcB, and a response regulator, ArcA. ArcA is converted to the active form, phosphorylated ArcA (ArcA-P), by ArcB-mediated phosphorylation. The active ArcA-P binds to the promoter regions of target genes, thereby regulating their transcriptional activities. The phosphoryl group of ArcA-P is unstable with a half-life of 30 min. However, we were able to inhibit the dephosphorylation for more than 12 h by the addition of EDTA; this allowed us to characterize ArcA-P. Gel-filtration and glycerol sedimentation experiments demonstrated that ArcA exists as a homo-dimer. ArcA phosphorylated by either ArcB or carbamyl phosphate multimerizes to form a tetramer of dimers; this multimer binds to the ArcA DNA binding site. Isoelectric focusing gel electrophoresis and nitrocellulose-filter binding analyses indicated that the ArcA multimer is composed of both ArcA-P and ArcA in a ratio, 1:1. The ArcA(D54E) mutant protein was unable to be phosphorylated by ArcB. This defect resulted in the inability of ArcA(D54E) to form a multimer or to bind to the ArcA DNA binding site. These results indicate that phosphorylation of ArcA induces multimerization prior to DNA binding, and the multimerization is a prerequisite for binding. Our results suggest a novel model that phosphorylation of ArcA by ArcB regulates multimerization of ArcA, which in turn functions as a response regulator.

Bacterial Outer Membrane Proteins↗
PubMed2001

A novel method for convenient assessment of arthritic pain in voluntarily walking rats.

Quantification of arthritic pain can be very useful in elucidating the mechanisms of arthritis and in assessing the effect of anti-arthritic medication or treatment. Here we report a novel method that allows convenient measurements of the severity of arthritic pain in voluntarily walking rats. We constructed a device to measure the weight load on each leg while the animal was walking through a path, the bottom of which was equipped with strain gauge weight sensors. Using this device, we measured the weight load on the right hind leg before and after induction of arthritis by carrageenan injection into the knee joint cavity of this leg. The carrageenan injection resulted in a significant reduction of weight load on the affected leg; the load decreased to the minimum level at 4 h after the injection and gradually returned to the pre-injection level by the fifth day. Intraperitoneal administration of morphine at 5.5 h after carrageenan injection could reverse the weight load change. These results suggest that our new device is an effective tool for convenient measurements of arthritic pain in dynamic conditions like walking.

Analgesics, Opioid↗
PubMed2001

Gene delivery using a receptor-mediated gene transfer system targeted to hepatocellular carcinoma cells.

For gene therapy to be effective in cancers, it is necessary to deliver therapeutic genes into cells with high specificity and efficiency. In this study, we examined the in vitro and in vivo gene delivery efficiency of a new, growth receptor-mediated gene transfer system in hepatocellular carcinoma (HCC). The effects of transfection of wild-type p53 using this system were also studied. The system consisted of a ligand oligopeptide for epidermal growth factor receptor (EGFR) recognition, a polypeptide for DNA binding, and an endosome-releasing oligopeptide for endosomolysis. Two human HCC cell lines and a normal liver cell line were used, and pCMV-beta-galactosidase (beta-gal) was used as a reporter gene. Both HCC cell lines had strong expression of EGFR and the in vitro transfer efficiency peaked at day 5 at about 50%. This finding was in contrast to the normal liver cell line, which had weak EGFR expression and less than 1% transfer efficiency throughout. For in vivo gene transfer in tumors produced by inoculating HCC cells in nude mice and with the vector-beta-gal gene complex injected peritumorally, beta-gal expression was detected within the tumors at 12 hr, peaked at day 5 involving about 50% of the tumor cells and persisted at 2 weeks. Using this vector system, transfection of wild-type p53 into Huh-7 cells that had mutated p53 resulted in significant growth inhibition of cancer cells accompanied by a decreased G2/M phase and increased p53 protein. In conclusion, this receptor-mediated gene transfer system appears to work specifically in HCC cells with high efficiency, and may be promising in delivering apoptotic and other genes into HCC cells.

Antineoplastic Agents↗
PubMed2001

Amygdala is critical for stress-induced modulation of hippocampal long-term potentiation and learning.

Stress is a biologically significant factor shown to influence synaptic plasticity and memory functioning in the hippocampus. This study examined the role of the amygdala, a brain structure implicated in coordinating stress behaviors and modulating memory consolidation, in mediating stress effects on hippocampal long-term potentiation (LTP) and memory in rats. Electrolytic lesions of the amygdala effectively blocked the adverse physiological and behavioral effects of restraint and tailshock stress, without impeding the increase in corticosterone secretion to stress. Physiologically, hippocampal slices from stressed animals exhibited impaired LTP relative to slices from unstressed control animals, whereas hippocampal slices from stressed animals with amygdalar lesions exhibited normal LTP. Behaviorally, stressed animals were impaired in retention of a hippocampal-dependent hidden platform version of the Morris water maze task, and this impairment was blocked by amygdalar lesions. In a fixed location-visible platform water maze task that can be acquired by independent hippocampal and nonhippocampal memory systems, stress enhanced the use of nonhippocampal-based memory to acquire the task. These results indicate that an intact amygdala is necessary for the expression of the modulatory effects of stress on hippocampal LTP and memory.

Amygdala↗
PubMed2001

Nocistatin, a peptide reversing acute and chronic morphine tolerance.

It has been reported that intracerebroventricular (i.c.v.) injection of nociception/orphanin FQ (OFQ) can antagonize morphine analgesia, whereas i.c.v. OFQ antibody can reverse morphine tolerance. Nocistatin (NST) is a recently characterized neuropeptide possessing an antagonizing effect on OFQ. Here we examine whether i.c.v. NST would result in a reversal of morphine tolerance. The results showed that: (1) i.c.v. NST at doses of 0.005, 0.05, 0.5, 5 or 50 ng per rat produced a bell-shaped dose-dependent reversal of chronic morphine tolerance, with maximum response at 0.5 ng. (2) Acute morphine tolerance could also be reversed, albeit partially, by i.c.v. NST at 0.5 ng. (3) The reversal of acute and chronic morphine tolerance by NST was completely abolished when NST (0.5 ng) was co-injected with (8 microg) OFQ. Since OFQ and NST are derived from the same preprohormone, the profile of its splicing in the CNS may play an important role in determining the effectiveness of morphine analgesia.

Analgesics, Opioid↗
PubMed2001

Discrimination between peptide and non-peptide opioid agonists on the transcription of opioid receptors in two cell lines.

The aim of the present study was to characterize the effects of prolonged use of peptide mu- and delta-receptor agonists [D-Ala2, N-me-phe, Gly5-ol]-enkephalin (DAMGO) and [D-Pen2, D-Pen5]-enkephalin (DPDPE) and non-peptide agonists ohmefentanyl (OMF) and BW373U86 on the transcription of opioid receptors of cultured NG108-15 cell and SHSY5Y cells, respectively using the method of reverse transcription-polymerase chain reaction (RT-PCR). It was found that (1) The abundance of mu- and delta- receptor mRNA decreased significantly up to 48h after the administration of DAMGO and DPDPE, respectively; whereas the inhibitory effect of OMF and BW373U86 lasted only for 24h; (2) DAMGO and DPDPE produced a significant decrease of the mRNA coding for mu-receptor and delta-receptor at concentrations as low as 10(-8) mol/L and 10(-6) mol/L, respectively, whereas OMF and BW373U86 were effective at concentrations one order of magnitude higher, respectively. These results suggested that (1) Long-term administration of either peptide or non-peptide opioid agonist to cultured cell line produced a significant decrease of the gene expression of opioid receptor at transcription level. (2) The effect of peptide agonists was stronger and lasted longer than that of corresponding nonpeptide agonists.

Benzamides↗
PubMed2001

The metabolic evidence of synergistic interaction between DAMGO and DPDPE on undifferentiated SH-SY5Y cells.

Recent studies have demonstrated the analgesic synergy between mu- and delta-opioid receptor, but evidence obtained at the cellular level is scanty. This work was designed to find the evidence of synergy between the actions of D-Ala2-Mephe4-glyol5 enkephalin (DAMGO) and D-Phe2, D-Phe5 enkephalin (DPDPE) on undifferentiated SH-SY5Y cells. Microphysiometer was used to detect the functional activity of cells by measuring the real-time extracellular acidification rate (ECAR). The results demonstrate the unequivocal synergy between DAMGO and DPDPE at least within certain ratios. In addition, combined administration of the two drugs in the synergistic ratios attenuates receptor desensitization. These data indicate that DAMGO and DPDPE have a synergistic effect at cellular level.

Analgesics, Opioid↗
PubMed2001

The metabolic evidence of synergistic effect between ohmefentanyl and [D-Pen2, D-Pen5] enkephalin on differentiated SH-SY5Y cells in humans.

Interactions between selective opioid agonists acting at mu- and delta-opioid receptors were evaluated by co-administering a low-effective dose of the selective mu-opioid receptor agonist ohmefentanyl (OMF) with sequentially increasing doses of the selective delta-opioid receptor agonist [D-Pen(2), D-Pen(5)] enkephalin (DPDPE). Microphysiometer was used to measure the extracellular acidification rate (ECAR) of living cells in real-time, which reflected the functional activity after agonist-receptor binding. The synergy (i.e. a more than additive effect) was observed with combinations of these two opioid agonists on differentiated SH-SY5Y cells functionally expressing both mu- and delta-opioid receptors. The demonstration of the synergy suggests that the agonists of the subtypes of opioid receptors can interact at cellular level.

Acids↗
PubMed2001

Genetic heterogeneity in Korean families with autosomal-dominant polycystic kidney disease (ADPKD): the first Asian report.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease in adults, and the prevalence of this disease within the chronic haemodialysis patient population is known to be approximately 2% in Korea. So far, three genetic locus have been identified as being responsible for ADPKD, and approximately 85% of the cases in Western countries are related to the PKD1 gene. However, little information is available concerning the pattern of linkage analysis in Asian populations. METHODS: 48 families with hereditary renal cysts were recruited by consent and their molecular genetic characteristics were studied. Linkage analysis was done with microsatellite markers (PKD1: SM7, UT581, AC2.5, KG8, D16S418; PKD2: D4S423, D4S1534, D4S1542, D4S1544, D4S2460). Genomic DNA polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) gel run were performed, and the resultant allele patterns were compared with sonographic findings. RESULTS: The results of this study showed that the ratio PKD1:PKD2 was 31:8, and that the PKD2 families exhibited a tendency toward a milder renal prognosis than the PKD1 families. CONCLUSION: We confirmed the applicability of linkage analysis for ADPKD in the Korean population, and our data confirmed a similar incidence of PKD1 (79%) and PKD2 (21%) in Korean patients as in the Western population.

Adolescent↗
PubMed2001

Hypothalamic-pituitary-adrenal axis function and corticosterone receptor expression in behaviourally characterized young and aged Long-Evans rats.

In the current investigation, hypothalamic-pituitary-adrenal (HPA) axis function was examined in young and aged male Long-Evans rats that were initially assessed on a version of the Morris water maze sensitive to cognitive impairment during ageing. In behaviourally characterized rats, a 1-h restraint stress paradigm revealed that plasma corticosterone concentrations in aged cognitively impaired rats took significantly longer to return to baseline following the stressor than did those in young or aged cognitively unimpaired rats. No differences in basal or peak plasma corticosterone concentrations, however, were observed between young or aged rats, irrespective of cognitive status. Using ribonuclease protection assays and in situ hybridization, we evaluated mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA abundance in young and aged rats characterized on the spatial task. Abundance of MR mRNA was decreased as a function of age in stratum granulosum but not hippocampus proper, and the decrease in MR mRNA was largely unrelated to cognitive status. However, GR mRNA was significantly reduced in several hippocampal subfields (i.e. stratum granulosum and temporal hippocampus proper) and other related cortical structures (medial prefrontal and olfactory regions) of aged cognitively impaired rats compared to either young or aged cognitively unimpaired cohorts, and was significantly correlated with spatial learning ability among the aged rats in each of these brain regions. In agreement with previous stereological data from this ageing model, no changes were detected in neuron density in the hippocampus of the rats used in the in situ hybridization analysis. These data are the first to describe a coordinated decrease in GR mRNA in a functional brain system including hippocampus and related cortical areas that occurs in tandem with impairments of the HPA response to stress and cognitive decline in ageing.

Adrenal Cortex Hormones↗
PubMed2001

Heterogeneous distribution of cardioplegic solution in pigs.

Septal dyskinesia in the left ventricle is detected frequently in many patients after open-heart surgery. The present study was designed to determine whether the antegrade delivery of cardioplegic solution to the regional wall categorized in echocardiography is homogeneous, and whether the distribution to the septal wall differs from that to the lateral wall in the absence of coronary artery disease. To assess these hypotheses quantitatively, radioactive microspheres were mixed into the cardioplegic solution and infused by an antegrade method in eight normal pigs. The cardioplegic distribution to the septal wall was significantly less than to the lateral wall close to the base of the left ventricle (P<0.05). Therefore, antegrade perfusion of cardioplegic solution was non-uniformly distributed to the regional and transmural wall of normal pig hearts. Absence of functional correlation was a limitation of this study. However, these findings suggest that inadequate protection of the ventricular septum by antegrade cardioplegia might be an explanation for the abnormalities of septal wall motion after open-heart surgery.

Animals↗
PubMed2001

Th1/Th2 predominance and proinflammatory cytokines determine the clinicopathological severity of IgA nephropathy.

BACKGROUND: IgA nephropathy is one of the most common forms of primary glomerulonephritis in adults. Its pathogenesis is complex. The nature of infiltrating and proliferating cells and of cellular mediators could contribute to the progression of IgA nephropathy towards end-stage renal failure. METHODS: To evaluate this hypothesis, we attempted to quantify the magnitude of intrarenal gene expression of various cytokines (IL-1 beta, TNF-alpha, IL-6, IL-15, IL-2, IFN-gamma, IL-10) and chemokines (IL-8, RANTES, MCP-1) in 48 renal core biopsy specimens, diagnosed as IgA nephropathy by immunofluorescence microscopy. Semi-quantitative reverse-transcriptase polymerase chain reaction using internal competitors was used for the quantification of gene transcripts. RESULTS: The expression of intrarenal gene transcripts of various cytokines and chemokines was closely interrelated, but not associated with the pathological grading system. The IFN-gamma/IL-10 ratio was higher in patients with renal dysfunction than in those with normal renal function (P=0.0483). Gene transcript levels of proinflammatory cytokines were related to the amount of proteinuria. In patients with severe glomerular sclerosis, the ratio of IFN-gamma/IL-10 gene transcripts was high (P=0.04). IL-10 gene transcript level was related to the severity of tubulointerstitial damage. The levels of gene expression of IL-10 (P=0.009), IFN-gamma (P=0.03), and TNF-alpha (P=0.005) were related to the degree of mesangial matrix expansion and the extent of intrarenal arteriolar changes correlated with the expression of the IL-8 gene transcript (r=0.43, P=0.004). CONCLUSIONS: We propose that Th1/Th2 predominance and the level of proinflammatory cytokines could determine the pathogenetic processes and the severity of the clinical manifestations of IgA nephropathy.

Adolescent↗
PubMed2001

Uteroglobin gene polymorphisms affect the progression of immunoglobulin A nephropathy by modulating the level of uteroglobin expression.

Uteroglobin (UG) is an anti-inflammatory/immunomodulatory protein. Targeted disruption of UG rendered mouse glomerulonephritis resembling immunoglobulin (Ig)A nephropathy (IgAN). Sequence analysis on exon 1 of UG showed several putative binding sites for transcription factors, and polymorphisms in this site might influence the expression level of UG as a competitive protein. We speculated that the single nucleotide polymorphism at the 38th nucleotide (A to G) from the transcription initiation site of UG exon 1 would impact the progression of IgA nephropathy (IgAN). Polymerase chain reaction-restriction fragment length polymorphism and single-strand conformation polymorphism were instituted to determine the genetic polymorphism. Luciferase assay was performed using the gene constructs containing a region 404-bp long located upstream of UG exon 1 initiation site to analyse whether this polymorphism would affect the expression level. UG polymorphism was distributed no differently in patients with IgAN (n = 111) compared to 60 healthy control subjects. An excess of A genotype was found in one patient having progressive disease (P = 0.03) and the risk for the disease progression increased as the number of A alleles increased (P for trend = 0.03) after follow-up for 116 months. The odds ratio for progression with the AA genotype was 4.9 (95% Cl = 1.0-23.9) compared to patients having the GG genotype. Significant interactive effects of hypertension and genetic polymorphisms of UG on the disease progression were observed (P for interaction = 0.001). In the luciferase assay, the gene construct with A at the 38th site showed a decreased activity of 74 +/- 8.4% compared to that showed by G gene construct. Our results suggest that polymorphism at the 5' UTR region of UG exon 1 is an important marker for the progression of IgAN and may modulate the level of protein expression.

5' Untranslated Regions↗
PubMed2001

Does albumin preinfusion potentiate diuretic action of furosemide in patients with nephrotic syndrome?

The aim of this cross-over study was to investigate whether albumin infusion before furosemide administration could potentiate the diuretic action of furosemide. Seven patients with nephrotic syndrome were given the following infusions in random order on two separate days: 1) a sham solution followed by 160 mg of furosemide, 2) 100 ml of 20% human albumin followed by 160 mg of furosemide. Urine and serum furosemide concentrations were measured by high-performance liquid chromatography. The increment of urine volume was greater in albumin preinfusion than in furosemide alone. However, the increments of sodium and chloride excretions between furosemide alone and albumin preinfusion were not different. No significant differences in the pharmacokinetic parameters between the two treatments were observed: area under the concentration-time curve (AUC: 12.7+/-2.2 vs 15.1+/-4.4 g/ml hr), total plasma clearance (253+/-41 vs 256+/-54 ml/min), volume of distribution (341+/-34 vs 494+/-153 ml/kg), elimination half life (4.0+/-1.1 vs 4.6+/-0.8 hr), and urine furosemide excretion of the administered amount (16.5+/-7.3 vs 7.5+/-1.6%). In conclusion, these data show that albumin preinfusion potentiated diuresis, but not natriuresis, of furosemide without any change in the pharmacokinetics of the agent in patients with nephrotic syndrome.

Adolescent↗
PubMed2001

Differential effects of adenovirus-p16 on bladder cancer cell lines can be overcome by the addition of butyrate.

High frequency of p16 alteration and high local recurrence rate of bladder cancer make this cancer an ideal target for p16 gene therapy. However, a low transduction rate of p16 via adenoviral vector causes an inconsistent result. In this study, we have tested adenovirus-p16 in several bladder cancer cell lines and investigated a way of improving the low transduction rate. Adenovirus-p16 showed a strong antitumor effect on bladder cancer cell lines (253J and T24) with strong Coxackie-adenoviral receptor (CAR) expression but little antitumor effect on bladder cancer cell lines (J82 and HT1376) with little CAR expression. In this study, we suggest a simple way of overcoming the differential effects of the adenovirus. The addition of butyrate to media was found to increase the transduction rate of adenovirus remarkably and increase the antitumor effect of adenovirus-p16 in bladder cancer cell lines with little CAR expression. Butyrate effects were related with increased CAR expression on the cell surface as well as increased transgene expression from adenoviral vector. From these observations, application of adenovirus-p16 gene therapy with butyrate can overcome the obstacle of low gene transfer and enhance the antitumor effect of adenovirus-p16 in bladder cancer.

Adenoviridae↗