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Biomedical subjects

H Han

Publications and source records attributed to H Han.

At least 37 records · Page 2Linked to original sources
PubMed1997

Rapsyn and agrin slow the metabolic degradation of the acetylcholine receptor.

Rapsyn is a 43-kDa cytoplasmic protein that clusters nicotinic acetylcholine receptors (AChR) in the postsynaptic membrane. Here we examine the effect of rapsynmediated AChR clustering on the metabolic stability of the AChR. When transfected into QT-6 fibroblasts, cell surface AChRs (alpha, beta, epsilon, and delta subunit combination) pulse labeled with 125I-alpha-bungarotoxin were degraded with a half-life of 16.4 +/- 1.1 h (mean +/- SEM). Cotransfection of rapsyn with AChR caused extensive AChR clustering and increased AChR half-life to 20.5 +/- 1.0 h. Anti-AChR antibodies such as mab 35 cause an increased AChR degradation often associated with myasthenia gravis: 80.8 +/- 2.5% of AChRs labeled at zero time were degraded over a 12-h period. Contransfection of rapsyn reduced this AChR loss to 66.4 +/- 3.8%. Rapsyn also reduced normal AChR degradation, from 53.2 +/- 2.1 to 44.2 +/- 2.2%. Muscle cell lines from wild-type myotubes displayed few AChR clusters, but treatment with neural agrin increased the number of AChR clusters 30-fold. Clustering was accompanied by reductions in AChR degradation (both in the presence and absence of mab 35) similar in magnitude to those produced by overexpression of rapsyn in QT-6 cells. In rapsyn-deficient myotubes, treatment with neural agrin neither caused AChR clustering nor reduced AChR degradation. Thus neural agrin may slow AChR degradation by inducing the rapsyn-dependent clustering of AChRs.

Agrin↗
PubMed1997

Early and late results of excision of choledochal cysts.

BACKGROUND/PURPOSE: Reports on the late results of choledochal cyst excision with hepaticojejunostomy in children are relatively few. METHODS: Of the 84 patients who had choledochal cyst who came under our care, 79 have had definitive surgery, three are awaiting surgery, one is being observed with Caroli's disease, and the parents of one child have refused surgery. Thirty-eight patients treated decades ago had internal drainage procedures. Since 1972, 41 patients have had cyst excision with hepaticojejunostomy using a 40-cm Roux loop without an antireflux procedure. Early complications in those who underwent cyst excision with hepaticojejunostomy included anastomotic leak in three patients who required reoperation, cholangitis in two, and fluid collection in the gall-bladder bed that required no intervention in one. RESULTS: During a follow-up period ranging from 4 months to 17 years (mean, 8.5 years), anastomotic stricture, cholangitis, and intrahepatic stone formation developed in two children after being well for 8 years and over 11 years. These children required additional surgical procedures to overcome their problems. Asymptomatic intrahepatic stones 2 years after cyst excision with hepaticojejunostomy developed in a third child. There was no mortality in the entire group that underwent cyst excision and they are all enjoying a good quality of life. CONCLUSIONS: Careful, long-term follow-up is important in children who have choledochal cyst excision with hepaticojejunostomy.

Adolescent↗
PubMed1997

Oxidized low density lipoproteins stimulate galactosyltransferase activity, ras activation, p44 mitogen activated protein kinase and c-fos expression in aortic smooth muscle cells.

Previously, our laboratory has shown that oxidized low density lipoproteins (Ox-LDL) can exert a concentration-dependent stimulation in the proliferation of aortic smooth muscle cells, "a hallmark in the pathogenesis of atherosclerosis" (Chatterjee, S. (1992) Mol. Cell. Biochem., 111, 143-147). Here we report a novel aspect of Ox-LDL-mediated signal transduction. We demonstrate that in aortic smooth muscle cells, Ox-LDL stimulates the activity of a UDP-galactose:glucosylceramide beta1-->4 galactosyltransferase (GalT-2) and phosphorylation/activation of p44 mitogen-activated protein (MAP) kinase (p44 MAPK). The activity of GalT-2 increased about 2-fold within 2.5-5 min of incubation of cells with Ox-LDL (10 microg/ml). After 5 min of incubation of cells with Ox-LDL, but not LDL, there was a 2-fold increase in the activity of p44 MAPK. Phosphoamino acid analysis employing thin layer chromatography revealed that the tyrosine and threonine moieties of p44 MAPK was phosphorylated by Ox-LDL. D-1-Phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP; a potent inhibitor of GalT-2) impaired the Ox-LDL mediated induction of p44 MAPK activity and the phosphorylation of tyrosine and threonine residues in p44 MAPK. This phenomenon was bypassed by the simultaneous addition of lactosylceramide. The upstream and downstream parameters in MAP kinase signaling pathways were investigated next. We found that Ox-LDL stimulated (9-fold) the loading of GTP on Ras. Interestingly, Ox-LDL specifically induced c-fos mRNA expression (6.5-fold) in these cells, as compared to the control. Thus, one of the biochemical mechanisms in Ox-LDL mediated induction in the proliferation in aortic smooth muscle cells may involve GalT-2 activation, lactosylceramide production, Ras GTP loading, activation of the kinase cascade, and c-fos expression.

Aorta↗
PubMed1997

The impact of HLA-DRB1*0405 on disease severity in Korean patients with seropositive rheumatoid arthritis.

Many reports have described HLA-DRB1 genes as having an influence on disease severity and susceptibility in rheumatoid arthritis (RA). Studies were undertaken to define the effect of RA-associated alleles on disease severity in Korean patients with seropositive RA. The results indicate that the most common RA susceptibility allele, HLA-DRB1*0405, is significantly associated with bony erosion, joint deformity and extra-articular manifestations. However, RA-associated alleles in Koreans have less effect on nodular disease than in Caucasians. This suggests that the presence of RA-associated alleles, especially HLA-DRB1*0405, seems to be a prognostic marker for severe erosive disease in Koreans.

Adult↗
PubMed1997

Paget bone disease involving young adults in 3 generations of a Korean family.

Although the etiology of Paget bone disease (PBD) is unknown, increasing evidence implicates a "slow virus" infection of the skeleton, perhaps in genetically predisposed individuals. PBD is rare in Asia. We describe a Korean family with PBD. The propositus noticed bowed limbs at approximately 25 years of age. Radiologic studies made when he was 55 years old revealed essentially panostotic PBD. Serum alkaline phosphatase (ALP) activity and osteocalcin (OC) levels were markedly elevated. An iliac crest specimen showed classic histopathologic changes of PBD. Additionally, palpable swellings were first observed at age 45 years at his occiput, pubic ramus, ileum, and facial bones. They contained numerous multinucleated cells and were originally diagnosed as giant cell tumors. However, we found that, like osteoclasts, these cells expressed considerable tartrate-resistant acid phosphatase activity. These "extraskeletal osteoclastomas" resolved rapidly with dexamethasone treatment. Two daughters, 20- and 24-years-of-age, were discovered by study of his 5 children to have elevated serum ALP activity and OC levels and widespread PBD. Both women, however, are without palpable masses and are asymptomatic. The propositus' father, who died at age 55 years, had similar skeletal deformities beginning at age 20 years, but was not examined. Leukocytopenia was found in the 3 living family members with PBD. There was no evidence for linkage of the PBD to HLA loci. The condition appears to be transmitted as an autosomal dominant trait and is manifest in young adult life. Multicentric extraskeletal osteoclastomas with remarkable sensitivity to dexamethasone treatment appear to be another unusual feature of this family's disorder. In this family, the stimulus for PBD is so great that the PBD is apparent at an early age, affects essentially the entire skeleton, and leads to the formation or extension of osteoclast-like cells into nonosseous tissues (extraskeletal osteoclastomas). This 3-generation kindred in Korea, where PBD is rare, shows a strong clustering of PBD compatible with autosomal dominant inheritance. Leukocytopenia appears to distinguish affected family members, but any role for this abnormality in the pathogenesis of PBD is unclear. Our findings support a heritable diathesis for PBD, perhaps mediated by an immune deficiency.

Adult↗
PubMed1997

Decreased tumour necrosis factor-beta production in TNFB*2 homozygote: an important predisposing factor of lupus nephritis in Koreans.

Low TNF production and its association with TNF gene restriction fragment length polymorphism (RFLP) was demonstrated in (NZW/NZB) F1 mice. However, little is known about the significance of TNF production in association with TNF gene polymorphism in human SLE. This study was designed to evaluate the role of TNF production of peripheral blood mononuclear cells (PBMC) and its association with TNFB gene polymorphism in SLE, particularly lupus nephritis. TNFB gene polymorphism was defined by PCR-NcoI RFLP. TNF productions of phytohemagglutinin (PHA)-stimulated PBMC and T cells were examined by bioassay using L929 cell line and ELISA. The PBMC stimulated by PHA from patients with SLE (n = 60) tended to secrete less amounts of TNF by bioassay (1032 +/- 184 pg/ml vs 1524 +/- 224 pg/ml, P = 0.094), and TNF-beta by ELISA (P = 0.0082) than that from normal controls (n = 38). The low TNF-alpha producer was more frequent in nephritis than non-nephritis (34.4% vs 7.1% respectively, P < 0.01). TNF-beta also revealed similar results (53.1% vs 21.4%, P < 0.05). In SLE, mean production of TNF-beta was decreased in TNFB*2 homozygote (n = 18) than that in TNFB*1 homozygote (n = 9) (1126.3 +/- 145 pg/ml) vs 642 +/- 118.4 pg/ml, respectively, P = 0.021), whereas TNF-alpha production showed little difference between the two groups (710.1 +/- 56.4 vs 542.4 +/- 71.1 pg/ml, respectively, P = 0.149). Our results demonstrate that decreased TNF production of PBMC, which was significantly associated with TNFB*2 homozygosity, could be an important predisposing factor of lupus nephritis in Koreans.

Alleles↗
PubMed1997

Serum and urine soluble HLA class I antigen concentrations are increased in patients with hemorrhagic fever with renal syndrome.

OBJECTIVES: In order to evaluate the association between the Hantaan virus-induced cellular-immune response and clinical severity in patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: We serially measured the serum (n = 16) and urine (n = 6) concentrations of soluble HLA class 1 antigen (sHLA-l) and clinical powameters in patients with HFRS. RESULTS: Serum sHLA-I concentrations in patients with HFRS were significantly higher than those in controls throughout all clinical phases (p < 0.01). The highly elevated Serum sHLA-I concentrations peaked in the oliguric phase and declined gradually through the phases of HFRS. Serum sHLA-l concentrations in patients with hypotensive episode were higher than in those without the episode (5,85 +/-2,184 vs. 2,389 +/- 860 ng/ml in oliguric phase, 4.11 +/- 1,952 vs. 1,502 +/- 592 ng/ml in diuretic phase, p < 0.05), and serum sHLA-l levels showed a significant correlation with blood WBC count (r = 0.75 in the febrile and hypotensive phase, p < 0.01) and serum creatinine concentrations (r = 0.64 in the oliguric phase, p < 0.01), respectively, Urine sHLA-I levels in the oliguric phase were significantly higher than those in the diuretic phase (390 +/- 155 vs. 214 +/- 45 ng/mg Cr, p < 0.05) and urine sHLA-I levels are associated with severe illness in patients with HFRS. The higher serum sHLA-I are associated with severe illness in patients with HFRS. The persistent elevation of serum sHLA-I during all phases of HFRS might be related to increased production due to prolonged cellular immunologic stimulation by the Hantaan virus rather than decreased excretion of sHLA-I through the kidney. CONCLUSION: We suggest that the serum and urine sHLA-I concentrations can be used as a stable and objective parameter for monitoring clinical severity and renal dysfunction in patients with HFRS.

Adult↗
PubMed1997

[The establishment and evaluation of abdominal aorta thrombosis model in rat].

An animal model of abdominal aorta thrombosis based on Virchow's thrombosis principle was induced by endothelium denudation with a polyethylene catheter combining severe stenosis with an aortic constriction in rats. A total of 37 rats were involved in thrombosis induction. Among them thrombus developed in 27 rats. Mean length of thrombus was 8.53 +/- 1.42 mm. The contractibility of vascular wall in the thrombotic group significantly reduced.

Animals↗
PubMed1997

Involvement of the cyclin-dependent kinase inhibitor p27Kip1 in negative signaling through the antigen-receptor of B lymphocytes.

Several lines of evidence suggest that interaction with antigens generates a negative signal via the antigen receptor of B lymphocytes (cell surface immunoglobulin; sIg), resulting in apoptosis, growth arrest or functional inactivation, and that activation of B cells requires an additional co-stimulatory signal such as a T cell-derived signal through the B cell membrane molecule CD40. In the B cell line WEHI-231, sIg crosslinking induces apoptosis and cell cycle arrest at the late G1 phase, both of which are reversed by CD40 signaling. Crosslinking of sIg reduces the activity of cyclin dependent kinase (Cdk)2 required for cell cycle progression in the late G1 phase by induction of a Cdk inhibitor (CKI) p27Kip1, but the induction of p27Kip1 is abrogated by CD40 signaling. These results strongly suggest that p27Kip1 plays some role in negative signaling via sIg, resulting in growth arrest of antigen-stimulated B cells.

Animals↗
PubMed1996

Lactosylceramide stimulates Ras-GTP loading, kinases (MEK, Raf), p44 mitogen-activated protein kinase, and c-fos expression in human aortic smooth muscle cells.

Previously, our laboratory has shown that lactosylceramide (LacCer) can serve as a mitogenic agent in the proliferation of aortic smooth muscle cells "a hallmark in the pathogenesis of atherosclerosis" (Chatterjee, S. (1991) Biochem. Biophys. Res. Commun. 181, 554-561). Here we report a novel aspect of LacCer-mediated signal transduction. We demonstrate that LacCer (10 microM) can stimulate the phosphorylation of mitogen-activated protein (MAP) kinase p44MAPK to phosphorylated p44MAPK in aortic smooth muscle cells from rabbit or human origin. Western immunoblot assays and direct measurement of activity in immunoprecipitated MAP kinase revealed that within 5 min of incubation of cells with LacCer there was a 3.5-fold increase in the activity of p44MAPK. This continued up to 10 min of incubation; thereafter, the MAP kinase activity decreased in these cells. Phosphoamino acid analysis revealed that the tyrosine and threonine moieties of p44MAPK was phosphorylated by LacCer. Incubation of cells with ceramide and glucosylceramide did not significantly stimulate p44MAPK activity. Preincubation with tyrphostin (20 microM; a potent and specific inhibitor of tyrosine kinase) markedly inhibited the LacCer mediated stimulation in p44MAPK activity. Next we investigated the upstream and downstream parameters in MAP kinase signaling pathways. We found that lactosylceramide stimulated (7-fold) the loading of GTP on Ras. Concomitantly, LacCer stimulated the phosphorylation of MAP kinase kinases (MEK) and Raf within 2.5 min. Lactosylceramide specifically induced c-fos mRNA expression (3-fold) in these cells as compared to control. In summary, one of the biochemical mechanisms in LacCer mediated induction in the proliferation of aortic smooth muscle cells may involve Ras-GTP loading, activation of the kinase cascade (MEK, Raf, p44MAPK), and c-fos expression.

Animals↗
PubMed1996

Differential modulation of cyclin-dependent kinase inhibitor p27Kip1 by negative signaling via the antigen receptor of B cells and positive signaling via CD40.

The cross-linking of surface immunoglobulins (sIg) of B cells can transmit a negative signal, resulting in cell cycle arrest, apoptosis or both. Signaling via the B cell antigen CD40 reverses the sIg-mediated negative signaling and induces activation and proliferation of B cells. We investigated the molecular mechanism for cell cycle regulation by negative and positive signaling via sIg and CD40, respectively, by using the B cell line WEHI-231. Cross-linking of sIg almost completely reduced the activity of cyclin-dependent kinase (Cdk) 2, essential for cell cycle progression in the late G1 phase, although the level of Cdk2 was not reduced. Among the factors that regulate Cdk2 activation, the activity of the Cdk-activating kinase (CAK) appeared intact and cyclin E was reduced only partially in sIg-cross-linked WEHI-231. In contrast, sIg cross-linking induced a significant Cdk inhibitor (CKI) activity. Since a 27-kDa protein was co-precipitated with Cdk2 in anti-Ig-treated, but not untreated WEHI-231, and the CKI activity in anti-Ig-treated WEHI-231 was neutralized by anti-p27Kip1 antibodies, it is most likely that p27Kip1 is responsible for the CKI activity induced by sIg cross-linking. p27Kip1 may thus play a role in growth inhibition of B cells by negative signaling via sIg. In contrast, CD40 signaling enhanced Cdk2 activity and reduced the p27Kip1 level in anti-Ig-treated WEHI-231, suggesting that the reduction of p27Kip1 plays an important role in the abrogation of sIg-mediated growth arrest by CD40 signaling. Taken together, p27Kip1 is likely to be a crucial target molecule of the negative signaling via sIg and the positive signaling via CD40 essential for T cell-dependent immune responses.

B-Lymphocytes↗
PubMed1996

Liquid-phase combinatorial synthesis: in search of small-molecule enzyme mimics.

The applications, advantages and recent advances in liquid-phase combinatorial chemistry using poly-(ethyleneglycol) as a soluble polymer support are reviewed. Our recent efforts towards the synthesis of peptide-based catalysts on polyethyleneglycol are reported. The screening of libraries of peptides for catalysis is discussed.

Biphenyl Compounds↗
PubMed1996

Systemic lupus erythematosus with nephritis is strongly associated with the TNFB*2 homozygote in the Korean population.

To evaluate the association of TNFB NcoI polymorphism with SLE in the Korean population, we investigated the frequencies of the TNFB and HLADRB1 alleles in 281 controls and 97 SLE patients, including 56 patients with nephritis and 41 patients without nephritis. The frequency of the TNFB*2 homozygote in SLE was significantly increased over controls (43.3% vs 28.5%, RR = 1.9,p < 0.01). In SLE with nephritis, the TNFB*2 homozygote was more significantly increased (57.1% vs 28.5%, RR = 3.4,p < 0.0001), whereas there was no significant difference between SLE without nephritis and controls. The study of HLA-DRB 1 alleles revealed the increased frequencies of DRB1*02 and *03 (30.9% vs 18.2%, RR = 2.0,p < 0.01; 8.2% vs 2.1%, RR = 4.1,p < 0.05). There was no significantly different distribution of HLA-DRB1 alleles between SLE patients with nephritis and without nephritis. We found positive LD between TNFB*1 and HLA-DR1B1*13, and between TNFB*2 and the particular DRB1 allele: *15, *04, and *07 in controls and/or in SLE patients. After stratification for each HLADRB1 allele, SLE with nephritis showed a higher frequency of TNFB*2 homozygote compared with the corresponding controls in DRB1*15, *08, and *09 positives. Our results suggest that the TNFB*2 homozygote may be a strong susceptibility gene of SLE with nephritis in the Korean population.

Alleles↗