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Biomedical subjects

S H Han

Publications and source records attributed to S H Han.

At least 145 records · Page 8Linked to original sources

The expression of acidic ribosomal phosphoproteins on the surface membrane of different tissues in autoimmune and normal mice which are the target molecules for anti-double-stranded DNA antibodies.

Affinity-purified polyclonal anti-double-stranded DNA (anti-dsDNA) antibodies from patients with systemic lupus erythematosus (SLE) exert a cytostatic effect on cultured rat glomerular mesangial cells (MC). The cognate antigens expressed on the surface of MC have been proved to be acidic ribosomal phosphoproteins (P proteins) in our previous study. The mesangial cytostatic effect of anti-dsDNA antibodies is attributed to the cross-reactivity of the antibodies with membrane-expressed P proteins, but not to the effect of minute amounts of anti-ribosomal P proteins antibodies contained in the anti-dsDNA preparations. Immunofluorescence staining of the native cells demonstrated that anti-dsDNA antibodies bound to the surface of rat mesangial cells, rat brain astrocytes (RBA-1) and mouse fibroblasts (3T3). Anti-dsDNA antibodies also exert potent cytostatic effects on these cells in a dose-dependent manner. In addition, the plasma membranes of different cell lines and tissues from normal and autoimmune mice were isolated and probed by anti-dsDNA antibodies in Western blot analysis. We found the actively proliferating cells such as MC, RBA-1 and 3T3 may express both P0 (38,000 MW) and P1 (19,000 MW) on the surface membrane. In addition, the kidney, liver and spleen from either autoimmune MRL-lpr/lpr or BALB/c mice may constantly express P0 protein, but the expression of P1 is inconsistent. In contrast, brain and muscle from either mice failed to express P proteins on their surface. Unexpectedly, a high molecular weight substance (larger than 205,000 MW) with unknown nature appears in the membrane of brain and muscle tissues in both mice. Immunoprecipitation of the surface-biotinylated MC-lysate by anti-dsDNA antibodies further confirmed that P1 (19,000 MW) and P2 (17,000 MW) are really expressed on the cell surface. These results suggest that P proteins expressed on the surface of different tissues become the targets for anti-dsDNA antibodies mediating pleomorphic tissue damage in patients with SLE.

Animals↗

Efficacy of rhenium-186-etidronate in prostate cancer patients with metastatic bone pain.

UNLABELLED: Rhenium-186-etidronate has been developed for pain relief of bone metastases and has previously been studied with regard to toxicity, pharmacokinetics and dosimetry. Its palliating effect on bone pain has not been studied extensively. To justify further efficacy investigations, patients participating in two toxicity studies were studied using a strict pain assessment methodology. METHODS: Forty-three patients entered the study, 37 of whom were evaluable for pain assessment. Administered dosages ranged from 1295 MBq (35 mCi) to 3515 MBq (95 mCi) 186Re-etidronate. Pain relief was assessed using a handwritten diary containing questions reflecting the multidimensional character of chronic pain. The diary was marked twice daily for a maximum of 10 wk (2 wk prior to and 6/8 wk after the injection). A response was determined using a specific decision rule, in which pain intensity, medication index and daily activities were core determinants. RESULTS: A response was reached in 54% (20 of 37) of the patients and varied from 33% (n = 6) in the "35-mCi" group to 78% (n = 7) in the "50/65-mCi" group to 70% (n = 7) in the "80/95-mCi" group. CONCLUSION: Pain assessment using the multidimensional pain model showed that 186Re-etidronate is an effective agent in the treatment of metastatic bone pain in prostate cancer and warrants further placebo-controlled studies.

Bone Neoplasms↗

Homogeneous assays for riboflavin mediated by the interaction between enzyme-biotin and avidin-riboflavin conjugates.

Homogeneous-type enzyme-linked competitive binding assays utilizing the synthetic enzyme-biotin and avidin-riboflavin conjugates are developed for the detection of riboflavin as well as its binder protein. The activity of the enzyme-biotin conjugate is inhibited in the presence of the avidin-riboflavin conjugate, and the observed inhibition is reversed in an amount dependent on the concentration of riboflavin binding protein (RBP) added. Upon additions of free riboflavin to the mixture, activity is reinhibited in an amount proportional to the riboflavin concentration. Three different enzymes are examined as the labels: glucose-6-phosphate dehydrogenase, adenosine deaminase, and alkaline phosphatase. The catalytic activity of these enzymes, when conjugated with biotin, is shown to be inhibited to a significant degree (> 90%) by the binding of the avidin-riboflavin conjugate, and reversed upon additions of RBP.

Adenosine Deaminase↗

Limited regulatory effect of T cell receptor-derived peptides.

T cell receptor (TCR)-derived peptides have been used to induce regulatory T cells which recognize T cells of specific elements and downregulate the autoimmune response. Consistent with these observations, priming of peptides corresponding to V beta 8 complementarity-determining region 2 (CDR2) was found to specifically suppress the proliferation of V beta 8+ T cells in the draining lymph nodes. Similarly, the generation of V beta 8-dominant T cell responses was prevented locally by vaccination with V beta 8 CDR2 peptides. There was a good correlation between the downregulation of V beta 8+ T cells and the inhibition of the corresponding T cell responses in different lymphoid tissues. No systemic inhibition could be detected even after an interval which would allow the redistribution of the "regulatory T cells." T cells specific for V beta 8 CDR2 peptides was generated following peptide immunization. However, the appearance of these TCR peptide-specific T cells was independent of the downregulation of V beta 8+ T cells. The transient and localized inhibitory effects of TCR-derived peptides indicate that these peptides have very limited use in regulating specific T cell response.

Amino Acid Sequence↗

Light- and electron-microscopic study of substance P-immunoreactive neurons in the guinea pig retina.

Substance P (SP) immunoreactivity in the guinea pig retina was studied by light and electron microscopy. The morphology and distribution of SP-immunoreactive neurons was defined by light microscopy. The SP-immunoreactive neurons formed one population of amacrine cells whose cell bodies were located in the proximal row of the inner nuclear layer. A single dendrite emerged from each soma and descended through the inner plexiform layer toward the ganglion cell layer. SP-immunoreactive processes ramified mainly in strata 4 and 5 of the inner plexiform layer. SP-immunoreactive amacrine cells were present at a higher density in the central region around the optic nerve head and at a lower density in the peripheral region of the retina. The synaptic connectivity of SP-immunoreactive amacrine cells was identified by electron microscopy. SP-labeled amacrine cell processes received synaptic inputs from other amacrine cell processes in all strata of the inner plexiform layer and from bipolar cell axon terminals in sublamina b of the same layer. The most frequent postsynaptic targets of SP-immunoreactive amacrine cells were the somata of ganglion cells and their dendrites in sublamina b of the inner plexiform layer. Amacrine cell processes were also postsynaptic to SP-immunoreactive neurons in this sublamina. No synaptic outputs onto the bipolar cells were observed.

Animals↗

Characterization of the isoforms of the group I allergen of Cynodon dactylon.

BACKGROUND: The group I allergen of Cynodon dactylon, Cyn d I, was found to consist of four to 10 isoforms. METHODS: We studied the isoforms with the use of two-dimensional gel electrophoresis. The antigenic difference of the isoforms was evaluated by radioimmunoprecipitation with monoclonal antibodies (MAbs). The acidic isoforms and the basic and neutral isoforms were further isolated by MAb-affinity chromatography for RAST and competitive RAST. In addition, the N-terminal sequence was evaluated by microsequencing. RESULTS: A total of 11 isoforms were found in Cyn d I in extracts prepared from different sources of Bermuda grass pollen (BGP). They were either acidic (Cyn d I-A, I-B, I-C, I-D, I-E, I-F, I-G, I-H, and I-I), neutral (Cyn d I-X), or basic (Cyn d I-J). Cyn d I-G, with an isoelectric point of approximately 6.4, was constantly present in all the pollen preparations, whereas the content of the basic Cyn d I-J varied from less than 5% to greater than 20%. The molecular weight of the basic and neutral isoforms were slightly lower than those of the acidic isoforms. All isoforms shared a common antigenic determinant(s) recognizable by MAb 4-37, and the basic and neutral isoforms possessed a unique antigenic determinant(s) recognizable by MAb 1-61. RAST showed that both the acidic Cyn d I and the basic and neutral Cyn d I were recognized by human IgE in the pooled sera of persons allergic to BGP. Competitive RAST showed a high crossreactivity between the acidic and the basic and neutral isoforms. A 95% sequence identity also existed between the N-terminal 20 amino acid residues of basic Cyn d I-J and the dominant acidic isoform Cyn d I-G. CONCLUSIONS: The present study disclosed that basic Cyn d I-J is an important allergen and that the content of this isoform varies in different lots of BGP.

Allergens↗

Defective spontaneous and bacterial lipopolysaccharide-stimulated production of interleukin-1 receptor antagonist by polymorphonuclear neutrophils of patients with active systemic lupus erythematosus.

Interleukin-1 receptor antagonist (IL-1ra) binds competitively to IL-1 receptors but does not transduce the signal which blocks the biological activities induced by IL-1. In this study, polymorphonuclear neutrophils (PMN) and mononuclear cells (MNC) from the patients with active systemic lupus erythematosus (SLE) (n = 11), inactive SLE (n = 13) and normal individuals (n = 13) were compared for the IL-1ra producing capacity of these cells. PMN and MNC at a concentration of 1 x 10(6) cells/ml were incubated with medium alone (spontaneous) or stimulated with lipopolysaccharide (LPS, 100 ng/ml) for 24 h. The IL-1ra concentration in the supernatants was quantified by ELISA method. Both spontaneous and LPS-stimulated production of IL-1ra by PMN, but not by MNC, of active SLE were significantly lower than that of inactive SLE or normal groups. Prednisolone (1 and 5 micrograms/ml) did not change the production of IL-1ra by normal PMN either spontaneously or LPS-stimulation in in vitro study. Moreover, the IL-1ra producing capacity of PMN in seven active SLE on admission and after intensive immunosuppressive treatment was measured. These results suggest that the defective IL-1ra production by SLE-PMN is relevant to disease activity and may be regarded as a new indicator of disease activity in patients with active SLE.

Adolescent↗

Molecular cloning of cDNA coding for the 68 kDa allergen of Penicillium notatum using MoAbs.

To characterize the 68 kDa allergen of Penicillium notatum (also known as P. chrysogenum), a molecular antibody (MoAb) (P40) was previously generated. For cDNA cloning, three more MoAbs (3F, 5A3, 5G2) were generated in the present study. A mixture of all the four MoAbs was used in cloning of the gene coding for the 68 kDa allergen from a lambda gt11 cDNA library of P. chrysogenum. A cDNA clone (A6) with DNA insert of about 0.5 kb which encodes for the 3'-terminal nucleotide sequence of the 68 kDa allergen was obtained. The cloned sequence contained two putative N-glycosylation sites. The reduction in molecular weight from 68 to 62 kDa in immunoblotting after treatment of the crude extract of P. notatum with N-glycosidase F indicates that the 68 kDa allergen is a glycoprotein. Nucleotide sequence determination showed that 188 (54%) of the 348 nucleotides of the cDNA sequence obtained were identical to the same region of the nucleotide sequence of the beta-N-acetylglucosaminidase gene of Candida albicans. Although the cDNA clone obtained did not encode the full-length gene of the 68 kDa allergen, polypeptide expressed from the A6 cDNA showed positive immunological reactivities to all four MoAbs used in the cloning experiment and to IgE antibodies in sera of asthmatic patients. There was a loss of immunoblotting activity to the 68 kDa component after absorption of MoAb P40-containing culture supernatant with filters blotted on plaque lawns of cDNA clone A6. Moreover, the immunoblotting activity remained when the MoAbs affinity-purified with filters containing polypeptides encoded by the cDNA insert of clone A6 were used.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Abnormal splenic and thymic IL-4 and TNF-alpha expression in MRL-lpr/lpr mice.

The MRL-lpr/lpr and MRL-(++) mice were studied for the expression of cytokines in the spleen, lymph node, thymus, kidney and brain through the reverse transcription-polymerase chain reaction (RT-PCR). The frequencies of IL-4 and TNF-alpha expression in the thymus and spleen were significantly higher in MRL-lpr/lpr mice than in MRL-(++) mice from the age of 17 to 32 weeks. More importantly, IL-4 transcript was demonstrated in the early rather than in the terminal stage of the lupus disease. At the 20th week, MRL-lpr/lpr mice with active disease exhibited higher concentrations of IL-1 alpha, IL-6 and TNF-alpha in serum than MRL-(++) mice. Interestingly, in MRL-lpr/lpr but not MRL-(++) mice, the IL-6 concentration in cultured supernatants of the thymic cells was significantly higher than that of the splenic or lymph node cells. On the other hand, IL-6 and IL-1 beta were expressed in the brain and kidney of MRL-lpr/lpr mice but not of MRL-(++) mice. Cultured MRL-lpr/lpr mesangial cells could also express IL-6 but to a lesser extent. These results suggest that the abnormal splenic and thymic IL-4 and TNF-alpha expression may predispose the development of autoimmune reactions. The expression of IL-1 beta and IL-6 in the brain and kidney may be implicated in the damage of these two organs in MRL-lpr/lpr mice.

Animals↗

Chemical denaturation of ovalbumin abrogates the induction of oral tolerance of specific IgG antibody and DTH responses in mice.

We have examined the effects of ingestion of chemically denatured ovalbumin (OVA) in mice. Both 8 M urea-denatured OVA (UD-OVA) and carboxymethylated UD-OVA (CM-OVA) were purified by gel filtration. Specific IgG antibody and systemic delayed-type hypersensitivity (DTH) responses to OVA were not suppressed by CM-OVA fed prior to or after immunization with OVA in complete Freund's adjuvant (CFA). When CM-OVA was used instead of OVA, for immunization, serum IgG and DTH responses to CM-OVA were orally tolerized by OVA, but not by UD-OVA or CM-OVA. Studies of antigen uptake in mice using sandwich ELISA tests showed that OVA, but not CM-OVA, was absorbed after antigen ingestion. In vitro studies further demonstrated that CM-OVA was digested much more rapidly than OVA. Moreover, studies using bovine serum albumin (BSA) demonstrated that both IgG and DTH responses to BSA were orally tolerant to BSA, but not to denatured BSA. Finally, studies using human gamma-globulin (HGG), a well-known tolerogen, also found that the IgG antibody response to HGG was not orally tolerized by denatured HGG. These results suggest that complete denaturation of globular proteins may affect their processing and absorption in the gut and thus abrogates oral tolerance induction.

Administration, Oral↗

Reliability of the ICD-10 diagnostic criteria for research in mental disorders in the Republic of Korea.

The interrater reliability, confidence and ease of use of ICD-10 diagnostic criteria for research were assessed in the Republic of Korea as part of the field trials of World Health Organization collaborative study. A total of 279 patients were diagnosed according to the ICD-10 diagnostic criteria for research. Interrater reliability, calculated by kappa statistics, was found to be between 0.74 and 0.91 on 2-character categories and between 0.64 and 0.90 on 3-character categories except schizotypal disorder (F21). On the 4-character categories, the agreement in the affective states between raters was lower. The reasons are discussed based on cultural differences.

Adolescent↗

Study on the Korean adult cranial capacity.

Cranial capacity was measured in Korean adult skulls. The cavity was filled with rice seeds and the volume of the seeds were measured in a graduated cylinder. The results were 1470 +/- 107 (mean +/- standard deviation) in male and 1317 +/- 117 cc in female skulls. These values were in good accordance with those previously reported. In addition, regression formulae were obtained with the product of the length, breadth, and height of the skull as an independent parameter and the measured capacity as a dependent one. With known external measurements, the expected cranial capacity was as follows: when using baso-bregmatic height, male: capacity = 307.5 + 333 x 10(-6) x (length.breadth.baso-bregmatic height) female: capacity = -12.0 + 435 x 10(-6) x (length.breadth.baso-bregmatic height) and, when using auriculo-bregmatic height, male: capacity = 214.6 + 429 x 10(-6) x (length.breadth.auriculo-bregmatic height) female: capacity = 131.6 + 461 x 10(-6) x (length.breadth.auriculo-bregmatic height).

Adult↗

Anti-dsDNA antibodies cross-react with ribosomal P proteins expressed on the surface of glomerular mesangial cells to exert a cytostatic effect.

Affinity-purified human polyclonal anti-double-stranded DNA antibodies (anti-dsDNA) exerted a cytostatic effect towards human and rat glomerular mesangial cells (MC). In order to identify the cognate antigens for anti-dsDNA on the surface of MC, we used these autoantibodies to probe a human renal lambda gt11 cDNA expression library. Two cDNA clones encoding the cognate proteins for the autoantibodies were isolated. Sequencing analysis of the two cDNA showed that they had 98.6% homology with the gene of the P0 and 99.2% homology with the gene of the P1 human acidic ribosomal phosphoproteins (P protein). Two galactosidase fusion proteins (125,000 and 150,000 MW) derived from the two cDNA inserts expressed in lysogenic Escherichia coli Y1089 could react with the original screening antibodies in an immunoblotting analysis. After transformation and expression of the full-length P1 clone in prokaryotic cells, the purified P1 protein was able to react with anti-dsDNA. In a cross-inhibition experiment, the dsDNA binding activity of anti-dsDNA was inhibited by a synthetic polypeptide corresponding to the carboxyl-terminal 20 amino acids of P protein and purified P1 protein in a dose-dependent manner, but this was less potent than the inhibition caused by calf thymus dsDNA. By use of well-defined systemic lupus erythematosus (SLE) sera, we found only sera containing a high titre of anti-dsDNA activity (> 300 IU/ml) reacted with P1 of rat MC lysate. Furthermore, the 38,000 and 19,000 MW macromolecules were proved to be the cognate antigens for anti-dsDNA expression on the surface of the MC, by Western blot of the MC plasma membrane lysates. These results suggest that anti-dsDNA may cross-react with ribosomal P proteins expressed on the surface of the MC and exert cytostasis towards these cells.

Animals↗

Review of hepatic abscess from Klebsiella pneumoniae. An association with diabetes mellitus and septic endophthalmitis.

I present the only comprehensive review of hepatic abscess from Klebsiella pneumoniae. The world literature contains 46 individually reported cases and 3 large studies of K pneumoniae liver abscess. The source of the abscesses frequently was not found. Diabetes mellitus was a frequent underlying condition and may predispose patients to the development of liver abscess with this organism. The exact mechanism is unclear, and further investigation is necessary. In addition, extrahepatic metastases, such as septic endophthalmitis, often occurred with serious complications, particularly in patients with diabetes. The association between K pneumoniae liver abscess and diabetes is so close that a search for underlying diabetes mellitus is warranted in all patients with K pneumoniae liver abscess. Fortunately, earlier diagnoses and better treatment modalities have improved the outcome for these patients.

Adult↗

Influence of the susceptibility genes apolipoprotein E-epsilon 4 and apolipoprotein E-epsilon 2 on the rate of disease expressivity of late-onset Alzheimer's disease.

Apolipoprotein E-epsilon 4 (APOE4, gene; apoE4, protein) is a susceptibility gene or risk factor for Alzheimer's disease. The genetic relevance of APOE4 has been widely confirmed. The APOE gene is not a disease locus, with specific mutations causing Alzheimer disease. Allelic variations at the APOE locus affect the rate of disease progression. The association of specific inherited APOE alleles with age of onset distributions describes biological effects based on genotype. The inheritance of polymorphic genes with single amino acid differences between apoE4 and apoE3 (and between apoE3 and apoE2) at the protein level is associated with differences in the mean age of disease onset spanning almost two decades. The isoform-specific metabolism of apoE resulting in a faster rate of disease expression can now be studied with the expectation that genetically relevant processes are being investigated. There is now an opportunity to develop theories directed at the genetically relevant apoE metabolism that can significantly delay disease expression.

Age of Onset↗

The modulatory effect of antigen- and PAF-induced asthmatic reaction by aerosol administration of OKY-046 in guinea pigs.

The therapeutic effect of a thromboxane A2 (TXA2) synthetase inhibitor on asthma is still controversial. This study was aimed at clarifying its effect on asthmatic reactions in guinea pigs. Both ovalbumin (OVA)- and platelet activating factor (PAF)-induced dual phase airway spasm and hyperreactivity in guinea pigs were used as the asthma model. Our results demonstrated that aerosol administration of OKY-046 could inhibit both OVA- and PAF-induced late phase bronchoconstriction and airway hyperreactivity to methacholine in OVA sensitized guinea pigs. PAF administration could also induced dual phase bronchoconstriction in normal guinea pigs. Similarly, late phase airway spasm and airway hyperreactivity after PAF exposure was also blocked by OKY-046. In conclusion, aerosol administration of OKY-046 is a safe and effective way to modulate OVA- and PAF-induced asthmatic reactions. The protective effect of OKY-046 on OVA- and PAF-induced late phase bronchoconstriction and airway hyperreactivity indicates that TXA2 might play an important role in the late phase asthmatic reaction and airway hyperreactivity. The normalization of PAF-induced airway hyperreactivity by OKY-046 also indicates that PAF induced airway inflammation might be through the generation of TXA2.

Animals↗