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Biomedical subjects

H Han

Publications and source records attributed to H Han.

At least 163 records · Page 9Linked to original sources
PubMed1994

Association of complement C4 and HLA-DR alleles with systemic lupus erythematosus in Koreans.

OBJECTIVE: To examine the association of complement C4 and HLA-DR to systemic lupus erythematosus (SLE) susceptibility in Korea. METHODS: Complement C4 protein typing was carried out by immunofixation and immunoblotting methods using EDTA-plasma from 60 patients with SLE and 72 healthy controls. Restriction fragment length polymorphism analysis of C4 genes was also carried out using TaqI or HindIII for restriction enzymes. HLA-DR was determined by polymerase chain reaction amplification with sequence specific primers using genomic DNA from 67 patients with SLE and 72 healthy controls. RESULTS: The frequency of the C4AQ0 allele was significantly higher in the patients with SLE than in controls (41.7 vs 25.0%, p < 0.05). The deletion of the C4A gene commonly found in Caucasian patients with SLE was not observed in any patients. For HLA-DR, a significant increase of the haplotype DRB1*1501 was observed in the patients (26.9 vs 12.5%, p < 0.05) and DR9 was also significantly increased (23.9 vs 11.1%, p < 0.05). An increase in each DR2 and DR9 was independent of an increase in C4AQ0. The frequencies of DR2 and DR9 were significantly decreased in patients with renal involvement and alopecia, respectively. CONCLUSION: Our data suggested that the presence of C4AQ0 allele, DRB1*1501-DRB5*0101 haplotype and DR9 contributed to susceptibility to SLE in Koreans and that Korean SLE is based on a different genetic background from Caucasian patients.

Adult↗
PubMed1994

Cloning of the human glycine transporter type 1: molecular and pharmacological characterization of novel isoform variants and chromosomal localization of the gene in the human and mouse genomes.

We report the molecular cloning of a cDNA encoding a high affinity human glycine transporter. An open reading frame of 1914 nucleotides encodes a 638-amino acid protein that transports glycine in a Na+/Cl(-)-dependent manner. In common with other Na+/Cl(-)-dependent transporters, it possesses 12 putative transmembrane domains, according to its hydropathicity profile. This protein is the human homologue of a glycine transporter previously isolated from rat [glycine transporter type 1b (GlyT-1b)]. In addition to the human GlyT-1b, we also characterized a novel functional isoform produced by alternative splicing. This isoform, GlyT-1c, which is distinct from GlyT-2 recently characterized in rat, contains an additional exon encoding 54 amino acids in the amino-terminal part of GlyT-1b and is mainly expressed in brain. These two isoforms are products of the same gene and are localized on human chromosome 1p31.3, as well as on mouse chromosome 4, close to the locus for the spontaneous mouse neuromuscular mutation clasper. When expressed in COS-7 cells, both the human GlyT-1b and GlyT-1c display a time- and dose-dependent uptake of glycine, which is abolished when either Na+ or Cl- is substituted with other ions. For both GlyT-1b and GlyT-1c the affinities for glycine are similar, with Km values of 70-90 microM, and this uptake is inhibited by sarcosine with similar potencies. In addition to the three transporter isoforms present in the human genome, i.e., GlyT-1a, GlyT-1b, and GlyT-1c, point-mutated variants, which appear to be totally devoid of glycine uptake activity when expressed in COS-7 cells, were obtained by polymerase chain reaction amplification of mRNA from human substantia nigra. These variants point to regions of the glycine transporter that might be important in the processing or transport function of this protein.

Amino Acid Sequence↗
PubMed1993

Allelic loss in ovarian cancer.

Loss of heterozygosity (LOH) was examined at 86 loci distributed on every chromosomal arm in 50 human ovarian tumors. Frequent allele losses were observed on chromosomes 13q (42%), 17p (42%), 17q (45%), and Xp (41%). Deletion mapping on chromosome 17 revealed a candidate gene on the long arm distal to D17S41/S74 for ovarian cancer which is distant from the locus for early onset breast cancer. LOH on chromosome 17q was found to be concordant with LOH on chromosomes 3p, 13q, 17p and Xp suggesting that it may be an early event in neoplastic development. These findings indicate that multiple tumor-suppressor genes for ovarian cancer possibly exist on chromosomes 13q, 17, and/or Xp and provide the basis for the identification of candidate gene(s) associated with ovarian cancer. The chromosomal mechanisms resulting in allele losses in ovarian cancer include deletion, deletion/duplication, mitotic recombination and monosomy, in concordance with the developed genetic model.

Alleles↗
PubMed1993

Sequence-specific recognition of double helical RNA and RNA.DNA by triple helix formation.

The stabilities of eight triple helical pyrimidine.purine.pyrimidine structures comprised of identical sequence but different RNA (R) or DNA (D) strand combinations were measured by quantitative affinity cleavage titration. The differences in equilibrium binding affinities reveal the importance of strand composition. For the sequences studied here, the stabilities of complexes containing a pyrimidine third strand D or R and purine.pyrimidine double helical DD, DR, RD, and RR decrease in order: D + DD, R + DD, R + DR, D + DR > R + RD, R + RR >> D + RR, D + RD (pH 7.0, 25 degrees C, 100 mM NaCl/1 mM spermine). These findings suggest that RNA and DNA oligonucleotides will be useful for targeting (i) double helical DNA and (ii) RNA.DNA hybrids if the purine Watson-Crick strand is DNA. However, RNA, but not DNA, oligonucleotides will be useful for sequence-specific binding of (i) double helical RNA and (ii) RNA.DNA hybrids if the purine Watson-Crick strand is RNA. This has implications for the design of artificial ligands targeted to specific sequences of double helical RNA and RNA.DNA hybrids.

Base Composition↗
PubMed1993

Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization.

A Na(+)- and Cl(-)-coupled serotonin (5-hydroxytryptamine, 5HT) transporter is expressed on human neuronal, platelet, placental, and pulmonary membranes. The brain 5HT transporter appears to be a principal site of action of therapeutic antidepressants and may mediate behavioral and/or toxic effects of cocaine and amphetamines. Oligonucleotides derived from consensus transporter sequences were used to identify human placental cDNAs highly related to the rat brain 5HT carrier. Transfection of one of these cDNAs into HeLa cells yields a high-affinity (Km = 463 nM), Na(+)- and Cl(-)-dependent 5HT transport activity which can be blocked by selective 5HT transport inhibitors, including paroxetine, fluoxetine, and imipramine, and which is antagonized by cocaine and amphetamine. Sequence analysis reveals a 630-amino acid open reading frame bearing 92% identity to the cloned rat brain 5HT transporter, with identical predicted topological features and conserved sites for posttranslational modifications. Unlike the rodent, where a single mRNA appears to encode 5HT transporters, multiple hybridizing RNAs are observed in human placenta and lung. Somatic cell hybrid and in situ hybridization studies are consistent, however, with a single gene encoding the human 5HT transporter, localized to chromosome 17q11.1-17q12.

Amino Acid Sequence↗
PubMed1993

Enhanced interaction of L-selectin with the high endothelial venule ligand via selectively oxidized sialic acids.

The selectins are adhesion receptors that play key roles in leukocyte trafficking. Each has an N-terminal C-type lectin domain that binds to specific carbohydrates in a calcium-dependent manner. L-selectin recognizes sulfated, sialylated ligands on lymph node high endothelial venules. This recognition is abolished by strong periodate oxidation under conditions that destroy oligosaccharides. In contrast, mild periodate oxidation, which selectively oxidizes the side chain of sialic acid residues without affecting the underlying oligosaccharide, markedly enhances this interaction. The enhancement is calcium dependent, indicating that lectin recognition is maintained. Reduction of the sialic acid aldehydes generated by mild periodate to alcohol groups abolishes this effect. Covalent cross-linking of the oxidized ligand to L-selectin can be demonstrated, suggesting Schiff base formation between lysine residues of the selectin and the newly formed aldehydes. Such selectively oxidized sialylated ligands could be used to probe the lectin domains of the selectins and to identify lysine residues near the binding site. Also, this approach could be used to design drugs for disrupting leukocyte-endothelial interactions leading to pathological inflammation.

Animals↗
PubMed1993

Advanced ovarian carcinoma: molecular evidence of unifocal origin.

The clonal origin has sometimes been disputed in advanced epithelial cancers when multiple sites of peritoneal tumors were present because of the developmental similarity of the surface epithelium of the ovary and the peritoneal mesothelium. We have taken two independent approaches to study the clonality of advanced epithelial carcinoma. Tumor samples of both ovaries, and/or omentum, and/or peritoneum from nine patients were examined. The analysis of loss of heterozygosity (LOH) at 86 polymorphic chromosomal loci distributed on every chromosome revealed the loss of the same allele in every tumor of each patient when LOH was detected. In addition, we used a restriction-fragment-length polymorphism in an X-linked sequence (DXS255) to examine the pattern of X-chromosome inactivation based on the differential methylation of DXS255 in active and inactive X chromosomes. Inactivation of the same X chromosome in various tumors from the same patient was observed in each of the five informative patients. Our results strongly suggest that the advanced epithelial cancers are monoclonal in origin.

Adult↗
PubMed1993

Aggregation of macrophages in the tips of intestinal villi in guinea pigs: their possible role in the phagocytosis of effete epithelial cells.

Numerous macrophages were found aggregated in the lamina propria at the tips of villi in the small intestine of guinea pigs. These macrophages extended their pseudopodia into the epithelial lining and internalized fragments of effete enterocytes in their phagosomes. The epithelium of the villus tips was found to be infiltrated with numerous lymphocytes. They possessed electron-dense granules characteristic of natural killer cells, and actively interdigitated with the enterocytes. The latter were either fragmented or extensively lost in their basal cytoplasm, often leaving an attenuated apical cytoplasm of the cell. Immunohistochemical labeling using bromodeoxyuridine demonstrated that at 96 h after its administration, immunolabeled nuclei were encountered in the cytoplasm of macrophages in the lamina propria at the villus tips. These findings suggest that in the guinea pig, effete enterocytes are not simply exfoliated into the lumen, but are damaged by intraepithelial lymphocytes possessing a natural killer cytotoxicity, and subsequently phagocytosed by subepithelial macrophages.

Animals↗
PubMed1993

A novel mechanism for disposing of effete epithelial cells in the small intestine of guinea pigs.

BACKGROUND: We previously showed that at the villus tips in the small intestine of guinea pigs effete enterocytes are not simply exfoliated into the lumen but phagocytosed by subepithelial macrophages, leaving only a thin apical cell portion in the epithelial lining. The aim of the present study is to investigate the fate of these apical pieces of enterocytes. METHODS: The ileum of guinea pigs was perfusion-fixed and processed for transmission and scanning electron microscopic observation. RESULTS: The apical cytoplasmic plates were found to be pushed by neighboring enterocytes and protruded from the epithelial surface, finally being pinched off into the lumen. In this process observed at the villus tips, the junctional complexes between the apical cytoplasmic plate and the adjacent enterocytes were preserved until the pinching-off of the plate. Luminal cell elements revealed a rich existence of cup-shaped or spherical cell fragments covered with microvilli; nuclei were never observed in the luminal fragments. CONCLUSIONS: The findings in the small intestine of the guinea pig are the first to account for the mechanism of the epithelial barriers being preserved while apoptotic enterocytes drop out at the tips of the villi.

Animals↗
PubMed1993

Receptor affinity purification of a lipid-binding adhesin from Helicobacter pylori.

Our previous work has shown that Helicobacter pylori specifically recognizes gangliotetraosylceramide, gangliotriaosylceramide, and phosphatidylethanolamine in vitro. This binding specificity is shared by exoenzyme S from Pseudomonas aeruginosa, and monoclonal antibodies against this adhesin prevent the attachment of H. pylori to its lipid receptors. We now report the use of a novel, versatile affinity matrix to purify a 63-kDa exoenzyme S-like adhesin from H. pylori which is responsible for the lipid-binding specificity of this organism.

Adhesins, Bacterial↗
PubMed1993

A strong association between thyrotropin receptor-blocking antibody-positive atrophic autoimmune thyroiditis and HLA-DR8 and HLA-DQB1*0302 in Koreans.

We investigated whether the associations between HLA alleles of patients with autoimmune hypothyroidism varied according to the presence or absence of TSH receptor-blocking antibody (TRBab). We analyzed the HLA-A, -B, -C, and -DR antigens by serotyping and the DQA1 and DQB1 genes using both enzymatic DNA amplification and sequence-specific oligonucleotide hybridizations. The patient population consisted of 47 Korean patients with atrophic autoimmune thyroiditis and 62 patients with goitrous autoimmune thyroiditis. The antigen frequency of HLA-DR8 was significantly increased in 23 atrophic autoimmune thyroiditis patients that were positive for TSH binding inhibitor immunoglobulin (TBII) compared to 136 controls [52% vs. 16%; chi 2 = 13.1; Pc (corrected P value) = 0.003]. This relative risk was 5.7; the etiological fraction was 0.43. HLA-DQB1*0302 was also increased in patients with TBII-positive atrophic autoimmune thyroiditis (24% vs. 7%; chi 2 = 11.2; Pc = 0.012; relative risk = 4.4; etiological fraction = 0.19). No specific DR antigens or DQB1 alleles were increased in either TBII-negative atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis. A significant decrease in the frequency of HLA-DR6 antigen was observed in both TBII-positive atrophic autoimmune thyroiditis (0% vs. 32%; chi 2 = 8.4; Pc = 0.03) and goitrous autoimmune thyroiditis (0% vs. 32%; chi 2 = 23.2; Pc < 0.001) patients. The frequency of the HLA-Cw1 antigen was significantly increased in all patient groups. We conclude that TRBab-positive atrophic autoimmune thyroiditis is immunogenetically different from both goitrous autoimmune thyroiditis and TRBab-negative atrophic autoimmune thyroiditis. It is possible that HLA-DR8 and/or DQB1*0302 may be related to the susceptibility genes involved in the production of TRBab in Koreans.

Adult↗
PubMed1993

Species-differences in the process of apoptosis in epithelial cells of the small intestine: an ultrastructural and cytochemical study of luminal cell elements.

Our previous study demonstrated that in the small intestine of guinea pigs, apoptotic epithelial cells at the villus tips were phagocytosed by lamina propria macrophages, leaving only apical cytoplasmic plates, which thereafter were domed and extruded into the lumen. This finding contrasts with the generally accepted view that effete epithelial cells are simply exfoliated into the lumen. In order to explain this discrepancy, the present study examined luminal cell elements of the small intestine in the guinea pig, rat and mouse; the latter two have been favored species for studying the kinetics of intestinal cells. Light and electron microscopic observations indicated that the luminal fluid of the guinea pig contained numerous cytoplasmic fragments covered with long microvilli and not containing a nucleus; these fragments corresponded with the apical cytoplasm of apoptotic epithelial cells. In the rat and mouse, in contrast, luminal cell elements were represented by round cell bodies possessing a nucleus and microvillous border; the nucleus displayed compaction and segregation of chromatin at the periphery, a microscopic figure characteristic of apoptosis. As far as the rat and mouse are concerned, the present findings support the accepted view that epithelial cells undergoing apoptosis are exfoliated as total, nucleus-containing cells. In the guinea pig, in contrast, only an apical thin plate of effete cells is shed off, as our previous studies have suggested.

Animals↗
PubMed1993

Distribution of HLA class I alleles and haplotypes in Korean.

The antigen (phenotype), gene (allele) and haplotype frequencies of HLA class I were analysed in 4,622 Koreans. With allele frequencies of over 0.05, the most frequent HLA-A,-B and -C antigens were A2, A24, A33, A11, A26, A31; B62, B51, B44, B54, B61, B35, B58, B60; Cw3, Cw1, Cw4, Cw7. Of these A2, A24, Cw1 and Cw3 were present in very high frequencies, respectively (0.3211, 0.2200, 0.2204, and 0.3737). The most common haplotypes with frequencies larger than 0.02 were A2-Blank, A33-B44, A33-B58, A11-B62, A24-B51, A24-B54, A2-B27, B54-Cw1, B58-Cw3, B51-Blank, B61-Cw3, B62-Cw4, B35-Cw3, B44-Blank, B60-Cw3, B27-Cw1, A2-Cw3, A2-Cw1, A24-Cw1, A33-Cw3, A26-Cw3, and A11-Cw4. A significant negative linkage disequilibrium was found for the haplotypes of A2-B7, A2-B44, A2-B58, A24-B13, A24-B27, A33-B54 and A33-B62, of which frequencies were larger than 0.003. The B-C and A-C haplotypes which showed the significant negative linkage disequilibrium were B44-Cw1, B51-Cw1, B44-Cw3,B62-Blank, A2-Cw4, A2-Blank, A11-Cw3, A11-Blank and A33-Cw1 and had frequencies higher than 0.01. The findings presented here could be used per se to estimate the populational relationships or as the control data for HLA-disease investigation. Furthermore they could provide the scope for the definition of new antigens.

Alleles↗
PubMed1993

[Aggregations of macrophages in the digestive tract of several mammals and their functional significance].

Our previous finding in the guinea pig that macrophages are aggregated at the villus tips of the small intestine and phagocytose effete enterocytes, in contrast to the accepted view that the enterocytes are exfoliated into the lumen, was extended in the present study to the large intestine of this animal and to the intestines of other mammals. In the large intestine of guinea pigs, aggregations of macrophages with an acid phosphatase activity were found beneath the epithelial lining, linearly surrounding the crypts. The macrophages contained debris of epithelial cells in their phagosomes, suggesting that the macrophages phagocytose apoptotic epithelial cells. This finding was supported by tracing BrdU-marked enterocytes, which were found to be taken up by the macrophages in the lamina propria. The macrophage aggregation was also recognized in the ileum of newborn guinea pigs, a finding favoring the idea that it represents a constant and intrinsic phenomenon and is not induced by penetration of foreign particles or other immunological events. In the monkey small intestine, macrophages with abundant phagosomes aggregated in large numbers in the lamina propria of the villus tips and were found to phagocytose enterocytes. In the hamster and rat, macrophages were numerous in the villi of the small intestine but they did not reveal images suggesting their involvement in the enterocyte removal. The mouse and rabbit showed only few macrophages with an acid phosphatase activity in the lamina propria of villi. The present finding in the monkey urges an investigation as to whether the novel mechanism of enterocyte disposition by subepithelial macrophages might be taking place in the human intestine.

Animals↗
PubMed1992

Frequent loss of heterozygosity on chromosomes Xp and 13q in human ovarian cancer.

Loss of heterozygosity (LOH) was examined at 27 loci on chromosomes 3p, 6q, 11p, 13q, 17 and X in 42 human ovarian tumors. LOH was detected in 12 of 26 (46%) and 5 of 12 (42%) informative cases at 2 chromosome 13q loci, D13S32 and D13S34 respectively. On chromosome Xp, tumor-specific allele loss was observed in 9 out of 15 informative cases (60%) at the ornithine transcarbamylase (OTC) gene locus. Examination of 12 additional Xp and 13q loci has mapped the common deletion regions to Xp21.1-->p11.4 and 13q33-->q34. The observation of significant LOH on Xp represents a strong indication of genetic changes in the X chromosome in a human malignancy. The allele losses on 13q which have been reported for other cancers suggest that chromosome 13, in addition to the retinoblastoma gene, may contain other growth-regulating gene(s) important in the development of several tumor types, including ovarian malignancies.

Chromosome Deletion↗
PubMed1992

Clones of a spontaneously metastatic human lung carcinoma cell line differ in their in vitro and in vivo phenotypic characteristics.

In order to isolate subpopulations of cells with differing metastatic capacity, a spontaneously metastatic human lung carcinoma cell line was cloned in vitro, using limiting dilution methods. The karyotypic profile, in vitro and in vivo growth as subcutaneous xenotransplants in athymic mice of 11 randomly selected clones were very similar. No consistent differences were seen in the adhesion to a variety of substrates or in the integrin profile of the few subunits examined. However, the in vivo metastatic capacities differed. Most of the isolated cell lines, in spontaneous metastasis assays, formed variable numbers of microscopically visible metastatic foci in only the lungs and lymph nodes of these animals. One of the 11 cell lines examined, TV9, was observed to form grossly visible metastases in the lungs as well as in the ovaries, pancreas and omental lymph nodes. Immunoprecipitation analyses detected a decrease in the expression of the previously described low-metastasis-associated H7 molecule within the high metastatic TV9. The low and high metastatic subpopulations thus isolated will provide a means to dissect the metastatic mechanisms of this human lung carcinoma cell line.

Animals↗
PubMed1992

Cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter.

We have screened a human substantia nigra cDNA library with probes derived from the rat dopamine transporter. A 3.5-kilobase cDNA clone was isolated and its corresponding gene was located on the distal end of chromosome 5 (5p15.3). This human clone codes for a 620-amino acid protein with a calculated molecular weight of 68,517. Hydropathicity analysis suggests the presence of 12 putative transmembrane domains, a characteristic feature of sodium-dependent neurotransmitter carriers. The rat and the human dopamine transporters are 92% homologous. When permanently expressed in mouse fibroblast Ltk- cells, the human clone is able to induce a saturable, time- and sodium-dependent, dopamine uptake. This transport is blocked by psychostimulant drugs (cocaine, l- and d-amphetamine, and phenyclidine), neurotoxins (6-hydroxydopamine and N-methyl-4-phenylpyridine (MPP))+), neurotransmitters (epinephrine, norepinephrine, gamma-aminobutyric acid, and serotonin), antidepressants (amitriptyline, bupropion, desipramine, mazindol, nomifensine, and nortriptyline), and various uptake inhibitors (mazindol, GBR 12783, GBR 12909, and amfonelic acid). The rank orders of the Ki values of these substances at the human and the rat dopamine transporters are highly correlated (r = 0.998). The cloning of DNA human dopamine transporter gene has allowed establishment of a cell line stably expressing the human dopamine transporter and, for the first time, an extensive characterization of its pharmacology. Furthermore, these newly developed tools will help in the study of the regulation of dopamine transport in humans and in the clarification of the potential role of the dopamine transporter in a variety of disease states.

Amino Acid Sequence↗