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H Han

Publications and source records attributed to H Han.

At least 181 records · Page 10Linked to original sources
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↗
PubMed1991

Role of divalent cations in the 3',5'-exonuclease reaction of DNA polymerase I.

X-ray studies of the proofreading 3',5'-exonuclease site of the large (Klenow) fragment of DNA polymerase I have detected a binuclear metal complex consisting of a pentacoordinate metal (site A) which shares a ligand, Asp-355, with an octahedral metal (site B) [Freemont, P. S., Friedman, J. M., Beese, L. S., Sanderson, M. R., & Steitz, T. A. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 8924-8928; Beese, L. S., & Steitz, T. A. (1991) EMBO J. 10, 25-33]. Kinetic studies of the activation of the 3',5'-exonuclease reaction by Co2+, Mn2+, or Mg2+, at low concentrations of DNA, reveal sigmoidal activation curves for the three metal ions with Hill coefficients of 2.3-2.4 and K0.5 values of 16.6 microM, 4.2 microM, and 343 microM, respectively. The binding of Co2+ to the enzyme results in the appearance of an intense visible absorption spectrum of the metal ion with maxima at 633, 570, and 524 nm and extinction coefficients of 190, 194, and 150 M-1 cm-1, respectively, suggesting the formation of a pentacoordinate Co2+ complex. Optical titration with Co2+ yields a sigmoidal titration curve which is best fit by assuming the cooperative binding of three Co2+ ions with a K0.5 of 39.9 microM, comparable to the value of 16.6 microM obtained kinetically. Displacement of Co2+ by 1 equiv of Zn2+, which binds tightly to the A site of the 3',5'-exonuclease, shifts the optical spectrum to 524 nm and lowers the extinction coefficient to 30 -1 cm-1, indicative of octahedral coordination.2+ the formation of the binuclear complex.

Binding Sites↗
PubMed1991

Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene.

We analyzed the molecular mechanism for the immunoglobulin (Ig) multiple isotype expression using a transgenic mouse (TG.SA) model system. Though most of the endogenous mu chain expression was excluded by the expression of the human rearranged mu transgene in the TG.SA mouse, a significant portion of splenic B lymphocytes could express the transgenic human IgM and endogenous mouse IgG simultaneously after stimulation with lipopolysaccharide and interleukin 4. The fluorescence-activated cell sorter-purified population of the human IgM+/mouse IgG+ cells expressed mRNA that consisted of properly spliced sequences of the transgenic VHDJH and the endogenous mouse C gamma genes (trans-mRNA), together with the transgenic human mu mRNA and germline transcripts of the mouse C gamma gene, without apparent rearrangement of the transgene. We also found that a lymphoma tumor, derived from the cross between the TG.SA mouse and another transgenic mouse carrying Ig H chain enhancer-driven c-myc oncogene, expressed about equal levels of the trans-mRNA and the transgenic mu mRNA without DNA rearrangement in either the transgene or the endogenous mouse switch region. These findings strongly support our previous proposal that the trans-splicing can account for the multiple isotype expression in this transgenic model and also suggest that novel molecular mechanism(s) might be involved in this reaction.

Animals↗
PubMed1991

Chronobiologic approach to beat-to-beat variations of cultured murine myocardial cells.

An earlier demonstration of a circadian rhythm in rat atria by others is complemented herein by observations in culture: A single murine myocardial cell and two sets of grouped cells beating in culture for several days reveal several features of an anticipated, presumably built-in spectrum of multifrequency rhythms and trends, the chronome. Circadian and about 12-h (circasemidian) components are modulated by an approximately 84-h (circasemiseptan) component, which cannot be separated from trends in view of the brevity of the series. The circumstance under which the culture is aging and in which fibroblasts proliferate is a further complication that limits the findings to a single cycle reproduced in three separate cultures. Whether it is a rhythm that repeats itself of a response to placement into culture, an approximately 3.5-d component in the beating of myocardial cells in culture is to be aligned with a very prominent similar component found in the incidence of 85,819 human myocardial infarctions.

Animals↗