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Biomedical subjects

Y H Ko

Publications and source records attributed to Y H Ko.

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

CD99 regulates the transport of MHC class I molecules from the Golgi complex to the cell surface.

The down-regulation of surface expression of MHC class I molecules has recently been reported in the CD99-deficient lymphoblastoid B cell line displaying the characteristics of Hodgkin's and Reed-Sternberg phenotype. Here, we demonstrate that the reduction of MHC class I molecules on the cell surface is primarily due to a defect in the transport from the Golgi complex to the plasma membrane. Loss of CD99 did not affect the steady-state expression levels of mRNA and protein of MHC class I molecules. In addition, the assembly of MHC class I molecules and the transport from the endoplasmic reticulum to the cis-Golgi occurred normally in the CD99-deficient cells, and no difference was detected between the CD99-deficient and the control cells in the pattern and degree of endocytosis. Instead, the CD99-deficient cells displayed the delayed transport of newly synthesized MHC class I molecules to the plasma membrane, thus causing accumulation of the molecules within the cells. The accumulated MHC class I molecules in the CD99-deficient cells were colocalized with alpha-mannosidase II and gamma-adaptin in the Golgi compartment. These results suggest that CD99 may be associated with the post-Golgi trafficking machinery by regulating the transport to the plasma membrane rather than the endocytosis of surface MHC class I molecules, providing a novel mechanism of MHC class I down-regulation for immune escape.

12E7 Antigen↗
PubMed2001

CHOP followed by involved field radiation: is it optimal for localized nasal natural killer/T-cell lymphoma?

The present study aimed to analyse the treatment outcome of four cycles of CHOP (cyclophosphamide-vincristine-doxorubicin-prednisolone) followed by involved field radiation therapy (IF RT) for the treatment of stage I-II nasal natural killer (NK)/T-cell lymphoma. From March 1995 to December 1999, 17 patients (median age 41 years; range 30-66) with localized nasal NK/T-cell lymphoma were enrolled. B symptoms were noted in five patients (31%). Sixteen of seventeen patients (94%) were of low risk when classified according to the International Prognostic Index (IPI). The treatment plan consisted of four cycles of CHOP chemotherapy followed by IF RT of 45 Gy. Two patients received radiation during the first or second cycle of CHOP because of bleeding from the primary tumour site. Both patients achieved complete responses (CRs). In the remaining 15 patients, after 4 cycles of CHOP, 6 CRs and 3 partial responses (PRs) were achieved (53% of response rate). IF RT was given to six patients (four in CR, one in PR and one in PD), and all six patients achieved CR. Overall, CR was achieved in 10 of 17 patients (58%). The planned sequential chemoradiotherapy was completed in only 6 of 17 patients (35%) because of the progression during chemotherapy. None of the patients who achieved CR experienced relapse of lymphoma during follow-up. The estimated overall three-year survival rate was 59%. In univariate analysis, B symptoms and stage were significant prognostic factors for response and overall survival (P < 0.05). The present study suggests that four cycles of CHOP followed by IF RT is not satisfactory for treating patients with localized nasal NK/T-cell lymphoma, and that further exploration for improved therapy is needed.

Adult↗
PubMed2001

Cystic fibrosis: a brief look at some highlights of a decade of research focused on elucidating and correcting the molecular basis of the disease.

The disease Cystic Fibrosis (CF) is caused by mutations in the protein called CFTR, cystic fibrosis transmembrane conductance regulator, an ABC-transporter-like protein found in the plasma membrane of animal cells. CFTR is believed to function primarily as a Cl- channel, but evidence is mounting that this protein has other roles as well. Structurally, CFTR consists of a single polypeptide chain (1480 amino acids) that folds into 5 distinct domains. These include 2 transmembrane domains that are involved in channel formation; 2 nucleotide-binding domains (NBF1 and NBF2), the first of which clearly binds and hydrolyzes ATP; and 1 regulatory domain (R) that is phosphorylated in a cAMP-dependent process. Currently, the 3D structure of neither CFTR nor its domains has been elucidated, although both nucleotide domains have been modeled in 3D, and solution structures in 3D have been obtained for peptide segments of NBF1. The most common mutation causing CF is the deletion (delta) of a single phenylalanine (F) in position 508 within a putative helix located in NBF1. CF patients bearing this deltaF508 mutation frequently experience chronic lung infections, particularly by Pseudomonas aeruginosa, and have a life span that rarely exceeds the age of 30. Since the CFTR gene was cloned and sequenced in 1989, there has been over a decade of research focused on understanding the molecular basis of CF caused by the deltaF508 mutation, with the ultimate objective of using the knowledge gained to carry out additional research designed to correct the underlying defect. In general, this pioneering or "ground roots" research has succeeded according to plan. This brief review summarizes some of the highlights with a focus on those studies conducted in the authors' laboratory. For us, this research has been both exciting and rewarding mainly because the results obtained, despite very limited funding, have provided considerable insight, not only into the chemical, molecular, and pathogenic basis of CF, but have made it possible for us and others to now develop novel, chemically rational, and "cost effective" strategies to identify agents that correct the structural defect in the deltaF508 CFTR protein causing most cases of CF.

ATP-Binding Cassette Transporters↗
PubMed2001

Expression of p21Waf1, p27Kip1 and cyclin D1 proteins in breast ductal carcinoma in situ: Relation with clinicopathologic characteristics and with p53 expression and estrogen receptor status.

p21Waf1 (p21), p27Kip1 (p27) and cyclin D1 have recently been reported as useful prognostic markers for patients with breast carcinoma. However, studies on these cell cycle regulators in ductal carcinoma in situ (DCIS) have been extremely limited. Therefore, we studied the immunohistochemical expression of p21, p27 and cyclin D1 proteins in 49 DCIS cases and compared the findings with the clinicopathologic parameters (age, tumor size, gross type, histologic type, histologic grade, necrosis and mitotic index), p53 and estrogen receptor (ER) status. A significant correlation was found between positive p21 immunoreactivity (67.3% of the cases) and well-differentiated histologic grade, non-comedo type, ER-positive and p53-negative (p53-) status. DCIS with p21+/p53- is likely to be the non-comedo type. The overexpression of cyclin D1 (59.2% of the cases) correlated positively with the ER expression (P = 0.001). The p27 protein expression (46.9% of the cases) correlated with the cyclin D1 immunopositivity (P = 0.0003) and ER expression (P = 0.005). No significant associations were seen in the p27 or cyclin D1 expression and other clinicopathologic parameters. Our results suggest that p21 might be more related to the useful biologic markers in DCIS than p27 or cyclin D1. The significant positive association between p21, p27 or cyclin D1 and ER status, and close association of p27 and cyclin D1 expression might be implicated in the tumor biology of DCIS.

Adult↗
PubMed2001

Coexpression of Bcl-6 and CD10 in diffuse large B-cell lymphomas: significance of Bcl-6 expression patterns in identifying germinal center B-cell lymphoma.

Most follicular lymphomas (FLs) transform to diffuse lymphoma eventually, comprising a significant proportion of diffuse large B-cell lymphoma (DLBCL). Judging by bcl-2 rearrangement (bcl-2R), one third of DLBCLs are believed to be of FL derivation in the Western population. However, bcl-2R is not specific and is not detectable in every case of FL. In East Asia, FL is uncommon but DLBCL is not. The proportion of tumors of FL origin in DLBCL is not known in this region. The coexpression of Bcl-6 and CD10 proteins, a reliable marker to identify germinal center (GC) B-cell lymphoma including FL, was analyzed in primary nodal DLBCLs (n = 104) diagnosed at major hospitals in Seoul during a recent 2-year period, along with well-defined cases (n = 17) of nodal FL as controls. Bcl-2 protein expression (n = 77) was also studied along with bcl-2R (n = 64), by polymerase chain reaction. Formalin-fixed archival specimens were used in all these assays. The Bcl-6/CD10 coexpression was observed in 35 DLBCLs (34%) and 14 FLs (82%), and most of them showed a pattern of Bcl-6 expression similar to that of the GC. Bcl-2 expression or bcl-2R did not correlate with Bcl-6/CD10 coexpression. Histologically, compartmentalizing sclerosis was associated with a high rate of the coexpression (8 of 10). In conclusion, to detect GC B-cell lymphoma in routine biopsy specimens, a pattern of Bcl-6 staining similar to the GC must be identified. Bcl-6+/CD10+ GC B-cell lymphomas thus defined comprised one third of primary nodal DLBCLs in Korea. The incidence rate is similar to that in the West. The reasons for the discrepancy between the incidence of GC B-cell lymphoma and the paucity of the follicular pattern in East Asian subjects warrant further studies.

Adolescent↗
PubMed2001

Erdheim-Chester disease with extensive marrow necrosis: a case report and literature review.

Erdheim-Chester disease is a rare systemic disorder characterized by a fibrosing xanthogranulomatous infiltration of multiple organs. We report a case of Erdheim-Chester disease with diffuse necrosis leading to difficulty in making a prompt diagnosis. Radiologically, osteosclerotic lesions with osteolytic element involved metadiaphyses of both proximal tibia, and retroperitoneal infiltrations encasing both kidneys, both adrenals, and aorta were found. A biopsy of the tibia showed diffuse infiltration of foamy histiocytes, Touton-type giant cells, and fibroblastic cells associated with extensive coagulative necrosis. Immunohistochemically, foamy histiocytes were positive for CD68 and peanut agglutinin and negative for S-100 protein. A few Langerhans' cells, which were difficult to identify in hematoxylin-eosin stain, were highlighted by immunostain for S-100 protein. The patient received supportive therapy and was alive 1 1/2 years after diagnosis, with newly developed bilateral retrobulbar lesions and worsened heart failure.

Bone Diseases↗
PubMed2000

Clinicopathologic and genotypic study of extranodal nasal-type natural killer/T-cell lymphoma and natural killer precursor lymphoma among Koreans.

BACKGROUND: This study aimed to define genotypic profile and to describe the clinicopathologic features of nasal-type natural killer (NK)/T-cell lymphoma of nasal and extranasal origin and NK precursor lymphoma. METHODS: NK/T-cell lymphomas from the upper aerodigestive tract (n = 45), skin (n = 2), gastrointestinal tract (n = 3), and soft tissue (n = 2) and NK precursor neoplasms (n = 3) were studied. Immunophenotype was analyzed by immunohistochemistry and flow cytometry. In situ hybridization with EBER 1/2 RNA probes was performed. T-Cell Receptor (TCR)-gamma gene rearrangement was analyzed by seminested polymerase chain reaction with heteroduplex analysis. Overall survival rate was correlated with clinicopathologic parameters and compared by Wilcoxon test. RESULTS: Clonal TCR-gamma gene rearrangement was detected in 3 of 31 upper aerodigestive and 1 of 2 skin tumors. When immunostained using paraffin embedded tissue, 6 upper aerodigestive lymphomas were negative for CD56 in which 4 cases lacked clonal TCR gene rearrangement. Epstein-Barr virus (EBV) mRNA was detected in 33 upper aerodigestive tumors including 26 of 29 nasal tumors (90%), and 7 of 10 extranasal tumors (70%). There was no histologic, immunophenotypic, or genotypic differences according to the lineage and EBV association in upper aerodigestive lymphomas. Among the patients with upper aerodigestive tumors, overall 1-year survival rate was 41%, and correlated well with the stage (P < 0.05) but not with the size of tumor cells, EBV status, and lineage (P > 0.05). Median survival rate of lymphomas from other sites excluding upper aerodigestive tract was not significantly different from that of upper aerodigestive lymphomas with same stage (P > 0.05). Unlike nasal-type NK/T-cell lymphomas, NK precursor lymphoma involved the bone marrow and lymph nodes at initial presentation or in the course of disease. Tumor cells were positive for TdT in all and myeloid markers in two. TCR gene rearrangement was germ line. CONCLUSIONS: Most upper aerodigestive nasal-type NK/T-cell lymphomas among Koreans are genotypically of NK derivation and few belong to T lineage. Presence or absence of EBV has no significant correlation with the histologic changes and the lineage of these lymphomas.

Adult↗
PubMed2000

Mitochondrial F(0)F(1) ATP synthase. Subunit regions on the F1 motor shielded by F(0), Functional significance, and evidence for an involvement of the unique F(0) subunit F(6).

Studies reported here were undertaken to gain greater molecular insight into the complex structure of mitochondrial ATP synthase (F(0)F(1)) and its relationship to the enzyme's function and motor-related properties. Significantly, these studies, which employed N-terminal sequence, mass spectral, proteolytic, immunological, and functional analyses, led to the following novel findings. First, at the top of F(1) within F(0)F(1), all six N-terminal regions derived from alpha + beta subunits are shielded, indicating that one or more F(0) subunits forms a "cap." Second, at the bottom of F(1) within F(0)F(1), the N-terminal region of the single delta subunit and the C-terminal regions of all three alpha subunits are shielded also by F(0). Third, and in contrast, part of the gamma subunit located at the bottom of F(1) is already shielded in F(1), indicating that there is a preferential propensity for interaction with other F(1) subunits, most likely delta and epsilon. Fourth, and consistent with the first two conclusions above that specific regions at the top and bottom of F(1) are shielded by F(0), further proteolytic shaving of alpha and beta subunits at these locations eliminates the capacity of F(1) to couple a proton gradient to ATP synthesis. Finally, evidence was obtained that the F(0) subunit called "F(6)," unique to animal ATP synthases, is involved in shielding F(1). The significance of the studies reported here, in relation to current views about ATP synthase structure and function in animal mitochondria, is discussed.

Adenosine Triphosphate↗
PubMed2000

The relationship between the angiographic findings and the clinical features of carotid artery plaque.

The purpose of this study was to investigate the histological characteristics of atheromatous carotid plaque, and to analyze the relationship between the angiographic findings and the clinical features. We retrospectively reviewed 55 cases of carotid endarterectomy for extracranial internal carotid artery stenosis, who were treated at our institute from January 1995 to December 1997. The histological examination included hematoxylin-eosin staining, Masson-trichrome staining, and immunostaining for antismooth muscle antibody and anti-CD68 antibody. The main compositions of the carotid plaque included synthetic type vascular smooth muscle cells and extracellular matrix. The histological findings showed ulceration in 49 (89.1%) cases, calcium deposits in 42 (76.4%) cases, and an inflammatory reaction in 44 (80.0%) cases. Neurological abnormalities were strongly associated with plaque ulceration (P = 0.045) and an inflammatory reaction (P = 0.013), whereas no correlation existed regarding calcium deposits (P = 0.173). The angiographic findings showed ulceration in 46 (83.6%) cases. Plaque ulceration in the angiography findings showed no statistically significant correlation with the histologic findings (P = 0.410) and preoperative neurologic abnormalities (P = 0.059). All of the atherosclerotic risk factors such as hypertension, smoking, diabetes mellitus, hyperlipidemia, and myocardial infarction had no statistically significant correlation with the histological features of the carotid plaque. In conclusion, the main compositions of carotid plaque were synthetic-type vascular smooth muscle cells and extracellular matrix. The histological ulceration and inflammatory reaction of the plaque showed a statistically significant correlation with the preoperative neurologic symptoms, whereas no correlation was seen in the calcium deposits. Angiographic ulceration showed no correlation with the histological findings or preoperative neurologic abnormalities. In addition, the histological findings showed no correlation with the atherosclerotic risk factors.

Aged↗
PubMed2000

ATP synthases in the year 2000: evolving views about the structures of these remarkable enzyme complexes.

This introductory article briefly summarizes how our views about the structural features of ATP synthases (F0F1) have evolved over the past 30 years and also reviews some of our current views in the year 2000 about the structures of these remarkably unique enzyme complexes. Suffice it to say that as we approach the end of the first year of this new millinium, we can be conservatively confident that we have a reasonably good grasp of the overall "low-resolution" structural features of ATP synthases. Electron microscopy techniques, combined with the tools of biochemistry, molecular biology, and immunology, have played the leading role here by identifying the headpiece, basepiece, central stalk, side stalk, cap, and in the mitochondrial enzyme, the collar around the central stalk. We can be reasonably confident also that we have a fairly good grasp of much of the "high-resolution" structural features of both the F1 moiety comprised of fives subunit types (alpha, beta, gamma, delta, and epsilon) and parts of the F0 moiety comprised of either three (E. coli) or at least ten (mitochondria) subunit types. This information acquired in several different laboratories, either by X-ray crystallography or NMR spectroscopy, includes details about the active site and subunit relationships. Moreover, it is consistent with recently reported data that the F1 moiety may be an ATP driven motor, which, during ATP synthesis, is driven in reverse by the electrochemical proton gradient generated by the electron transport chain. The real structural challenges of the future are to acquire at high resolution "complete" ATP synthase complexes representative of different stages of the catalytic cycle during ATP synthesis and representative also of key regulatory states.

Crystallography, X-Ray↗
PubMed2000

ATP synthases in the year 2000: defining the different levels of mechanism and getting a grip on each.

ATP synthases are unusually complex molecules, which fractionate most readily into two major units, one a water soluble unit called F(1) and the other a detergent soluble unit called F(0). In almost all known species the F(1) unit consists of 5 subunit types in the stoichiometric ratio alpha(3)beta(3)gammadeltaepsilon while the F(0) unit contains 3 subunit types (a, b, and c) in E. coli, and at least 10 subunit types (a, b, c, and others) in higher animals. It is now believed by many investigators that during the synthesis of ATP, protons derived from an electrochemical gradient generated by an electron transport chain are directed through the F(0) unit in such a way as to drive the rotation of the single gamma subunit, which extends from an oligomeric ring of at least 10 c subunits in F(0) through the center of F(1). It is further believed by many that the rotating gamma subunit, by interacting sequentially with the 3 alphabeta pairs of F(1) (360 degrees cycle) in the presence of ADP, P(i), and Mg++, brings about via "power strokes" conformational/binding changes in these subunits that promote the synthesis of ATP and its release on each alphabeta pair. In support of these views, studies in several laboratories either suggest or demonstrate that F(0) consists in part of a proton gradient driven motor while F(1) consists of an ATP hydrolysis driven motor, and that the gamma subunit does rotate during F(1) function. Therefore, current implications are that during ATP synthesis the former motor drives the latter in reverse via the gamma subunit. This would suggest that the process of understanding the mechanism of ATP synthases can be subdivided into three major levels, which include elucidating those chemical and/or biophysical events involved in (1) inducing rotation of the gamma subunit, (2) coupling rotation of this subunit to conformational/binding changes in each of the 3 alphabeta pairs, and (3) forming ATP and water (from ADP, P(i), and Mg(++)) and then releasing these products from each of the 3 catalytic sites. Significantly, it is at the final level of mechanism where the bond breaking/making events of ATP synthesis occur in the transition state, with the former two levels of mechanism setting the stage for this critical payoff event. Nevertheless, in order to get a better grip in this new century on how ATP synthases make ATP and then release it, we must take on the difficult challenge of elucidating each of the three levels of mechanism.

Adenosine Triphosphate↗
PubMed2000

Polymerase chain reaction detection of Mycobacterium tuberculosis from fine-needle aspirate for the diagnosis of cervical tuberculous lymphadenitis.

BACKGROUND: Despite its well-established usefulness in the diagnosis of cervical tuberculous lymphadenitis, fine-needle aspiration cytology (FNAC) has several limitations in its clinical applications, especially when the presence of acid-fast bacilli is not proven. Furthermore, fine-needle aspirate is sometimes inadequate for diagnosis, and the sensitivity and specificity of this technique for cervical tuberculous lymphadenitis has not been firmly established. OBJECTIVE: The authors performed Mycobacterium tuberculosis polymerase chain reaction (PCR) for mycobacterial DNA sequences from the remainder of fine-needle aspirate after cytological examination and evaluated its diagnostic efficacy in clinical situations. METHODS: Conventional diagnostic procedures including FNAC and M tuberculosis PCR were performed simultaneously in 29 cases that had been suspected to be cervical tuberculous lymphadenitis on patients' first visit. The results of FNAC and M tuberculosis PCR were compared with the clinical outcomes after several months of follow-up and pathological results from open biopsy of some cases. RESULTS: Among the 17 cases of cervical tuberculous lymphadenitis diagnosed in clinical situations, M tuberculosis DNA was found by PCR in 13 cases (76.4%). Negative findings on PCR were achieved in 12 cases, which revealed non-granulomatous lymphadenopathy. CONCLUSION: From these results, we conclude that M tuberculosis PCR using the remainder of aspirate for cytological examination is a very useful tool for the diagnosis of cervical tuberculous lymphadenitis, and its clinical application with FNAC could reduce the necessity for open biopsy.

Adolescent↗
PubMed2000

Expression of CD34, bcl-2, and kit in inflammatory fibroid polyps of the gastrointestinal tract.

The histogenesis of inflammatory fibroid polyps (IFP) of the gastrointestinal tract, focused on the cell of origin of the stromal cells, is a controversial subject. The reported CD34 reactivity in gastric IFP has implied a histogenetic relationship with a variety of CD34-reactive tumors, including gastrointestinal stromal tumors (GIST). In addition to bcl-2, the majority of GIST has expressed Kit, suggesting an origin in interstitial cells of Cajal (ICC), which are selectively localized around nerve plexuses. Gastric (12) and colonic (two) IFP from 13 patients were studied, using antibodies against CD34, bcl-2, and Kit. IFP expanded muscularis mucosae with prominent vascular channels, inflammatory infiltrates, proliferating stromal cells, and extracellular matrix material. Eleven gastric IFP exhibited concentric stromal proliferations (CP), particularly, around vessels, glands, and muscle bundles. Their stromal cells were CD34 reactive, bcl-2 nonreactive, and Kit nonreactive and showed fibroblast-like appearances with thin, long cytoplasmic processes. In contrast, one gastric and two colonic IFP showed no CP, and their stromal cells were CD34 nonreactive, bcl-2 nonreactive, and Kit nonreactive. IFP with CP may have a different histogenesis from IFP without CP. IFP with CP may originate from a subpopulation of dendritic interstitial cells other than ICC, predominantly localized around blood vessels and muscle fibers in muscularis mucosae of the stomach.

Adult↗
PubMed2000

Salivary gland tumors: evaluation with two-phase helical CT.

PURPOSE: To evaluate two-phase helical computed tomography (CT) in the characterization of salivary gland tumors. MATERIALS AND METHODS: Sixty-four patients with major salivary gland tumors underwent two-phase helical CT. The histopathologic diagnosis was obtained by means of surgical resection or biopsy in all patients. After the injection of 90 mL of contrast material at a rate of 3 mL/sec, helical CT scans were obtained at early and delayed phases with scanning delays of 30 and 120 seconds, respectively. The attenuation change and enhancement patterns in the tumors were assessed. The attenuation change in the tumor also was assessed quantitatively as the ratio of the CT number (in Hounsfield units) at delayed phase scanning to that at early phase scanning. RESULTS: There were 35 pleomorphic adenomas, nine Warthin tumors, and 20 malignant tumors. Two-phase helical CT showed increase in attenuation in 30 (86%) pleomorphic adenomas, decrease in eight (89%) Warthin tumors, and increase in 11 (55%) and no change in eight (40%) malignant tumors at delayed phase scanning. A multinodular enhancement pattern was found in only 12 (34%) pleomorphic adenomas. The ratio of CT numbers was significantly different between Warthin tumors and pleomorphic adenomas and between Warthin tumors and malignant tumors. CONCLUSION: The analysis of enhancement patterns by using two-phase helical CT will be helpful in the differential diagnosis of salivary gland tumors.

Adolescent↗
PubMed2000

A case report of primary T-cell lymphoma of the liver.

The patient was a 50-year-old woman who presented intermittent mild fever with elevated liver enzymes for 12 years. The liver biopsy showed diffuse portal and sinusoidal involvement of lymphoid cells with minimal atypia and epithelioid histiocytic granuloma formation. Subsequent bone marrow biopsy showed lymphomatous involvement. The lymphocytes infiltrating the liver were reactive for T-cell marker and showed TCR gamma gene rearrangement. The patient was diagnosed as primary peripheral T-cell lymphoma of the liver. Indolent clinical course and resemblance with hepatitis were considered to be a rare and unique feature of this case.

DNA, Neoplasm↗