Search PubMed⌕ Search

Biomedical subjects

Y H Ko

Publications and source records attributed to Y H Ko.

At least 55 records · Page 3Linked to original sources

Prevalence of foam cells and helper-T cells in atherosclerotic plaques of Korean patients with carotid atheroma.

BACKGROUND: Inflammation and activation of immune cells have important roles in the pathogenesis of atherosclerosis. We analyzed the involvement of various immune cells in the pathogenesis of atherosclerosis. METHODS: We investigated the presence of foam cells, lymphocytes and killer cells in 11 atherosclerotic plaque specimens removed from Korean patients who underwent carotid endoarterectomy. Atherosclerotic plaques were analyzed by immunohistochemistry using monoclonal antibody specific to foam cells (anti-CD68), pan-T cells (anti-CD3), helper-T cells (anti-CD4), cytotoxic T cells (anti-CD8), granular component of killer cells (anti-TIA-1) and pan-B cells (anti-CD20). RESULTS: Analysis revealed a general infiltration of immune cells not only in atherosclerotic plaques but also in the vascular wall adjacent to the plaque. Heavy infiltration of CD68+ macrophage was observed in all cases. In addition, significant infiltration of CD3+ T-lymphocytes was observed in all cases, while CD20+ B-cells were observed in only a few cases. Majority of the CD3+ cells was found to be CD4+ helper-T cells. CD8+ cytotoxic T cells and TIA-1+ cells were less prominent. CONCLUSION: Analysis of the human atherosclerotic plaques suggested that helper-T cells and foam cells had a major role in the plaque development.

Aged↗

Chemical mechanism of ATP synthase. Magnesium plays a pivotal role in formation of the transition state where ATP is synthesized from ADP and inorganic phosphate.

The chemical mechanism by which ATP synthases catalyze the synthesis of ATP remains unknown despite the recent elucidation of the three-dimensional structures of two forms of the F(1) catalytic sector (subunit stoichiometry, alpha(3)beta(3)gammadeltaepsilon). Lacking is critical information about the chemical events taking place at the catalytic site of each beta-subunit in the transition state. In an earlier report (Ko, Y. H., Bianchet, M. A., Amzel, L.M., and Pedersen, P. L. (1997) J. Biol. Chem. 272, 18875-18881), we provided evidence for transition state formation in the presence of Mg(2+), ADP, and orthovanadate (V(i)), a photoreactive phosphate analog with a trigonal bipyramidal geometry resembling that of the gamma-P of ATP in the transition state of enzymes like myosin. In the presence of ultraviolet light and O(2,) the MgADP.V(i)-F(1) complex was cleaved within the P-loop (GGAGVGKT) of a single beta-subunit at alanine 158, implicating this residue as within contact distance of the gamma-P of ATP in the transition state. Here, we report that ADP, although facilitating transition state formation, is not essential. In the presence of Mg(2+) and V(i) alone the catalytic activity of the resultant MgV(i)-F(1) complex is inhibited to nearly the same extent as that observed for the MgADP. V(i)-F(1) complex. Inhibition is not observed with ADP, Mg(2+), or V(i) alone. Significantly, in the presence of ultraviolet light and O(2,) the MgV(i)-F(1) complex is cleaved also within the P-loop of a single beta-subunit at alanine 158 as confirmed by Western blot analyses with two different antibodies, by N-terminal sequence analyses, and by quantification of the amount of unreacted beta-subunits. These novel findings indicate that Mg(2+) plays a pivotal role in transition state formation during ATP synthesis catalyzed by ATP synthases, a role that involves both its preferential coordination with P(i) and the repositioning of the P-loop to bring the nonpolar alanine 158 into the catalytic pocket. A reaction scheme for ATP synthases depicting a role for Mg(2+) in transition state formation is proposed here for the first time.

ATP Synthetase Complexes↗

Cystic fibrosis transmembrane conductance regulator: solution structures of peptides based on the Phe508 region, the most common site of disease-causing DeltaF508 mutation.

Most cases of cystic fibrosis (CF), a common inherited disease of epithelial cell origin, are caused by the deletion of Phe508 located in the first nucleotide-binding domain (NBF1) of the protein called CFTR (cystic fibrosis transmembrane conductance regulator). To gain greater insight into the structure within the Phe508 region of the wild-type protein and the change in structure that occurs when this residue is deleted, we conducted nuclear magnetic resonance (NMR) studies on representative synthetic 26 and 25 amino acid peptide segments. 2D 1H NMR studies at 600 MHz of the 26-residue peptide consisting of Met498 to Ala523 in 10% DMSO, pH 4.0, at 25 degrees C show a continuous but labile helix from Gly500 to Lys522, based on both NH-NH(i,i+1) and alphaH-NH(i,i+1) NOEs. Phe508 within this helix shows only short-range (i, </=i + 2) NOEs. The corresponding 25-residue peptide lacking Phe508 also forms a labile helix from Gly500 to Lys522. However, the relative intensities of the NH-NH(i, i+1)/alphaH-NH(i,i+1) NOEs, fewer intermediate-range NOEs, and downfield alphaH and NH chemical shifts indicate a lower helical propensity of the 25-mer between residues 505 and 517, surrounding the missing residue, Phe508. 2D 1H NMR studies of both peptides in saturating (43%) TFE reveal stable alpha-helices from Gly500 to Lys522, based on NH-NH(i,i+1,2,3), alphaH-NH(i,i+2,3,4), alphaH-betaH(i,i+3), and weak alphaH-NH(i,i+1) NOEs. However, downfield shifts of the alphaH resonances from residues Gly500 to Ile507 and fewer intermediate-range NOEs suggest a less stable alpha-helix in the 25-mer even in saturating TFE. These findings show that the Phe508-containing region of CFTR has a propensity to form an alpha-helix, which is destabilized by the DeltaF508 mutation found in most patients with CF. These studies have direct relevance to better understanding the CFTR misfolding problem associated with CF and to identifying chemical agents, which correct this problem.

Amino Acid Sequence↗

Bcl-6 expression in reactive follicular hyperplasia, follicular lymphoma, and angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers: heterogeneity of intrafollicular T-cells and their altered distribution in the pathogenesis of angioimmunoblastic T-cell lymphoma.

BACKGROUND: The Bcl-6 gene product, a nuclear phosphoprotein, is expressed independently of Bcl-6 gene rearrangement. In lymph nodes, expression of Bcl-6 protein is restricted to germinal center (GC) B-cells and 10% to 15% of CD3/CD4+ intrafollicular T cells. Interfollicular cells are negative for Bcl-6 protein, except for rare CD3+/CD4+ T cells. Recently, we reported cases of angioimmunoblastic T-cell lymphoma (AITL) with hyperplastic GCs (AITL/GC), and observed that borders of enlarged GCs were ill defined, with features suggestive of an outward migration of GC cells to surrounding interfollicular zones. This prompted a study of follicular borders with Bcl-6 staining in reactive follicular hyperplasias and follicular lymphomas to compare with AITL/GC. MATERIALS AND METHODS: Formalin-fixed paraffin sections were used for immunostaining of Bcl-6. Six cases of AITL/GC, 12 nonspecific reactive follicular hyperplasia (FH), 7 HIV adenopathy, 10 follicular lymphoma (FL), and 8 typical AITL (ie, AITL without GC) were studied. Double staining for Bcl-6/CD20, Bcl-6/CD3, and Bcl-6/CD57 was performed in selected cases. RESULTS: In FH and HIV adenopathy, staining for Bcl-6 revealed densely populated GCs with well-defined and regular GC borders, whereas Bcl-6+ cells were rare in the interfollicular areas. An occasional GC with an ill-defined border was invariably surrounded by a broad mantle zone; those with indistinct mantle zones had well-defined, regular borders. In FL, follicles were densely populated, and their borders were irregular, with some Bcl-6+ cells in the interfollicular zones. In AITL/GC, GCs were less dense, GC borders were ill defined and irregular, and the number of interfollicular Bcl-6+ cells was markedly increased. Double staining revealed that these interfollicular Bcl-6+ cells in AITL/GC were Bcl6+/CD3+/CD20-/CD57- T cells. Moreover, CD3+ intrafollicular T cells were depleted in AITL/GC, whereas they were abundant in FH. Intrafollicular CD57+ cells did not stain for Bcl-6, and were also depleted in AITL/GC. In typical AITL, some neoplastic cells were positive for Bcl-6, showing variable degrees of staining. CONCLUSIONS: (1) GCs of AITL/GC differed from those of other reactive follicular hyperplasias and follicular lymphomas, and staining for Bcl-6 was useful to discern them. (2) Intrafollicular CD3+ T cells, many of which were also positive for Bcl-6, were markedly depleted in AITL/GC, with increased interfollicular Bcl-6+/CD3+ cells, suggesting an outward migration of intrafollicular T cells in this condition. (3) Interfollicular Bcl-6+/CD3+ cells in AITL/GC were too numerous to be accounted for by migration alone, suggesting local proliferation. (4) Intrafollicular CD57+ cells were negative for Bcl-6, indicating heterogeneity of the intrafollicular T-cell population. (5) Some neoplastic cells in AITL stained for Bcl-6, suggesting up-regulation of Bcl-6 expression in this tumor.

Adult↗

Discordant evolution of asymptomatic proteinuria in identical twins.

We describe a pair of 17-year-old identical twin brothers with asymptomatic proteinuria, one of whom showed focal segmental glomerulosclerosis (FSGS) while the other showed immunoglobulin M (IgM) nephropathy. For each twin, audiological examination was normal. There was no family history of renal failure, deafness, or hematuria. HLA typing revealed an identical phenotype consisting of A25, A33, B44, B54, Cw1, Cw7, DR7 and DRB1. There is still controversy about whether minimal change disease, IgM nephropathy, and FSGS are discrete entities or different aspects of the same disease. The coexistence of IgM nephropathy and FSGS in identical twins suggests that the same genetic factors may be involved in the development of both diseases. However, although the brothers are identical twins, they had different eating habits and body weight. The twin who preferred to eat a protein-rich diet and who was heavier developed early proteinuria and manifested FSGS on renal biopsy. The discordant evolution of asymptomatic proteinuria in identical twins may provide a clue for the existence of environmental factors on the progression from IgM nephropathy to FSGS. Therefore, this report provides indirect support for the hypothesis that IgM nephropathy and FSGS represent different aspects in the spectrum of a single disease.

Adolescent↗

Granulomatous mastitis: mammographic and sonographic appearances.

OBJECTIVE: The objective of our study is to describe the mammographic and sonographic appearances of granulomatous mastitis. CONCLUSION: Granulomatous mastitis can mimic breast carcinoma clinically and mammographically, but the sonographic appearance of multiple clustered, often contiguous tubular hypoechoic lesions that are sometimes associated with a large hypoechoic mass should suggest the possibility of granulomatous mastitis.

Adult↗

Failure to demonstrate Borna disease virus genome in peripheral blood mononuclear cells from psychiatric patients in Korea.

RNA, extracted from peripheral blood mononuclear cells (PBMC) obtained from 81 Korean psychiatric patients (39 with schizophrenia, 33 with bipolar affective disorders and nine with major depression), was analyzed for a 391-nucleotide, highly conserved region of the p24 protein-encoding ORF II of Borna disease virus (BDV), using nested reverse transcription-polymerase chain reaction (RT-PCR). BDV genomic RNA was not detected in PBMC from any of the 81 Korean psychiatric patients. These data do not support an etiologic association between BDV infection and neuropsychiatric disorders in humans.

Adult↗

Benign papillary lesions of the breast: sonographic-pathologic correlation.

We reviewed the sonographic findings of 42 benign papillary lesions of the breast and correlated them with pathologic findings. Sonography detected 95% of papillomas (22 intraluminal masses, four extraductal masses, nine purely solid masses, and five mixed type masses). The sonographic margins of the mass were well defined in 20 lesions and poorly defined in 14 lesions. Poorly defined margins on sonography were frequent in papillomas with pathologic pseudoinvasion and in juvenile papillomatosis. Most benign papillary lesions of the breast have the sonographic findings suggestive of intraductal origin. The sonographic findings of papillary lesions correlated well with pathologic findings.

Adolescent↗

Detection of an anhydride intermediate in the carboxypeptidase A catalyzed hydrolysis of a peptide substrate by solid state NMR spectroscopy and its mechanistic implication.

We have detected an anhydride intermediate in the CPA catalyzed proteolytic reaction of Gly-Tyr. It appears that since the zinc-bound water molecule which is believed to attack the scissile amide carbonyl carbon in the hydrolysis reaction is excluded by the N-terminal amino group of Gly-Tyr, the carboxylate of Glu-270 becomes to attack the amide bond to generate the anhydride intermediate.

Anhydrides↗

REAL classification of malignant lymphomas in the Republic of Korea: incidence of recently recognized entities and changes in clinicopathologic features. Hematolymphoreticular Study Group of the Korean Society of Pathologists. Revised European-American lymphoma.

BACKGROUND: The clinicopathologic characteristics of malignant lymphomas vary according to geography. The aim of this study was to determine the clinical characteristics of malignant lymphomas and the relative frequency in the Republic of Korea of lymphomas belonging to the newly described REAL (revised European-American lymphoma) classification categories. METHODS: The Hematolymphoreticular Study Group of the Korean Society of Pathologists conducted a consensus-based morphologic review of a nationwide collection of 1548 malignant lymphomas, including Hodgkin's disease (HD), diagnosed at 23 institutes over a recent 2-year period. Slides stained with hematoxylin and eosin or other immunohistochemical stains were reviewed. All cases were classified according to the histologic criteria proposed by the International Lymphoma Study Group. Clinical data, including age, gender, and site of disease involvement, were reviewed. RESULTS: The Republic of Korea had lower rates of HD and follicle center lymphoma and higher rates of extranodal lymphoma, diffuse large B-cell lymphoma, and angiocentric lymphoma compared with Western countries. The most frequent subtypes of non-Hodgkin's lymphoma (NHL) were diffuse large B-cell lymphoma, extranodal marginal zone B-cell lymphoma, peripheral T-cell lymphoma, unspecified type, and angiocentric lymphoma, in decreasing order. Compared with a previous nationwide study, the rates for follicular lymphoma and NHL involving the stomach, orbit, and central nervous system were increased. The rate of T-cell NHL in the current study was much lower than that reported in a previous study for the Republic of Korea and was also lower than that reported for other Far East countries. For HD, the relative frequency of nodular sclerosis subtype was higher compared with that in the previous study, and lymphocyte predominance and lymphocyte depletion were lower. CONCLUSIONS: The occurrence rates for various subtypes of malignant lymphoma in the Republic of Korea are distinct from those in Western countries and similar in many ways to those in other countries in the Far East. Compared with other Far East countries, the Republic of Korea has a higher rate of extranodal lymphoma, rare adult T-cell lymphoma, and a relatively low rate of T-cell lymphomas. It appears that over time there have been changes in the relative rates for follicular lymphoma, subtypes of Hodgkin's disease, and gastric and orbital lymphoma. The authors attribute these changes primarily to refined criteria for diagnosing new clinicopathologic entities.

Adolescent↗

Mechanism of action of human P-glycoprotein ATPase activity. Photochemical cleavage during a catalytic transition state using orthovanadate reveals cross-talk between the two ATP sites.

Human P-glycoprotein (P-gp), an ATP-dependent efflux pump responsible for cross-resistance of human cancers to a variety of lipophilic compounds, is composed of two homologous halves, each containing six transmembrane domains and an ATP-binding/utilization domain. To determine whether each site can hydrolyze ATP simultaneously, we used an orthovanadate (Vi)-induced ADP-trapping technique (P-gp.MgADP.Vi). In analogy with other ATPases, a photochemical peptide bond cleavage reaction occurs within the Walker A nucleotide binding domain consensus sequence (GX4GK(T/S)) when the molecule is trapped with Vi in an inhibited catalytic transition state (P-gp.MgADP.Vi) and incubated in the presence of ultraviolet light. Upon reconstitution into proteoliposomes, histidine-tagged purified P-gp from baculovirus-infected insect cells had drug-stimulated ATPase activity. Reconstituted P-gp was incubated with either ATP or 8-azido-ATP in the presence or absence of Vi under ultraviolet (365 nm) light on ice for 60 min. The resultant products were separated by SDS-polyacrylamide gel electrophoresis and subjected to immunoblotting with seven different human P-gp-specific antibodies covering the entire length of the molecule. Little to no degradation of P-gp was observed in the absence of Vi. In the presence of Vi, products of approximately 28, 47, 94, and 110 kDa were obtained, consistent with predicted molecular weights from cleavage at either of the ATP sites but not both sites. An additional Vi-dependent cleavage site was detected at or near the trypsin site in the linker region of P-gp. These results suggest that both the amino- and carboxyl-terminal ATP sites can hydrolyze ATP. However, there is no evidence that ATP can be hydrolyzed simultaneously by both sites.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Delta subunit of rat liver mitochondrial ATP synthase: molecular description and novel insights into the nature of its association with the F1-moiety.

The F1 moiety of ATP synthase complexes consists of five subunit types in the stoichiometric ratio alpha 3, beta 3, gamma, delta epsilon. Of these, the delta subunit has received very little attention in the study of F1 preparations from eukaryotic cells. Although recently shown to associate tightly with the beta subunit [Pedersen, P. L., Hullihen, J., Bianchet, M., Amzel, L. M., and Lebowitz, M. S. (1995) J. Biol. Chem. 270, 1775-1784], the delta subunit is not resolved in the X-ray structure of either the rat liver or bovine heart enzyme. For these reasons, the novel studies reported here were designed both to provide a molecular description of the rat liver delta subunit and to gain insight into the nature of its interaction with F1. The rat liver delta subunit was cloned from a lambda gt11 library, sequenced, overexpressed in Escherichia coli (E. coli) in fusion with the maltose binding protein, and, after cleavage of the latter protein, purified to homogeneity. The purified delta subunit (MW = 14.7 kDa) was shown by circular dichroism spectroscopy to be highly structured and to exhibit about 25% sequence identity to the chloroplast and E. coli epsilon subunits, frequently regarded as homologues of higher eukaryotic delta subunits. Significantly, and in contrast to the chloroplast and E. coli epsilon subunits, which are readily removed from their parent F1 moieties after treatment respectively with ethanol and lauryldimethylamine oxide, the rat liver delta subunit remained tightly bound to F1 under these relatively mild conditions. For the above reasons, four types of experiments were carried out on rat liver F1 in order to (1) determine the accessibility of the delta subunit to both specific antibodies and to proteases, (2) establish the effect of nucleotides on this subunit's accessibility, (3) identify in cross-linking studies with disuccinimidyl glutarate this subunit's most reactive neighbor, and (4) determine whether this subunit can be dissociated from F1 by using ionic detergents while leaving the remaining complex intact. The data derived from this detailed set of studies (a) supports the view that the rat liver F1-delta subunit is in very close proximity to the gamma subunit near the bottom of the F1 molecule but does not penetrate deeply into the central core, (b) shows that within F1 the delta subunit's N-terminus is exposed while its C-terminus is masked, (c) indicates that access to the delta subunit is shielded in part by the alpha, beta, and gamma subunits and changes during the catalytic cycle of F1, and (d) implicates the delta subunit as important for the structural stability of the F1 unit. These novel findings on a higher eukaryotic F1-delta subunit are discussed in relationship to earlier studies on the related epsilon subunits from both chloroplasts and E. coli.

Amino Acid Sequence↗

Effects of glucose and glycerol on gamma-poly(glutamic acid) formation by Bacillus licheniformis ATCC 9945a.

Bacillus licheniformis ATCC 9945a is one of the bacterial strains that produce gamma-poly(glutamic acid) (gamma-PGA). The use of carbohydrate medium components for gamma-PGA production was explored. Cells were grown in shake flasks or in controlled pH fermentors using medium formulations that contain different carbon sources. During the cultivations, aliquots were removed to monitor cell growth, carbon utilization, polymer production, and polymer molecular weight. Glucose was a better carbon source than glycerol for cell growth. Furthermore, glucose was utilized at a faster rate than glycerol, citrate, or glutamate. However, by using mixtures of glucose and glycerol in medium formulations, the efficiency of gamma-PGA production increased. For example, by increasing the glycerol in medium formulations from 0 to 40 g/L, the gamma-PGA broth concentration after 96 h increased from 5.7 to 20.5 g/L. Considering that glycerol utilization was low for the glucose/glycerol mixtures studied, it was unclear as to the mechanism by which glycerol leads to enhanced product formation. Cell growth and concomitant gamma-PGA production (12 g/L) at pH 6.5 was possible using glucose as a carbon source if trace amounts (0.5 g/L each) of citrate and glutamate were present in the medium. We suggested that citrate and glutamate were useful in preventing salt precipitation from the medium. In addition, glutamate may be preferred relative to ammonium chloride as a nitrogen source. The conversion of glucose to gamma-PGA by the strain ATCC 9945a was believed to occur by glycolysis of glucose to acetyl-CoA and tricarboxylic acid (TCA) cycle intermediates that were then metabolized via the TCA cycle to form alpha-ketoglutarate, which is a direct glutamate precursor.

Bacillus↗

Blastic NK-cell lymphoma expressing terminal deoxynucleotidyl transferase with Homer-Wright type pseudorosettes formation.

AIMS: Rosette-forming malignant lymphoma is very rare. We report a blastic NK-cell lymphoma expressing terminal deoxynucleotidyl transferase (TdT) with formation of Homer-Wright type pseudorosettes. METHODS AND RESULTS: An 18-year-old boy presented with an enlarged inguinal lymph node. Histologically, the nodal architecture of the lymph node was diffusely effaced by small to medium sized monomorphic blastoid lymphoid cells which frequently formed Homer-Wright type pseudorosettes. Immunophenotyping of the tumour using immunohistochemistry and flow cytometry revealed LCA+, CD4+, CD56+, CD43+, TdT+, CD2-, cCD3-, CD8-, CD7-, CD34- and TIA-1-. DNA analysis revealed no gene rearrangement of TCR beta and gamma genes. In situ hybridization for EBER 1 & 2 was negative. No azurophilic granules were found in the Wright stain. Complete remission was achieved with six cycles of chemotherapy with the CHOP regimen. The disease recurred in the paranasal sinuses and bone marrow 2 years later. CONCLUSIONS: Immunophenotypic and genotypic similarities of the present case to those of TdT-negative blastic NK-cell lymphoma suggest that these diseases might be categorized as one entity irrespective of expression of TdT.

Adolescent↗

Angioimmunoblastic lymphoma (AILD-type T-cell lymphoma) with hyperplastic germinal centers.

Angioimmunoblastic T-cell lymphoma (or angioimmunoblastic lymphadenopathy with dysgammaglobulinemia [AILD]) was originally considered to be an abnormal immune reaction in which reactive follicles with germinal centers (GCs) are usually absent. When hyperplastic GCs are present along with an angioimmunoblastic reaction, the lesion has been interpreted as a benign hyperimmune reaction. We report seven patients with angioimmunoblastic T-cell lymphoma (AITL) who initially had hyperplastic GCs, shown to be malignant lymphoma by further studies and clinical follow-up. Clonal T-cell populations were observed in all specimens evaluated, and sequential biopsies showed histologic progression to typical AITL in two patients. Clinical presentation was characterized by generalized lymphadenopathy of acute onset, constitutional symptoms, hepatosplenomegaly, skin rash, and polyclonal hypergammaglobulinemia in five patients; regional adenopathy preceded generalized adenopathy in two patients. Five patients had rapid progression of disease, and three patients whose treatment was delayed due to inadequate evidence to diagnose lymphoma died of infection. The initial biopsy findings of each patient were similar and showed angioimmunoblastic proliferation, hyperplastic GCs with ill-defined borders, and interfollicular tingible-body macrophages. These GCs differed from occasional residual follicles of typical AITL in that the GCs were enlarged and hyperplasia of follicular dendritic cells was not seen. Diagnostic clear cells were not observed. Apoptotic bodies were markedly increased and bcl-2+ lymphocytes were sparse compared with typical AITL. Results of in situ hybridization for Epstein-Barr virus were positive in each case. We conclude that hyperplastic germinal centers with ill-defined borders and frequent interfollicular tingible-body macrophages occur in a histologic variant of AITL that is necessary to recognize for early diagnosis and treatment.

Adult↗