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Y H Ko

Publications and source records attributed to Y H Ko.

At least 73 records · Page 4Linked to original sources
PubMed1998

Hybrid verrucous squamous cell carcinoma of sinonasal tract: a case report.

Verrucous carcinoma is a variant of squamous cell carcinoma and should be distinguished from benign papilloma and well-differentiated nonverrucous squamous cell carcinoma. It is rare tumor of the sinonasal tract. Occasionally, conventional squamous cell carcinomatous components may be seen in verrucous carcinoma. This entity is called a hybrid verrucous squamous cell carcinoma. We report a case of hybrid verrucous squamous cell carcinoma occurring in the nasal cavity and paranasal sinus of a 67-year-old male. The removed mass shows the typical feature of verrucous carcinoma, but focally conventional squamous cell carcinomatous area is also noted. The treatment of this case follows verrucous carcinoma, but close follow up is mandatory because it may potentially spread to regional lymph nodes in contrast to pure form of verrucous carcinoma.

Aged↗
PubMed1997

Novel insights into the chemical mechanism of ATP synthase. Evidence that in the transition state the gamma-phosphate of ATP is near the conserved alanine within the P-loop of the beta-subunit.

The chemical mechanism by which the F1 moiety of ATP synthase hydrolyzes and synthesizes ATP remains unknown. For this reason, we have carried out studies with orthovanadate (Vi), a phosphate analog which has the potential of "locking" an ATPase, in its transition state by forming a MgADP.Vi complex, and also the potential, in a photochemical reaction resulting in peptide bond cleavage, of identifying an amino acid very near the gamma-phosphate of ATP. Upon incubating purified rat liver F1 with MgADP and Vi for 2 h to promote formation of a MgADP.Vi-F1 complex, the ATPase activity of the enzyme was markedly inhibited in a reversible manner. When the resultant complex was formed in the presence of ultraviolet light inhibition could not be reversed, and SDS-polyacrylamide gel electrophoresis revealed, in addition to the five known subunit bands characteristic of F1 (i.e. alpha, beta, gamma, delta, and epsilon), two new electrophoretic species of 17 and 34 kDa. Western blot and N-terminal sequencing analyses identified both bands as arising from the beta subunit with the site of peptide bond cleavage occurring at alanine 158, a conserved residue within F1-ATPases and the third residue within the nucleotide binding consensus GX4GK(T/S) (P-loop). Quantification of the amount of ADP bound within the MgADP. Vi-F1 complex revealed about 1.0 mol/mol F1, while quantification of the peptide cleavage products revealed that no more than one beta subunit had been cleaved. Consistent with the cleavage reaction involving oxidation of the methyl group of alanine was the finding that [3H] from NaB[3H]4 incorporates into MgADP.Vi-F1 complex following treatment with ultraviolet light. These novel findings provide information about the transition state involved in the hydrolysis of ATP by a single beta subunit within F1-ATPases and implicate alanine 158 as residing very near the gamma-phosphate of ATP during catalysis. When considered with earlier studies on myosin and adenylate kinase, these studies also implicate a special role for the third residue within the GX4GK(T/S) sequence of many other nucleotide-binding proteins.

Adenosine Diphosphate↗
PubMed1997

Cystic fibrosis transmembrane conductance regulator: the first nucleotide binding fold targets the membrane with retention of its ATP binding function.

Most cases of cystic fibrosis are caused by a single deletion mutation (deltaF508) within the first nucleotide binding fold (NBF1) of the CFTR protein (cystic fibrosis transmembrane conductance regulator). NBF1 is classically defined as amino acid residues phenylalanine 433 through serine 589, encoded by exons 10-12, and only part of exon 9, of the CFTR gene. This assignment is based on sequence homology of this region of the CFTR protein with that of other nucleotide binding proteins. Here, we report that when the complete modular unit encoded precisely by exons 9-12 is expressed in Escherichia coli as glycine 404 through serine 589, i.e., as [G404-N432]NBF1 or as deltaF508[G404-N432]NBF1, the resultant proteins target the cytoplasmic membrane. Significantly, [G404-N432]NBF1 is readily labeled from the outside of intact E. coli spheroplasts with the water soluble, membrane impermeable probe Biotin-X-NHS, sulfosuccinimidyl-6-(biotinamido)-hexanoate. Similar findings were observed with the disease causing mutant deltaF508[G404-N432]NBF1. Three different control experiments which involved (1) assays for known cytosolic E. coli enzymes, (2) immuno-gold electron microscopy with antibody having an epitope for the biotin moiety, and (3) tests for biotinylation of the cytosolic component, Enzyme 1 of the glucose phosphotransferase system, demonstrated that the spheroplasts used in this study are neither leaky nor permeable to Biotin-X-NHS. In addition, membrane-associated [G404-N432]NBF1, upon solubilization with Triton X-100, was found to bind to an ATP-agarose column and be released therefrom by elution with ATP, emphasizing retention of a native-like structure. In sharp contrast, NBF1 localizes to the cytosol when the [G404-N432]-N-terminal region is replaced with the maltose binding protein. The novel findings reported here implicate a role of the N-terminal region of NBF1 in its subcellular localization and are directly relevant to our understanding of the membrane structure, function, and trafficking of CFTR.

ATP-Binding Cassette Transporters↗
PubMed1997

Cystic fibrosis, lung infections, and a human tracheal antimicrobial peptide (hTAP).

In order to understand how lungs of healthy people, unlike those of cystic fibrosis (CF) patients, are protected against bacterial infections such as Pseudomonas aeruginosa, the following three key findings were made. First, P. aeruginosa do not multiply when planted onto tracheal epithelial cells from healthy humans but do so profusely on cells from deltaF508 CF patients. Second, some bacteria bind, and gain entrance into CF cells, even at a physiological salt concentration (104 mM). Third, human tracheal epithelial cells express an approximately 4 kDa peptide (hTAP), which is known in its bovine form to exhibit bactericidal action against P. aeruginosa. A model is proposed depicting both how normal epithelial cells, in a first-line self defense mechanism, may be protected against bacterial infection and how this mechanism may fail during the initial stages of CF.

Amino Acid Sequence↗
PubMed1997

Frontiers in research on cystic fibrosis: understanding its molecular and chemical basis and relationship to the pathogenesis of the disease.

In recent years a new family of transport proteins called ABC transporters has emerged. One member of this novel family, called CFTR (cystic fibrosis transmembrane conductance regulator), has received special attention because of its association with the disease cystic fibrosis (CF). This is an inherited disorder affecting about 1 in 2000 Caucasians by impairing epithelial ion transport, particularly that of chloride. Death may occur in severe cases because of chronic lung infections, especially by Pseudomonas aeruginosa, which cause a slow decline in pulmonary function. The prospects of ameliorating the symptoms of CF and even curing the disease were greatly heightened in 1989 following the cloning of the CFTR gene and the discovery that the mutation (deltaF508), which causes most cases of CF, is localized within a putative ATP binding/ATP hydrolysis domain. The purpose of this introductory review in this minireview series is to summarize what we and others have learned during the past eight years about the structure and function of the first nucleotide binding domain (NBF1 or NBD1) of the CFTR protein and the effect thereon of disease-causing mutations. The relationship of these new findings to the pathogenesis of CF is also discussed.

Cystic Fibrosis↗
PubMed1997

Modeling of nucleotide binding domains of ABC transporter proteins based on a F1-ATPase/recA topology: structural model of the nucleotide binding domains of the cystic fibrosis transmembrane conductance regulator (CFTR).

Members of the ABC transporter superfamily contain two nucleotide binding domains. To date, the three dimensional structure of no member of this super-family has been elucidated. To gain structural insight, the known structures of several other nucleotides binding proteins can be used as a framework for modeling these domains. We have modeled both nucleotide binding domains of the protein CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) using the two similar domains of mitochondrial F1-ATPase. The models obtained, provide useful insights into the putative functions of these domains and their possible interaction as well as a rationale for the basis of Cystic Fibrosis causing mutations. First, the two nucleotide binding domains (folds) of CFTR are each predicted to span a 240-250 amino acid sequence rather than the 150-160 amino acid sequence originally proposed. Second, the first nucleotide binding fold, is predicted to catalyze significant rates of ATP hydrolysis as a catalytic base (E504) resides near the y phosphate of ATP. This prediction has been verified experimentally [Ko, Y.H., and Pedersen, P.L. (1995) J. Biol. Chem. 268, 24330-24338], providing support for the model. In contrast, the second nucleotide binding fold is predicted at best to be a weak ATPase as the glutamic acid residue is replaced with a glutamine. Third, F508, which when deleted causes approximately 70% of all cases of cystic fibrosis, is predicted to lie in a cleft near the nucleotide binding pocket. All other disease causing mutations within the two nucleotide binding domains of CFTR either reside near the Walker A and Walker B consensus motifs in the heart of the nucleotide binding pocket, or in the C motif which lies outside but near the nucleotide binding pocket. Finally, the two nucleotide binding domains of CFTR are predicted to interact, and in one of the two predicted orientations, F508 resides near the interface. This is the first report where both nucleotide binding domains of an ABC transporter and their putative domain-domain interactions have been modeled in three dimensions. The methods and the template used in this work can be used to analyze the structures and function of the nucleotide binding domains of all other members of the ABC transporter super-family.

ATP-Binding Cassette Transporters↗
PubMed1997

Intravascular lymphomatosis: a clinicopathological study of two cases presenting as an interstitial lung disease.

AIMS: Intravascular lymphomatosis is an uncommon type of non-Hodgkin's lymphoma characterized by intravascular proliferation of neoplastic lymphoid cells. Although the tumour is basically a systemic disease, eventually involving multiple organs, primary presentation in the lung is rare. METHODS AND RESULTS: We describe the clinicopathological features of two patients with intravascular lymphomatosis presenting in the lung. One patient complained of fever, headache and chest pain; the other, of dyspnoea on exertion and headache. Both patients showed reticulonodular density on chest radiography and decreased diffusion capacity. Lung biopsy showed features characteristic of intravascular lymphomatosis. Malignant lymphoid cells were CD30 positive T-cells of anaplastic large cell type in one patient and B-cells of large cell type in the other. There was a poor response to chemotherapy and both patients died of the disease within 3 months of diagnosis. CONCLUSIONS: These cases and 10 previous reports illustrate the need to include intravascular lymphomatosis in the differential diagnosis of interstitial lung disease.

Aged↗
PubMed1997

Differential diagnosis of cervical lymphadenopathy: usefulness of color Doppler sonography.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of color Doppler sonography in differentiating benign from malignant cervical lymphadenopathy. MATERIALS AND METHODS: We used color Doppler sonography to evaluate 117 lymph nodes in 105 patients. The patients were pathologically and clinically confirmed to have benign reactive lymphadenitis (n = 28), tuberculosis (n = 17), lymphoma (n = 14), and metastasis (n = 46). The patterns of hilar vascularity, central nodal vascularity, and peripheral vascularity were assessed. The highest resistive index and pulsatility index in 116 lymph nodes were measured from spectral waveforms. Histologic findings of nodal vessels were analyzed in 14 nodes and compared with findings on color Doppler sonograms. RESULTS: Thirty-two (94%) of 34 nodes with benign reactive disease showed normal patterns of nodal vascularity; central hilar vascularity, radial symmetric central vascularity, and no peripheral vascularity. At least one of six abnormal patterns of vascularity (eccentric or absent hilar vascularity; deformed radial, aberrant multifocal, or absent central vascularity; and peripheral vascularity) was observed in 98% (65/66) of nodes with malignant disease and in all tuberculous nodes. We established cutoff values of 0.8 for the resistive index and 1.5 for the pulsatility index that were 100% specific for malignancy. However, sensitivities for these cutoff values were 47% and 55%, respectively. Also, histologic examinations showed that most flow signals in nodes with malignant disease represented arterioles or veins in the septa between tumor nests or near the capsule. CONCLUSION: Unlike nodes with benign reactive disease, 98% of nodes with malignant disease and 100% of tuberculous nodes showed abnormal patterns of nodal vascularity. Also, high values for the resistive and pulsatility indexes were highly specific for malignant lymphadenopathy. Color Doppler sonography combined with analysis of spectral waveforms was useful in differentiating benign from malignant cervical lymphadenopathy.

Adolescent↗
PubMed1997

Lysophosphatidic acid and platelet-derived growth factor synergistically stimulate growth of cultured rat mesangial cells.

Lysophosphatidic acid (LPA) is a structurally simple, platelet-derived phospholipid, capable of eliciting a variety of physiological responses. We have demonstrated previously that LPA elicited a marked contractile response in rat mesangial cells (Inoue CN, Forster HG, Epstein M. Circ Res 77:888-896, 1995). In the present study, we examined the potential of this vasoactive substance to induce mesangial cell proliferation. Serum-starved quiescent rat mesangial cells were incubated with either LPA or in combination with platelet-derived growth factor (PDGF). DNA synthesis was assessed by [3H]thymidine incorporation after 24 hr, and cell numbers were determined at 0, 4, and 7 days. LPA- (1 nM-30 microM) stimulated mesangial cell DNA synthesis in a dose-dependent manner. The DNA synthesis stimulated by PDGF (1-100 ng/ml) was characterized by a bell-shaped response curve with a maximum at 40 ng/ml PDGF. The ability of LPA (30 microM) to synergize PDGF was observed over the entire range of PDGF concentrations (1-100 ng/ml). Under optimal concentrations of LPA/PDGF (30 microM40 ng/ml, respectively), mesangial cells displayed a 67-fold increase in [3H]thymidine incorporation, and a 1.9-fold (Day 4) and 2.5-fold (Day 7) increase in cell number as compared with that of quiescent mesangial cells. With an in vitro assay with myelin basic protein as the substrate, both LPA and PDGF induced stimulation of mitogen-activated protein (MAP) kinase activity. In addition, LPA augmented PDGF-induced increase in MAP kinase activity. In summary, these results demonstrate that LPA is mitogenic alone and also acts synergistically in combination with PDGF to promote mesangial cell proliferation. We postulate that these actions of LPA have the potential to play a crucial role in the mitogenic response of mesangial cells seen in a wide array of inflammatory and thrombotic glomerular disorders.

Animals↗
PubMed1997

Cleaved variant of plasmacytoma with myelomonocytic differentiation--immunohistochemical and ultrastructural studies.

Although plasma cells are terminally differentiated B cells, neoplastic plasma cells frequently express not only pre-B cell antigen, but also megakaryocytic, myelomonocytic, or erythroid markers. Since morphologic diagnosis of plasmacytoma is based on the recognition of neoplastic cells closely resembling normal plasma cells, unusual morphologic variants of neoplastic cells associated with these aberrant immunohistochemical features frequently cause diagnostic difficulty. The authors report a case of plasmacytoma with cleaved nuclei and myelomonocytic features occurring in the clavicle. The tumor was composed of immature plasma cells showing irregular, cleaved, and multilobated nuclei and abundant cytoplasm with prominent eosinophilic granules. A few tumor cells showing recognizable plasmacytic differentiation were admixed within the tumor. Immunohistochemically, the tumor cells expressed CD45RB, CD68, lysozyme, myeloperoxidase and kappa light chain with focal positivity for lambda chain. Ultrastructurally, the tumor cells contained numerous membrane bound electron dense lysosomal granules, some of them resembling Auer rods, as well as rough endoplasmic reticula arranged in lamellated stacks. Small biopsied nasal mucosal tissue in same patient revealed well differentiated plasmacytoma composed of tumor cells showing round, eccentric nuclei devoid of marked nuclear cleavage and cytoplasmic granularity. Immunohistochemically, these cells were kappa(+), lambda(-), myeloperoxidase(-), lysozyme(-) and CD68(-).

Adult↗
PubMed1997

Kikuchi disease: CT and MR findings.

Two cases of Kikuchi disease showed variable nodal enhancing features, including homogeneous enhancement and focal or extensive nodal necrosis on contrast-enhanced CT scans. At MR imaging, the area of central necrosis was isointense or hypointense on T1-weighted images and had a lower signal than nonnecrotic areas on T2-weighted images. The CT appearance of Kikuchi disease can be variable and can mimic not only lymphoma but various nodal diseases with nodal necrosis, including metastasis and tuberculosis.

Adult↗
PubMed1996

Long Y-associated (GATA)n alleles were observed in a few ethnic groups in Asia.

A Y-associated polymorphic locus, DYS19, was analyzed in a few ethnic groups in Asia and compared with that in Caucasians and Negroes. The locus contains 4-nucleotide repeats, (GATA)n, and the length of the repeated segments can be determined by the polymerase chain reaction (PCR). The predominant allele was 202 bp followed by 198 bp in all the 3 Asian populations examined. Long repeats that were rare in other populations were found more frequently in these Asian populations.

Alleles↗
PubMed1996

Atypical Fabry's disease. An oligosymptomatic variant.

Fabry's disease is a rare, inherited, X-linked metabolic storage disease with ceramide hexoside due to alpha-galactosidase A deficiency. Patients with typical Fabry's disease usually present with several clinical manifestations of corneal dystrophy, neurologic abnormalities, cardiovascular disease, heavy proteinuria, and characteristic cutaneous angiokeratoma. However, atypical Fabry's disease with oligosymptomatic phenotype presents with symptoms restricted solely to cardiocytes or kidney and might be diagnosed by chance during a routine endomyocardial or renal biopsy examination. In this article, we report a case of Fabry's disease incidentally diagnosed in a 34-year-old man who presented with intermittent trace or 1(+) proteinuria only. This patient had no history of renal disease in any other family member. A renal biopsy to evaluate trace proteinuria revealed histologic and ultrastructural findings compatible with Fabry's disease. Subsequent to the renal biopsy, a skin biopsy on a few initially unrecognized, scattered, dark-pinkish scrotal papules showed typical angiokeratoma. A biochemical enzymatic assay of alpha-galactosidase in urine and plasma revealed a markedly decreased enzyme level in the hemizygous range.

Adult↗
PubMed1996

Detection of EBER nuclear RNA in T-cell lymphomas involving the skin--an in situ hybridization study.

To examine the relationship of Epstein-Barr virus (EBV) to cutaneous T-cell lymphoma (CTCL), a retrospective study was performed using formalin-fixed paraffin-embedded skin biopsies from 12 patients with cutaneous T-cell lymphoma. All cases were immunophenotyped with a panel of monoclonal antibodies including CD45RO, CD43, MB-2, CD20, and CD68. In situ hybridization studies to detect the EBV genome were performed, using the EBV-RNA probes for the early RNAs of EBV, namely EBER and BHLF. Among the 12 patients, six had primary CTCL, and six had secondary CTCL. The nasal cavity was the most frequent extracutaneous primary site. Immunophenotypically, all of the cases were of the T-cell lineage. In situ hybridization demonstrated a diffuse strong positive reaction for EBV transcripts (EBER) nuclear RNA in five out of 12 cases (41.7%) and a negative reaction for BHLF nuclear RNA probe in all the cases studied. Angiocentric lymphomas were positive in three out of the five cases (60%) studied. Secondary CTCL had a higher correlation with EBV than did primary CTCL, especially primary nasal T-cell lymphoma with subsequent cutaneous involvement. The EBV genome in lymphoma cells existed in a latently infected form but not in an actively replicating form. Three out of the five EBV-positive patients died, 8 months to 4 years after diagnosis. EBV infection alone in the lymphoma does not seem to affect the prognosis of CTCL patients significantly.

Adolescent↗
PubMed1995

The first nucleotide binding fold of the cystic fibrosis transmembrane conductance regulator can function as an active ATPase.

Cystic fibrosis is caused by mutations in the cell membrane protein called CFTR (cystic fibrosis transmembrane conductance regulator) which functions as a regulated Cl- channel. Although it is known that CFTR contains two nucleotide domains, both of which exhibit the capacity to bind ATP, it has not been demonstrated directly whether one or both domains can function as an active ATPase. To address this question, we have studied the first CFTR nucleotide binding fold (NBF1) in fusion with the maltose-binding protein (MBP), which both stabilizes NBF1 and enhances its solubility. Three different ATPase assays conducted on MBP-NBF1 clearly demonstrate its capacity to catalyze the hydrolysis of ATP. Significantly, the mutations K464H and K464L in the Walker A consensus motif of NBF1 markedly impair its catalytic capacity. MBP alone exhibits no ATPase activity and MBP-NBF1 fails to catalyze the release of phosphate from AMP or ADP. The Vmax of ATP hydrolysis (approximately 30 nmol/min/mg of protein) is significant and is markedly inhibited by azide and by the ATP analogs 2'-(3')-O-(2,4,6-trinitrophenyl)-adenosine-5'-triphosphate and adenosine 5'-(beta, gamma-imido)triphosphate. As inherited mutations within NBF1 account for most cases of cystic fibrosis, results reported here are fundamental to our understanding of the molecular basis of the disease.

Adenosine Triphosphatases↗
PubMed1995

Systemic lupus erythematosus with obstructive uropathy. Case report and review.

We report a case of patient with documented SLE who displayed dysuria, gastrointestinal (GI) symptoms and renal insufficiency associated with the unusual occurrence of bilateral hydroureteronephrosis due to urterovesical junction stricture (obstructive uropathy). Pathologic investigations disclosed chronic interstitial cystitis (IC) with evidence of focal immune complex deposition in the blood vessel walls of the bladder. The GI symptoms and dysuria regressed with initial therapy for SLE with steroids. However, the persistent obstructive uropathy (OU) and renal insufficiency required bilateral nephrostomy followed by steroids plus intravenous pulse injection of cyclophosphamide. The obstructive uropathy was relieved even after removing the nephrostomy tube and renal function remained stable. Including this case, nineteen SLE patients associated with clinical and radiographic findings of OU were found in the world literature and reviewed to find any consistent pattern of clinical features. Most of the patients with OU in SLE were female (mean age, 31.7 yr) and orientals (63%), and had interstitial cystitis (89%) as a common underlying cause with concomitant involvement of the GI tract (89%) and WHO class IV or V advanced glomerulonephritis (67%). Despite the remarkable response (68%) to steroids in majority of OU patients associated with SLE, certain patients still required surgical correction (32%) and some even died (32%). OU, potentially reversible, was not an exception in patients with SLE, which might be overshadowed by other major organ involvement of SLE.

Adolescent↗
PubMed1995

Population genetic study of selected tetranucleotide repeat DNA polymorphisms on chromosomes Y and 12.

Microsatellite polymorphisms of 75 unrelated Taiwanese males were analyzed for (GATA) repeats in DYS19 on chromosome Y and tetranucleotide simple repeats in D12S67 on chromosome 12. A simple nonisotopic technique based on polymerase chain reaction electrophoresis on native polyacrylamide gels followed by silver staining was used. In the 75 unrelated males, four alleles on DYS19 and five alleles on D12S67 were detected. Different allele frequencies, heterozygosity rates and information on the nature of the repeat loci were determined in these unrelated individuals. The resulting polymorphisms are of great assistance in ethnologic studies, forensic investigation and deficiency cases in paternity testing.

Base Sequence↗