Esophageal aspergillosis in a patient with acute leukemia.
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Aspergillosis↗
Biomedical subjects
D W Kim
Publications and source records attributed to D W Kim.
Mouse fibroblasts defective in thrombin mitogenesis possess functional proteolytically activated receptor for thrombin: requirement for a second signaling pathway.
Thrombin mitogenesis in fibroblasts requires two distinguishable subsets of signals; one generated by proteolytic cleavage, the other by high-affinity cell surface binding. Characterizing two closely related mouse embryo (ME) cell lines with high numbers of thrombin binding sites, we found that one line, B11-A, responds mitogenically to thrombin, epidermal growth factor (EGF), and serum, whereas the B11-B cell line is responsive to EGF and serum, but not to thrombin. The B11-B defect responsible for loss of thrombin responsiveness is not due to differences in the number of high-affinity binding sites, the affinity of thrombin binding to these sites, or to differences in cell surface expression of proteolytically activated receptors for thrombin (PART). The defect is also not associated with an inability of thrombin to activate PART since thrombin stimulates the cleavage-dependent induction of the proto-oncogene c-fos in both B11-A and B11-B cells. Various combinations of thrombin, synthetic thrombin receptor peptide, TRP-14 (SFFLRNPGENTFEL), platelet-derived growth factor (PDGF), and phorbol 12-myristate 13-acetate (PMA) were used to better define the defect in thrombin-mediated mitogenesis in B11-B cells. Direct activation of protein kinase C with PMA in combination with thrombin did not overcome B11-B nonresponsiveness. However, mitogenic responsiveness was regained in B11-B cells by simultaneous addition of PDGF and either thrombin or TRP-14. Therefore, the B11-B defect may involve a set of signals initiated by nonproteolytic thrombin interactions distinct from those initiated by PART, but related to the downstream signals initiated by the tyrosine kinase-associated growth factors, EGF and PDGF.
Amino Acid Sequence↗
Thrombin stimulates fibroblast-mediated collagen lattice contraction by its proteolytically activated receptor.
Fibroblast contraction is proposed to play an important role in tissue contraction during events such as wound healing. Thrombin has been implicated to promote force generation in fibroblasts; however, its extracellular mode of action is unclear. The purpose of this study was to determine the role thrombin and the activation of its receptor plays in promoting the contraction of human fibroblasts in an in vitro collagen lattice contraction assay. Human alpha-thrombin promoted fibroblast contraction in a dose-dependent manner with maximal activity at 0.2 nM. In contrast, both hirudin-alpha-thrombin and D-phenylalanyl-L-propyl-L-arginyl chloromethyl ketone-alpha-thrombin, which lack enzymatic activity, failed to elicit fibroblast contraction. Thus, the enzymatic activity of thrombin appears to be necessary for promotion of fibroblast contraction. Northern analysis confirmed that these human fibroblasts expressed mRNA for the human alpha-thrombin receptor. Moreover, the synthetic peptide (SFLLRNPND-KYEPF) representing the "tethered ligand" portion of the activated alpha-thrombin receptor promoted fibroblast contraction, while a control isomer peptide, in which the first two amino acids were reversed, failed to elicit this response. These findings indicate that alpha-thrombin promotes the contraction of adult human fibroblasts and that cleavage of the human alpha-thrombin receptor is sufficient to produce this response.
Amino Acid Chloromethyl Ketones↗
Replacement of active-site lysine-239 of thermostable aspartate aminotransferase by S-(2-aminoethyl)cysteine: properties of the mutant enzyme.
The active-site lysine residue of thermostable aspartate aminotransferase, Lys-239, to which the cofactor, pyridoxal 5'-phosphate (PLP), is bound, has been converted to Cys by site-directed mutagenesis. The thiol group of Cys-239 was chemically aminoethylated with ethylenimine. Amino acid analysis of the modified enzyme showed that it contained about 1 mol of S-(2-aminoethyl)cysteine (SAEC) per mol subunit. The activity of the mutant enzyme (K239SAEC) was about 14% of that of the wild-type enzyme. No significant difference in thermostability was found between the wild-type and K239SAEC enzymes. The UV-visible spectrum of K239SAEC showed a peak (lambda max 380 nm), due to absorption by the cofactor, at a 20 nm longer wavelength than that of the wild-type enzyme. The circular dichroism band due to the bound cofactor of K239SAEC also shifted toward a 20 nm longer wavelength. We determined kinetic parameters (rate constants, kmax, and dissociation constants, Kd, for the substrates) for each half transamination catalyzed by the wild-type and K239SAEC mutant enzymes by the stopped-flow method. The kmax values for the mutant enzyme reactions were 2.6-24 times lower than those for the wild-type enzyme ones. The two enzymes showed similar Kd values for the same substrates except glutamate; the mutant enzyme showed higher affinity for glutamate than the wild-type enzyme.
Aspartate Aminotransferases↗
Studies of the active-site lysyl residue of thermostable aspartate aminotransferase: combination of site-directed mutagenesis and chemical modification.
The gene technological substitution of the cysteinyl residue for the pyridoxal 5'-phosphate-binding lysyl residue (K239) of thermostable aspartate aminotransferase of Bacillus sp. YM-2 led to loss of the activity of the enzyme, which inherently contains no cysteinyl residues. The cysteinyl residue of the mutant enzyme was modified to lysine sulfur analog residues, S-(beta-aminoethyl)cysteine (SAEC), S-(beta-aminopropyl)cysteine (SAPC), and S-(beta-aminoethylthio)cysteine (SATC) with 2-bromoethylamine, 3-bromopropylamine, and 2-mercaptoethylamine, respectively. The modified mutant enzymes showed absorbance at 379 (K239SAEC), 400 (K239SAPC), and 365 nm (K239SATC), whereas the spectrum of the wild-type enzyme exhibited an absorption maximum at 360 nm derived from the internal Schiff base at pH 8.0. The absorption of the modified mutant enzymes at these wavelengths disappeared on reduction with NaCNBH3. This suggests that omega-amino groups of the introduced lysine sulfur analog residue form an internal Schiff base with pyridoxal 5'-phosphate. The modified mutant enzymes showed kcat values of 19.6-0.065% of that of the wild-type enzyme in the overall reaction, and were 10(6)-10(8) times more active than the K239C mutant enzyme. These results suggest that omega-amino groups of the introduced residues of the modified mutant enzyme serve as a catalytic base, and catalysis of the enzyme was affected by the length of the functional side-chain.
Aspartate Aminotransferases↗
Familial clustering of hepatitis B and C viruses in Korea.
In order to evaluate the familial clustering of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections and to elucidate the possible routes of HCV transmission among Korean adults with chronic liver disease, 137 household contacts of 51 chronic carriers of HBsAg and 111 household contacts of 38 controls, and 181 household contacts of 96 anti-HCV positives and 102 household contacts of 76 anti-HCV negatives were tested from July 1990 to March 1994. Of 71 non-vaccinated household contacts of HBsAg carriers, 10 gave positive result for HBsAg(14.1%), but none of the household contacts of the controls were positive for HBsAg(p < 0.05). Familial clustering of HBV infection was found, when the offspring of carriers and controls were compared. A significantly higher percentage of the offspring of carriers were positive for HBV infection(54.6% vs 15.4%, p < 0.05) with OR of 6.6(95% Cl; 1.3-34.5). No evidence of familial clustering of HCV infection was found with 2.2%(4/181) anti-HCV positivity among the household contacts of index cases, similar to 1.0%(1/102) among those of controls. History of acute hepatitis(OR 3.2), transfusion(OR 3.2), and acupuncture(OR 2.5) were associated with an increased risk of HCV infection. In conclusion, HBV has strong familial clustering whereas HCV does not in Korea.
Acupuncture Therapy↗
Trans-suppression of gene expression by hepatitis C viral core protein.
We have demonstrated that the truncated hepatitis C (HCV) core protein with its C-terminal hydrophobic domains deleted is translocated to the nucleus of transfected cells (22). In this study, intact and truncated core proteins of HCV were transiently expressed in a human hepatoblastoma cell line, HepG2, and their effects on the expression of the chloramphenycol acethyl transferase (CAT) gene driven by viral and cellular promoters were examined. The intact core protein of 22 kDa which is localized in the cytoplasm of the transfected cells suppressed the expression in all of the promoters tested. They were promoters of the SV40 early region, the c-fos oncogene, the retinoblastoma susceptibility gene, the beta-interferon gene and the beta-actin gene. In contrast, the truncated HCV core protein located in the nucleus did not show such a suppressive activity. The HCV core protein appears to function not only as a viral structural protein but as a regulator of gene expression and it might act as a suppressive factor for the cellular gene expression.
Antibodies, Viral↗
Lipid composition of the stratum corneum of the sole in patients with leprosy.
Several reports support the view that changes of composition of the stratum corneum (SC) lipids may be the cause of impaired barrier function which, in turn, gives rise to xerosis and ichthyotic skin in leprosy. Many reports about abnormalities of serum lipids and cutaneous manifestations, such as xerosis and ichthyotic changes in leprosy, led us to the idea that the composition of SC lipids in patients with leprosy may be different from that in normal subjects. However, the many studies done in the past do not sufficiently account for this. To investigate the composition of SC lipids in patients with leprosy, thin-layer chromatography (TLC) was undertaken. Extraction of the SC lipids with a methanolchloroform-H2O mixture (4:2:1.6, v/v/v, Bligh-Dyer solvent) was carried out after shaving of the SC from the sole. TLC was performed and the composition of lipids was quantitated by photodensitometry. Our study revealed that the composition of SC lipids in the anesthetic lesions of leprosy patients was higher in cholesterol sulfate and triglycerides and lower in sphingolipids and cholesterol esters than that of normal subjects.
Aged↗
Intercellular adhesion molecule expression in rejecting murine heart-lung allografts.
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Animals↗
Allogeneic bone marrow transplantation in Korea: 1983-92.
Between March 1983 and December 1992, we performed 178 allogeneic BMTs for patients with hematopoietic stem cell disorders: 48 acute myelogenous leukemia (AML), 27 acute lymphoblastic leukemia (ALL), 40 chronic myelogenous leukemia (CML), 55 severe aplastic anemia (SAA), 6 myelodysplastic syndrome (MDS), 1 non-Hodgkin's lymphoma and 1 hybrid leukemia. Twenty-five of 48 AML are in disease-free survival (DFS). Fifteen of 27 ALL are in unmaintained remission. Twenty-four of 40 CML are in DFS. Forty-four out of 55 SAA patients are alive and well. Comparing the survival between standard (< or = CR1: 21 of 31 (68%)) and high risk (> or = CR2: 4 of 17 (24%)) AML, our data suggest that the preparative regimen for high risk AML was not potent enough to eradicate the residual disease in advanced AML. Although our cases are limited and the follow-up period is short, the result of ALL (overall: 56%, standard risk (adult < or = CR1, children < or = CR2: 10 of 14 (71%) and high risk (adult > or = CR2, children > CR2): 5 of 13 (38%)) and CML (overall: 60%; CP: 19 of 27 (70%), AP or BC: 5 of 13 (38%)) are promising. The probability of 5 year survival of SAA was 80 +/- 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
An efficient expression vector for stable expression in human liver cells.
The expression of the bacterial neomycin resistance (NmR)-encoding gene was examined under control of the promoter region of the gene encoding the human polypeptide chain elongation factor 1 alpha (EF-1 alpha). In a human liver cell line, HepG2, the plasmid pEF321-neo directed higher expression of the bacterial neo gene than the NmR gene expression vectors using other promoters, like the SV40 early region or thymidine kinase of Herpes simplex virus and SV40 early region promoter linked to human T-cell leukemia virus-1 enhancer sequences.
Cell Line↗
Hallervorden-Spatz syndrome in two siblings diagnosed by the clinical features and magnetic resonance imaging (MRI).
Hallervorden-Spatz syndrome (HSS) is a heredodegenerative disorder characterized by both progressive pyramidal and extrapyramidal signs, dysarthric speech, and mental deterioration. No diagnostic biochemical test is yet available, and diagnosis of HSS can be confirmed only at autopsy by the characteristic neuropathology including abnormal iron storage, disordered myelination, and loss of brain substance. We present two siblings with clinical features consistent with HSS, in whom magnetic resonance imaging (MRI) demonstrated the deposition of iron in the globus pallidus and the substantia nigra thus allowing an antemortem diagnosis of HSS.
Child↗
Degradation and intracellular accumulation of a residualizing hyaluronan derivative by liver endothelial cells.
The release and intracellular accumulation of 125I-hyaluronan degradation products was studied in cultured liver endothelial cells with hyaluronan oligosaccharides (relative molecular mass = approximately 44,000) uniquely modified and radiolabeled at the terminal reducing sugar. Two methods were combined to measure 125I-hyaluronan degradation by liver endothelial cells. (a) Cetylpyridinium chloride precipitation of hyaluronan oligosaccharides was used as a rapid, convenient assay to monitor the appearance of hyaluronan degradation products. Hyaluronan oligosaccharides less than 54 to 60 monosaccharides in length were not precipitated with cetylpyridinium chloride and thus were assessed as degraded. (b) Gel filtration chromatography was used to estimate the size range of oligosaccharides produced by liver endothelial cells. After internalization of 125I-hyaluronan, liver endothelial cells released radioactive degradation products into the culture media after a lag period of 2.5 to 3.0 hr. The intracellular accumulation of degraded 125I-hyaluronan was linear for at least 2 hr even though no degradation products were released. The long lag before release of degraded 125I-hyaluronan is likely caused by the modified chemical structure at the reducing end of the hyaluronan derivative; the derivative acts like a residualizing label. After this lag the release of degraded 125I-hyaluronan proceeded linearly for up to 12 hr. The extracellular 125I-hyaluronan degradation products eluted with a distribution coefficient of 1.3 on a gel filtration column. The major intracellular 125I-labeled degradation product showed the same retardation (distribution coefficient = 1.3). This retention may be caused by the hydrophobic aromatic and alkyl modifications to the former reducing sugar, also characteristics of a residualizing label. In addition, at least two larger minor intermediates were observed intracellularly. The rate of intracellular 125I-hyaluronan degradation was dependent on hyaluronan concentration and reached a maximal rate (159 molecules/cell/sec) at 2 x 10(-7) mol/L. This was about half the maximal rate of endocytosis (285 molecules/cell/sec) at a hyaluronan concentration of 1.3 x 10(-7) mol/L. The apparent ligand concentration that gives half-maximal responses for endocytosis and intracellular degradation was 0.6 x 10(-7) and 1.0 x 10(-7) mol/L, respectively.
Animals↗
Use of an epitope-tagged cDNA library to isolate cDNAs encoding proteins with nuclear localization potential.
We have combined epitope tagging with an expression cDNA library in order to isolate cDNAs encoding nuclear proteins. This system allows us to detect proteins expressed from the cDNA library by using antibodies against the epitope tag. As a tag, we used the 85-aa N-terminal peptide of the SV40 T antigen which lacks the nuclear localization signal (NLS). A strong expression vector, pEF204 [Kim et al., Gene 91 (1990) 217-223], was modified into an epitope-tagging vector, pTkim, by putting the tag-coding region and a cDNA cloning site immediately after its promoter. From cDNA libraries constructed using pTkim, we isolated eight cDNA clones whose tagged proteins were localized within the nuclei. From partial sequence analysis, two cDNAs were shown to code for the ribosomal (r-) proteins, simian L44 and human L21, and the others were shown to be new. Furthermore, six cDNAs including those encoding the r-proteins could direct a non-karyophilic T antigen [Fischer-Fantuzzi et al., Virology 153 (1986) 87-95] into nuclei, showing that they have NLSs. These results indicate that this system is useful for isolating new cDNAs which code for nuclear proteins.
Animals↗
Comparative analysis of inositol phospholipid metabolism in viral and chemical transformation of mammalian cells.
1. Inositol phospholipid metabolites were measured from virally and chemically transformed cells. 2. Increased levels of PIP and PIP2 were observed from both transformed cell lines as compared with controls. 3. Intracellular levels of IP3 were also increased approximately three folds in BPV-1 infected ID 13 cells and in 3-MC transformed NIH 3T3 cells. 4. The results suggest that phosphorylation of phosphatidylinositols and enhanced generation of IP3 second messenger molecules are the common signal transducing process leading to the cell transformation.
Animals↗
Prevalence of hepatitis C virus antibody among Korean adults.
To estimate the prevalence of hepatitis C virus (HCV) infection among Korean adults and to present the putative route of HCV transmission among them, serum samples from 4917 adults older than 20 years of age were tested for antibody to HCV (anti-HCV), and histories of blood transfusion and other pertinent information were obtained by self-administered questionnaires. The overall prevalence of anti-HCV was 1.7%; prevalence was 1.4% in subjects with normal levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), 3.3% in those with slightly elevated and 5.9% in those with markedly elevated levels of the enzymes. The prevalence of anti-HCV increased with increasing age (P < 0.01), but was not associated with blood transfusion. The present study suggests that the prevalence of HCV infection was 1.4% and that the major routes of HCV transmission may be other than blood transfusion in healthy Korean adults.
Adult↗
A new ensemble averaging technique in impedance cardiography for estimation of stroke volume during treadmill exercise.
In this study, a new ensemble average technique is developed to measure cardiac output during treadmill exercise. Each dz/dt peak is used as a starting point for ensemble averaging, instead of the conventionally used R point of the ECG, in order to prevent the peak dz/dt waveform (C point) from smoothing, which results in increased dz/dtmax. The R-Z interval from the R point of the ECG to the peak dz/dt varies for each heart beat especially during strenuous exercise. Signal-to-noise ratios of five subjects obtained with the new technique are 0-32.6% higher than those obtained with the conventional technique at rest and during four levels of treadmill exercise. Power spectral densities of the averaged dz/dt waveforms by the peak dz/dt and R point references are also analyzed. Stroke volumes of the five subjects averaged by the peak dz/dt are 0-23.5% higher than those obtained by the R point at rest and during four levels of exercise.
Cardiography, Impedance↗
Epitope changes on the haemagglutinin molecule of recently isolated H1N1 influenza viruses.
We have studied changes of epitopes on the haemagglutinin molecule (HA) of H1N1 influenza viruses isolated between 1977 and 1986. For this purpose monoclonal antibodies (MAbs) were raised against the HA of the influenza A/England/333/80 and A/Yamagata/120/86 strain viruses. In order to define the amino acid residues responsible for the change of epitopes, we prepared several HA cDNAs modified by site-directed mutagenesis and cloned them into a simian virus 40 expression vector (SVHA). The substitution of glycine with serine at position 125c (suffix indicates presence in H1 but not in H3 subtype HAs) on the HA of the influenza A/USSR/90/77 strain virus resulted in the loss of epitope 110 (epitopes were named after MAbs) and created new epitopes 139 and 15, which were observed on the HA of A/England/333/80 and a few isolates from 1983. These new epitopes disappeared from the HA in some of the isolates in 1983 and most of the isolates in 1984 and 1986. The disappearance of epitopes 139 and 15 seems to be associated with the loss of epitope W18, which was identified on the HA of A/USSR/90/77. We suggested previously that amino acid residue 189 was involved in epitope W18. We therefore expressed an HA protein with two amino acid substitutions at positions 189 and 125c and found that the conversion of glutamine to lysine at position 189 in SVHA-67 prevented the expression of epitopes 139 and 15.
Animals↗