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Biomedical subjects

C K Ho

Publications and source records attributed to C K Ho.

At least 145 records · Page 8Linked to original sources
PubMed1988

Assessment of HBV persistent infection in an adult population in Taiwan.

In order to study the prevalence of hepatitis B virus (HBV) in the adult population of Taiwan, we screened for the presence of HBV DNA in 205 blood samples from adult (20-59-year-old) volunteers. According to the serological markers of HBV, samples were divided into three groups: group I (173 subjects) was negative for both HBsAg and HBeAg; group II (14 subjects) was positive for both HBsAg and HBeAg; and group III consisted of 18 subjects who were HBsAg-positive but HBeAg-negative. Plasma HBV DNA was not detected in group I, but it was found in 85.7% and 11.8% of samples in group II and group III, respectively. A free-form HBV DNA was found in 14.3% of the leukocyte samples in group II. Furthermore, an integrated form of HBV DNA was detected in the leukocytes of two cases of group I who remained healthy based on clinical data. HBV DNA was also detected in the spermatozoa and liver cells of one of the cases.

Adult↗
PubMed1988

The effect of lipopolysaccharide on the production of GM-EA, GM-CSA, and PGE2 by human monocyte-derived lipid-containing macrophages.

Monocyte-derived lipid-containing macrophage (MDLM) was the major source of granulomonopoietic enhancing activity (GM-EA) but these well-differentiated cells were unable to synthesize constitutively the granulocyte-macrophage colony-stimulating activity (GM-CSA) that was contributed mostly by the younger monocytoid cells. The presence of various concentrations (0.5-10 micrograms/ml) of lipopolysaccharide (LPS) potentiated the production of GM-EA by MDLM. Enhancement of GM-EA production peaked at about 0.5 micrograms/ml of LPS, but at higher doses (10-40 micrograms/ml) LPS became suppressive. In parallel, LPS-induced production of prostaglandin E2 (PGE2) was observable only at higher doses (10-40 micrograms/ml), suggesting a correlation between PGE2 production and LPS-mediated suppression of GM-EA synthesis. At optimal concentration (0.5 micrograms/ml), LPS could effectively override the inhibitory effect of interferon-gamma on the production of GM-EA. In addition, GM-CSA production by MDLM can be partly restored by stimulation with high doses of LPS (10-40 micrograms/ml). These results suggest that MDLMs have functional potentials similar to the younger macrophages and may play an important role in the regulation of myelopoiesis through the release of GM-EA and related regulators.

Colony-Stimulating Factors↗
PubMed1988

Down regulation of myelopoiesis by mediators inhibiting the production of macrophage-derived granulomonopoietic enhancing activity (GM-EA).

Monocyte-derived lipid-containing macrophages (MDLMs) constitutively synthesize a granulomonopoietic enhancing activity (GM-EA) that potentiates the function of granulocyte-macrophage colony-stimulating activity (GM-CSA). In the study reported, we show that GM-EA is distinct from interleukin-1 (IL-1) in biochemical and functional properties and that its production is negatively regulated by several mediators. Thus, MDLM cultures pretreated with interferon-gamma (IFN-gamma, 3 to 900 U/mL), prostaglandin E2 (PGE2, 10(-13) to 10(-8) mol/L), or lactoferrin (LF, 10(-13) to 10(-8) mol/L) invariably produced less GM-EA than untreated controls. The relative potency of inhibition was in the order of IFN-gamma greater than or equal to PGE2 greater than LF. The extent of the inhibitory effects was proportional to dosage and the duration of treatment and could be observed following only a brief exposure (two hours) of the MDLMS to physiologic doses of the mediators. Under optimal conditions, IFN-gamma (300 U/mL for 24 to 48 hours) and PGE2 (10(-9) mol/L for 24 to 48 hours) could totally abrogate the ability of the MDLMs to produce GM-EA. However, the drug-inhibited MDLMs could be reactivated to produce GM-EA by treatment with zymosan (60 micrograms/mL). These results demonstrate that a mechanism for the control of myelopoiesis by mediators such as IFN-gamma, PGE2, and LF may involve the inhibition of GM-EA production. Furthermore, this negative feedback control is reversible and can be overridden when a proper stimulatory signal is given.

Cells, Cultured↗
PubMed1987

Establishment and characterization of a tumorigenic trophoblast-like cell line from a human placenta.

A trophoblast-like cell line, TL, was established from a normal-term human placenta. The TL cells were epithelial in morphology with relatively large vesicular nuclei, prominent nucleoli, and numerous microvilli on the cell surface. Cytoplasmic organelles were generally sparse but mitochondria and polysomes were abundant. The cells grew as compact sheets with close membrane approximation interconnected occasionally by desmosome-like junctions. TL cells contained placental alkaline phosphatase, a placenta-associated antigen, cytokeratin, and prekeratin, but not keratin. In parallel, they were negative for factor VIII, vimentin, and fibronectin. Population doubling time was estimated to be about 34 h. TL cells were tumorigenic in nude mice and an increase in tumorigenicity was observed after a certain number of passages in vitro. Chromosome analysis revealed that TL cells were highly heterogenous and had a female aneuploid karyotype with a hypotriploid mode. Unlike trophoblastic cell lines established from neoplastic tissues, TL cells did not synthesize human chorionic gonadotropin or other gonadal hormones, and only a small amount of ferritin (40.3 ng/10(6) cells) could be detected in the cell supernatant and cell extract. Based on various morphological and histochemical criteria, we suggest that the TL cells are derived from the Langhans cells (villous cytotrophoblast), and due to their special features, the cells may be valuable for the study of the differentiation and tumorigenesis of trophoblastic cells.

Animals↗
PubMed1987

A patient with partial duplication 2q and partial deficiency 11q.

A patient with partial duplication 2q and partial deficiency 11q is reported. The propositus was delivered at 30 weeks gestation, with a birth weight of 1,390 g. He had severe hyaline membrane disease, intraventricular hemorrhage, bronchopulmonary dysplasia, hypotonia, psychomotor retardation, hearing loss, and other anomalies including a short bitemporal diameter, prominent occiput, low-set ears, exophthalmos, short nose with depressed nasal root, downturned mouth corners, narrow high-arched palate, micrognathia, a deep longitudinal groove over the sacrococcygeal region, clinodactyly, and abnormal dermatoglyphics. Chromosome analysis showed the following karyotype: 46,XY,der11,t(2:11)(q32.2;q25)pat.

Abnormalities, Multiple↗
PubMed1987

Comparison of stem cell viability of bone marrow cryopreserved by two different methods.

Two different cryogenic methods were used to study the preservation of murine bone marrow cells. Compared to the classical methods, in which separated mononuclear marrow cells in 10% dimethyl sulfoxide (DMSO) were cryopreserved in liquid nitrogen (-196 degrees C), a modified technique was carried out by cryopreservation of unfractionated marrow cells in a mixed protectant of 5% DMSO and 6% hydroxyethyl starch (HES) at -80 degrees C. Samples that were separately thawed after storage for 1, 4, 8, and 12 weeks were assayed for cell viability and recovery of CFU-GM and CFU-S. No macroscopic clumping of cells was noted either in fractionated or in unfractionated marrow cell cryopreservations. A mild damage, about 25% reduction of stem cells, was found at 1 week and did not deepen further. It seems that the greatest loss of stem cells occurred in the process of cryopreservation itself. Compared to prefreeze values, both a high number of cells that excluded trypan blue (87 +/- 3.4%) and a high recovery of CFU-GM (75 +/- 9.8%) and CFU-S (74 +/- 11.2) were observed in unfractionated marrow samples cryopreserved with the DMSO/HES mixture at -80 degrees C for 3 months and these results were very similar to those obtained from fractionated mononuclear marrow cells cryopreserved at -196 degrees C. The DMSO/HES protectant provides a simplified bone marrow cryopreservation technique that should be favorable to clinical application because of its high stem cell recovery and avoidance of cell-separation manipulation.

Animals↗
PubMed1987

Biological characteristics of interferon-r-induced resistant histiocytic lymphoma cell line U937.

A brief exposure (for 6 h) of U937 cells to interferon (IFN)-gamma (500 U/ml) followed by a long term incubation of cells in normal medium for 8 or more weeks resulted in the induction of cells that were refractory to the anticellular and differentiating effects of not only IFN-gamma but also IFN-alpha and IFN-beta at concentrations up to 10(4) U/ml. In addition, the cells became insensitive to the potent differentiating effect of the phorbol ester--tumor promoting agent (TPA). However, the resistant cells retained their sensitivity to the antiviral effect of different IFNs and were fullu responsive to the induction of endonuclease 2',5'-oligoadenylate (2-5A) synthetase by IFN. Furthermore, the resistant cell population appeared to be homogeneous because clones derived from single cells from this population all exhibited the same resistant phenotype to IFN and TPA. These results suggest that induction of resistant U937 cells may involve a dedifferentiation process which results in the formation of an immature cell population that do not respond to the differentiating and/or anticellular effects of various types of IFNs.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

Free energy of hydrolysis of tyrosyl adenylate and its binding to wild-type and engineered mutant tyrosyl-tRNA synthetases.

The equilibrium constant for the formation of tyrosyl adenylate and pyrophosphate from ATP and tyrosine in solution has been measured by applying the Haldane relationship to wild-type and three mutant tyrosyl-tRNA synthetases from Bacillus stearothermophilus. The formation constant (=[Tyr-AMP] [PPi]/[ATP] [Tyr]) at pH 7.78, 25 degrees C, and 10 mM MgCl2 is (3.5 +/- 0.5) X 10(-7). This corresponds to a free energy of hydrolysis of tyrosyl adenylate at pH 7.0 and 25 degrees C of -16.7 kcal mol-1. All necessary rate constants had been determined previously for the calculations apart from the dissociation constant of tyrosyl adenylate from its enzyme-bound complex. This was measured by taking advantage of the 100-fold difference in hydrolysis rates of the tyrosyl adenylate when sequestered by the enzyme and when free in solution. These are technically difficult measurements because the dissociation constants are so low and the complexes unstable. The task was simplified by using mutants prepared by site-directed mutagenesis. These were designed to have different rate and equilibrium constants for dissociation of tyrosyl adenylate from the enzyme-bound complexes. The dissociation constants were in the range (3.5-38) X 10(-12) M, with that for wild type at 13 X 10(-12) M. The four enzymes all gave consistent data for the formation constant of tyrosyl adenylate in solution. This not only improves the reliability of the measurement but also provides confirmation of the reliability of the measured kinetic constants for the series of enzymes.

Adenosine Monophosphate↗
PubMed1986

Internal thermodynamics of position 51 mutants and natural variants of tyrosyl-tRNA synthetase.

Natural variation and evolution impose structural changes on an enzyme that can affect the energetics of catalysis. The energy profile of reaction could, in theory, be altered in three distinct ways: uniform binding changes, differential binding changes, and catalysis of elementary steps. Residue threonine-51 of tyrosyl-tRNA synthetase from Bacillus stearothermophilus is subject to natural variation, being replaced by alanine and proline in the enzymes from Bacillus caldotenax and Escherichia coli, respectively. The consequences of this variation on the energetics of formation of tyrosyl adenylate have been investigated by constructing free energy profiles for wild-type and mutant enzymes constructed by introducing these amino acids into the B. stearothermophilus enzyme. Mutation of Thr-51 to alanine, proline, and cysteine by site-directed mutagenesis improves the stabilization of the transition state in the formation of tyrosyl adenylate. Most marked is the mutation Thr-51----Pro-51 which stabilizes the transition state by 2.2 kcal/mol and accelerates the forward rate 20-fold to a level near that of the enzyme from E. coli. However, the improved transition-state binding is accompanied by an even greater stabilization of tyrosyl adenylate. This reduces the rate of pyrophosphorolysis of tyrosyl adenylate and/or weakens the binding of pyrophosphate in the reverse reaction, shifting the equilibrium between enzyme-bound reactants greatly in favor of the enzyme-intermediate complex. The more stable mutant enzyme-tyrosyl adenylate complexes have lower rates of aminoacylation, suggesting that mutations which stabilize the intermediate slow down the subsequent transfer of tyrosine from tyrosyl adenylate to tRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1985

Drugs affecting bilirubin uptake by human erythrocyte ghosts.

Drugs known to affect the red blood cell membrane and used clinically in neonates were tested for their ability to cause increased 14C-bilirubin uptake by erythrocyte ghosts. The additional uptake of bilirubin by ghosts in the presence of penicillin G, phenobarbital, furosemide and theophylline may be explained by the effect of these drugs on free bilirubin levels as measured with a horseradish peroxidase assay. In contrast, the effect of chlorpromazine in causing increased bilirubin uptake by ghosts could not be totally explained by either ghost lysis or increased free bilirubin levels, as measured by light scattering, and was due to a direct effect of chlorpromazine on the ghost membrane. Our results demonstrate that drugs may act through different mechanisms in causing increased bilirubin uptake by erythrocytes.

Bilirubin↗
PubMed1985

Hematin and bilirubin binding to human serum albumin and newborn serum.

In jaundiced newborn infants, hemolytic disease is considered a risk factor for kernicterus due to the suspected competition between bilirubin and other hemoglobin breakdown products for albumin binding. We have studied the effect of hematin on bilirubin-albumin binding using the peroxidase assay and a light-scattering technique for measuring unbound bilirubin. Our results show that hematin does not affect bilirubin-albumin binding. To determine if other albumin binding functions are affected by hematin, we used a microdialysis rate technique employing two ligands, diazepam and monoacetyldiaminodiphenyl sulfone (MADDS). Hematin does not utilize the diazepam binding function of albumin, but does decrease the albumin binding of MADDS. The results of this study indicate that the MADDS and bilirubin binding functions are not identical. The clinical usefulness of reserve albumin equivalent determination using MADDS is discussed.

Bilirubin↗
PubMed1985

Susceptibility of different leukemic cell lines to the anticellular and antiviral effects of interferons.

A total of 18 different types of human leukemic cell lines were tested for their susceptibility to the anticellular and antiviral effects of interferons (IFNs) alpha, beta and gamma. In general, only the three myelogenous leukemic cell lines U937, KG-1 and HL-60 were found to be highly susceptible to the anticellular effect of the different IFNs while cells of the other lineages were relatively resistant. In order to determine whether the cell lines were sensitive to the antiviral effects of IFNs, the cells were first screened for their ability to support the replication of vesicular stomatitis virus (VSV), sindbis virus (SBV) and semliki forest virus (SFV). Unexpectedly, only three cell lines--Raji, K562 and U937 were highly susceptible to SFV while other cell lines were relatively refractory to all three viruses. Using SFV as indicator virus, the antiviral activity of all IFNs could be detected in all three cell lines and their relative efficiency was in the order of alpha greater than beta greater than gamma. The significance of these results were discussed.

Cell Line↗
PubMed1985

Synergistic anticellular effect of a combination of beta-interferon and retinoic acid against U937 cells.

Both human beta-interferon (IFN-beta) and retinoic acid (RA) are able to induce the differentiation of the human histiocytic lymphoma cell line U937, but neither one alone can effectively eliminate the leukemic cells. When U937 cells are incubated with a combination of IFN-beta (200 units/ml) and RA (0.1-1.0 microM), extensive cell death can be observed as early as day 3 posttreatment, and IFN-beta alone at a concentration as high as 10(4) units/ml is ineffective. These data suggest that there is a strong synergistic cell killing effect between IFN-beta and RA against the U937 cells. This effect is so highly selective that similar enhancement has not been detected using a closely related cell line, HL-60, and RA enhances neither IFN-alpha nor IFN-gamma in the killing of U937 cells. The mechanism of such synergism is unknown in the present study, but it appears that cytostasis or promotion of differentiation alone cannot account for this phenomenon since neither activity is enhanced to any appreciable extent.

Antineoplastic Combined Chemotherapy Protocols↗