Biomedical subjects

C C Lau

Publications and source records attributed to C C Lau.

48 records · Page 3Linked to original sources

PubMed1986

The effect of coupling force on bone conduction audiometry.

The present research is devoted to the study of the effect of coupling force on bone conduction threshold determination. The following characteristics of this investigation are listed: A systematic range of coupling forces from 250 to 750 grams (in 100-gram intervals) is used by means of some adopted mechanical devices; A Brüel & Kjaer mechanical impedance head type 8000 (with a mini-shaker) is employed for testing; Test-retest variabilities of bone conduction thresholds are analysed under different coupling forces; Variation of hearing levels under the effect of coupling force is studied.

Adult↗

PubMed1985

Plasmid-induced "hit-and-run" tumorigenesis in Chinese hamster embryo fibroblast (CHEF) cells.

The Chinese hamster embryo fibroblast cell line CHEF/18 is readily transfected by plasmid DNA. In the present transfection studies with CHEF/18 cells, focus formation induced by plasmids containing the mutant human c-Ha-ras gene EJ was compared with that of control plasmids without the EJ insert. The focus-forming activity of the transfected plasmid J132, a recombinant of the Harvey murine sarcoma virus LTR and the normal human c-Ha-ras1 in pBR322, also was assessed. Foci were recovered after transfection with either pSV2gpt or pSV2neo at about 10% the frequency obtained with the EJ-containing plasmids, and J132 gave a similar frequency, all well above background obtained with salmon sperm DNA. Whereas foci from transfection with EJ-containing plasmids contained the EJ DNA, no plasmid DNA was detected in either tumorigenic or tumor-derived cells from foci transfected with pSVgpt, pSVneo, or J132. Evidence that genomic changes were induced by plasmid transfection is based on finding chromosomal aberrations in all expanded foci and tumor-derived cells examined. The results suggest the occurrence of "hit-and-run" tumorigenesis induced by transient plasmid transfection.

Animals↗

PubMed1984

Comparative analysis of caffeine and 3-aminobenzamide as DNA repair inhibitors in Syrian baby hamster kidney cells.

The effects of caffeine and 3-aminobenzamide (3-AB) on Syrian baby hamster kidney cells treated with DNA-alkylating agents and ultraviolet-light suggest that two different DNA-repair mechanisms are involved. Both these agents enhanced the cell kill after methyl methanesulfonate (MMS) treatment. However, enhanced lethality was observed only with caffeine post-treatment when cells were exposed to nitrogen mustard (HN2) or ultraviolet light (UV); 3-AB did not appreciably change cell killing by these agents. With MMS-treated cultures, the effect of caffeine was maximal about 16 h later. The effect of 3-AB on the other hand, was exerted during the first 4 h after exposure to MMS. Caffeine's effect on cell survival could be abolished by low concentrations of cycloheximide, whereas 3-AB's effect could not. Furthermore, the G2 block in cell cycle progression, after MMS treatment, was not observed if the cells were post-treated with caffeine. In the presence of 3-AB, MMS-treated cells were arrested in G2 phase at a much earlier time compared to cells not treated with 3-AB. Finally caffeine post-treatment produced a 10-fold increase in nuclear fragmentation in MMS-treated cells. 3-AB did not cause nuclear fragmentation by itself but further enhanced the nuclear fragmenting effect of caffeine when both agents were present during the posttreatment. Therefore, we propose that 3-AB and caffeine each prevent a different repair mechanism from being effective.

Animals↗

PubMed1983

Resistance of human cells to tumorigenesis induced by cloned transforming genes.

The transformation of human cells was examined by transfection of cloned oncogenic DNAs derived from the tumor virus simian virus 40 and from the human bladder carcinoma cell line EJ into diploid fibroblasts derived from foreskin (FS-2 cells). The simian virus 40 DNA was found to induce a morphologically transformed phenotype, leading to easily detectable focus formation. Tumor antigen was produced, but the transformed cells were not tumorigenic in the nude mouse. The EJ gene, a mutant form of the cellular c-Ha-ras gene, actively transforms NIH/3T3 mouse cells and CHEF/18 hamster cells but is inactive in FS-2 cells. Morphological transformation, focus formation, and tumorigenicity in nude mice were not induced when EJ DNA was transfected into FS-2 cells by using the selectable vector pSVgptEJ. The intactness of the transfected EJ DNA was established by restriction fragment analysis. This result raises the question of what role, if any, the mutated gene derived from the EJ cells played in the origin of the EJ bladder carcinoma.

Animals↗

PubMed1983

Interference with DNA repair mechanisms of mammalian cells: cell cycle dependence.

Agents that prevent repair of lesions in DNA increase cell death. Caffeine enhances lethality of agents such as HN2. We propose that damaged cells stop in G2 phase until repair is completed, and caffeine prevents this G2 arrest. Therefore caffeine lets damaged cells go through mitosis; their chromosomes are shattered and they die. This action of caffeine requires rapid synthesis of protein(s). Some classes of damage by alkylating agent (methyl methane sulfonate (MMS] are removed slowly in human cells, followed by rapid repair synthesis. Lethality results if gaps created during repair of DNA are present during semiconservative replication. Nicotinamide analogs prevent ligation, the gaps persist, and lethality is greater. This effect is S phase specific. Further experiments may specify conditions and agents giving better therapeutic results than can be obtained with anticancer drugs used alone.

Alkylating Agents↗

PubMed1982

Mechanism by which caffeine potentiates lethality of nitrogen mustard.

Caffeine is synergistic with many DNA-damaging agents in increasing lethality to mammalian cells. The mechanism is not well understood. Our results show that caffeine potentiates the lethality of the nitrogen mustard 2-chloro-N-(2-chloroethyl)-N-methylethanamine (HN2) by inducing damaged cells to undergo mitosis before properly repairing lesions in their DNA. Treatment with low doses of HN2 (0.5 microM for 1 hr) caused little lethality in baby hamster kidney cells (90% survival). These cells were arrested in G2 shortly after treatment with HN2 as shown by flow microfluorimetry and autoradiography. After an arrest of 6 hr, HN2-treated cells began to move into mitosis and from then on behaved like normal cells. Repair synthesis was shown to continue during the G2 arrest by using synchronized cells pulse labeled with [3H]thymidine after HN2 treatment and autoradiography. Caffeine (2mM) increased the lethality of HN2 by 5- to 10-fold. It prevented the G2 arrest. Caffeine did not prevent these HN2-treated cells from entering or completing S phase but rather allowed them to divide without finishing the repair processes and as a consequence caused nuclear fragmentation after mitosis. Caffeine-induced nuclear fragmentation and enhanced lethality were proportional, as shown with dose--response curves and time dependence. In addition, both lethality and nuclear fragmentation were abolished by low doses of cycloheximide, an inhibitor of protein synthesis.

Animals↗

PubMed1982

Abolition by cycloheximide of caffeine-enhanced lethality of alkylating agents in hamster cells.

Greatly enhanced lethality for Syrian hamster cells (baby hamster kidney cells and polyomavirus-transformed derivative of baby hamster kidney cells) that had been treated with alkylating agents or ultraviolet light is produced by caffeine. Thus, nitrogen mustard [methylbis(beta-chloroethyl)amine] (HN2) at 0.5 microM decreased cell viability by only a few percent in the absence of caffeine. The addition of 2 mM caffeine during the first 24 hr after nitrogen mustard decreased viability more than 95%. Further kinetic studies of the caffeine effects using other alkylating agents indicate the existence of two modes which damaged cells become caffeine sensitive. Treatment with ultraviolet light or nitrogen mustard makes cells immediately sensitive to caffeine; cells treated with methyl methanesulfonate or N-methyl-N'-nitro-N-nitrosoguanidine, on the other hand, express their maximal caffeine sensitivity only about 15 to 20 hr later. A low concentration of cycloheximide completely abolished this caffeine effect. When 0.36 microM cycloheximide was present, loss of viability was negligible even in the presence of caffeine. Based on further experiments involving the timing of caffeine and cycloheximide additions, caffeine does not affect viability by itself but is involved with some substance such as a protein the rapid synthesis of which is prevented by cycloheximide. This substance does not appear to be needed for recovery from damage, but rather for the action of caffeine in fixing the damaging caused by alkylating agents.

Alkylating Agents↗

PubMed1980

Phorbol related esters have similar structure-activity relations in Swiss 3T3 cells and chicken embryo fibroblasts.

We have examined the activity of nine phorbol-related diterpene esters for stimulation of 2-deoxyglucose uptake in the Swiss 3T3 mouse cell line. The half-maximally effective doses (ED50's) of these derivatives ranged over four orders of magnitude. The potencies of the seven phorbol esters studied correlated well with their previously determined potencies in vitro for stimulation of 2-deoxyglucose uptake in chicken embryo fibroblasts and with thier potencies in vivo in the mouse ear inflammation assay. Two esters of 12-deoxyphorbol which are highly inflammatory but weakly promoting showed the same low potency in 3T3 cells as in chick embryo fibroblasts. These results suggest that 3T3 cells and chick embryo fibroblasts have homologous targets for the phorbol related diterpene esters. All phorbol related diterpene esters were of comparable efficacy in the 3T3 system with the exception of 4-O-methylphorbol 12-myristate 13-acetate. The lower efficacy of 4-O-methylphorbol 12-myristate 13-acetate may help account for its inactivity as a tumor promoter.

Animals↗

PubMed1977

Bioavailability of tetracycline and doxycycline in fasted and nonfasted subjects.

The influence of various test meals and fluid volumes on the relative bioavailability of commercial formulations of doxycycline hyclate and tetracycline hydrochloride was studied in healthy human volunteers. Serum levels of tetracycline were uniformly reduced by approximately 50% by all test meals, whereas serum levels of doxycycline were reduced by 20%. The reduction of tetracycline serum levels will likely be of clinical significance. The bioavailability of each drug was almost identical from an oral solution and from capsules in fasted subjects. The rate of doxycycline absorption was reduced when capsules were administered with a small volume of water, but the overall efficiency of absorption of both drugs was essentially independent of co-administered fluid volume. The use of 8-h serum data provides a reliable estimate of drug bioavailability for tetracycline and, to a lesser extent, for doxycycline.

Adult↗

PubMed1977

Netilmicin pharmacokinetics after single intravenous doses to elderly male patients.

The pharmacokinetics of the new aminoglycoside antibiotic netilmicin were examined after single intravenous injections at two different dose levels to elderly male patients. The durg obeyed two-compartment model kinetics in serum, and elimination was monoexponential from 1 to 2 h after dosing. Netilmicin levels in serum were above minimum inhibitory concentration values for most susceptible organisms for up to 8 h after dosing in normal individuals and for at least 12 h in uremic patients. Urine levels of netilmicin were uniformly above minimum inhibitory concentration values throughout 24 h after dosing. Netilmicin distribution characteristics were largely independent of both dose level and renal function. Netilmicin elimination kinetics were independent of dose level but were markedly influenced by renal function. Relationships are described between netilmicin elimination and renal function indicators, which provide a basis for dosage adjustment in individuals with renal function impairment.

Aged↗

PubMedDate not supplied

Disposition of epirubicin in an oily contrast medium after intravenous and intrahepato-arterial administration in liver cancer: a preliminary report.

The present study reports findings on the disposition of epirubicin after an intrahepato-arterial administration of the Lipiodol-drug complex, prepared by mixing the drug-aqueous phase with the iodized oil by ultra-sonification, in 14 patients with histologically proven hepatoma or hepatomegaly with serum alpha-fetoprotein level above 500 micrograms.l-1. The volume of Lipiodol used was 5 ml and the epirubicin dose was 50 mg.m-2. Blood samples were obtained at various time intervals up to 72 h post-dose. Serum concentrations of epirubicin were measured by liquid chromatography with fluorometric detection. The area under serum concentration-time curve (AUCinfinity0) was higher in the Lipiodol-epirubicin group (n = 8) while the clearance was faster and elimination t1/2 and mean residence time shorter in the plain epirubicin group (n = 3). However, interindividual variation in metabolism of epirubicin would affect serum level of the drug. In three patients who were given intravenous and intrahepato-arterial injections (90 mg.m-2) of plain epirubicin and Lipiodol-drug complex, the relative bioavailability of Lipiodol-epirubicin complex (F = 0.76 and 0.45) was lower than that of plain epirubicin (F = 0.80 and 0.73) in two patients while it was approximately 100% (F = 1.06 and 1.20) in one patient. It is likely that liver function of the patients might be modified by the disease state over a period of 3 months in the cross-over study. Further studies with larger patient samples are required to confirm if there is a targeting effect of the Lipiodol-drug complex toward hepatoma using a better formulation of the drug in Lipiodol.

Adult↗

PubMedDate not supplied

Involvement of p53 gene in the allelic deletion of chromosome 17p in human ovarian tumors.

Previous reports have shown that one copy of the chromosome 17 was frequently lost in human ovarian cancers (1). The position of the allelic deletion has not been mapped and involvement of p53 gene has not been determined. In this study, we have shown that in human ovarian carcinoma, the commonest region of allelic loss in chromosome 17p is 17p 13.3 (65%) and 17p13.1 (63.7%; 6 out of 9 informative cases). Allelic loss was also observed at region 17p12 - 11.1 but at a lower frequency (38.6% to 37.5%). The pattern of allelic loss of p53 gene was consistent in both primary and secondary metastatic tumors of the same patient. No gross rearrangement of p53 was however observed at the remaining allele using Southern blot analysis. Allelic loss of p53 gene was closely associated with 17p 13.3, the terminal portion of chromosome 17p. The high frequency of allelic loss of p53 gene in ovarian carcinomas conformed with recent findings in cancers of colon, breast, lung and brain suggesting inactivation of p53 gene play a rate limiting step in pathogenesis of human malignancies.

Alleles↗