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Biomedical subjects

W Kang

Publications and source records attributed to W Kang.

At least 73 records · Page 4Linked to original sources

Structural organization of the mouse DNA repair gene, N-methylpurine-DNA glycosylase.

N-Methylpurine-DNA glycosylase (MPG), a ubiquitous DNA repair enzyme, removes N-alkylpurines and other purine lesions induced in DNA by simple alkylating carcinogens. A mouse MPG cDNA clone was isolated from a lambda recombinant phage library of BALB/c mouse lung cell and characterized. Using the mouse MPG cDNA as a probe, the complete mouse MPG gene was isolated in two overlapping lambda recombinant genomic clones. The 6-kb gene has four exons containing 1,002 bp of coding sequence. The transcription start site was identified in the genomic sequence by primer extension of MPG mRNA from a mouse lung fibroblast cell line. The location of this transcription start site was confirmed by in vitro transcription with the promoter-containing plasmid template. Promoter function of the sequence 5' upstream of the transcription initiation site was shown by transient expression of the firefly luciferase reporter gene under the control of this sequence in transfected human and mouse cells. The mouse MPG promoter contains no TATA box, but has a CAAT element and is G.C-rich with putative AP2 elements and SP1-complementary sequences.

3T3 Cells↗

Marked enhancement by rifampicin and lack of effect of isoniazid on the elimination of quinine in man.

The effect of rifampicin and isoniazid pretreatment on the pharmacokinetics of quinine after a single oral dose (600 mg quinine sulphate) was studied in nine healthy young Thai male volunteers using a three-way randomized crossover design. Subjects were studied over three 2 day periods, during which they received no pretreatment, or pretreatment with daily 600 mg p.o. rifampicin for 2 weeks, or isoniazid 300 mg p.o. daily for 1 week, prior to quinine administration. The mean (+/- s.d.) clearance (CL/F) of quinine coadministered with rifampicin (0.87 +/- 0.35 1 h-1 kg-1) was significantly greater than that of quinine alone (0.14 +/- 0.05 1 h-1 kg-1). The mean difference in clearance from the control treatment was 0.73 1 h-1 kg-1, with 95% confidence interval (C.I.) of 0.48 to 0.98. The unbound clearance (CLu/F) of quinine, which reflects the activity of the drug-metabolizing enzymes, was considerably greater (6.9-fold) in subjects when rifampicin was coadministered with quinine than that of quinine alone (6.9 +/- 3.6 vs 1.0 +/- 0.5 1 h-1 kg-1; the 95% C.I. for the mean difference was 3.3 to 8.5). The mean elimination half-life of quinine when coadministered with rifampicin (5.5 +/- 3.0 h) was significantly shorter than when quinine was given alone (11.1 +/- 3.0 h; the 95% C.I. for the mean difference was -8.6 to -2.6). In contrast to rifampicin, pretreatment for 1 week with 300 mg oral isoniazid had no significant effects on the pharmacokinetics of quinine.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Radioautographic study of the macromolecular synthesis of Leydig cells in aging mice testis.

The studies on DNA, RNA and protein synthesis of Leydig cells in aging mice testis of several groups were carried out by light microscopic radioautography. The cells labelled with 3H-thymidine, 3H-uridine and 3H-leucine were observed in various aging groups. The labeling index with 3H-thymidine was low at embryonic and early postnatal stages. It increased slightly at 6 months, reached its peak at 9 months and maintained a relatively high level at a later period. The number of the silver grains labelled with 3H-uridine over the nuclei and cytoplasm were observed from embryonic day 19 and increased from 3 months onwards. From adult to old ages, the activity of 3H-uridine incorporation was maintained at a high level in the nuclei and a relatively low level in the cytoplasm. The aging change of 3H-leucine incorporation was found from this experiment. The labeling indices between embryonic and early postnatal stages showed no obvious differences while the number of the silver grains over both cytoplasm and nucleus increased from 6 months onwards and was maintained a high level until old age.

Aging↗

Large-scale spraying of bednets to control mosquito vectors and malaria in Sichuan, China.

Since 1987, up to 2.42 million bednets owned by rural householders in over 40 counties in seven prefectures of Sichuan Province, China, have been sprayed annually with deltamethrin at a dose of about 10 mg/m2. Data for the years 1987-89 indicate that there were marked reductions in the biting populations and survival of the two vector species Anopheles anthropophagus and A. sinensis. Extensive tests in 1992 in areas where bednet spraying had been carried out for 5 years showed that mortality was 100% with the WHO-recommended discriminating dose of deltamethrin, i.e., there was no indication of resistance. Malaria data obtained by passive surveillance of reported cases, mass blood surveys of schoolchildren, and active surveillance of reported blood slides from fever cases all indicated marked reductions after introduction of the net spraying. In contrast, in the control areas, where the nets were not treated, the situation remained static or deteriorated slightly.

Animals↗

A simultaneous study of Doppler-echo and catheterization in noninvasive assessment of the left ventricular dp/dt.

To confirm the feasibility and accuracy of the method for the noninvasive measurement of the left ventricular dp/dt, 53 patients with mitral regurgitation underwent simultaneous determination of left ventricular dp/dt by continuous-wave Doppler echocardiography and cardiac catheterization. Doppler-determined left ventricular dp/dt is derived from the Doppler mitral regurgitant spectrum by dividing the magnitude of the left ventricular-atrial pressure gradient rise between 1 and 3 m/s of the mitral regurgitant velocity signal by the time taken for this change. Left ventricular dp/dt by Doppler ranged from 629 to 3494 mmHg/s (mean +/- SD, 1971 +/- 785 mmHg/s), and that by catheterization varied between 716 and 3650 mmHg/s (mean +/- SD, 1974 +/- 727 mmHg/s). There was a high correlation (r = 0.93, y = 0.862x + 274.77, SEE = 271 mmHg/s, p < 0.001) of left ventricular dp/dt between the two techniques. It is concluded that left ventricular dp/dt is one of the most commonly used parameters for the evaluation of left ventricular systolic function and that Doppler echocardiography provides a new, accurate and noninvasive method of evaluation.

Adolescent↗

Noninvasive evaluation of right ventricular and pulmonary artery systolic pressures in patients with ventricular septal defects: simultaneous study of Doppler and catheterization data.

The method for evaluating right ventricular and pulmonary artery systolic pressures by subtracting the systolic pressure gradient across the ventricular septal defect from the cuff systolic blood pressure is documented. To confirm the reliability and accuracy of this method, simultaneous continuous wave Doppler echocardiography and left and right cardiac catheterization were performed in 66 patients with congenital ventricular septal defects. The comparisons between the Doppler-derived right ventricular or pulmonary artery systolic pressures and those measured by catheterization yielded an excellent correlation (r = 0.969, y = 1.035x - 3.627, SEE = 8.2 mm Hg, p < 0.001 and r = 0.972, y = 1.012x - 2.904, SEE = 7.6 mm Hg, p < 0.001), respectively. There was a close agreement between the Doppler-derived right ventricular or pulmonary artery systolic pressures and those measured by catheters, and the differences between the two measurements did not differ significantly from zero. It is concluded that Doppler echocardiography offers a reliable and accurate method for noninvasive assessment of right ventricular and pulmonary artery systolic pressures in patients with ventricular septal defects.

Adolescent↗

A cell culture model system for genetic analyses of the cell cycle by targeted homologous recombination.

Analysis of how external proliferation signals impinge on the regulation of the cell cycle is ideally performed in cells that are capable of normal physiological withdrawal into the quiescent (G0) phase of the cell cycle as well as resumption of growth following appropriate stimuli. Targeted homologous recombination (gene targeting) provides an important new approach to determine the function of specific genes in these cellular processes. Current gene targeting methodology necessitates the use of immortal and stably diploid cell lines. This report investigates several rodent cell lines, by both genetic and physiological criteria, for use in gene targeting studies of the G0 to G1 transition. All murine cell lines examined were aneuploid. Some rat cell lines were euploid by chromosome number, but three specific genes, c-myc, c-raf-1 and Rb, were not always diploid. Only one cell line, an early-passage subclone of the Rat-1 cell line, was diploid for c-myc, c-raf-1 and Rb. An hprt- derivative of this cell line was isolated (designated TGR-1) and its karyotype was established by G-banding. TGR-1 cells were shown to withdraw into G0 upon serum starvation and to uniformly enter S phase after refeeding. Expression patterns of the c-myc, c-raf-1 and Rb genes and several properties of the gene products were found to be normal. The frequency of targeted homologous recombination of the c-myc and c-raf-1 loci was found to be within values observed with other cell lines. Thus, by both genetic and physiological criteria the TGR-1 cell line is a good model system for the analysis of the roles of c-myc, c-raf-1 and Rb in signal transduction, and will probably prove useful in studies involving other genes.

Animals↗

Noninvasive evaluation of interventricular pressure gradient across ventricular septal defect: a simultaneous study of Doppler echocardiography and cardiac catheterization.

Simultaneous continuous-wave Doppler echocardiography and left- and right-sided cardiac pressure measurements were performed during cardiac catheterization in 64 patients with a congenital ventricular septal defect (VSD). The peak-to-peak pressure gradient across the VSD on cardiac catheterization ranged from 0 to 109 mm Hg (61 +/- 31.7 mm Hg). The peak shunt velocity and peak pressure gradient across the VSD on Doppler ultrasound imaging ranged from 0.96 to 5.21 m/sec (3.75 +/- 1.16 m/sec) and from 4 to 105 mm Hg (62 +/- 29.8 mm Hg), respectively. Doppler measurements of the peak interventricular pressure gradient correlated well with measurements obtained by cardiac catheterization (r = 0.98, standard error of estimate = 6.3 mm Hg, p less than 0.001). Doppler ultrasound imaging yielded information comparable to that obtained by catheterization and provided an accurate method of measuring the pressure gradient across the VSD, which is a useful parameter for the assessment of pulmonary artery systolic pressure in patients with a VSD, without a left or right ventricular outflow tract obstruction.

Adolescent↗