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K H Sit

Publications and source records attributed to K H Sit.

77 records · Page 5Linked to original sources
PubMedDate not supplied

Adding Zn2+ induces DNA fragmentation and cell condensation in cultured human Chang liver cells.

Zinc (Zn) is a trace element in human cells and regarded as an essential nutrient with established deficiency states affecting multiple organs in the body. However, it has been reported that Zn uptake is associated with some serious harmful effects, such as inhibition of DNA synthesis and enhanced toxicity from reactive oxygen species. We have previously shown that in vivo administration of Zn2+ in C57/6J mice induces weight loss and massive hair loss where the normal course hair becomes replaced by fine vello hair, simulating the side effects from cancer chemotherapy where oxidative free radical damage is implicated in association with DNA fragmentation and programmed cell death (PCD). Here, in vitro flow cytometric studies on human Chang liver showed Zn2+ causing cell condensation with DNA fragmentation that occurred in a dose-dependent manner, an effect replicated by micrococcal nuclease digestion. Specific terminal deoxynucleotidyl transferase-(TdT) mediated labeling of 3'-OH ends of DNA nicks corroborated the flow cytometric profiles of propidium iodide-DNA binding where degradation of both 2 and 4 N genomic DNA resulted in a solitary 1N peak presentation. DNA degradation concomitant with cell condensation is seen as an established hallmark of PCD. We further showed that Zn2+ could enhance the generation of hydroxyl free radicals (OH.) by the transition metal vanadium. Glutathione, the cell's main reducing agent, underwent corresponding reduction. The results suggested that Zn supplementation could induce features resembling PCD.

Apoptosis↗
PubMedDate not supplied

Rheumatic fever susceptibility in four ascertainments: regressive segregation on a geometric ascertainment pattern.

On resolving the ascertainment biases of the observed data in the geometric continuum vaffected-1 x P(sibship), where 0 less than v----infinity, four published ascertainments of rheumatic fever show excellent conformation with Mendelian recessive segregation, even in multiplex sibships. In two surveys in which ascertainment bias is near or a little above random sampling (v = 1), this conclusion is further corroborated by classical segregation analysis. The other two surveys have bias trends declining (v less than 1) very much below random sampling. Such levels of ascertainment bias, if defined through the ascertainment probability parameter pi, would be out of range because the range is from single ascertainment, where pi----0 to random sampling where pi = 1 and probability cannot exceed unity. Highly successful antimicrobial measures that would reduce the number of diseased sibs independent of the distribution of susceptible sibs could produce a dissociation of the gene-to-"rheumatic" relationship and thus explains the declining ascertainment bias.

Adult↗
PubMedDate not supplied

Genistein inhibits DNA synthesis but has no effect on levels of DAG and IP3, cell rounding and alkalinization in sulphate-treated Chang liver cells.

Agonist-activated phosphoinositide (PI)-specific phospholipase C initiates PI hydrolysis to produce signals implicated in mitogenic signaling in which the cyclin-dependent cdc2-protein kinase of the maturation-promoting factor is a major protein-tyrosine kinase (PTK) substrate. It has been suggested that PI mitogenic signals are separable into PTK-dependent and non-PTK-dependent by genistein, a tyrosine-specific protein kinase inhibitor. However, we show here that DNA synthesis was abolished in human Chang liver cells although the sulphate-induced PI second messengers, i.e. inositol 1,4,5-trisphosphate and sn-1,2,diacylglycerol, were at equivalent dose-response levels with or without genistein (0.5 mM, 135 microgram/ml). This genistein dosage had been demonstrated to be effective in suppressing tyrosyl phosphorylation in cells. There was no increase in the trypan blue dead cell index. We have shown previously that human Chang cells stimulated by this 'non-growth-factor' agonist, i.e. sulphate, as well as extracellular ATP, became rounded with raised intracellular pH. ATP-induced cell rounding and intracellular alkalinization were not affected by the presence of genistein (0.5 mM). In the present investigation, that genistein dosage had also no effect on these cellular responses when initiated by added sulphate. It seems that the mitogenic signaling function of PI second messengers is dissociable and requires unsuppressed PTK activity.

Adenosine Triphosphate↗
PubMedDate not supplied

Cytosolic calcium mobilization concomitant with cell retraction induced by sulphate in oral KB carcinoma cells.

Inorganic sulphate is known to induce cell retraction, a process which is important in the cancer metastatic cascade. Using laser scanning confocal microscopy, we showed that sulphate mobilizes intracellular Ca2+ from cytosolic stores in human KB oral cavity epidermoid carcinoma cells as shown by a three fold rise in Ca2+ sensitive Fluo-3 dye fluorescence. As Ca2+ stores are known to be located in the endoplasmic reticulum (ER), we demonstrated the rich network of ER channels in the KB cells by microinjecting live cells with an ER membrane-specific dye (DiI). Within 16 minutes after incubation with sulphate, KB cells had retracted and were easily detachable. The reduction in cell profile area as quantified by image analysis with the confocal microscope was statistically significant (p < 10(-6), ANOVA test). This suggests an alternative novel pathway of cell rounding and retraction involving Ca2+ release, induced via inorganic sulphate.

Carcinoma, Squamous Cell↗