Search PubMed⌕ Search

Biomedical subjects

Y H Tan

Publications and source records attributed to Y H Tan.

At least 127 records · Page 7Linked to original sources

Genetic control of the interferon system.

Now that some studies have been done on the genetics of the human interferon system, it would appear that the primary constraint to interferon research imposed by the lack of human interferon can be overcome as indicated herein with mutagenized human cell lines containing multiple copies of chromosome 5. Purified interferon from these mutants has allowed us to label it radioactively. However the amount required for a complete amino acid and sugar sequence of human interferon is still very large but within the realm of possibility when the use of these mutant cell lines is considered (23, 24).

Animals↗

Somatic cell genetic analysis of the interferon system.

Current advances in the use of somatic cell hybrid systems have enhanced the value of these systems for studying eukaryotic cell functions. We have reviewed the use of somatic cells to investigate the human interferon system. It has been shown that interspecific heterokaryons and hybrid cells can produce interferon(s) of both parental types and may be protected from viral challenge by interferon(s) from either parent. Using mouse-human hybrid cells we have assigned a human gene(s) responsible for regulating interferon to chromosome 21 and genes involved in the production of human interferon to chromosomes 2 and 5. Our data also suggest possible assignment of a locus involved in control of interferon production to chromosome 16. Suggested further uses of the somatic cell system for interferon studies include study of the subunit structure of interferons and the development of hybrid lines that produce human interferon at high levels (interferon/somatic cell hybrids/human gene assignment.

Animals↗

Human chromosome 21 dosage: effect on the expression of the interferon induced antiviral state.

Human primary skin fibroblasts trisomic for chromosome 13, 18, or 21 and diploid human skin fibroblasts were induced for an antiviral response with human interferon. The cells that were trisomnic for chromosome 21 were three to seven times more sensitive to protection by human interferon than the normal diploid or trisomic 18 or 13 fibroblasts. The differential response in trisomnic 21 cells is consistent with the known assignment of the human antiviral gene to chromosome 21.

Alleles↗

The somatic cell genetics of human interferon: assignment of human interferon loci to chromosomes 2 and 5.

A total of 40 mouse-human cell hybrids were induced with poly(I).poly(C) and with Newcastle disease virus. Ten hybrid clones produced low levels of human interferon in response to both the virus and poly(I).poly(C). Concurrent enzymic and chromosomal analysis of the hybrid clones indicated a concordant segregation of these levels of human interferon with chromosomes 2 and 5. The presence of both chromosomes 2 and 5 was necessary for interferon production; neither was sufficient alone. Based on this finding, we postulate that there are at least two asyntenic gene loci for the expression of interferon in human cells.

Animals↗

The linkage of genes for the human interferon-induced antiviral protein and indophenol oxidase-B traits to chromosome G-21.

13 independent mouse-human somatic cell hybrid clones derived from beta-propiolactone-inactivated Sendai stimulated cell fusion of human cells with mouse cells were tested for their sensitivities to human and mouse interferon. All of them were protected by mouse interferon and only six of the clones were protected by both human and mouse interferon. Only the six that were protected by human interferon were shown to express the human dimeric form of indophenol oxidase. Complete chromosomal analysis of the clones indicated human chromosome G-21 to be the only human chromosome in common for the six clones which had both phenotypes present. Nine subclones were derived from one of the clones expressing both phenotypes. Eight of the nine subclones were shown to retain both phenotypes, whereas one subclone lost both. Chromosomal analysis of the subclones indicated the loss of chromosome G-21 from the subclone which lost both phenotypes. It is apparent from these findings that the gene(s) for indophenol oxidase (IPO-B) and the gene(s) for the antiviral protein are syntenic and that they are linked to human chromosome G-21.

Animals↗

Regulation of cellular interferon production: enhancement by antimetabolites.

Cycloheximide, at a protein-inhibitory concentration, when given to rabbit kidney cell cultures that had been exposed either to UV-irradiated Newcastle Disease virus or to a complex of polyinosinic and polycytidylic acids (poly I.poly C), enhanced the production of interferon. The enhancement was greater if, in addition to cycloheximide, the cells were also treated with actinomycin D. On the basis of these findings, a mechanism, consisting primarily of the production of a control protein which normally checks interferon production, is postulated for interferons stimulated by these two substances.

Animals↗