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J Balke

Publications and source records attributed to J Balke.

6 recordsLinked to original sources

Two inflammatory mediator cytokine genes are closely linked and variably amplified on chromosome 17q.

Mitogenic stimulation of resting T cells results in the de novo transcription of a large number of genes including those encoding regulatory molecules such as lymphokines. The genomic organization of two newly described induced lymphokine genes, 464.1 and 744.1, has been determined. 464.1 and 744.1 appear to be the human homologues of the recently cloned murine macrophage inflammatory proteins, MIP-1 alpha and MIP-1 beta, respectively. The 464.1 and 744.1 genes share 55% amino acid homology and demonstrate parallel regulation of induced expression in T cells. It was therefore of interest to observe that these genes are closely linked in the human genome, separated by 14 kb, and are organized in a head to head fashion. Each of the genes is present in an additional nonallelic copy (referred to as 464.2 and 744.2) as part of an apparent amplification unit in the genome of many individuals. The 464.2 gene is expressed and potentially encodes a protein highly related to 464.1, varying in 5 of 92 amino acids. As expected, 464.2 and 744.2 are also closely linked to each other as determined by population linkage disequilibrium studies. Individuals bearing a chromosome with a third amplification event, involving a 464-related gene but not a 744-related gene, are also infrequently observed. These genes are all located on chromosome 17 in bands q11-q21, the region implicated in von Recklinghausen neurofibromatosis (NF1) and in acute promyelocytic leukemia (AML-M3).

Amino Acid Sequence↗

Failure to maintain interspecific pregnancy after transfer of Dall's sheep embryos to domestic ewes.

Over a 3-year period, 32 Dall's sheep (Ovis dalli dalli) embryos were transferred into 24 domestic sheep (O. aries) recipients and 4 were transferred into 2 Dall's sheep recipients. In the first year, none of the 10 O. aries recipients was diagnosed pregnant. In the following 2 years, 9 (37%) of the domestic sheep recipients were pregnant on Day 18, 8 (33%) on Day 40, 6 (25%) on Day 90 and 4 (16%) on Day 120; 1 aborted at Day 125 and another at Day 145. Pregnancies were established only in ewes that had previously been recipients of Dall's sheep embryos. The 2 remaining pregnant sheep were treated with progesterone from Day 125 until the fetuses were determined to be dead at Day 145. Both of the Dall's sheep recipients (Year 2) established pregnancies; 1 live Dall's sheep lamb was born 174 days after mating. No differences in serum progesterone, oestrone, prostaglandin F-2 alpha metabolites or cortisol concentrations could be detected during pregnancy between recipients carrying Dall's sheep embryos, recipients receiving progesterone treatment or domestic ewes carrying domestic sheep pregnancies. Six fetuses were necropsied (1 at Day 125 and 5 at Day 145-146): all fetuses were premature and had various degrees of hydranencephaly. No significant differences were found when cotyledon numbers were compared among domestic ewes carrying Dall's sheep lambs. Dall's sheep ewes lambing naturally and domestic ewes lambing naturally. These results demonstrate that the transfer of Dall's sheep embryos to domestic ewes results in the establishment but subsequent loss of pregnancy and that these losses occur throughout gestation.

Animals↗

Mitogenic activation of human T cells induces two closely related genes which share structural similarities with a new family of secreted factors.

Previously we have isolated about 60 novel cDNA clones whose corresponding mRNAs are induced by mitogenic activation in human peripheral blood T cells. Here we describe the primary structure and regulation of two such cloned genes, pAT 464 and pAT 744, which may encode new lymphokines/cytokines. Similar to IL-2, both genes require the synergy of agents such as PHA and PMA for optimal expression, and, in addition, the induction of both is sensitive to the immunosuppressive drug cyclosporin A. The two genes can be expressed in T cells, B cells, and the promyelocytic cell line HL60, but they are not expressed in human fibroblasts, suggesting that their expression is restricted to hematopoietic lineages. The predicted peptides encoded by these two clones feature hydrophobic N-terminal leaders characteristic of secreted proteins. The predicted size of both proteins is about 8 kDa upon cleavage of the putative leader peptide. pAT 464 and pAT 744 are very similar to each other and also share some critical amino acid similarity with a newly emerging family of secreted factors including connective tissue activating factor III, platelet factor 4, an IFN-gamma-induced factor, macrophage inflammatory protein, and a factor chemotactic to neutrophils (3-10C, monocyte-derived neutrophil chemotactic factor, neutrophil-activating factor). Some of these factors have been shown to display functions associated with an inflammatory response and/or have mitogenic activities. Collectively, the data presented here suggest that pAT 464 and pAT 744 encode novel lymphokines/cytokines which may play roles during an immune response similar to those enacted by these structurally related factors.

Amino Acid Sequence↗