Molecular basis of the soluble and membrane-bound forms of the murine leukemia inhibitory factor receptor alpha-chain. Expression in normal, gestating, and leukemia inhibitory factor nullizygous mice.

The murine leukemia inhibitory factor receptor alpha-chain (mLIFR) exists in a membrane-bound and a soluble form. The two major classes of mRNA transcript correspond to either the soluble or membrane-bound form of the mLIFR. In this study we have identified a complex and heterogeneous pattern of expression of mRNA transcripts for this receptor in normal mouse tissues and cell lines. In order to understand the molecular basis of these transcripts, genomic clones encompassing the region of divergence from the soluble to the membrane-bound form of the receptor were isolated. cDNAs encoding the membrane-bound form of the mLIFR were generated by an alternative splicing event where an exon that is specific to the soluble mLIFR was skipped. The membrane-bound form of the mLIFR was heterogeneously polyadenylated with at least five different sites of polyadenylation. The mRNA transcript encoding the soluble form of the mLIFR contained a region highly homologous to a murine B2 repetitive element, thus providing a possible explanation for the genesis of this transcript. The different forms of the mLIFR were analyzed in a wide range of mouse tissues in pseudopregnant mice and in mice at various stages of pregnancy. Only liver, placenta, and uterus showed an increase in the levels of mLIFR mRNA expression during pregnancy, indicating an important role for the LIFR in this process. However, somewhat surprisingly, there was no detectable difference in mLIFR mRNA levels or levels of soluble protein in leukemia inhibitory factor nullizygous mice when compared with normal mice.

A study of granular lymphoproliferative disorders including a CD3 negative case with a rearrangement of the T-cell receptor locus.

The clinical, and laboratory features of 9 patients presenting with chronic proliferations of large granular lymphocytes (LGL) are described. The median patient age was 61 years (33-80) and median patient follow up was 3.5 years (28 mo-10 years) with all patients surviving. Clinical features and blood and bone marrow findings are documented. Immunophenotypic analysis showed lymphocytes from 4 patients were CD3 negative and 5 were CD3 positive with natural killer associated cell surface antigens expressed in both these groups. Analysis of the T-cell receptor (TCR) loci revealed a clonal rearrangement in 4 samples including one CD3 negative sample. Clonality did not correlate with immunophenotype or clinical or haematological features. We conclude that patients with persistent LGL have a wide diversity of cell surface marker expression and that whilst some patients with CD3 negative LGL proliferations have cells which are most likely of natural killer (NK) cell origin, in others TCR rearrangements can be demonstrated suggesting these cells are possibly of T-cell, not NK cell, origin.

Idiopathic thrombocytopenic purpura: predictors of chronic disease.

We studied the extent to which patient characteristics influenced outcome in childhood idiopathic thrombocytopenic purpura in a historical cohort of 289 children over a 20 year period (1968-87). Outcome was classified as acute or chronic depending on whether the platelet count had returned to normal (150 X 10(9)/l) by six months after diagnosis. Fifty three cases (18%) had chronic idiopathic thrombocytopenic purpura. The likelihood of chronic disease was determined by logistic regression analysis of five patient variables: age, sex, season of onset of symptoms, history of recent viral illness, and duration of symptoms at presentation. A history of symptoms of greater than 14 days at presentation, adjusted for the other variables, was strongly predictive of chronic idiopathic thrombocytopenic purpura; the other variables did not significantly affect outcome. At 28 days after diagnosis 138 (47%) of the study cohort had normal platelet counts. Children whose platelet counts were less than 150 X 10(9)/l had a threefold risk of progressing to chronic idiopathic thrombocytopenic purpura, which increased to fivefold if counts were less than 50 X 10(9)/l. Two thirds of patients in the chronic group, irrespective of treatment, remained thrombocytopenic two years after diagnosis. We conclude that a history of symptoms for greater than two weeks at presentation is strongly predictive of chronic idiopathic thrombocytopenic purpura. If platelet counts are subnormal 28 days after diagnosis the risk of chronic idiopathic thrombocytopenic purpura is increased with prolonged thrombocytopenia being very likely if platelet counts remain low three months after diagnosis.