gamma-beta-Thalassaemia studies showing that deletion of the gamma- and delta-genes influences beta-globin gene expression in man

In gamma-beta-thalassaemia, human gamma- and beta-globin gene expression is suppressed; this results in a severe anaemia in newborns which subsequently develops into a beta-thalassaemia syndrome in adult life. This hereditary disease is now shown to be the result of a deletion of at least 40,000 base pairs of the gammadeltabeta-globin gene locus. The gamma- and delta-globin genes are deleted in the affected chromosome but, surprisingly, the beta-globin gene is still present, together with a large segment of the DNA sequences flanking the gene on its 5'-side and the entire region on the 3'-side of the gene. Hence, a deletion of DNA far from the beta-globin gene results in the suppression of its activity.     

Myosin isoenzyme redistribution in chronic heart overload.

Since the first observation by Spann et al., it has become clear that in cardiac hypertrophy induced by a mechanical overloading, the velocity of shortening of the cardiac muscle (Vmax) is reduced (see ref. 2 for review). Most authors agree that this mechanical alteration is accompanied by a decrease in the Ca2+-dependent ATPase activity of myosin (see ref. 3 for review). The molecular basis of such changes was unknown because the structural modifications of the myosin molecule were ill-defined. Nevertheless, it has recently been shown that, like skeletal muscle myosin, cardiac myosin is composed of several polymorphic forms, comparable to isoenzymes. In the skeletal muscle, new functional requirements can induce changes in both contractile activity and type of myosin isoenzyme synthesised. We now report that an increase in cardiac work produced by mechanical overloading in rats induces the preferential synthesis of a cardiac myosin isoenzyme characterised by specific immunological and electrophoretic properties and exhibiting a lower ATPase activity. This adaptive change could account for the reduced shortening speed of this hypertrophied cardiac muscle.     

Lymphopenia and lymphocyte transformation in alcoholics

Summary The basis of peripheral blood lymphopenia observed in patients with chronic alcoholism and liver disease was investigated by examining the effect of sera of these patients on in vitro transformation of normal human peripheral blood lymphocytes. A positive correlation was demonstrated between the serum inhibition of phytohaemagglutinin- and pokeweed mitogen-induced transformation and the degree of lymphopenia. Thus serum factors may contribute to the observed lymphopenia by inhibiting lymphocyte production in vivo.This study was supported by grants from the National Health and Medical Research Council of Australia, Royal Australasian College of Physicians and Alfred Hospital Henry Laurie Scholarship Fund.     

Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus

A role for proto-oncogenes in the regulation and modulation of cell proliferation has been suggested by the findings that the B-chain of platelet-derived growth factor (PDGF) is encoded by the proto-oncogene sis and that the erb-B oncogene product is a truncated form of the epidermal growth factor (EGF) receptor. Furthermore, the product of the proto-oncogene fms (c-fms) may be related or identical to the receptor for macrophage colony-stimulating factor (CSF-1). v-fms is the transforming gene of the McDonough strain of feline sarcoma virus (SM-FeSV) and belongs to the family of src-related oncogenes which have tyrosine-specific kinase activity. Furthermore, nucleotide sequence analysis of the v-fms gene product revealed topological properties of a cell-surface receptor protein. To elucidate the features involved in the conversion of a normal cell-surface receptor gene into an oncogenic one, we have now determined the complete nucleotide sequence of a human c-fms complementary DNA. The 972-amino-acid c-fms protein has an extracellular domain, a membrane-spanning region, and a cytoplasmic tyrosine protein kinase domain. Comparison of the feline v-fms and human c-fms sequences reveals that the proteins share extensive homology but have different carboxyl termini.     

A cloned cell with NK function resembles basophils by ultrastructure and expresses IgE receptors

Natural killer (NK) cells are defined by their ability to lyse certain tumour cells in vitro without previous exposure to them, and have been postulated as effectors of immune surveillance against spontaneous neoplasms. Because they kill some non-neoplastic lymphoid cells, they may also have a role in immunoregulation. NK cell activity resides in a small proportion of normal mouse spleen cells (less than 5%) that have been difficult to characterize completely. They may represent a heterogeneous group of effector cells whose precise relationship to other myelopoietic or immunological cells has remained obscure. We have previously described a cloned mouse cell line (Cl. Ly 1-2-NK-1+/11) with the functional characteristics of natural killer cells activated by interferon or other factors. We now find that this cloned line, like basophils and mast cells, expresses high-affinity plasma membrane receptors (Fc epsilon R) specific for IgE antibody. In addition, the clone contains cytoplasmic granules similar by ultrastructure to those of basophils of the mouse and other species. Our findings indicate that cells sharing morphological and biochemical features of basophilic granulocytes can mediate NK lysis.