Generation of ligand-receptor alliances by "SEA" module-mediated cleavage of membrane-associated mucin proteins.

A mechanism is described whereby one and the same gene can encode both a receptor protein as well as its specific ligand. Generation of this receptor-ligand partnership is effected by proteolytic cleavage within a specific module located in a membrane resident protein. It is postulated here that the "SEA" module, found in a number of heavily O-linked glycosylated membrane-associated proteins, serves as a site for proteolytic cleavage.

MUC1 isoform specific monoclonal antibody 6E6/2 detects preferential expression of the novel MUC1/Y protein in breast and ovarian cancer.

The products of the MUC1 gene are known to be highly expressed in human breast cancer cells. The best characterized MUC1 protein is a polymorphic, type 1 transmembrane molecule containing a large extracellular domain composed primarily of a variable number of 20 amino acid tandem repeats. We have recently identified a novel protein product of the MUC1 gene, the MUC1/Y protein, that is also a transmembrane protein but is devoid of the tandem repeat array and its immediate flanking sequences.

The breast cancer-associated MUC1 gene generates both a receptor and its cognate binding protein.

MUC1 proteins, some of which contain a mucin-like domain and others lacking this region, can be generated from the human breast cancer-associated MUC1 gene by alternative splicing. The MUC1/Y isoform is devoid of the mucin domain and is a cell membrane protein that undergoes transphosphorylation on both serine and tyrosine residues. We have identified cognate binding proteins that specifically interact with the extracellular domain of MUC1/Y.

A genetic investigation of virulence in a rodent malaria parasite.

The genetic basis of virulence in a line (YM) of Plasmodium yoelii yoelii was investigated in a cross with a mild line (A/C). The blood forms of the virulent line developed extensively in mature erythrocytes of mice, causing death of the host within 7 days; infections with the mild line were normally restricted to reticulocytes, infected animals recovering after three weeks. Lines YM and A/C differed additionally in enzyme and drug-sensitivity markers.

Effects of lowered environmental temperature on the growth of exoerythrocytic stages of Plasmodium berghei.

The effect of lowered host-environmental temperature upon the development and maturation of the preerythrocytic tissue stages of rodent malaria parasites has been investigated in two strains of Plasmodium berghei originating from the highlands of Katanga. Young albino rats inoculated with massive sporozoite doses of P. berghei NK 65 and maintained for 48 hours at 12 degrees C developed small, stunted tissue schizonts, averaging 11 X 15 microns, of a distinct morphology.

Immunological studies in rodent malaria. I: Protective immunity induced in mice by mild strains of Plasmodium berghei yoelii against a virulent and fatal line of this plasmodium.

Mild and virulent lines of Plasmodium berghei yoelii are readily distinguished both by their course of infection and by the preference of the virulent line for mature red blood cells. Mice given either mild line were fully protected against the virulent P.b.

Sudden increase in virulence in a strain of Plasmodium berghei yoelii.

The mild and chronic 17X strain of Plasmodium berghei yoelii showed a sudden increase in virulence following a period of 110 days in the deep freeze. The enhanced virulence was seen in a very high and early parasite peak in the blood and a 100% mortality of all infected mice. The exalted virulence remained unaltered following a number of blood transfers of the strain and after four cyclical transmissions through Anopheles stephensi.

Brain capillary blockage produced by a virulent strain of rodent malaria.

A sudden enhancement in virulence of a mild Plasmodium berghei yoelii 17 x strain resulted in fulminating and fatal infections in CF1 and A/J mice. The virulent strain has maintained its characteristics after ten cyclical transmissions through Anopheles stephensi. The visible expression of virulence of the mutated strain is its ability to cross the blood-brain barrier and cause intravascular sequestration of injected erythrocytes and blockage of brain capillaries.