Biomedical subjects

J V Ravetch

Publications and source records attributed to J V Ravetch.

110 records · Page 7Linked to original sources

PubMedDate not supplied

Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins.

Interferons are a family of proteins first identified by their ability to induce cellular resistance to infection by many viruses. In addition to the antiviral properties it shares with the alpha- and beta-interferons, gamma-interferon (IFN-gamma), a lymphokine secreted by activated T cells, activates macrophages, stimulates B cells, increases fibroblast and endothelial cell resistance to many nonviral intracellular parasites and modulates cell-surface proteins central to immune cell regulation. To identify molecules involved in the IFN-gamma response and characterize their modulation, we have isolated genes that are induced following recombinant IFN-gamma treatment of U937 cells, a histiocytic lymphoma cell line with monocytic characteristics. We report here the molecular cloning and characterization of a gene regulated by rIFN-gamma in U937 cells as well as in human mononuclear cells, fibroblasts and endothelial cells. Messenger RNA from this gene is induced within 30 min of rIFN-gamma treatment and demonstrates maximal (greater than 30-fold) accumulation within 5 h. Increased transcription is partly responsible for this accumulation. This gene encodes a protein of relative molecular mass (Mr) 12,378 which has significant amino-acid homology to platelet factor-4 and beta-thromboglobulin, two chemotatic proteins released by platelets on degranulation. This IFN-gamma-inducible protein may be a member of a family of proteins involved in the inflammatory process.

Blood Platelets↗

PubMedDate not supplied

A chromosomal rearrangement in a P. falciparum histidine-rich protein gene is associated with the knobless phenotype.

The significant morbidity and mortality associated with Plasmodium falciparum malaria results, in part, from the sequestration of parasitized erythrocytes in postcapillary venules, which may protect the parasite from splenic clearance and contribute to the pathogenesis of cerebral malaria. This sequestration has been linked to the expression of parasite-induced knob structures on the surface of the infected erythrocyte which mediate the cytoadherence phenomenon. While knobs are necessary for cytoadherence, they are not sufficient, requiring both parasite- and host-encoded proteins. Spontaneous mutants of P. falciparum have been isolated from in vitro cultures which lack the ability to express knobs and fail to cytoadhere. A histidine-rich protein has been described which is associated with the knobby phenotype and may be a constituent of the knob. We now report the isolation of complementary DNA clones for a knob-associated histidine-rich protein (KAHRP) and demonstrate that in knobless mutants the gene for this protein has undergone a rearrangement, resulting in a deletion in the 3' coding sequence. Moreover, the chromosome to which the KAHRP gene maps is rearranged in these mutants, producing a telomeric location of the truncated gene. These observations explain the loss of expression of the messenger RNA and protein in such mutants and may explain the loss of the knob itself. The implications for the generation of spontaneous mutations in the parasite by this novel mechanism are discussed.

Chromosome Mapping↗