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Biomedical subjects

M A Kane

Publications and source records attributed to M A Kane.

89 records · Page 5Linked to original sources
PubMed1975

Studies of the biologic effects of selective C4 deficiency.

The role of the several pathways of complement activation in mediating a number of the biologic activities of complement has been examined in an animal model, the C4-deficient guinea pig. It has been shown that the presence of an intact classic pathway (C1, 4, 2) is requisite for damage of antibody-sensitized mammalian cell membranes and for the development of thrombocytopenia and the hypercoagulable state following in vivo endotoxin administration. Both the classic and alternate pathways participate in defense against the lethal effects of endotoxin, in opsonization and lysis of bacteria and in mediation of the events of inflammation.

Antigen-Antibody Complex↗
PubMed1973

Interactions of the classical and alternate complement pathway with endotoxin lipopolysaccharide. Effect on platelets and blood coagulation.

The contributions of the classical and alternate pathways of complement activation to the biological effects of endotoxin have been examined in the guinea pig, with particular reference to thrombocytopenia, leukopenia, and the development of the hypercoagulable state. Injection of endotoxin into normal guinea pigs led to a 95% fall in the level of circulating platelets within 15 min as well as a fall in circulating granulocytes. C4-deficient guinea pigs, known to have a complete block in the activity of the classical complement pathway, but with the alternate pathway intact, sustained no fall in platelets. The development of granulocytopenia proceeded normally. Endotoxin did activate the alternate complement pathway in C4D guinea pigs, as evidenced by the fall in C3-9 titers. With restoration of serum C4 levels, endotoxin-induced thrombocytopenia was observed in C4D animals. Thus, function of the classical complement pathway was an absolute requirement for the development of thrombocytopenia. Experiments performed in cobra venom factor (CVF)-treated normal guinea pigs, with normal levels of C1, C4, and C2, but with less than 1% of serum C3-9 demonstrated the importance of the late components in the development of thrombocytopenia but not leukopenia.C4-deficient guinea pigs had normal clotting times demonstrating that C4 was not required for normal clotting. In addition, development of the hypercoagulable state, evidenced by a marked shortening of the clotting time, was not observed on injection of endotoxin into C4D animals. Therefore, development of the hypercoagulable state paralleled the development of thrombocytopenia and required function of the classical complement pathway. Again, the importance of the late components of complement was emphasized by the failure of CVF-treated normal animals to develop hypercoagulability. These results demonstrate that endotoxin is capable of activating both the classical and alternate complement pathways in guinea pigs but that function of the classical pathway is an absolute requirement for the development of thrombocytopenia and the hypercoagulable state.

Animals↗
PubMedDate not supplied

Isolation of a gastrin releasing peptide receptor from normal rat pancreas.

The presence of a putative GRP receptor on rat pancreatic particulate membranes was demonstrated by covalent cross-linking to 125I-gastrin releasing peptide (GRP), which revealed a radioactive band with Mr = 80-90 kDa on reduced SDS-PAGE. Fresh rat pancreatic membranes contained a GRP receptor which was solubilized with Triton X-100 as assessed by its failure to sediment at 100,000 x g for one hour and its ability to pass through a 0.22 mu filter. When 125I-GRP binding was studied using Sephadex G50 gel filtration chromatography to separate bound from unbound ligand, substantial amounts of 125I-GRP binding were observed in rat crude solubilized pancreatic membranes, but essentially no specific binding was observed until the crude solubilized membranes were fractionated by ammonium sulfate precipitation. Specific 125I-GRP binding was 500, 700 and 1400 fmol/mg protein, respectively, in the 0-25%, 25-50% and 50-80% saturated ammonium sulfate fractions (125I-GRP concentration = 1 nM). Specific binding was temperature dependent, saturable and of high affinity, (KD = 2.3 nM). A unique 70 kDa band was visualized by silver staining of the SDS-PAGE of eluates of GRP(14-27) affinity gel compared with eluates of control affinity gels incubated with the 25-50% (NH4)2SO4 fraction. The lower Mr than that observed with covalent cross-linking may represent the binding subunit of a larger receptor protein. This ligand-affinity isolated protein is thus a good candidate for the GRP receptor, or the binding subunit of it, from normal rat pancreas.

Ammonium Sulfate↗
PubMedDate not supplied

Global control of hepatitis B through vaccination: role of hepatitis B vaccine in the Expanded Programme on Immunization.

Hepatitis B is a disease that affects people throughout the world, and over 200 million are persistent carriers of the hepatitis B virus (HBV). The chronic sequelae of this infection include chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma. The development of safe and highly effective hepatitis B vaccines now provides the means by which HBV infection, including the HBV chronic carrier state, can be prevented and the related mortality significantly reduced. The cost of these vaccines has significantly decreased and will soon approach levels at which the cost-effectiveness (cost per death prevented) of hepatitis B vaccine will be similar to that of other childhood vaccines. Integration of hepatitis B vaccine into the Expanded Programme on Immunization for mass vaccination of infants in areas where HBV infection is endemic and morbidity is high would be the most effective means of providing the coverage necessary for effective control and prevention.

Carrier State↗