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M Axelrad

Publications and source records attributed to M Axelrad.

7 recordsLinked to original sources
PubMed1977

The role of inflammatory cells in the pathogenesis of amyloidosis.

In the presence of amyloid enhancing factor, a variety of inflammatory stimuli, many of them nonantigenic, trigger amyloid deposition in 48 hours. There is a striking correlation between the extent of splenic amyloid deposition and the severity of inflammation at the injection site of the various irritants. Sublethal irradiation results in a parallel effect on the local inflammatory response and the accompanying extent of amyloid deposition produced in the spleen. Evidence that a product of local acute inflammatory responses is related to the deposition of amyloid is also presented. It is proposed that this product is a protease derived from the infiltrating polymorphonuclear leukocytes.

Acute Disease↗
PubMed1976

Effects of amyloid induction on plasma protein turnover, and its implication.

Using polyacrylamide gel electrophoresis and radioiodinated plasma proteins, data on the rate constant for synthesis and fractional degradation rates for albumin, alpha1-, alpha2-, beta-, and gamma-globulins were obtained during accelerated amyloid induction in a murine model. The results indicate that during amyloid induction there is an increased rate of synthesis of alpha2-, beta-, and gamma-globulins but only the alpha2-globulin degradation rate is accelerated. In this experimental system, should amyloid protein be a degradation product of a plasma fraction, the alpha2-globulin appears as the most likely precursor. The implications of our findings are discussed, and a new general mechanism of amyloid production is proposed.

Alpha-Globulins↗
PubMed1975

Acceleration of amyloidosis by syngeneic spleen cells from normal donors.

Intravenous administration of syngeneic spleen cells from normal donors was found to markedly shorten the induction time for casein-associated splenic amyloid diposition in the mouse. The effect of intravenous donor cells seemed purely one of acceleration; it did not provoke amyloid deposition either by itself or in combination with independently ineffective heterologous proteins. The accelerator effect did not depend on the viability of the cell suspension, and after physical disruption of the cells all the accelerator activity seemed localized to the sedimentable fraction of damaged cells, nuclei and coarse debris. It is suggested that the accelerator acts through affecting the function of perifollicular splenic macrophages.

Amyloid↗
PubMed1968

Hypersensitivity: specific immunologic suppression of the delayed type.

Delayed-type cutaneous hypersensitivity to sheep erythrocytes was induced in rats by intradermal injection of the antigen mixed with Freund's adjuvant; hypersensitivity was sustained by weekly injections. Either passive immunization with rat antiserum to sheep erythrocytes or intravenous injection of sheep erythrocytes partially suppressed induction of hypersensitivity; these procedures used together specifically and completely suppressed induction of hypersensitivity. Complete suppression was sustained by antigen given intravenously before each weekly injection of the mixture of antigen and adjuvant. These findings provide the rational basis of a simple method for prolonging survival of allografts with only the biological agents, antigen and antibody, of the immunological response.

Animals↗
PubMedDate not supplied

The pathogenesis of amyloid deposition: a new hypothesis.

Amyloid proteins are probably derived from a variety of precursor glycoproteins. It is postulated that there may be at least two key events in the pathogenesisi of amyloidosis. The first is an increase in the load of glycoprotein being brought to a site of degradation. In the case of myeloma this might be in the form of excess immunoglobulin light chains. In the case of secondary amyloidosis the form taken could be enzyme-alpha-globulin complexes. The second is an inability of the degrading site to handle the arriving substrate at a sufficiently rapid rate, the rate limiting step being at some point along the degradation pathway. We postulate that an acquired enzyme deficiency prevents removal of the carbohydrate moiety of the presented glycoprotein. This results in the accumulation of a normal intermediate (amyloid protein) during the breakdown of the glycoprotein substrate. Evidence for the operation of these mechanisms is discussed and their detailed nature and implications considered.

Alpha-Globulins↗