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Biomedical subjects

A Michael

Publications and source records attributed to A Michael.

At least 127 records · Page 7Linked to original sources

Radioimmunoassay of the attack complex of complement in serum from patients with systemic lupus erythematosus.

We developed a radioimmunoassay to measure the attack complex of complement (SC5b-9) in serum from patients with systemic lupus erythematosus. The radioimmunoassay used a monoclonal antibody to an antigen of C9, which is absent from native C9 but present on SC5b-9. SC5b-9 was detectable in 13 of 63 normal subjects, with a mean value of 0.5 unit (range, 0 to 4.8), and elevated in 13 of 14 patients with active lupus. Analysis of 108 samples from the patients with lupus revealed a mean value of 10.1 units (range, 0 to 35) when the disease was active and 1.0 unit (range, 0 to 433) when it was clinically stable. SC5b-9 was a more sensitive measure of disease activity than C3, C4, or CH50; its specificity was equivalent to that of C3 and C4. SC5b-9 was elevated in serum from 6 of 49 patients with other forms of glomerulonephritis. Our study documents the presence of SC5b-9 in abnormal serum and correlates its elevation with clinical disease activity in patients with active systemic lupus erythematosus.

Adolescent↗

The distribution of the CR3 receptor on human cells and tissue as revealed by a monoclonal antibody.

The mouse monoclonal antibody MN-41 has been characterized as an anti-human iC3b receptor (CR3) antibody on the basis of its ability to inhibit the binding of EC3bi indicator cells to monocytes and polymorphonuclear cells while having no effect on their Fc and C3b receptors. Use of this monoclonal antibody in indirect immunofluorescence studies with dual fluorochrome labels established the widespread distribution of CR3 in man--detected on 97% of circulating monocytes, 90% of granulocytes, 17% of T lymphocytes, and 28% of B lymphocytes while erythrocytes and platelets were negative. Isolated peritoneal macrophages were 90% positive while pulmonary macrophages were 83% positive. Monocytes in culture for 8 days were universally positive. Within tissues, CR3 reactive cells displayed unique topographical localization within the spleen, tonsil, and lymph nodes whereas numerically fewer positive cells were scattered within hepatic sinusoids, papillary dermis, medullary regions of the thymus, and submucosa of the small intestine. CR3 was not detected on Raji cells, glomerular epithelial cells, or placental stromal cells. Immunoprecipitation and electrophoretic separation of two glycoprotein bands of 150,000 and 95,000 Da suggest possible structural homology of CR3 in man and mouse (Mac-1 antigen).

Animals↗

Effect of dextran gelatin on cholinesterase of rats.

This study has been carried out by measuring the cholinesterase (ChE) activity in blood serum and in some organs (brain, liver, spleen, kidney, small intestine, lung, and cardiac muscle) of rats before and at different time intervals after infusion of 65 dextran 70, and 5% gelatin 40 solutions (1 ml/100 g body weight). The controls received infusions of the diluent of the gelatin preparation. The data obtained showed that the infusion of the diluent in rats has no effect on ChE activity neither in blood serum nor in other organs at any time intervals after infusion. In case of dextran and gelatin, a significant increase in ChE activity in blood serum and the tested organs was observed at different time intervals after infusion. The increase in case of dextran was more marked than in case of gelatin. These measurements returned to base-line values during 72 h after infusion. Furthermore, the study failed to disclose any untoward reactions, either immediate or delayed, which could be attributed to the infusion solutions.

Animals↗

A vaccine strain of Pasteurella multocida obtained by mutagenesis.

A virulent avian septicemia strain of Pasteurella multocida (P. multocida) serotype 1 was mutagenized with N-methyl-N'-nitro-N-nitroso guanidine. A selection procedure was devised to isolate mutants with changed growth properties. Mutants were isolated that had either prolonged doubling time or temperature sensitivity for growth at 41 degrees C. A correlation was observed between growth properties in vitro and multiplication in vivo. Mutants defective in growth were avirulent. A positive correlation was observed between the rates of multiplication of mutant strains in vitro and their ability to protect against heterologous challenge.

Animals↗

Effect of gelatin infusion on urinary excretion of water and electrolytes in rats.

The effect of gelatin infusion on water and electrolyte excretion in urine was studied by measuring the volume of excreted urine and the urinary excretion of Na+, K+, Ca++ and Mg++ in a group of male rats before and after receiving infusions of a 5% autoclaved gelatin solution containing 1% glycine (1 ml/100 g body). A similar group of rats received the diluent only (control group). The results obtained showed that the diluent had a diuretic and natriuretic effect but with a less marked degree than gelatin solution which caused marked diuresis, natriuresis and increased excretion of Ca++ and Mg++ in the urine. The K+ excretion was significantly decreased following gelatin infusion. All of these measurements returned to the base-line level after 72 h following gelatin infusion.

Animals↗

Mesangial function in ureteral obstruction in the rat. Blockade of the efferent limb.

The kinetics for mesangial uptake and transport of radiolabeled aggregated human immunoglobulin (Ig)G (AHIgG(125)I) deviated markedly from normal in male Sprague-Dawley rats with ureteral obstruction. Four experimental groups, each containing 25 rats, were used: (a) bilateral ureteral ligation (BUL) with release of one ureter 24 h later; (b) unilateral ureteral ligation with release 24 h later [UUL(R)]; (c) unilateral ureteral ligation without release (unreleased) [UUL(U)]; (d) uremia-control, which consisted of rats with ligated left ureter and a severed right ureter. A similar number of sham-operated rats served as control for each group. AHIgG(125)I (45 mg/100 g body wt) was given intravenously 1 h after release of the ureteral obstruction (25 h after ureteral obstruction or sham surgery). Groups of five control and five experimental animals were sacrificed at 2, 4, 8, 16, and 24 h after injection. At all time intervals, concentrations of AHIgG(125)I in isolated glomeruli from control animals were similar to values obtained from nonobstructed kidneys of UUL(U) and UUL(R) rats: a linear decrease in concentration over a period of 24 h was observed when the logarithm of glomerular AHIgG(125)I concentration was plotted against time. Aberrations in the kinetics were apparent in obstructed kidneys but not in liver, spleen, or blood concentrations of AHIgG(125)I: (a) At 2 h in all obstructed kidneys, glomerular concentration of AHIgG(125)I was markedly reduced. (b) In BUL (released or unreleased), glomerular concentrations of AHIgG(125)I from 4 to 16 h were congruent with 10-fold those in UUL(U) or UUL(R) kidneys. (c) The significant decline in glomerular concentration between 4 and 16 h in control and nonobstructed kidneys was not observed in UUL(R), UUL(U), or BUL (released or unreleased) kidneys; in all obstructed kidneys, a plateau in glomerular concentrations of AHIgG(125)I was observed between 4 and 16 h. (d) After 16 h at a time when the blood level of AHIgG(125)I had decreased to 3% of initial values, there was progressive fall in glomerular AHIgG(125)I. Similar results were obtained in the uremia-control group in rats, which indicated that uremia per se had no measurable effect on mesangial kinetics. These studies demonstrate that ureteral occlusion induces alterations in mesangial uptake (afferent limb) and egress (efferent limb) of macromolecules. Particularly evident is the "blockade" of the efferent limb which is demonstrable at high blood levels of AHIgG(125)I. These alterations in the transit of macromolecules through the mesangium may be mediated in part by the hemodynamic changes that accompany ureteral obstruction.

Animals↗

The fate of intravenously infused gelatin.

The fate of i.v. infused gelatin was studied by measuring the rise in the level of total hydroxyproline (HP) in some organs of the rat following the infusion of a 5% autoclaved gelatin solution (1 ml/100 g body weight). The results obtained showed that HP levels were consequently increased in all of the organs studied, then the levels were generally normalised during the 3rd day post infusion. Small concentrations of HP were still retained by the kidneys and blood plasma, at the end of the first week after infusion. The rat ratio HP/creatinine (HP/C index), which increased from 0.33 to 3.78 during the first 24 h post infusion, declined gradually to the base-line level after 4 weeks, during which time 94% of the HP infused could be accounted for in the urine. Most of the HP was excreted in the bound form.

Animals↗

C2 deficiency. Development of lupus erythematosus.

The study of serum from a patient with C2 deficiency is described. The patient had an episode of pneumococcal meningitis at 5 mo of age with seizures and transient hemiparesis and apparent purpuric skin lesions. He was first admitted to the University of Minnesota Hospitals at 10 yr of age following the discovery of proteinuria accidentally by his mother. Since then he has been admitted repeatedly to this hospital with numerous clinical findings including arthralgia, recurrent abdominal pain, proteinuria, membranous nephropathy, malar butterfly rash, seizures, personality aberrations, and recurrent fever. In June 1971, the patient developed positive DNA and DNP antibodies and positive LE cells. When the C profile was studied before and after recognition of lupus, C1q, C1s, and C4 dropped. C3 levels were elevated as were C5, C6, and C7, C3 proactivator had been reduced in the patient even before he developed lupus. Also because of a traumatic renal biopsy leading to a perirenal hematoma, he required surgery and a blood transfusion. 1 h after blood transfusion, a C2 titer of 23 hemolytic units was detected. Almost immediately levels of C3, C5, C6, and C7 dropped, C8 and C9 remained elevated. The addition of C2 from normal blood permitted dramatic activation of C3. These findings support the view that the rare deficiency in production of C2 predisposes to serious susceptibility to infection, vascular and mesenchymal disease as well as to renal disease and a lupus syndrome.

Antibodies↗

The association of respiratory infection, recurrent hematuria, and focal glomerulonephritis with activation of the complement system in the cold.

The study of the activation of C3, C5, and C7 associated with the conversion of C3 in the serum of a 9-yr old girl after incubation at 0 degrees C for 6-8 h without utilization of C1, C4, and C2 is described. The patient has upper respiratory infections associated with recurrent gross hematuria, focal glomerulonephritis, and transient renal insufficiency. Histological lesions demonstrated the presence of B1c globulin IgA and properdin in the glomeruli. The activation of complement (C) in the cold requires the patient's IgA. Removal of IgA from the serum by immunoadsorption prevents activation and conversion of C3. Bactericidal and phagocytic activity is also impaired after incubation. C3 proactivator (C3PA) level is reduced before and after incubation. Properdin level drops after incubation. These findings suggest that the activation of C3 which is demonstrable in vitro may be a continuous process in vivo.

Child↗