Biomedical subjects
Publications and source records attributed to A I Grayzel.
A patient presented with bilateral brachial plexus neuropathy which 2 weeks later evolved into a polyneuropathy involving all four extremities. On further investigation, the patient was found to have systemic lupus erythematosus. Treatment with steroids was accompanied by complete resolution of the neurologic findings.
A prospective study was carried out in 25 patients with systemic lupus erythematosis (SLE) on the effect of normalizing serum complement (CH50) and anti-DNA antibodies on the course of lupus nephritis. In 16 of the 25 patients, CH50 was maintained within the normal range for two years. Urinary protein excretion increased or remained low in all 16. Repeat renal biopsies were performed in 10 of these 16, and disclosed either stabilization of glomerular disease or diminution. In the nine patients in whom CH50 could not be normalized with tolerated doses of drugs, urinary protein excretion increased or remained increased. Repeat renal biopsies in six of these nine patients were carried out and showed worsening of glomerular disease in five. No clear-cut correlation was found between urinary protein excretion or renal disease and the serum levels of anti-DNA antibody. We conclude from these observations that continuous normalization of CH50 by drug therapy in patients with SLE is associated with stabilization or diminution of lupus nephritis.
The relationship of the immunoglobulin class of anti-double stranded DNA antibodies to the histological and clinical evidence of glomerulonephritis was examined in patients with systemic lupus erythematosus using a quantitative solid-phase fluorometric immunoassay. Patients with anti-DNA antibodies of the IgG class had more severe histologic changes on renal biopsy, more clinical evidence of active renal disease and lower hemolytic complement levels. The class of anti-DNA antibodies in the serum did not always correspond with the class of immunoglobulin deposited in the glomeruli of renal biopsy specimens.
A proteinase active at physiologic pH was isolated from unstimulated human peripheral blood lymphocytes with gel filtration and affinity chromatography. The proteinase with a molecular mass of approximately 30,000 daltons was completely inhibited by diisopropylfluorophosphate (DFP) and soybean trypsin inhibitor (STI). Incubation of the lymphocyte enzyme with 3H-proline labeled T24 human bladder carcinoma cells resulted in significant cytoxicity of the target cells. Cytotoxicity was only observed with much higher concentrations of trypsin. Similar results were obtained with a 51Cr release assay. This investigation demonstrates that unstimulated human peripheral blood lymphocytes contain a cytotoxic proteinase capable of killing pre-labeled target cells. The proteinase may be involved in lymphocyte-mediated cytotoxicity.
Two adult patients with hypogammaglobulinemia and chronic synovitis were studied. Synovial tissue and fluid were examined by histologic, virologic, and immunologic methods. The synovium lacked characteristic histologic features of rheumatoid arthritis, and B lymphocytes were absent from the synovial tissue, fluid, and peripheral blood. These 2 patients may represent a form of chronic synovitis produced in the absence of any B lymphocyte response.
Total hemolytic complement activity (CH50) and levels of C4, C5, and Factor B determined by commercially available radial immunodiffusion plates were compared in sera from patients with systemic lupus erythematosus. There was a significant correlation between CH50, C4 and C5, but no correlation between Factor B and any of the other indices of complement activity measured.
Potassium cyanate (400 mug/ml) inhibited the blastogenesis of lymphocytes in response to PHA and the response of lymphocytes in mixed lymphocyte cultures. Cyanate administered to mice at a dose of 30 mg per kg per day did not delay allograft rejection.
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The mechanism of growth stimulation in allogeneic lymphocytes mixed in vitro was studied at the cell level by means of cytophotometric techniques. A pronounced increase in fluorescence intensity of fixed and acridine orange (AO) stained lymphocytes was observed as soon as after 1-3 hr in mixed culture. No increase in the amount of DNA took place during this time. The higher fluorescence intensity was due to an increased accessibility of AO binding sites in the deoxyribonucleoprotein (DNP) complex, most probably as a result of weakened bonds between the DNA and the protein moiety in the DNP complex. Similar DNP changes have been found in other systems of growth stimulation and may be one prerequisite for later induction of cellular synthetic processes. Increased AO binding only occurred when the lymphocyte donors were incompatible at the major histocompatibility locus (HL-A); there was no change in AO binding in cases of HL-A identity. The AO binding reaction probably reflects a specific recognition of HL-A antigens, whereas other antigenic discrepancies between the individuals do not seem to cause an analogous response.
The synthesis of globin has been studied in a reticulocyte cell-free system in which the initiation of polypeptide chain synthesis can proceed for as long as ten minutes of incubation. With this system, we have found evidence for a soluble factor in the reticulocyte that stimulates protein synthesis and appears to act by promoting initiation.
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