Arthur I. Grayzel

The effect of normalization of serum complement and anti-DNA antibody on the course of lupus nephritis: a two year prospective study.

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.

Effect of long-term normalization of serum complement levels on the course of lupus nephritis

PURPOSE We compared the long-term outcome of patients with lupus nephritis in whom normalization of complement levels (CH50) was sustained by adjustment of immunosuppressive therapy to those patients with persistently low complement levels despite similar immunosuppression in whom therapy was adjusted solely on the basis of clinical disease activity. PATIENTS AND METHODS Thirty-nine female patients with lupus nephritis recruited from 1972 to 1979 were prospectively studied (mean follow-up, 116.7 +/- 11 months). Entry criteria included initial renal biopsy, low CH50, and elevated anti-DNA antibody levels. A second biopsy was performed in 24 patients after an interval of 40.6 +/- 5 months. Treatment was started with prednisone (1 mg/kg/day). Azathioprine at a dose of 1.5 to 2.0 mg/kg/day was added if complement was not normalized by prednisone alone. Twenty-five of 39 patients had normal complement levels within six months (Group 1), and immunosuppressive therapy was tapered but continuously readjusted to the lowest dosage that preserved normal CH50 and maintained clinical remission. Eight of these 25 patients subsequently became persistently hypocomplementemic due to inadequate drug intake (Group 1B), whereas the complement levels continued to be controlled in the other 17 patients (Group 1A). Despite similar therapy, the remaining 14 patients did not achieve normalization of complement within the initial six months of therapy, and therefore future treatment decisions were based solely on clinical symptoms (Group 2). Renal pathologic lesions were classified according to World Health Organization criteria and a semi-quantitative chronicity index. RESULTS During the first six months, there were no significant differences in clinical or histologic features between patients in whom complement levels were controlled and patients in whom complement levels were not controlled. After a mean observation period of 10 years, however, patients with consistent normalization of complement (Group 1A) did much better than patients with only short-term complement control (Group 1B) or persistent hypocomplementemia (Group 2). Both groups with low complement levels had a similar outcome with significantly worse kidney and patient survival. Life-table analysis demonstrated that the differences in outcome between complement-controlled and complement-uncontrolled groups became apparent only after five or more years of follow-up. Patients with a low chronicity score on initial biopsy whose complement level was controlled did uniformly well with no renal failure or death. (ABSTRACT TRUNCATED AT 400 WORDS)

Nitrogen mustard: An “in vitro” inhibitor of erythrocyte sickling

Abstract Sickling of erythrocytes from patients with sickle cell anemia can be completely inhibited by exposure to nitrogen mustard (HN2). Reaction of hemoglobin (Hb) S with increasing quantities of HN2 produces a progressive rise in the minimum concentration of hemoglobin required for gelation on deoxygenation. Quantities of HN2 sufficient to alter gelation cause no observable change in oxygen affinity or in heme:heme interaction. Preliminary studies of osmotic fragility and autohemolysis showed no abnormalities after erythrocytes were treated with HN2. Due to the known toxicity of HN2, no “in vivo” intravenous therapy with this agent can be considered.

Psychologically Distinguishable Groups of Rheumatoid Arthritis Patients: A Controlled, Single Blind Study

&NA; Systematic measures of mood and psychological symptoms were obtained for 68 ambulatory arthritis patients on two standard questionnaires, the Brief Symptom Inventory (BSI) and the Profile of Mood States (POMS). We studied two groups of rheumatoid arthritis patients, one positive and the other negative for rheumatoid factor and erosive joint changes. A third group of patients had other forms of arthritis. All were matched for chronicity and functional impairment as well as psychosocial background variables. We found a distinct psychometric response profile that allowed us to sort patients into the three clinical groups with an accuracy ranging from 63% to 100%.

The growth of vaccine strains of rubella virus in cultured human synovial cells.

Conclusion Two attenuated vaccine strains of rubella virus still retain their ability to grow in monolayer cultures of nonrheumatoid synovial cells, and by extension probably multiply within the synovial membrane of those recipients who develop arthritis post-vaccination. The growth characteristics of rubella in cultured synovial cells may reflect the degree of attenuation vis-à-vis growth in synovial membranes, and perhaps could be used to select strains of virus which would be unlikely to cause synovitis following immunization.

Erythroid Cell Differentiation and the Synthesis and Assembly of Hemoglobin

Publisher Summary This chapter focuses on erythroid cell differentiation and the synthesis and assembly of hemoglobin. The control of hemoglobin synthesis is concerned with the following: (1) the determination of the primary structure of each chain, (2) differentiation of erythroid cells and the induction of hemoglobin synthesis, (3) the switch from the synthesis of embryonic to fetal hemoglobin and of fetal to adult hemoglobin during gestation and early postnatal life, (4) the coordination of synthesis of alpha chains and of their complementary beta, gamma, delta, and epsilon chains, and (5) the regulation and coordination of the syntheses of heme and of globin. The sensitivity of hemoglobin synthesis to 5-fluorouracil and to bromodeoxyuridine only up to the head process stage suggests that DNA synthesis is necessary for hemoglobin synthesis only during these early stages. The differentiation of erythroid cells, the induction of hemoglobin synthesis, and the switch from embryonic and fetal to adult hemoglobin synthesis may be explicable in terms of control at the level of transcription of genes. The mechanism of action of heme in promoting the formation of polyribosomes, accelerating the synthesis of globin, and regulating the assembly of hemoglobin is under study. The synthesis of heme is controlled by feedback inhibition of the formation of ALA. Heme stimulates the synthesis of globin and promotes the coordinate assembly of hemoglobin. This schema of regulation is helpful in understanding the induction and control of hemoglobin synthesis in developing erythroid cells, and it provides a framework for clarifying various disorders of hemoglobin metabolism in man.

Potassium cyanate, an in vitro inhibitor of lymphocyte blast transformation without in vivo activity.

Summary Potassium cyanate (400 μg/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. The authors wish to thank Dr. Sandra Nehlsen for help with the skin grafting.