The production of collagenase by adherent mononuclear cells cultured from human peripheral blood.

Mononuclear cells were isolated from human peripheral blood by Ficoll-Hypaque centrifugation, and the cells adherent to plastic substrata were cultured in serum-free media supplemented with lactalbumin hydrolysate. These cell cultures, which consisted predominantly of monocyte-macrophages as judged by nonspecific esterase staining, accumulated collagenase in the medium. This collagenase resembled other vertebrate collagenases in that it cleaved native triple-helical type I collagen at a locus 3/4-length away from the amino-terminal end of the molecule. The collagenase activity was inhibited by Na2EDTA, dithiothreitol, and fetal calf serum, while the addition of Ca++ or N-ethylmaleimide enhanced the enzyme activity. The accumulation of collagenase in the culture media was markedly enhanced by the incubation of cells with concanavalin A or phorbol myristic acetate. In the presence of cycloheximide, the levels of collagenase activity were markedly reduced, suggesting that active protein synthesis was required to express the enzyme activity. In additional experiments, monocytes were further purified by counterflow centrifugation-elutriation. The collagenase production was markedly increased in cultures enriched in monocyte-macrophages and devoid of polymorphonuclear leukocytes. The accumulation of collagenase in monocyte cultures incubated for 48 hours in the presence of concanavalin A or phorbol myristic acetate was of the same order of magnitude as in parallel cultures containing the same number of polymorphonuclear leukocytes purified by Ficoll-Hypaque centrifugation and Plasmagel sedimentation.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoperoxidase staining of the choroid plexus in systemic lupus erythematosus.

Immune deposits in the choroid of patients with systemic lupus erythematosus (SLE) are thought to relate to the pathogenesis of central nervous system (CNS) SLE. Using an immunoperoxidase technique, we found the presence of immunoglobulin heavy and light chains in the choroid stroma and/or in the ependymal cells in all of 7 patients with SLE, 2 of 4 with rheumatoid arthritis, but not in 3 subjects without autoimmune disease. The occurrence, pattern or intensity of the immunoglobulin deposits did not distinguish the patients with or without clinical neuropsychiatric manifestations. Thus, the presence of immune deposits in the choroid plexus is not specific for CNS involvement in SLE.

Normal T cell regulation of IgG synthesis in systemic lupus erythematosus.

The regulation of pokeweed mitogen (PWM) stimulated IgG synthesis by peripheral blood mononuclear cells (PBL) was studied in patients with systemic lupus erythematosus (SLE) and controls. The helper-T, suppressor-T and B cell functions of SLE-PBL were separately evaluated and compared to the functions of control lymphocyte populations. SLE-T cells function normally both in helper and suppressor modulation of PWM-stimulated IgG secretion by control or autologous B cells. The SLE-B cell, however, fails to synthesize normal quantities of IgG when cultured under conditions that induce maximal stimulation. While other studies document abnormal Con A induced suppressor cell function in SLE, this study shows that normal functioning populations of SLE-suppressor T cells exist in the peripheral blood.

Acute monoarticular arthritis. A diagnostic approach.

A group of adult patients with acute nontraumatic monoarticular arthritis was studied. Using only the traditional clinical tools of history, physical examination, joint x-ray films, and synovial fluid culture, Gram's stain, and examination for crystals, 74% of the diagnoses made were achieved either immediately or within two to three days. Overall, 64% of the cases were diagnosed during follow-up. Other tests were not found to be helpful in the acute situation and should be utilized only if the tests already mentioned fail to yield a diagnosis. The prognosis of patients with acute monoarthritis that remains undiagnosed after thorough evaluation is generally good.

Correlation and predictive accuracy of circulating immune complexes with disease activity in patients with systemic lupus erythematosus.

Serial serum samples from 48 patients with systemic lupus erythematosus (SLE) were assayed for C3, anti-DNA antibody, and circulating immune complexes (CIC). CIC were measured by the fluid phase (FClq) and solid phase (SClq) Clq binding assays. Elevations of the SClq results were associated with the presence of manifestations of SLE (P less than 0.001), including active renal disease (P less than 0.005) and arthritis (P less than 0.001), as well as changes in degree of disease activity which prompted physician action. A change in the SClq results correctly predicted a change in disease activity 82% of the time (P less than 0.005). Abnormalities of FClq, anti-DNA antibody, and C3 were neither associated with nor predictive of changes in disease activity of SLE. These data suggest that the SClq method of determining CIC is the most reliable laboratory indicator of clinical activity in SLE.

Lymphoplasmacytic myeloma: an immunological, immunohistochemical and electron microscopic study.

An unusual case of a light chain plasma cell myeloma is described. The disease was initially characterized by a diffuse lymphoplasmacytic bone marrow involvement, but subsequently developed widespread extramedullary metastases with anaplastic tumors in the skin which histologically resembled a "histiocytic lymphoma." Electron microscopic examination, in vitro protein synthesis of bone marrow lymphoidal cells, chemical and immunochemical studies of serum and urine proteins, and intracellular immunoglobulin study by the immunoperoxidase technique on the skin biopsy and postmortem tumor tissue demonstrated evidence for lambda light chain synthesis and secretion. These findings provide further support to the notion that the wide spectrum of diverse morphologic patterns seen in lymphoplasmacytic disorders originates from the same progenitor B-lymphoid cell. Distinguishing anaplastic variant of plasma cell myeloma from other undifferentiated neoplasms offers a challenge.

Regional migratory osteoporosis. A denervation disease.

Regional migratory osteoporosis is an uncommon entity charcterized by sudden attacks of migrating lower extremity paraarticular pain, local edema, and muscle atrophy; the disease is verified by radiologic demineralization and bone scan uptake. The etiology and pathogenesis are unknown. We describe a case of regional migratory osteoporosis followed over nine years by serial electromyographic studies documenting denervation patterns coincident in time and location of each acute attack. The substantiation of denervation in regional migratory osteoporosis is of both diagnostic and pathogenetic significance.

Clinical and antibody responses after influenza immunization in systemic lupus erythematosus.

After immunization with A/New Jersey/76 and A/Victoria/75 influenza vaccines, 11 patients with systemic lupud erythematosus were serially evaluated for changes in disease activity, serologic abnormalities, and their capability to generate specific antibodies. One patient, with active disease, developed a diffuse, proliferative glomerulonephritis. None of the other patients or control subjects had significant local or systemic side effects. Significant levels of antibodies were generated to A/New Jersey/76 in eight of the 11 patients and in seven of eight control subjects and to A/Victoria/75 in seven of 11 patients and five of eight control subjects. The geometric mean responses of both total and IgG antibodies to each viral antigen were no different in patients with systemic lupus erythematosus than in control subjects. In patients with stable systemic lupus erythematosus, immunization with killed influenza viral vaccine appears to be safe and effective.

Sigmoid volvulus in two patients with progressive systemic sclerosis.

Sigmoid volvulus was diagnosed in two patients with progressive system sclerosis. In one case, this was initially confused with a high fecal impaction. Both cases responded to early surgical intervention. Sigmoid volvulus should be considered in the differential diagnosis of intestinal obstruction associated with progressive systemic sclerosis.

Impaired immunoglobulin synthesis by peripheral blood lymphocytes in systemic lupus erythematosus.

Pokeweed mitogen (PWM)-induced immunoglobulin (Ig) synthesis by peripheral blood mononuclear cells (PBL) from 33 patients with systemic lupus erythematosus (SLE) was compared to that synthesized by PBL from 22 normal individuals. Short-term unstimulated culture of SLE-PBL immediately after separation from PB revealed Ig synthesis 4 times that of normal PBL. However, SLE-PBL had a depressed PWM-induced Ig synthetic response that was partially, but not totally, related to active disease and was not correctable by co-culture with normal lymphocyte populations. In both the short-term-unstimulated and the PWM-stimulated cultures, IgM was the major Ig class synthesized by normal PBL, while IgM synthesis by SLE-PBL was depressed more than the other Ig classes. These results can best be explained by a preactivated PBL population in SLE.

Rapid progression of chronic active type B hepatitis in a patient with hypogammaglobulinemia.

Rapid progression of acute type B hepatitis to chronic active liver disease and cirrhosis in a young male with hypogammaglobulinemia is described. Absent circulating IgA, significantly low IgG, and normal IgM levels were detected during the acute phase of illness. Enumeration of peripheral lymphocytes revealed a decreased number of T cells and normal numbers of B cells. In vitro pokeweed stimulation of Ig synthesis correlated with the in vivo circulating levels of the three immunoglobulins. Cell-mediated immune responses were normal except for lymphocyte stimulation to hepatitis B surface antigen. It was concluded that the defective synthesis of IgG and IgA antibodies to hepatitis B surface antigen contributed to the accelerated progression to chronic active type B hepatitis in this person.

Acute venereal arthritis. Comparative study of acute Reiter syndrome and acute gonococcal arthritis.

Acute venereal arthritis, a syndrome of fever and inflammatory arthritis following recent sexual intercourse, is a frequently misdiagnosed arthritic presentation. Nearly half of 39 patients admitted with a diagnosis of acute gonococcal arthritis were subsequently recognized as having acute Reiter syndrome. A retrospective study of both diseases revealed differentiating features that, when prospectively applied to 21 consecutive patients, permitted a correct and prompt bedside diagnosis. Acute Reiter syndrome could be differentiated by characteristic mucucutaneous lesions, arthritis/tenosynovitis confined to lower extremities, massive recurrent knee effusions, low back pain, conjunctivitis, and genitourinary inflammation. Gonococcal arthritis could be differentiated by migratory arthralgias, high fevers, arthritis/tenosynovitis initially confined to upper extremities, typical cutaneous lesions, and dramatic defervescence to penicillin therapy. Laboratory data provided support for each diagnosis.

Immunological studies in familial primary biliary cirrhosis.

Tests for cell-mediated immunity and presence of autoantibodies were performed in a mother and daughter with primary biliary cirrhosis. Lymphocytes transformation to phytohemagglutinin, delayed cutaneous response to one or more skin test antigens, and percentage of peripheral T and B lymphocytes were normal in both patients. Although successful in the mother, dinitrochlorbenzene sensitization was not achieved in the daughter. Histocompatibility antigens 1 and 8, elevated levels of IgM, and antibodies to mitochondria, smooth muscle, and skeletal muscle were present in both patients. However, the clinical course was more severe in the daughter who developed portal hypertension with bleeding esophageal varices requiring portacaval anastomosis. Except for intermittent pruritus, the mother has remained asymptomatic.

Chronic lymphocytic leukemia with gamma chain cytoplasmic inclusions.

A case of lymphocytosis diagnosed clinically as chronic lymphocytic leukemia is described. The lymphocytes possessed cytoplasmic inclusions that contained IgG-kappa immunoglobulin. Studies of immunoglobulin synthesis showed that the cells synthesized but did not secrete the immunoglobulin. The migration on poly.acrylamide gels of the IgG heavy chain was anomalous, and it is proposed that this interfered with its normal secretion and allowed the development of cytoplasmic inclusions within the cell. These findings are unique when compared with previous studies of immunoglobulin biosynthesis by normal or leukemic peripheral blood lymphocytes.