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Biomedical subjects

M Ziff

Publications and source records attributed to M Ziff.

At least 109 records · Page 6Linked to original sources
PubMed1977

Treatment of Bechçet's syndrome with transfer factor.

Six patients with Behçet's syndrome were treated with transfer factor (TF) from randomly selected donors. Mucocutaneous symptoms and signs were predominant at the time that TF injections were started. Three patients showed great improvement, one moderate improvement, and one was unresponsive to multiple injections of TF from different donors. One case was uninterpretable because of concomitant administration of high doses of prednisone and chlorambucil and brief treatment with TF. These results indicate that TF therapy may be beneficial in some patients with Behçet's syndrome and that a trial of TF is warranted at least in the absence of severe ocular or neurologic manifestations.

Adult↗
PubMed1977

Enhancement of in vitro immunoglobulin synthesis of rheumatoid lymphocytes by aggregated human gamma globulin.

In vitro immunoglobullin synthesis by lymphocytes of patients with rheumatoid arthritis (RA) was enhanced by the addition of heat-aggregated human IgG. Stimulation occurred in the presence of fresh seropositive autologous plasma and was abolished by heat inactivation. By contrast, no significant stimulation was induced in lymphocytes from patients with miscellaneous arthritides and normal subjects cultured in the presence of either fresh autologous plasma or fresh normal AB serum. Although stimulation of RA lymphocytes did not occur in the presence of fresh AB serum, it did when purified IgM rheumatoid factor was added to this serum. These results suggest that immune complexes formed between aggregated IgG and rheumatoid factor in the presence of complement stimulate immunoglobulin synthesis in the peripheral blood lymphocytes of patients with RA.

Antigen-Antibody Complex↗
PubMed1977

Surface ultrastructure of rheumatoid articular cartilage.

Six rheumatoid articular cartilage specimens, which appeared grossly normal and were shown to be free of pannus when examined under the light microscope, were examined electron microscopically. For comparison, normal-appearing cartilage specimens from 2 patients with meniscus injury and 2 with degenerative joint disease (DJD) were also examined. In all cases the normal-appearing joint surface of rheumatoid cartilage was abnormal. Amorphous-appearing material was present to a depth varying between 6 and 25 micron. Some of this material had the appearance of fibrin deposited at the cartilage surface, but much appeared to represent breakdown products of the cartilage matrix, i.e. degraded collagen and proteoglycan. DJD cartilage did not show similar changes. The findings suggest that the surface of rheumatoid articular cartilage, even when grossly normal in appearance, is degraded by enzymes either present in the synovial fluid or released by polymorphonuclear cells in close contact with the cartilage surface.

Adult↗
PubMed1977

Inhibition of antigen- and mitogen-induced human lymphocyte proliferation by gold compounds.

Gold sodium thiomalate (GST) inhibited in vitro antigen- and mitogen-triggered human lymphocyte DNA synthesis. Inhibition of responsiveness was observed with concentrations of GST equivalent to gold levels found in serum or tissues of patients receiving chrysotherapy, Inhibition was dependent upon the gold ion itself since GST and gold chloride were both inhibitory whereas thiomalic acid was not. Inhibition could not be explained by nonspecific killing of cells or by an alteration in the kinetics of the responses. GST inhibited mitogen-induced proliferation most effectively when present from the initiation of culture and could not inhibit the responsiveness of cells which previously had been activated by concanvalin A. These findings indicated that GST blocked a critical early step in lymphocyte activation. The degree of GST-induced inhibition of proliferation was increased in cultures of cells partially depleted of monocytes. Moreover, inhibition was reversed by supplementation of these cultures with purified monocytes. These observations suggested that GST blocked thymus-derived (T)-lymphocyte activation by interfering with a requisite function of the monocyte population in initiating such responses. Prolonged incubation of peripheral blood mononuclear cells with GST resulted in diminished mitogen responsiveness upon subsequent culture in the absence of gold. The addition of fresh monocytes restored responsiveness to these populations. Furthermore, preincubation of purified monocytes with GST rendered them deficient in their ability to support mitogen-induced T-lymphocyte proliferation on subsequent culture. These observations indicate that the major effect of GST results from interference with the functional capability of the monocyte population.

Antigens↗
PubMed1977

Immunoglobulin classes of DNA binding activity in serum and skin in systemic lupus erythematosus.

36 systemic lupus erythematosus patients with native DNA binding activity (nDNA-BA) in the serum and subepidermal immunoglobulin deposits were studied to determine the relationship of the immunoglobulin (Ig) class distribution of serum nDNA-BA to the clinical characteristics of their disease and to the Ig class present at the dermal-epidermal junction (DEJ). The patients with predominantly (86-98%) IgM nDNA-BA in the serum had less active disease, mild or no renal involvement, and longer survival than those with predominantly (51-95%) IgG nDNA-BA in the serum. Renal biopsies in eight patients with predominantly IgM nDNA-BA in the serum showed relatively benign histologic changes in the kidney. In contrast, renal tissue from 23 patients with predominantly IgG nDNA-BA showed more severe histologic changes. All patients had multiple skin biopsies. Patients with predominantly IgM nDNA-BA consistently had only IgM at the DEJ. Patients with predominantly IgG nDNA-BA had IgG, usually in association with IgM, at the DEJ. The findings demonstrate that a minority of systemic lupus erythematosus patients may exhibit a limited anti-nDNA response characterized by the presence of chiefly IgM nDNA-BA in the serum and that this is reflected by the presence of mild disease and IgM alone at the DEJ. The development of IgG nDNA-BA is associated with more severe and active disease.

Centrifugation, Density Gradient↗
PubMed1977

Phagocytosis of immune complexes by polymorphonuclear leucocytes in patients with Felty's syndrome.

The possible role of phagocytosis of circulating immune complexes by neutrophils in the production of the neutropenia of Felty's syndrome has been investigated. Normal neutrophils phagocytosed massive inclusions from the sera from twelve of fifteen patients with Felty's syndrome when incubated with these sera. Such inclusions were phagocytosed from only three of fifteen patients with seropositive RA who did not have Felty's syndrome. Normal neutrophils were more effective than patient neutrophils with regard to phagocytosis of inclusions from the patients' serum suggesting a defect in phagocytic function of Felty's neutrophils. The titre of granulocyte-reactive antinuclear antibodies did not appear to be related to the degree of neutropenia. The data suggest that phagocytosis of circulating immune complexes by neutrophils may interfere with the function of these cells in combating infection and also render them susceptible to removal from the circulation thus leading to the development of neutropenia.

Antibodies, Antinuclear↗
PubMed1977

Enhancement of in vitro immunoglobulin synthesis of human lymphocytes by lysosomal enzymes from polymorphonuclear leucocytes.

The effect of human peripheral blood polymorphonuclear leucocyte (PMN) extracts and PMN granule lysates on in vitro immunoglobulin (Ig) synthesis by autologous peripheral blood mononuclear cells was studied. The mononuclear cells were cultured for 3 days with or without autologous plasma. Newly synthesized Ig in the culture supernatants was measured using 14C-labelled amino acids by an immune coprecipitation method. Upon addition of a PMN extract to plasma-free cultures Ig synthesis was stimulated, the mean stimulation index (SI) of cultures from thirteen individuals, including nine normals, three patients with rheumatoid arthritis and one with psoriatic arthritis being 1-8 +/- 0-2 in comparison with control cultures (P less than 0-05). By contrast, in 10% fresh autologous plasma, PMN extracts yielded a mean SI of 0-9 +/- 0-1 indicating inactivation of the active extracts by plasma inhibitors. In experiments using PMN granule lysates containing high concentrations of beta-glucuronidase and cultured in RPMI 1640, the mean stimulation index was 3-2 +/- 0-7. Stimulation of Ig synthesis was also produced by trypsin. Stimulation of Ig synthesis was also produced by trypsin. Stimulating factors in PMN extracts were inhibited by Trasylol, a protease inhibitor. These results indicate that trypsin and proteolytic lysosomal enzymes in PMN increase Ig synthesis of human peripheral blood mononuclear cells. They suggest a possible new role of PMN in the potentiation of immunoglobulin synthesis.

Aprotinin↗
PubMed1977

Quantitative studies of immunoglobulin deposition in the kidney, glomerular cell proliferation and glomerulosclerosis in NZB/NZW F1 hybrid mice.

Using the NZB and NZB/NZW F1 (B/W) hybrid mouse as a model for systemic lupus erythematosus, an effort has been made to quantitate: (1) immune complex deposition in the glomeruli by immunofluorescent staining of immunoglobulin, (2) glomerular cellular proliferation by radioautographic measurement of [3H]Tdr incorporation into the glomerular cells in vivo, and (3) glomerular scarring by PAS staining. The relationship between these changes and increasing age has been examined. By radioautography it was observed that dividing glomerular cells were labelled in vivo after injection of [3H]Tdr. This provided a reproducible measure of the proliferative process in the nephritis of B/W mice. In C57B1/6J and CBA/J mice, which have a low incidence of glomerular disease, little change in the amount of glomerular cell proliferation was observed with increasing age. The NZB strain of animals showed a somewhat increased level of proliferation but this did not increase with age. In striking contrast, glomerular cell proliferation in the B/W mice increased rapidly with age. The earliest change observed in the kidney was the deposition of immunofluorescent material in the mesangium and glomerular capillary basement membrane beginning between 3 and 5 months of age and reaching a peak at 9 months. Increase in glomerular cell proliferation began about 2 months after the onset of immune complex deposition but also reached a maximum at 7 months. Glomerular sclerosis was the last change to appear and continued after the other two parameters measured has begun to decline. These data suggest that the deposition of immune complexes in the glomerulus may be an important triggering mechanism for renal cell proliferation and glomerulosclerosis in the B/W mouse. The techniques described would provide a sensitive and reproducible quantitative method for analysing the differential effects of various types of treatment of immune complex nephritis in animals.

Age Factors↗
PubMed1977

The mechanism of action of cyclophosphamide on the nephritis of (NZB x NZW)F1 hybrid mice.

The effects of cyclophosphamide an antinuclear antibody levels, immune complex deposition in renal glomeruli, glomerular cell proliferation and glomerulosclerosis in the (NZB x NZW)F1 hybrid mouse have been investigated in order to better understand the mechanism of action of this drug on nephritis. Five groups of mice were injected daily with this agent (15 mg/kg) by the i.p. route over a 2-month period. Treatment periods began at 1, 3, 5, 7 and 9 months. Each group was killed at the end of the treatment period. During the last week [3H]Tdr(1 mu Ci/g) was injected daily i.p. Immune complex deposition was measured by quantification of glomerular immunofluorescent staining in both capillary loops and mesangium. Glomerular cell proliferation was quantified by measurement of the number of glomerular cells which incorporated [3H]Tdr during in vivo labelling. The number of [3H]Tdr-labelled cells in each of 100 glomeruli was counted using kidney autoradiographs of whole kidney slices. This technique provided a very reproducible and quantitative index of glomerular cell proliferation. Glomerulosclerosis was measured by determining percentage of PAS-positive material in each of 100 counted glomeruli. Immune complex deposition in the kidney preceded the glomerular cell proliferation. The proliferation reached a peak at 9 months of age. Glomerulosclerosis gradually increased with age until the animal's death. Cyclophosphamide significantly decreased antinuclear antibody levels, glomerular cell proliferation, and immunoglobulin staining in the glomeruli. Progression of glomerulosclerosis was significantly arrested. The present findings demonstrate a very significant effect of cyclophosphamide on three important pathological changes which occur in the nephritis of the (NZB x NZW)F1 hybrid mouse and provide information about possible mechanisms underlying these changes.

Animals↗
PubMed1977

Abnormal polyclonal B cell activation in NZB/NZW F1 mice.

Spleen cells from autoimmune (10-mont-old) NZB/NZW (B/W) mice failed to generate appreciable numbers of antibody-forming cells (AFC) in vitro to TNP-substituted sheep erythrocytes in response to the polyclonal B cell activators (PBA), LPS and PPD, despite normal DNA synthetic responses to these agents and normal AFC responses to TNP-Ficoll. The failure to respond to PBA in old B/W mice was not due to suppressor T cells since anti-brain-associated-theta-treated spleen cells still failed to generate AFC in response to PBA. The defect was age-related since cells from young B/W mice generated vigorous AFC responses to PBA. It is suggested that the failure of the spleen cells of old B/W mice to generate AFC is a result of in vitro polyclonal B cell activation in the course of autoantibody formation.

Aging↗
PubMed1976

The differential effects of cyclophosphamide and 6-mercaptopurine on the renal disease and skin immunoglobulin deposits of the NZB-NZW F1 hybrid mice.

The following differential effects of immunosuppressive therapy with Cyclophosphamide (CYCLOPH) and 6-mercaptopurine (6-MP) in the female NZB-NZW F1 hybrid strain have been observed: (1) CYCLOPH but not 6-MP significantly decreased antinuclear antibody level. (2) Both CYCLOPH and 6-MP significantly decreased glomerular cell proliferation. (3) Both CYCLOPH and 6-MP significantly arrested progression of glomerulosclerosis. (4) While CYCLOPH significantly diminished Ig deposition in the glomeruli, 6-MP had no effect on this phenomenon. (5) While CYCLOPH decreased subepidermal globulin deposition in the skin, 6-MP appeared actually to enhance subepidermal staining. Thus, the present studies demonstrated that CYCLOPH was superior to 6-MP in four of the five parameters studied. In the case of one parameter, Ig staining of the skin, 6-MP actually produced enhancement of the staining. Both CYCLOPH and azathioprine which is a derivative of 6-MP, are currently being used for the treatment of human SLE. The present findings suggest that of the two, CYCLOPH may be the drug of choice.

Animals↗
PubMed1976

Lymphokine stimulation of collagen accumulation.

Lymphokine-rich supernates from normal human peripheral blood mononuclear cells, stimulated by the mitogen phytohemagglutinin, have been shown to cause enhanced collagen accumulation by human embryonic lung fibroblasts (WI-38), as measured by hydroxyproline content of fibroblast monolayers, [14C] proline incorporation into soluble collagen and collagenase release of radioactivity in supernates and monolayers of cultures incubated with [14C] proline. This fibroblast-stimulating activity, demonstrable by suitable dilutions of the supernates, coexisted with a number of other lymphokine activities such as lymphotoxin, proliferation inhibitory factor, and cloning inhibitory factor, which tend to reduce the numbers of function of fibroblasts. The increased content of collagen appeared to be the product of selected surviving and responding fibroblasts. The factor causing this increased collagen accumulation was nondialyzable and stable at -70 degrees C. It represents the first described lymphoid cell-derived activity capable of enhancing collagen accumulation. Fibroblast-stimulating activity may be implicated in the abnormal fibrosis seen in association with chronic inflammation in a variety of disease states. It may have special relevance to progressive systemic sclerosis.

Cell Line↗
PubMed1975

Lymphokines in rheumatoid synovitis.

In antigen-induced experimental arthritis of rabbits, a macrophage migration inhibitory factor was released from the inflamed synovial tissues. A migration inhibitory factor, blastogenic factor, and B-cell-stimulating factor were also found in human rheumatoid synovial fluids and culture supernatants of rheumatoid tissue explants. Joint fluids from patients with inflammatory conditions other than RA sometimes also displayed these activities. OA fluids were usually inactive. At present, little is known of the origin or role in vivo of the lymphokine-like activities observed in the joints of rheumatoid patients. In related experiments, injection of lymphokine-rich antigen-free lymphocyte supernatants into normal rabbit knee joints produced a synovitis characterized by lining layer hyperplasia and infiltration of the sublining layer by macrophages. The lymphocytic and plasmacytic components seen in active antigen-induced synovitis were absent. It seems likely that some of the changes observed in active chronic synovitis are mediated by soluble factors of the lymphokine variety.

Animals↗
PubMed1975

Subepidermal deposition of immunoglobulin in NZB/NZW F hybrid mice.

The dermal-epidermal junction of NZB/NZW F1 hybrid mice is a site of immunoglobulin (Ig) deposition. This produces a fluorescent band which is very similar to that seen in the skin of patients with systemic lupus erythematosus. The deposition of Ig in the mouse skin is first observed at six months of age and increases in frequency thereafter. After an initial lag of 1 to 2 months, it parallels the age-related deposition of Ig in the kidney. The observed temporal relationship between glomerular and cutaneous Ig deposition supports the concept that the presence of immunoglobulin in the skin is highly indicative of the presence of immune complexes in the kidney.

Animals↗
PubMed1975

Experimental arthritis produced by injection of mediators of delayed hypersensitivity.

Synovitis was produced in the rabbit knee by repeated intraarticular injection of a preparation of mediators of cellular immunity. The mediators were prepared by incubation of KLH with lymph node cells of animals previously immunized with KLH in Freund's adjuvant. Following three intraarticular injections, a chronic synovitis resulted in which hyperplasia of the lining layer and infiltration of the sublining layer occurred. The cell types in the sublining layer were predominantly histiocytes and fibroblasts. These experiments demonstrate that mediators of cellular immunity may produce a chronic inflammatory reaction when injected repeatedly into normal joints. They indicate that the cellular immune response may play a role in the development of the synovitis of immunologically induced arthritides.

Animals↗