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Biomedical subjects

M Ziff

Publications and source records attributed to M Ziff.

At least 91 records · Page 5Linked to original sources
PubMed1980

Myocarditis in mixed connective tissue disease. Association of myocarditis with antibody to nuclear ribonucleoprotein.

A young black woman with clinical and serologic features of mixed connective tissue disease (MCTD) developed myocarditis with congestive heart failure and ventricular ectopic activity. Despite treatment with steroids and cyclophosphamide, progressive myocarditis resulted in death 20 months after cardiomegaly first developed. Necropsy findings in the myocardium included multiple areas of extensive lymphocytic infiltration and patches of fibrosis. Myocarditis has not previously been described in the adult with MCTD but may be an important complication in patients with a high titer of antibody to nuclear ribonucleoprotein.

Adult↗
PubMed1980

Absence of immunoglobulins in rheumatoid cartilage-pannus junctions.

Immune complexes (IC) present in the superficial region of rheumatoid articular cartilage may be an important factor in the invasion of the cartilage by pannus. The presence of such IC at the cartilage-pannus junction in rheumatoid articular cartilage invaded by pannus was investigated by using immunoelectron microscopy with horseradish peroxidase anti-human immunoglobulin (Ig). It was observed that, although the pannus-free surface of the cartilage contained easily detectable deposits of Ig, the areas covered by pannus failed to show any Ig in the 5 5 patients studied. This was true even in areas immediately adjacent to the advancing edge of the pannus which presumably had only recently been invaded by the granulation tissue. These results were confirmed by fluorescent antibody ultraviolet microscopy. It was concluded that rheumatoid pannus invasion of the free cartilage surface containing trapped IC results in the disappearance of such complexes.

Antibodies↗
PubMed1980

Inhibition of human helper T cell function in vitro by D-penicillamine and CuSO4.

The effect of d-penicillamine (Pen) and mixtures of Pen and copper sulfate on the capacity of normal human peripheral blood mononuclear cells (PBM) to generate immunoglobulin-secreting cells (ISC) in response to the T-cell-dependent polyclonal B-cell activators pokeweed mitogen (PWM) and staphylococcal protein A (SPA) was examined. PBM obtained from normal individuals were incubated for 1-2 h at 37 degrees C with medium alone, Pen, CuSO(4), or a mixture of Pen and CuSO(4). After washing, the cells were incubated for 6-7 d with PWM or SPA and then, with a reverse hemolytic plaque assay, assayed for the number of ISC generated. Preincubation of PBM with either Pen (100 mug/ml) or CuSO(4) (2 mug/ml) did not alter the subsequent capacity of the cells to generate ISC in response to PWM or SPA. In contrast, responsiveness to both mitogens was nearly abolished when PBM were similarly preincubated with a mixture of Pen and CuSO(4). Inhibition of responsiveness could not be ascribed to cell death, carry-over of the inhibitors, or an alteration in the concentration of PWM or the length of incubation yielding maximum responses. Co-culture experiments demonstrated that Pen and CuSO(4) preincubation had not caused augmented suppressor cell function. Experiments in which PBM were separated into adherent and nonadherent populations indicated that Pen and CuSO(4) preincubation inhibited the responsiveness of the nonadherent cells but did not alter the accessory cell function of monocytes. To determine whether Pen and CuSO(4) preincubation effected T- or B-cell function, PBM were separated into B- and T-cell-enriched populations, individually preincubated with Pen and CuSO(4), and then co-cultured with PWM. The results indicated that Pen and CuSO(4) markedly inhibited helper T-cell function and had little effect on the capacity of B cells to generate ISC. The observation that in the presence of CuSO(4) Pen inhibits helper T-cell activity may, in part, explain the therapeutic efficacy of Pen in rheumatoid arthritis and especially the capacity of Pen therapy to decrease antiglobulin titers in treated patients.

Adult↗
PubMed1979

Interaction of polymorphonuclear leukocytes with immune complexes trapped in joint collagenous tissues.

The present experiments were designed to investigate in vitro interactions between polymorphonuclear leukocytes (PMN) and rabbit joint collagenous tissues containing trapped immune complexes. Articular cartilages and menisci from antigen-injected and control joints were incubated with normal PMN isolated from rabbit peritoneal exudates or blood. After incubation of cartilage and menisci from antigen-injected joints with PMN, large numbers of PMN became attached to the articular surface. In areas of superficial erosion, the PMN invaded the tissue several cell diameters below the articular surface. Through immunoelectron microscopy, degranulated PMN were observed in scattered areas to phagocytose amorphous material containing rabbit Ig. Following addition of PMN to control tissues, only a few PMN became attached to the articular surface. When tissues from monosodium urate-injected joints were incubated with PMN, these cells were found attached to the surface in moderate numbers, but invasion into the tissues was not seen. These studies indicate that immune complexes trapped in joint collagenous tissues may lead to enhanced release of lysosomal hydrolases.

Animals↗
PubMed1979

Increased C1q binding immune complexes in Felty's syndrome: comparison with uncomplicated rheumatoid arthritis.

Sera from patients with Felty's syndrome (FS) and rheumatoid arthritis (RA) were examined for the presence of circulating immune complexes (IC) by using the 125I-C1q binding and monoclonal rheumatoid factor (mRF) techniques. Of 15 patients with FS, 9 (60%) had high 125I-C1q binding as compared to 3 of 26 RA patients (12%). The average C1q binding was significantly higher in the FS patients than in the RA patients without FS. C1q binding in both FS and RA patients was significantly higher than a group of 90 normal controls. In addition, serum C4 levels were significantly lower in the FS patients than in the RA patients. In contrast to these findings, IC levels in FS and RA patients were very similar when measured by the mRF technique. These studies indicate that FS patients have higher levels of complement-fixing IC in their sera than RA patients without FS. These findings raise the possibility that the complement-fixing IC found in these patients may play a role in the pathogenesis of neutropenia of FS.

Adult↗
PubMed1979

The rarity of Felty's syndrome in blacks.

Evidence is presented that Felty's syndrome (FS) is rare among black patients with rheumatoid arthritis (RA). All of 12 patients with FS seen at Parkland Memorial Hospital, Dallas, Texas betwen 1964 and 1978 were white. During this period 52% of patients admitted to the Parkland medical service were black and 31% of patients dischargd with a diagnosis of RA were black. The number of expected black cases of FS on the basis of the racial distribution of hospitalized patients with RA was 3.7 (P is less than 0.02 when the zero incidence in blacks was compared with the expected incidence). All 7 cases of FS observed at Charity Hospital, New Orleans, Louisiana between 1968 and 1978 were also white. During this period, 65% of patients discharged with a diagnosis of RA were black, and the number of expected black cases of FS was 4.5 (P is less than 0.001). These findings suggest a genetic basis for the development of leukopenia and splenomegaly in RA patients.

Adult↗
PubMed1979

Gold-induced changes in the morphology and functional capabilities of human monocytes.

The capacity of gold compounds to induce morphologic changes and alterations in the functional activity of human mononuclear phagocytes (M phi) in vitro was examined. Human peripheral blood mononuclear cells were incubated with gold sodium thiomalate (25 microgram/ml) for 96 hours. As a result, M phi developed electron dense precipitates within phagolysosomes, as well as marked dilatation of these organelles. Gold incubation also altered a number of M phi functions. While viability and adherence were unaffected, the capacity to spread on surfaces was diminished. Pinocytosis of soluble proteins and phagocytosis of opsonized sheep erythrocytes were impaired, but Fc mediated particle binding was not. These data indicate that gold can alter certain functional activities of M phi and support the idea that the major action of gold in rheumatoid arthritis results from its capacity to alter M phi function.

Cell Adhesion↗
PubMed1979

Alterations in human monocyte structure and function induced by incubation with gold sodium thiomalate.

The effect of in vitro indubation with gold sodium thiomalate (GST) on the morphology and functional activity of human mononuclear phagocytes (Mphi) was examined. Human peripheral blood Mphi that had been incubated with GST (25 micrograms/ml) for 4 days developed large intracytoplasmic vacuoles. Similar vacuolization developed after incubation with gold chloride but not with thiomalic acid. GST pre-incubation also induced a number of functional alterations in Mphi. GST incubation had little effect on glass adherence or FC receptor-mediated particle binding but markedly diminished pinocytosis of horseradish peroxidase and phagocytosis of IgG opsonized erythrocytes. These data indicate that the action of GST in rheumatoid arthritis may result from its capacity to alter the functional capability of Mphi.

Cell Survival↗
PubMed1979

General mechanisms of inflammation in rheumatoid arthritis.

Rheumatoid synovitis is characterized by the simultaneous occurrence of two major types of immunologically-induced inflammation. These usually occur concurrently in the same joint. A cellular immune response is present in the sublining layer of the synovial membrane and an immune complex-induced acute inflammatory reaction is present in the synovial effusion phase of the disease. The two reactions are closely related and mutually interdependent. The cellular immune response is reduced in rheumatoid arthritis, but the chronic inflammatory cells of the synovium are active in the synthesis of IgG and probably considerable amounts of IgG rheumatoid factor. Rheumatoid factor complexes, particularly IgG-RF complexes, appear to be responsible for the exudative, immune complex-induced inflammatory phase of the disease.

Arthritis, Rheumatoid↗
PubMed1978

Primary in vitro cell-mediated lympholysis reaction of NZB mice against unmodified targets syngeneic at the major histocompatibility complex.

T-cell cytotoxicity of NZV mice was tested after in vitro sensitization against a group of H-2 identical strains (BALB/c, B10.D2, DBA/2, HW19). A highly significant and unexpected unidirectional cell-mediated lympholysis (CML) reaction by the sensitized NZB effector cells on these targets was found. After sensitization in vitro with stimulator cells of one H-2d strain, NZB effector cells (H-2d) lysed all other H-2d targets and to a lesser degree, some non-H-2d targets (C57BL/10, DBA/1, B10.Q, CBA, B10.S, A.SW). NZB targets were not lysed. Differences in the major histocompatibility region between NZB and other H-2d strains could be excluded as a possible explanation for the observed reaction of NZB (H-2d) against other H-2d strains. These results consequently represent the first description of a primary in vitro CML directed against determinants not coded for in the major histocompatibility complex. The responsible effector cells are demonstrated to be T cells. The CML of NZB against H-2 identiical targets appears best explained by a reaction against minor histocompatibility antigens. This, and the observed cross-reactions, would indicate that the cytotoxic T-cell system in NZB mice is not subjected to restrictions found in all normal mouse strains tested until now under similar conditions. It is suggested that this hyperreactivity is related to the autoimmune responsiveness of the NZB strain.

Animals↗
PubMed1978

Comparison of the presence of immune complexes in Felty's syndrome and rheumatoid arthritis.

Evidence has been found to document the presence of circulating immune complexes in all patients with Felty's syndrome. The sera of all 12 patients studied showed intermediate complexes by analytical ultracentrifugation. The sera of 9 of 12 patients (75%) showed precipitin lines upon immunodiffusion against IgM rheumatoid factor. Both findings were statistically increased above those in a matched group of patients with classic rheumatoid arthritis. The presence of circulating immune complexes in the sera of the Felty patients was consistent with the observation that large inclusions containing IgG, IgM, and complement were phagocytized by normal polymorphonuclear cells when incubated with sera of Felty patients. Normal polymorphonuclear cells phagocytosed inclusions from 77% of Felty sera, compared with 27% classic rheumatoid arthritis sera. It is suggested that the uptake of immune complexes by polymorphonuclear cells plays a role in the neutropenia of Felty's syndrome.

Antigen-Antibody Complex↗
PubMed1978

An appraisal of tests for native DNA antibodies in connective tissue diseases. Clinical usefulness of Crithidia luciliae assay.

Antibody to native DNA was measured by five techniques: the Crithidia luciliae immunofluorescence (CL-IF) test; filter radioimmunoassays using either untreated human KB DNA, endonuclease-treated KB DNA, or a synthetic polynucleotide (poly dAT); and the Farr immunoprecipitation assay using KB DNA. The specificity and sensitivity of the CL-IF assay was similar to that of the filter radioimmunoassay procedures using KB DNA. The CL-IF test showed an increased frequency of positive tests in patients with active disease and severe renal involvement. In patients with severe renal involvement, high titers of serum nDNA antibodies were measured by this procedure. A unique advantage of the CL-IF test was its ability to identify complement-fixing nDNA antibody. The presence of such antibody was correlated with high antibody titer and the presence of severe renal disease. The CL-IF assay is a simple and useful procedure for measurement of anti-nDNA.

Antibodies, Antinuclear↗
PubMed1978

Control of human B lymphocyte responsiveness: enhanced suppressor T cell activity after in vitro incubation.

Human peripheral blood mononuclear cells (PBM) lost the capacity to generate immunoglobulin-secreting cells (ISC) in response to pokeweed mitogen (PWM) after a period of preincubation in vitro. When fresh PBM were co-cultured with preincubated PBM their response to PWM was inhibited, indicating that enhanced suppressor activity developed in the aged PBM concomitant with the loss of PWM responsiveness. Suppressor cell activity of aged PBM was present within the T lymphocyte population. The suppressor T cell inhibited PWM responsiveness of autologous and homologous PBM to an equivalent degree. The action of the suppressor cell was abrogated by inhibitors of DNA synthesis or by hydrocortisone. A suppressor T cell population with similar characteristics was found in freshly prepared PBM before in vitro incubation. Expansion of this suppressor T cell population during preincubation required cell division. There was no change in the functional capability of the helper T cell population as a result of similar in vitro culture. These observations indicate that a T cell population capable of suppressing PWM-induced generation of ISC can be selectively expanded by in vitro incubation of normal human PBM without additional mitogenic stimulation. Moreover, these data emphasize that control of B lymphocyte differentiation involves a critical interrelationship between T lymphocyte subpopulations exerting both positive and negative influences.

Antibody-Producing Cells↗
PubMed1978

Characterization of a B cell defect in the NZB mouse manifested by an increased ratio of surface IgM to IgD.

In an effort to define the cellular basis of abnormalities in polyclonal B cell activation previously noted in NZB mice, the surface immunoglobulin (sIg) isotypes of spleen cells from NZB mice were examined. After lactoperoxidase-catalyzed radioiodination, the cell surface immunoglobulins were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Spleen cells from 8- to 10-week-old NZB mice were found to have an increased ratio of cell surface IgM/IgD compared to cells from 11 control strains. The altered ratio of sIg isotypes was not a consequence of increased proteolytic activity present in NZB cell suspensions or of the presence of cytophilic antibody or autoantibody. Ontogenetic studies of the sIgM/sIgD (mu/delta) ration on splenocytes from NZB and BALB/c mice revealed that the former cells had higher mu/delta ratios as early as 2 weeks after birth. By 4 weeks of age the mu/delta ratios were equivalent. Between 4 weeks and 1 year of age, the mu/delta ratios on NZB splenocytes remained constant whereas those on BALB/c splenocytes decreased and reached adult levels at 6 weeks.

Animals↗
PubMed1978

The effect of D-penicillamine on mitogen-induced human lymphocyte proliferation: synergistic inhibition by D-penicillamine and copper salts.

The effect of D-penicillamine on in vitro mitogen-triggered human peripheral blood lymphocyte DNA synthesis was examined. D-penicillamine caused a modest degree of inhibition of responsiveness. Since D-penicillamine avidly chelates copper, a possible additive effect of D-penicillamine and copper salts on mitogen-induced lymphocyte proliferation was investigated. The addition of various copper salts to D-penicillamine-containing cultures resulted in a marked augmentation in the degree of inhibition observed. Specificity for the synergy between D-penicillamine and copper was suggested by the failure of iron, zinc, or gold salts to augment the inhibition produced by D-penicillamine alone. However, a number of other thiols, but not disulfides, could substitute for D-penicillamine in inhibiting mitogen responsiveness in the presence of copper salts. Preincubation of peripheral blood mononuclear cells with D-penicillamine and CuSO4 resulted in diminished mitogen responsiveness on subsequent culture in the absence of the inhibitors. Data are presented to indicate that preincubation with D-penicillamine and CuSO4 directly affected the ability of the T lymphocytes to respond to mitogens but did not alter the capacity of the monocytes to act as accessory cells in this response.

Acetates↗
PubMed1978

Association of interstitial nephritis with tubule cell injury and proliferation in NZB/NZW mice.

The relationship between renal interstitial mononuclear cell infiltration and renal tubule cell (TC) proliferation has been examined in (NZB X NZW) F1 hybrid (B/W) and control mice. TC proliferation was measured by tritiated thymidine ([3H]TdR) injection, autoradiographic examination of kidney sections and enumeration of labelled tubule cells. In B/W mice interstitial infiltration began at 5 months and reached a peak at 9 months. Proliferation of TC began at 7 months and also reached a peak at 9 months. Control mice consisting of NZB, CBA/J and C57Bl/6J mice showed no increase with age. When the percentages of labelled TC in areas adjacent to interstitial infiltrates and distant from them were compared, the TC adjacent to infiltrates showed an approximately four-fold greater amount of labelling. Ultrathin light and electron microscopic sections demonstrated TC injury in areas in close proximity to infiltrates. These studies suggest that mononuclear cells in the interstitial infiltrate may be injurious to TC, leading to a sequence of injury and subsequent regeneration of these cells. In diseases in which interstitial nephritis is present, such as Sjögren's syndrome, the interstitial infiltrate may contribute to the observed TC dysfunction.

Animals↗