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Biomedical subjects

J E Balow

Publications and source records attributed to J E Balow.

At least 109 records · Page 6Linked to original sources
PubMed1985

Pituitary-adrenal responsiveness to corticotropin-releasing hormone in patients receiving chronic, alternate day glucocorticoid therapy.

We examined the responsiveness of the pituitary-adrenal axis to ovine corticotropin-releasing hormone (oCRH) in 14 women with systemic lupus erythematosus receiving chronic, alternate day glucocorticoid therapy with prednisone. Testing was done twice and in a random order (at 2000 h) on the day when the steroid was taken (12 h after the last dose) and on the day when no glucocorticoid was administered (36 h after the last dose). Plasma ACTH and cortisol responses were markedly blunted on the day of treatment and mildly blunted on the day off treatment compared to those in normal subjects. Altered metabolic clearance of exogenous oCRF was not responsible for this difference, since the plasma disappearance curves of immunoreactive oCRH were similar on both days. The degree of suppression was dependent on the dose of prednisone, and the amount of cortisol secreted during the oCRH test was directly proportional to the logarithm of the concurrent plasma ACTH level. Thus, the cortisol response to ACTH was normal in all patients. These data suggest that the blunting of responsiveness to oCRH on both days of testing represents prednisolone suppression of the corticotroph cell. Despite this, the adrenal glands retain normal responsiveness to ACTH, suggesting that moderate decreases in daily ACTH secretion are compatible with sustaining normal adrenal function. Hence, the site of the mild suppression of the hypothalamic-pituitary-adrenal axis during chronic, alternate day treatment with glucocorticoids is central, whereas the adrenal glands appear to remain functionally unaffected.

Adolescent↗
PubMed1985

Immunosuppressive agents and plasmapheresis in immunological disorders.

Plasmapheresis (PA) was introduced in the treatment of immunologically mediated disease at the beginning of last decade and it was initially claimed to be the panacea for several diseases. It was quickly realized that PA on its own did not have a sustained therapeutic effect and it was the immunosuppressive drugs which could help in the maintenance of an established effect. In this communication we review the immunoregulatory effects of several immunosuppressive agents and discuss their role when used in conjunction with PA primarily in the treatment of rheumatological disorders.

Animals↗
PubMed1985

Enhancement of human allogeneic cytotoxic responses by interferons.

The ability of exogenous interferons (IFN) to modify human allogeneic cytotoxic responses was studied. alpha- and beta-, and gamma-IFN, enhanced the cytotoxic responses if added at early phases of the cultures. The effect of exogenous IFN was abrogated if antibody directed against the specific IFN were present in the cultures. Normal allogeneic cytotoxic responses were abrogated in the presence of any of the anti-IFN antibodies. This inhibition could be overcome if exogenous IFN of any type (alpha, beta, or gamma) was added in excess to the cultures. IFN participate in the generation of allogeneic cytotoxic lymphocytes during mixed lymphocyte culture. It seems that each of the types of IFN supports the generation of cytotoxic responses independently of the presence of an IFN of another type.

Antibodies↗
PubMed1985

Lupus nephritis and other autoimmune features in patients with diabetes mellitus due to autoantibody to insulin receptors.

The frequency of various autoimmune features in 14 patients with insulin-resistant diabetes mellitus (type B) was reviewed. Twelve patients had leukopenia, high titers of antinuclear antibodies (speckled pattern), and hypoalbuminemia; 11 had elevated serum levels of IgG and high erythrocyte sedimentation rates; 7 had proteinuria and high serum levels of antibodies to DNA; and 5 had alopecia and elevated serum levels of IgA. Lupus erythematosus preparations were negative in all patients. Eight patients met the conventional criteria for the diagnosis of systemic lupus erythematosus. Three patients developed renal involvement while under care at the National Institutes of Health. Kidney tissue samples showed proliferative and membranous glomerulonephritis, tubulointerstitial nephritis, and electron-dense deposits similar to those of lupus nephritis. The lupus nephritis in these 3 patients appeared to be independent of the level of insulin-receptor antibody and glucose dysmetabolism. This study documents the presence of systemic lupus erythematosus in a large proportion of patients with insulin resistance due to autoantibodies to insulin receptors and emphasizes that careful monitoring of such patients for major complications of lupus nephritis is warranted.

Adult↗
PubMed1985

Regulation of immunoglobulin secretion by factor H of human complement.

As human B lymphocytes and macrophages carry surface receptors for Factor H (B1H), we investigated the possibility that this complement component regulates their function. Factor H inhibits immunoglobulin secretion by peripheral mononuclear cells (MNC) stimulated with pokeweed mitogen if present at the initiation of the cultures and at concentrations greater than 50 micrograms/ml. Factor H also inhibited stimulation and differentiation of purified B cells into immunoglobulin-secreting cells by Epstein-Barr virus (EBV). The inhibitory effect of Factor H was abrogated if anti-Factor H antibody was present in the cultures. EBV-transformed B-cell lines secreted less immunoglobulin if Factor H was present in the culture for at least 4 days. Culture of MNC with Factor H did not lead to the generation of suppressor T cells or macrophages. In contrast, Factor H did not cause proliferation of human peripheral total MNC or enriched T-cell or B-cell subpopulations. Also, Factor H did not inhibit the proliferation of MNC in response to several mitogens and antigens. Our results strongly indicate that Factor H is able to block human B-cell differentiation in vitro without blocking the proliferative ability of the cells. Factor H seems to act directly on the B cells through its receptor on their surface, since it inhibited T-dependent and T-independent B-cell differentiation but generated no suppressor cells.

Antibody-Producing Cells↗
PubMed1984

Effect of treatment on the evolution of renal abnormalities in lupus nephritis.

We retrospectively studied the evolution of histopathologic features in successive renal biopsies in patients with lupus nephritis, to evaluate the effects of various treatment regimens. Repeat renal biopsies had been performed in 62 patients after more than 18 months of observation (median interval, 44 months) in randomized therapeutic trials comparing prednisone with cytotoxic drugs. Renal histopathologic features were graded individually, and a composite score reflecting the number and severity of irreversible lesions was defined as a chronicity index. The chronicity index for patients treated with conventional high-dose prednisone increased linearly with the interval between biopsies, whereas the index in the group receiving cytotoxic-drug treatments did not increase over time. After statistical adjustment for important prognostic factors (age and initial chronicity index) identified by multiple linear regression, the difference in the slopes between the group receiving prednisone and the group receiving cytotoxic drugs was significant (P less than 0.0001). We conclude that cytotoxic-drug treatment reduces the likelihood of progressive renal scarring in lupus nephritis.

Adult↗
PubMed1984

Lymphocyte subpopulations in patients with systemic lupus erythematosus.

A discrepancy between E-rosette-forming cells and total T cells identified by monoclonal antibodies (Leu-1+) was observed in patients with systemic lupus erythematosus (SLE). E-Rosette-forming cell percentages of peripheral blood mononuclear cells (MNC) were significantly lower than those observed in normal individuals, in contrast to the percentage of Leu-1+ cells in SLE patients which were not different from those of normal values. The cells which did not form E rosettes, but stained positively with the monoclonal anti-Leu-1 antibody (E-, Leu-1+) had certain functional capability evidenced by their ability to amount a proliferative response to T-cell mitogens, phytohemagglutinin and concanavalin A, but failed to provide T-helper-cell activity to support the differentiation of normal B lymphocytes into immunoglobulin-secreting cells following stimulation with pokeweed mitogen. Inhibition of E-rosette formation, but not of the staining for Leu-1, was demonstrated by incubating sera from SLE patients with normal MNC. These studies suggest that the T-cell markers, E+ and Leu-1+, do not necessarily characterize identical subpopulations of T cells. When referring to E- cells in studies with MNC from SLE patients, it should be realized that this population includes, in addition to B cells and macrophages, cells staining positively for Leu-1 antigen and reactive to T-cell mitogens.

Antibodies, Monoclonal↗
PubMed1984

Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome.

Prerandomization renal biopsy specimens were examined in 102 patients upon entry into prospective therapeutic trials of lupus nephritis in an attempt to identify early predictors of renal failure outcome. All 11 renal failures occurred among the 72 individuals with diffuse proliferative or membranoproliferative glomerulonephritis (DPGN/MPGN); thus, these patients were at modestly, but significantly, increased risk of endstage renal disease compared to those with focal proliferative, membranous, or mesangial glomerulonephritis. Considering the low incidence of endstage renal disease among patients with DPGN/MPGN, we sought to refine the prognostic information obtained from renal morphology by semiquantitative scoring of individual histologic features and by derivation of composite histologic scores specified by Activity (AI) and Chronicity (CI) Indices. Among the 72 patients with DPGN/MPGN, the composite AI was more strongly predictive of renal failure than were the individual active histologic features; cellular crescents and extensive fibrinoid necrosis yielded positive associations, while endocapillary proliferation, leucocytic exudation, and hyaline thrombi in glomeruli and interstitial inflammation by themselves did not emerge as useful prognostic indicators. However, chronicity items (glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis) considered individually, as well as in the composite CI, were highly predictive of renal failure outcome. Particularly striking was the prognostic value of tubular atrophy; all 11 renal failures were among the 43 patients with tubular atrophy on prerandomization renal biopsy. While no single pathologic variable improved outcome predictions among those with tubular atrophy, examination for interactions among variables revealed that glomerular sclerosis and cellular crescents had a synergistic effect which augmented the prognostic information derived from analysis of tubular atrophy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Modulation of human B cell immunoglobulin secretion by the C3b component of complement.

The human C3b component of complement was found to inhibit the differentiation of human B lymphocytes into immunoglobulin-secreting cells in vitro. Pokeweed mitogen (PWM)-induced plaque-forming cell (PFC) responses were inhibited by C3-coated zymosan particles and by purified human C3b. C3b inhibited the PWM-driven responses in a dose-dependent fashion, and it was necessary for C3b to be present in the early phases of the cultures. C3b acted directly on B cells rather than on helper T cells because it inhibited the PFC responses of MNC depleted of T cells and subsequently stimulated with a T cell-independent Epstein Barr virus mitogen. Furthermore, C3b failed to stimulate the generation of suppressor lymphocytes and/or monocytes that might have been responsible for the inhibition of B cell responses. Our results indicate that C3b or its fragments exert negative modulatory effects on human B lymphocyte responses.

Antibodies↗
PubMed1984

T and B lymphocyte function in patients with lupus nephritis: correlation with renal pathology.

The relationship between in vitro measures of T and B cell responses of peripheral blood lymphocytes and histological findings on renal biopsy was examined in 32 patients with lupus nephritis. T cell mediated responses, assessed by mixed leucocyte reaction (MLR) and cell mediated lympholysis (CML), were decreased, while spontaneous immunoglobulin secretion by B cells, measured by plaque forming cell (PFC) assay, was increased above normal in the whole patient population. There were no significant differences in these T or B cell responses between patients with the diffuse proliferative and the membranous forms of lupus nephritis. Using a semi-quantitative index of the histologic activity of diffuse proliferative lupus nephritis, a good correlation was noted between the degree of abnormality of B cell responses and the level of activity seen on renal biopsy. The nature of the relationship between B cell abnormalities and the expression of lupus nephritis warrants further study.

B-Lymphocytes↗
PubMed1983

Randomised trial of plasma exchange in mild systemic lupus erythematosus.

The effects of intensive plasma exchange on the serological and clinical manifestations of mildly active systemic lupus erythematosus were evaluated in a controlled, double-blind trial. Twenty patients were randomised to receive either six 4-litre plasma exchanges or a seemingly identical control procedure over a 2-week period. Plasma exchange produced significant reductions in serum levels of IgG, IgM, IgA, and circulating immune complexes measured by an 125I-Clq binding assay. These serological measures returned to baseline 4 weeks after plasma exchange without a rebound above baseline values. Antibodies to DNA were reduced immediately after plasma exchange; however, they often returned to pre-treatment levels before the next procedure. No changes in any of the serological measures were observed in the control group. In sixteen of the eighteen patients who completed the clinical trial activity had either remained stable or improved; the frequency and degree of clinical improvement was the same in both plasma exchange and control groups.

Adolescent↗
PubMed1983

Prognostic factors in lupus nephritis. Contribution of renal histologic data.

The predictive value of laboratory results and renal histologic data was examined in 102 patients upon entry into prospective, randomized, therapeutic trials of lupus nephritis. Three clinical features at the time of entry into the study were individually associated with increased rates of renal failure: age less than 24 years, male gender, and an elevated serum creatinine level. Subjects with diffuse proliferative or membranoproliferative glomerulonephritis were at a modest but significantly increased risk for the development of end-stage renal disease compared with patients with other classes of lupus nephritis. Semiquantitative scores of histologic features (specified by activity and chronicity indexes) identified subgroups of patients with comparatively high renal failure rates. To address the controversial issue of whether renal histologic data significantly improve the outcome predictions in patients with lupus nephritis, multivariate survival models were generated, permitting simultaneous consideration of multiple prognostic factors. Outcome predictions based on the strongest clinical predictors (age, sex, and serum creatinine level) were significantly enhanced by the addition of activity and chronicity indexes. Only age and chronicity index contributed significantly to the five-variable model and together constituted a two-variable model, the predictions of which were similar to observed outcomes. In the context of the highly significant prognostic indicators (age and chronicity index), immunosuppressive agents appeared to provide a slight therapeutic advantage over oral corticosteroids alone.

Adolescent↗
PubMed1983

Induction of monocytic suppression after stimulation of peripheral human mononuclear cells with staphylococcal protein A and Staphylococcus aureus.

Staphylococcal protein-A (SPA) and Staphylococcus aureus are known to be polyclonal human B-cell activators. It was noted that they induced plaque-forming-cell (PFC) responses lower than those induced by pokeweed mitogen (PWM) and the possibility of early triggering of a suppressor cell was investigated in the present series of experiments. Peripheral mononuclear cells (MNC) were passed through Sephadex G-10 columns to eliminate monocytes. The PFC responses to SPA and S. aureus were thereby increased. PWM-driven PFC responses are suppressed by the simultaneous presence of SPA in a dose-related way, if present in the early phases of the cultures. MNC precultured with SPA or S. aureus have the ability to suppress the PFC response of autologous MNC to PWM. Interestingly this suppressor cell activity was radiation resistant and could not be abrogated by treatment with anti-T-cell monoclonal antibody plus complement. The above experiments clearly demonstrate that the observed low PFC responses of MNC after stimulation with SPA and S. aureus are due to the induction of suppressor cells by these stimulants. The suppressor cells are apparently of monocytic origin.

Antibody-Producing Cells↗
PubMed1983

Phenotypes of T lymphocytes in systemic lupus erythematosus: decreased cytotoxic/suppressor subpopulation is associated with deficient allogeneic cytotoxic responses rather than with concanavalin A-induced suppressor cells.

Patients with systemic lupus erythematosus (SLE) have decreased precursors of cytotoxic/suppressor T lymphocytes in their peripheral blood, as determined by monoclonal antibodies. To determine whether decrease of the cytotoxic or the suppressor parts (or both) of this subpopulation of T lymphocytes is being reflected by this peripheral mononuclear cell (MNC) abnormality, a series of experiments was conducted in which both the suppressive function (concanavalin A induced and spontaneous) and the generation of cytotoxic responses against alloantigens were tested. Cytotoxic responses were consistently diminished while suppressor capacity of MNC from patients with SLE (measured on several assays of normal T- and B-lymphocyte functions) was comparable to that of MNC from normal individuals. The defect in cytotoxic responses to alloantigens by MNC from SLE patients persisted following secondary stimulation in mixed-leukocyte cultures; the cytotoxic responses were not amplified and remained well below the responses of normal MNC. These experiments indicate that the decreased peripheral population of cytotoxic/suppressor lymphocytes in SLE patients represents low or absent precursors of cytotoxic cells rather than of precursors of suppressor cells.

Antibodies, Monoclonal↗