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Biomedical subjects

R S Krakauer

Publications and source records attributed to R S Krakauer.

At least 19 recordsLinked to original sources

The influence of thymic humoral factor on systemic lupus erythematosus lymphocyte function.

The influence of thymic humoral factor, THF, on systemic lupus erythematosus, SLE, lymphocyte function was investigated. Increasing numbers of SLE T-cells, rosetted at 4 degrees C or 37 degrees C, were cultured with allogeneic normal B-cells and the change in IgM synthesis was assessed. Lymphocytes of some SLE patients showed improved suppression with THF when rosetted at 37 degrees C. Normal control lymphocytes did not show a net change in suppression with THF. The subgroup of SLE patients that showed improved suppression with THF in vitro might be a more appropriate group for in vivo therapeutic trials with thymic hormone, TH, than SLE patients in general.

B-Lymphocytes

Therapeutic trial of cryofiltration in patients with rheumatoid arthritis.

Cryofiltration, a new technique for on-line plasma separation and its treatment by cold filtration, enables the selective removal of immune complexes and eliminates the need for replacement proteins. Fifteen patients with rheumatoid arthritis were treated for nine to 10 consecutive sessions over a three- to five-week period. Circulating immune complexes decreased by an average of 78 percent and rheumatoid factor by 32 percent. This was accompanied by significant clinical improvement in morning stiffness, articular index, 50-foot walking time, grip strength, and target joint circumference. Cryofiltration might thus be beneficial for a subgroup of rheumatoid arthritis patients in whom conventional therapy has failed.

Arthritis, Rheumatoid

Circulating immune complexes in rheumatoid arthritis. Selective removal by cryogelation with membrane filtration.

We have developed a system of extracorporeal circulation that removes proteins of the molecular weight of the circulating immune complexes of rheumatoid arthritis by cryogelation with hollow-fiber membrane filtration. A 52-year-old woman with a 36-year history of severe, unremitting, high-titer, seropositive rheumatoid arthritis who had failed to respond to anti-inflammatory, antirheumatic, and cytotoxic drugs was chosen for a trial of this system. A rapid and sustained decrease in circulating immune complexes as measured by C1q binding occurred, accompanied by a much slower improvement in clinical factors of disease activity. Rheumatoid factor changed very little and loss of other serum proteins by the procedure was relatively modest. This new procedure was successful in removing circulating immune complexes in a patient with rheumatoid arthritis, and in inducing a remission in one who has not had such in 36 years, while sparing volume and other plasma proteins.

Antigen-Antibody Complex

Hydrocortisone reverses the suppression of immunoglobulin synthesis by concanavalin A-activated spleen cell supernatants.

Supernatants of concanavalin A (Con A)-activated human spleen cells have been previously shown to inhibit polyclonal immunoglobulin (Ig) biosynthesis by pokeweed mitogen (PWM)-stimulated human spleen and peripheral blood mononuclear cells. In the present study, hydrocortisone was added at the beginning of in vitro culture to determine whether it might influence the immunoregulation of polyclonal IgG, IgA and IgM biosynthesis by PWM-stimulated human spleen and peripheral blood mononuclear cells. Hydrocortisone (10(-5) m) mildly increased (15 +/- 9%; mean +/- s.e.m.) polyclonal Ig biosynthesis when added to PWM-stimulated human mononuclear cells. The addition of supernatants from Con A-activated human spleen cells to PWM-stimulated human spleen and peripheral blood mononuclear cells significantly (P less than 0 . 001) suppressed (94 +/- 2%) polyclonal Ig biosynthesis. In contrast, when hydrocortisone (10(-5) m) was added together with Con A supernatants to PWM-stimulated cells, there was no significant suppression (6 +/- 13%) of polyclonal Ig synthesis. Thus, one mechanism by which hydrocortisone can influence Ig biosynthesis is by blocking the suppressive effect of a soluble suppressor factor secreted by Con A-activated human spleen cells.

Antibody-Producing Cells

Lymphocyte kinetics in pustular psoriasis.

Generalized pustular psoriasis is a potentially lethal variant of psoriasis vulgaris characterized by the appearance of sterile pustules on inflamed psoriatic skin. We now report the finding of an absolute lymphopenia at the onset of pustular psoriasis. While the white blood cell count rises to a level of 25,000 to 40,000 in the initial stages of a pustular flare, the lymphocyte count drops from a normal level to an absolute lymphopenia. This "lymphocyte eclipse," as we have called it, appears to be a reliable sign of impending pustular activity and has now been documented in ten patients with pustular psoriasis. Immediate institution of therapy may abort a potentially lethal complication of psoriasis.

Adrenal Cortex Hormones

Abnormalities of immunoregulation in progressive systemic sclerosis. Evidence for excess helper-cell function and altered B-cell function.

We investigated immunoregulatory function in patients with progressive systemic sclerosis (PSS) in terms of in vitro IgM synthesis. Suppressor-cell function seems normal in regard to the ability of concanavalin A-treated cells to inhibit IgM synthesis by normal cells. At 4 x 10(5) T cells to 3 x 10(5) allogeneic normal B cells per milliliter, T cells from patients with PSS induce significantly more IgM synthesis by normal B cells than do normal T cells. This increased helper T-cell function might be involved in the pathogenesis of the disease.

Adult

Suppressor cell function in psoriasis.

Recent studies suggest that autoimmunity may play a role in the pathogenesis of psoriasis. In view of these findings, it is postulated that the immunologic defect may be associated with regulation of the immune system. A study was undertaken to determine whether a suppressor cell defect was present. Two groups of patients with active psoriasis who were receiving no therapy were selected. Peripheral blood lymphocytes were pulsed with concanavalin A, 40 microgram/cc, for 48 hours. Their ability to suppress a mixed lymphocyte reaction with both autologous and allogeneic responding cells was assessed. There was a significant decrease in suppressor activity in psoriasis patients compared with normal individuals. Although we have not demonstrated that this mechanism is implicated directly in a causal relationship to psoriasis, it nevertheless gives further support to the possible role of the immune system in the pathogenesis of psoriasis.

Concanavalin A

Effects of concanavalin A-stimulated spleen cell supernate on the redevelopment of autoimmunity in NZB/NZW mice in induced remission.

Because female NZB/NZW mice develop autoimmune abnormalities similar to those encountered in human systemic lupus erythematosus (SLE), a group of female NZB/NZW mice were used to study mechanisms of autoimmunity. These mice were treated daily with an immune suppressive material, 0.5 ml of a concanavalin A-stimulated spleen cell supernate (CONS), starting at 30 weeks of age after induced remission with prednisolone. This CONS treatment effectively reduced the proteinuria and the severity of the renal lesions, but failed to reduce the serum anti-DNA antibody level. Thus, the CONS effect on the autoimmunity in the NZB/NZW mice in induced remission appears to result from a more complicated mechanism than reduction in serum anti-DNA antibody level.

Animals