Late treatment of murine lupus erythematosus with dactinomycin. II. C1 and antibody to DNA.

(NZB x NZW)F1 hybrid (B/W) female mice were treated intermittently with dactinomycin beginning at 6--6.5 months of age. Survival was greatly prolonged relative to control mice. IgG antibody to DNA did not decline significantly in the treated mice until they were more than 18 months old, but circulating levels of the first complement component (Cl) rose during the first 4 weeks of treatment and were back into the normal range after 8 weeks. Thus these two humoral indexes of disease activity varied independently, and only Cl reflected the improved status of the treated mice.

The use of immunocytochemical techniques for the detection of steroid hormones in breast cancer cells.

Indirect immunofluorescence and immunoperoxidase assays were developed to detect estradiol and progesterone in breast cancer cells. Appropriate controls were used to confirm immunologic specificity. Studies of estradiol binding by human breast cancer cells identified three groups: no detectable binding (25%); all tumor cells exhibiting binding although to different degrees (4%); and tumors with varying numbers of positive and negative cells (71%). Similar observations were made with respect to progesterone binding. The percentage of cells with estradiol binding was correlated with the amount of estrogen receptors (ER) present in the tumor specimens. Post-hormone binding events e.g., nuclear binding of estradiol, were also evaluated. Some tumor cells showing cytoplasmic binding of estradiol did not show nuclear binding of estradiol; such tumors lacked detectable diethylstilbestrol under routine assay conditions, and relatively high concentrations of estradiol were needed to observe estradiol-specific staining. The results suggest that the immunocytochemical assays detect hormone-specific binding, but that the binding is probably due to multiple classes of steroid-binding sites.

Experimental IgA nephropathy.

An animal model for IgA immune complex nephritis was developed. IgA immune complexes formed in vitro with an IgA anti-dinitrophenyl (DNP) derived from MOPC-315 plasmacytoma, and dinitrophenylated bovine serum albumin (DNP-BSA) produced mild focal glomerulonephritis in mice. Similar, but more severe pathological changes were produced with complexes formed in vivo either in normal mice or MOPC-315 tumor-bearing mice. In contrast to the focal nature of the PAS-positive glomerular lesions observed by light microscopy, immunofluorescent examination revealed IgA deposits in all glomeruli. This discrepancy between immunofluorescent and histopathologic findings as well as the distribution of the immune complexes within the affected glomeruli, are some of the features which bear resemblance between this experimental model and human IgA nephropathy. Fixation of complements by DNP-BSA-IgA immune complexes, formed in vitro or in vivo, was shown to occur in the glomeruli of mice with IgA immune complex nephropathy. The pattern of C3 glomerular deposits was similar to that of IgA. However, complement proved to be nonessential for complex deposition. This conclusion is based on the observation that decomplemented mice, although showing no deposition of C3 in their glomerulus, developed glomerular immunohistological changes similar to those observed in experimental mice that were not decomplemented. Polymeric IgA was observed to be critical for renal deposition of complexes and induction of nephritic histological changes. In contrast, monomeric IgA immune complexes failed to produce glomerular deposits. This finding raises the possibility that secretory IgA, which is predominantly polymeric, may play a role in human IgA-associated glomerulonephritis.

Cryopathic gangrene with an IgM lambda cryoprecipitating cold agglutinin.

Immunochemical and serologic studies of cold agglutinis in patients with chronic cold agglutinin disease (CCAD) have shown the almost exclusive occurrence of IgM kappa antibodies with specificity for the I antigen of red cells. An unusual subgroup of patients has been delineated in which the cryoprotein is IgM lambda, frequently lacks I specificity and often cryoprecipitates. Studies of such a protein from a patient with an unusual array of immunoproliferative disorders including Grave's disease with exophthalmos and Waldenstrom's macroglobulinemia indicate that the cryoprecipitating and cold agglutinating properties probably derive from the sam protein. The occurrence of this type of antibody should suggest the presence of a more aggressive lymphoproliferative disorder than simple CCAD.

Admission screening for hepatitis B surface antigen in a university hospital.

Upon admission to the hospital, 7,984 patients were tested for hepatitis B surface antigen (HBsAg) by radioimmunoassay. Seventy-one patients had sera positive for HBsAg. Twenty-four (34%) were possible asymptomatic carriers in whom liver function was not further evaluated and occult liver disease could not be excluded: 16 (23%) had either a previous history or admitting diagnosis of hepatic dysfunction; eight(11%) had occult liver disease, revealed after HBsAg antigenemia was discovered; and 25 (34%) were unsuspected asymptomatic carriers whose liver function was normal. We concluded that screening for HBsAg was an effective preventive tool in identifying HBsAg-positive patients. Screening solely for the detection of occult liver disease is not an effective method because of the high cost. Perhaps because of the unsolicited nature of this data collection, screening for HBsAg was not clinically effective for the majority of patients, as evidenced by the high incidence of inadequate clinical evaluations and lack of serologic follow-up. Proposals to alleviate ineffectiveness are discussed.

Age-associated involution of cellular immune function. I. Accelerated decline of mitogen reactivity of spleen cells in adult thymectomized mice.

Autoimmune-susceptible (A/J and C57BL/6J) and nonautoimmune-susceptible (DBA/1J) strains of mice were adult thymectomized (aTx). Groups of mice treated by aTx, aTx and 330 rads (R), aTx and 650 R, and 330 R OR 650 R only, were compared to normal age-matched control (normal and sham Tx) mice. T cell functions were then followed as measured by in vitro spleen cell responsiveness to the T cell mitogens phytohemagglutinin (PHA) and staphylococcal enterotoxin B (SEB) in a long-term study. A decline in spleen cell responsiveness with natural aging up to 18 months of age was seen to PHA in all three strains and to SEB in A/J and C57BL/J mice. Adult Tx alone was followed by an accelerated decline in spleen cell responsiveness to PHA and SEB in all three strains of mice. Irradiation combined with aTx-reduced spleen cell responsiveness to SEB in A/J and DBA/1J mice. Irradiation with or without aTx diminished the bone marrow stem cell pool as measured by exogenous colony-forming units, and the hematocrit of all three strains of mice. Thus, the natural decline in cellular immunity with aging was accelerated by aTx in both autoimmune-susceptible and non-autoimmune-susceptible strains of mice. These results emphasize that physiologic thymic function(s) must continue throughout life in order to maintain T cell function.

Different responses of two mouse strains to 650 rads and protection by surgical stress.

Radiation survival of C57B1/6J mice after 650 rads improved from 1.7% to 66% when mice were stressed surgically one week before irradiation. Surgical stress one or three weeks before irradiation increased endogenous CFUs and decreased exogenous CFUs in C57B1/6J and DBA/1J mice. Survival may be related to the proportion of stem cells in different phases of the cell cycle, which was abnormal in C57B1/6J mice and compensated for by a greater number of nucleated cells per femur.