Soluble CD27 in thyroid disorders.

We measured the soluble cytokine CD27 in a variety of thyroid disorders. Soluble CD27 was increased in untreated Graves' hyperthyroidism and in euthyroid ophthalmopathy. Levels of sCD27 were normal after the establishment of euthyroidism with propylthiouracil (PTU) or radio iodine in primary hypothyroidism, chronic thyroiditis, and the hyperthyroid and euthyroid phases of subacute thyroiditis.

Soluble CD antigen (cytokine) expression in various hyperthyroid states and use in the assessment of propylthiouracil treatment.

The soluble CD antigens sCD8, sCD23, and sCD25 are increased in untreated Graves' hyperthyroidism. These levels remain elevated when euthyroidism is established in response to propylthiouracil (PTU) therapy but decrease to control values after PTU treatment is discontinued, when euthyroidism has been established and maintained. Neither sCD8 nor sCD23 are elevated in patients with euthyroid Graves' ophthalmopathy nor in the hyperthyroid phase of subacute thyroiditis.

Thyroid hormone administration in irradiated patients.

In a recall clinic for patients at risk for thyroid carcinoma due to a history of radiation in infancy or childhood, a group of patients were randomly offered prospective suppressive L-thyroxine therapy and matched to a radiated nontreated group. With an average of more than two years' follow-up, the thyroid hormone-treated radiated group developed fewer nodules and abnormalities to palpation and also had a statistically significant lessening of minimal palpable abnormalities compared to the nonthyroxine-treated radiated group.

Two histopathologic types of inflammatory vascular disease in MRL/Mp autoimmune mice. Model for human vasculitis in connective tissue disease.

We have recently described 2 histopathologic types of inflammatory vascular disease (IVD) in patients with Sjögren's syndrome (SS): neutrophilic IVD (NIVD) and mononuclear IVD (MIVD). Autoimmune MRL/Mp mice, which have many features of SS, spontaneously develop IVD which is histopathologically indistinguishable from that observed in human SS patients. Both MRL/Mp-+/+ and MRL/Mp-lpr/lpr mice develop MIVD which evolves into NIVD and results in decreased survival; the transition to NIVD is accelerated by the lpr gene.

Early onset of tetany following thyroidectomy: report of two cases.

The most common complication of total thyroidectomy is hypocalcemia. Following thyroidectomy, especially total thyroidectomy, the serum calcium usually falls gradually and patients do not usually require supplementary medication before 24 hours. Two cases of total thyroidectomy are presented in which the preoperative serum calcium levels were normal and hypocalcemic tetany developed in the recovery room immediately after the operation.

Induction of various autoantibodies by mutant gene lpr in several strains of mice.

The effect of the autosomal mutant gene lpr (lymphoproliferation) on the development of various autoantibodies and immune complex (IC) glomerulonephritis was investigated in four genetically distinct strains of mice: MRL/ MpJ , C3H/HeJ, C57BL/6J, and AKR/J. The presence of the lpr gene not only enhanced the production of autoantibodies in the autoimmune MRL/ MpJ strain, but also induced the formation of various kinds of autoantibodies in the three other strains of mice without any apparent predisposition to autoimmune disease. Autoantibodies induced by the lpr gene included anti-double-stranded DNA, anti-single-stranded DNA, anti-IgG, anti-thymocyte, and anti-serum glycoprotein gp70.

The influence of the lpr gene on B cell activation: differential antibody expression in lpr congenic mouse strains.

Spontaneous immunoglobulin production in four strains of lpr/lpr congenic mice was investigated to identify genetic interactions in lpr-induced polyclonal B cell activation. Sera were obtained from male and female lpr/lpr mice of the MRL, B6, C3H, and AKR strains as well as controls of +/+ genotypes. Antibody levels were compared at the time of peak response.

Mechanisms of polyclonal B-cell activation in autoimmune B6-lpr/lpr mice.

The influence of the lpr gene on spontaneous and lipopolysaccharide (LPS)-induced immunoglobulin production was studied in B6 mice homozygous for the mutant lpr gene (B6-lpr/lpr). Male and female mice of this congenic strain were followed for 1 year and sera serially tested by the enzyme-linked immunosorbent assay (ELISA) for the production of antibodies to single-stranded DNA (anti-sDNA), immunoglobulin (anti-IgG), and keyhole limpet hemocyanin (anti-KLH), models of autoantibody and non-autoantibody responses, respectively. Female B6-lpr/lpr mice demonstrated marked spontaneous responses to all three antigens; the responses of male B6-lpr/lpr mice were significantly lower but still exceeded those of the congenic B6-+/+ controls.

A new mutation, gld, that produces lymphoproliferation and autoimmunity in C3H/HeJ mice.

A newly discovered autosomal recessive mutation, generalized lymphoproliferative disease (gld), in the C3H/HeJ strain of mice, determines the development of early onset massive lymphoid hyperplasia with autoimmunity. Significant lymph node enlargement is apparent as early as 12 wk of age. By 20 wk, lymph nodes are 50-fold heavier than those of coisogenic C3H/HeJ-+/+ mice.

Congenic autoimmune murine models of central nervous system disease in connective tissue disorders.

Congenic mice of the MRL/Mp strain spontaneously develop an autoimmune connective tissue disease that shares immunological and histopathological features with systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome. The autoimmune disorder in these mice is accelerated markedly by the recessive gene lpr. By 6 months of age, MRL/Mp-lpr/lpr mice developed prominent mononuclear cell infiltrates restricted to the choroid plexus and meninges, whereas congeneric MRL/Mp- +/+ mice (which lack the lpr gene) showed delayed but widespread inflammatory infiltrates involving cerebral vessels and meninges, with sparing of the choroid plexus.

Trypanosoma cruzi: susceptibility in mice carrying mutant gene lpr (lymphoproliferation).

There is evidence that autoimmune aberrations may contribute to the immunopathological consequences of Chagas' disease and because of this we sought to determine whether four inbred strains of mice bearing the single autosomal recessive gene, lpr (lymphoproliferation), which controls certain autoimmune manifestations, are particularly susceptible to acute infection with the Y strain of Trypanosoma cruzi. MRL/MpJ-lpr/lpr, C57Bl/6J-lpr/lpr, AKR/J-lpr/lpr, C3H/HeJ-lpr/lpr showed parasitaemias 2-10 times higher when compared to their congenic partners. Mortality was significantly higher in three of the four lpr strains.

Abnormalities induced by the mutant gene Ipr: expansion of a unique lymphocyte subset.

Mice carrying the Ipr mutation develop massive lymphoadenopathy and severe autoimmune disease. The characteristics of the cell population that proliferates in lymphoid tissues were evaluated by the use of a) monoclonal antibodies and FMF, and b) molecular genetic studies of Ig heavy chain genes. The lymph node cells of different strains of mice homozygous for the Ipr mutation were shown to be almost uniformly Thy-1+, Ly-1+, Ly-2-, H-11+, Ly-5+, sIg-, ThB-, 2C2+, I-A-, 6B2+, and therefore to have surface characteristics of both T and B cells.

Ipr gene control of the anti-DNA antibody response.

The influence of the Ipr gene on the anti-DNA antibody response was investigated in MRL and B6 Ipr/Ipr inbred mice, MRL +/+ mice less than a yr of age produced low levels of anti-DNA antibody, whereas older animals of this strain demonstrated levels in some instances comparable to those of the more severely affected MRL Ipr/Ipr mice. This result indicates a tendency to autoreactivity in MRL mice independent of the Ipr gene. To determine whether other mice bearing the Ipr gene would also express autoantibodies, the anti-DNA antibody responses of B6 Ipr/Ipr mice were studied.

Deficient interleukin 2 activity in MRL/Mp and C57BL/6J mice bearing the lpr gene.

Spleen cells from MRL-lpr and B6-lpr mice have a marked defect in the ability to produce interleukin 2 (IL-2) in response to concanavalin A stimulation. This defect precedes the onset of clinical illness, increases with age, and eventually becomes virtually absolute. It is not due to cellular suppression of IL-2 production, nor does it reflect the presence of a soluble inhibitor of IL-2 activity.

Pituitary Cushing's syndrome and Nelson's syndrome: diagnostic criteria, surgical therapy, and results.

Eight patients with pituitary Cushing's syndrome and 2 with Nelson's syndrome were followed from one to ten years after removal of pituitary adenomas. A detailed assessment of the pituitary-adrenal axis was obtained in all patients when last seen, save the first, who had undergone a complete hypophysectomy ten years previously. Long-term observations have shown sustained endocrine cure in 7 of 8 patients with pituitary Cushing's syndrome.

Effects of thymectomy or androgen administration upon the autoimmune disease of MRL/Mp-lpr/lpr mice.

MRL/lpr and NZB X NZW F1 mice were neonatally thymectomized or treated with androgens from 2 weeks of age, and their natural histories were studied. Neonatal thymectomy of MRL/lpr mice led to marked reduction in the usual massive lymphadenopathy as well as significant reduction in antibodies to native DNA and prolonged survival. In contrast, neonatal thymectomy of NZB X NZW F1 mice led to accelerated disease.

Preoperative physical assessment of thyroid glands in previously irradiated patients.

The Evanston Hospital maintains an Irradiated Thyroid Evaluation Clinic that has evaluated 695 patients since 1975. One hundred fourteen patients were retrospectively analyzed, and an attempt was made to correlate the preoperative physical examination with the pathologic specimen after thyroidectomy. There was no statistically significant difference between the incidence of carcinoma in glands containing a single nodule (23 per cent) and in multinodular glands.

A Y chromosome associated factor in strain BXSB producing accelerated autoimmunity and lymphoproliferation.

Strain BXSB/Mp mice develop a spontaneous lupus-like syndrome which is strikingly accelerated in males. The accelerated autoimmune disease occurs in male F1 hybrids with strains NZB/BINJ, SJL/J, and C57BL/6J when the male parent is BXSB but not in the reciprocal hybrid male nor in females. The pattern is similar in F2 hybrids with strains NZB and SJL.

Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains.

MRL/1 and BXSB male mice have a systemic lupus erythematosus (SLE)-like disease similar to but more acute than that occurring in NZB X W mice. The common elements of lymphoid hyperplasia, B-cell hyperactivity, autoantibodies, circulating immune complex (IC), complement consumption, IC glomerulonephritis with gp70 deposition, and thymic atrophy were found in all three kinds of SLE mice. On the basis of these common elements, SLE seen in these mice can be considered a single disease in the same sense that human SLE is one disease.

Immunopathogenicity and oncogenicity of murine leukemia virus. III. Quantitation of spontaneous virus expression.

Electron microscopic determination of C-type virions in gut-associated and genital tract epithelia was made in various murine strains. The number of morphologically identifiable C-type virus particles varied more than 100-fold among strains, being high in all strains exhibiting immunologic disease, as well as several immunologically normal strains, and low in other immunologically normal strains. No relationship was seen between the number of virions found in epithelial and lymphoid tissues.