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Biomedical subjects

E D Murphy

Publications and source records attributed to E D Murphy.

At least 19 recordsLinked to original sources
PubMed1998

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 CD27 is a marker for cellular activation as in Graves' hyperthyroidism, but it is not predictive of the outcome of PTU therapy.

Acute Disease↗
PubMed1994

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. sCD25 is increased to an intermediate degree in these disorders. Soluble CD8 > or = 450 U/ml is sensitive, specific, and predictive of PTU success as sole therapy or need for definitive therapy in untreated and PTU-treated Graves' hyperthyroidism, exceeding the predictive values of thyroid-stimulating hormone receptor antibody, thyroid peroxidase antibody, and T3 radioimmunoassay.

Adult↗
PubMed1986

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.

Adult↗
PubMed1985

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. The presence of the lpr gene on other genetic backgrounds does not result in a similar acceleration of IVD and associated decreased survival. Thus, the spontaneous autosomal recessive mutation lpr appears to modulate the development of IVD in a strain of mice with an underlying propensity for vasculitis. Based on our observations on IVD in SS patients and MRL/Mp mice, we propose a new model which may enhance our understanding of the immunopathogenesis of IVD in connective tissue disease.

Animals↗
PubMed1985

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. The hypocalcemia was a temporary phenomenon, and neither patient requires supplementary calcium at the present time. There is no good explanation for this precipitous drop in the serum calcium levels in these two patients.

Adult↗
PubMed1984

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. There is a concomitant increase in the numbers of peripheral blood lymphocytes. Analysis of C3H-gld lymph node lymphocyte subsets by immunofluorescence indicates an increase in numbers of B cells, T cells, and null (Thy-1-, sIg-) lymphocytes by 6-, 15-, and 33-fold compared with congeneic control mice. Serologically, gld/gld mice develop antinuclear antibodies (including anti-dsDNA), thymocyte-binding autoantibody, and hypergammaglobulinemia with major increases in several immunoglobulin isotypes. Mutant gld mice live only one-half as long as normal controls (12 and 23 mo, respectively). Interstitial pneumonitis was found in virtually all C3H-gld mice autopsied when moribund. Although immune complexes were detected in the glomerulus by immunofluorescence techniques, only 14% of the autopsied mice had significant lupus-like nephritis. Vascular disease was not found. The pattern of early onset massive lymph node enlargement, hypergammaglobulinemia, and production of antinuclear autoantibodies resembles the basic abnormal phenotype induced by the lpr (lymphoproliferation) mutation. The mutations gld and lpr are not allelic. Linkage studies indicate that gld is located between Pep-3 and Lp on chromosome 1. This new mutation adds another genetically well-defined model to the list of murine lymphoproliferative/autoimmune disorders that may be exploited to gain a clearer understanding of immunoregulatory defects and for identifying common pathogenetic factors involved in systemic autoimmune diseases.

Aging↗
PubMed1984

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. These results demonstrate a generalized influence of sex on lpr associated responses. To determine whether this sex difference could be demonstrated with other forms of B-cell activation, young B6-+/+ and B6-lpr/lpr male and female mice were immunized with lipopolysaccharide and the induced responses determined. This immunization caused significant increases in the IgM response only. The levels of the induced responses produced after LPS treatment were comparable for +/+ and lpr/lpr mice. These results indicate that the enhanced responsiveness of female mice to lpr action is not reflected in the polyclonal response to LPS, which, furthermore, was unaffected by the presence of lpr. The differential influence of sex on lpr and LPS-induced responses and their apparent independence suggests that lpr and LPS promote B-cell activation by dissimilar mechanisms.

Animals↗
PubMed1984

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. Quantitative antibody determinations were performed by isotype-specific ELISA assays using responses to single-stranded DNA (sDNA), mouse IgG, rabbit IgG, and keyhole limpet hemocyanin as models. Among the strains studied there were significant differences in the antibody levels observed, with the strain producing highest levels dependent on the response measured. Thus, MRL-lpr/lpr produced the highest levels of IgG anti-sDNA while B6-lpr/lpr mice produced more anti-IgG than mice of other strains. Within each strain, the lpr gene appeared to affect the IgG more than the IgM response. A consistently high response by females was observed only in B6-lpr/lpr mice. These studies suggest that lpr-induced polyclonal B cell activation is influenced by the background genome with the extent of these genetic effects variable among responses.

Animals↗
PubMed1984

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. This indicates that the action of the lpr gene on the development of autoantibody response does not require the particular abnormalities of the MRL genome. The differences in amounts and types of autoantibodies among the lpr strains reflect the difference in the background genome of each strain, suggesting the participation of other genes or factors determining the quantity and/or specificity of autoantibodies. In addition to the development of autoantibodies, the three nonautoimmune strains of mice produced high levels of unidentified IC in the presence of the lpr gene, detectable by the C1q and the conglutinin binding tests. Their glomerular lesions, however, were relatively limited when compared with MRL/ MpJ -lpr/lpr mice, which developed severe glomerulonephritis early in their life. These results suggest that the lpr gene is able to induce the formation of various autoantibodies and IC at significant concentrations in nonautoimmune mice, but for the full manifestation of systemic lupus erythematosus there may be a requirement for supplemental genetic abnormalities or factors.

Animals↗
PubMed1983

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. These distinctive patterns of cerebral inflammation, which are comparable in many respects to those seen in human connective tissue disease, provide some of the first animal models of relevant central nervous system histopathological processes associated with underlying connective tissue disease.

Animals↗
PubMed1983

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. The results indicate that a single autosomal recessive gene which is associated with autoimmunity can influence susceptibility to acute T. cruzi infection in mice.

Animals↗
PubMed1982

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. This strain was development by matings to transfer the Ipr gene into another inbred background and allow evaluation of the action independent of other disturbances of the MRL mice. Mice of this strain produced antibodies to DNA, with female animals displaying significantly higher levels than males. This result demonstrates that the Ipr gene can stimulate autoantibody production in mice other than the MRL strain and does not require abnormalities unique to this background to potentiate autoreactivity.

Aging↗
PubMed1982

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. Molecular genetic studies of the arrangements of Ig heavy chain genes showed that they were not rearranged as in pre-B and B cells. These results suggest that an abnormal proliferating population of T cells in Ipr/Ipr mice aberrantly express B cell surface markers.

Animals↗
PubMed1981

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. Failure to restore IL-2 production with macrophage-replacing factors, such as interleukin 1 and phorbol myristic acetate, suggests that IL-2 deficiency reflects a primary T cell defect rather than a macrophage defect. MRL-lpr and B6-lpr spleen cells also have an age-dependent reduction in IL-2 response that apparently results from a deficiency of cell surface receptors for IL-2. Congenic MRL-+/+ and B6-+/+ mice, which lack the lpr gene responsible for accelerated autoimmunity and lymphoproliferation, have normal IL-2 activity. These findings suggest that a defect in IL-2 activity may contribute to impaired immunoregulation in mice bearing the lpr gene. The absence of such a defect in MRL-+/+ and B6-+/+ mice further suggests that a single autosomal recessive gene is responsible for IL-2 deficiency.

Absorption↗
PubMed1981

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. One patient with Nelson's syndrome was also cured. There was no operative morbidity or mortality. There were no instances of diabetes insipidus. The long-term results in this study indicate that patients with pituitary Cushing's syndrome have a better than 90% chance of being cured after transsphenoidal removal of the pituitary (micro) adenomas. Current diagnostic and therapeutic concepts in the management of pituitary Cushing's syndrome are discussed in detail.

Adrenocorticotropic Hormone↗