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Biomedical subjects

D Cary

Publications and source records attributed to D Cary.

10 recordsLinked to original sources
PubMed1996

Functional inactivation in mice of the gene for the interleukin-3 (IL-3)-specific receptor beta-chain: implications for IL-3 function and the mechanism of receptor transmodulation in hematopoietic cells.

The receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 and -5 (IL-3, IL-5) share a common signaling subunit (beta c). However, in the mouse, IL-3 can also use an alternative IL-3-specific receptor beta-chain (beta IL-3). To assess the relative contributions of beta c and beta IL-3 to IL-3 receptor formation and function, mice were generated in which the beta IL-3 gene was functionally inactivated by replacement of exons 9-13 with a neomycin resistance cassette. Bone marrow cells from these mice displayed a lower affinity IL-3 receptor than normal and were hyporesponsive to IL-3, but the mice displayed no obvious hematopoietic abnormalities. The data suggested that beta c and beta IL-3 are normally coexpressed on IL-3-responsive cells and have identical qualitative signaling capacities. Receptor transmodulation studies on bone marrow cells from wild-type, beta c -/-, and beta IL-3 -/- mice showed that the previously described hierarchical pattern of transmodulation was dependent on the relative numbers of both beta IL-3 and beta c receptor chains and also provided evidence for an unexpected interaction between beta c chains and G-CSF and M-CSF receptors.

Animals↗
PubMed1994

Elastofibroma dorsi: diagnostic problems and pitfalls.

The diagnostic cytomorphologic findings in a case of elastofibroma dorsi are described in this report. The correct diagnosis was initially overlooked on fine-needle aspiration, and was subsequently made by open biopsy. Review of the FNA material, however, demonstrated scanty but diagnostic material. Cytologic examination revealed a mixture of fibroblasts, adipose tissue, and swollen lightly staining cyanophilic elastic fibers in a background of collagenous matrix. Cross sections of the elastic fibers had the typical serrated and globular appearance. These fibers stained positive with elastin stains. The cytomorphology of elastofibroma dorsi with diagnostic pitfalls and differential diagnostic dilemmas are discussed in this article.

Aged↗
PubMed1993

Neutralizing and nonneutralizing monoclonal antibodies to the human granulocyte-macrophage colony-stimulating factor receptor alpha-chain.

A panel of monoclonal antibodies was raised against the low-affinity human granulocyte-macrophage colony-stimulating factor (hGM-CSF) receptor alpha-chain expressed as recombinant protein on murine FDC-P1 cells. All the selected antibodies were of the IgG2A isotype and bound to protein A. They each recognized both native and recombinant receptors by indirect surface immunofluorescence and by immunoprecipitation. Several of the antibodies also recognized presumably denatured receptors as detected by immunoblotting of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Three different epitopes on the extracellular domain of the GM-CSF receptor alpha-chain were defined by these antibodies, and two of the epitopes did not appear to be involved in binding hGM-CSF or in interactions with the beta-chain of the GM-CSF receptor that are required for high-affinity binding of GM-CSF. On the other hand, the epitope recognized by antibody 2B7-17-A appeared to be critically involved in the binding of GM-CSF because this antibody completely abrogated both high- and low-affinity binding of GM-CSF to native and recombinant receptors. Antibody 2B7-17-A had a relatively high affinity for the GM-CSF receptor alpha-chain (kd = 3 nmol/L) and slow dissociation kinetics (kd = 0.002 min-1). These properties made the 2B7-17-A antibody a potent inhibitor of hGM-CSF biologic action in several different bioassays, with a half-maximal inhibitory dose of about 6 nmol/L (1 microgram/mL). This antibody could prove useful in alleviating any pathologic states mediated by excess GM-CSF levels and in defining the domains of the GM-CSF receptor required for ligand binding.

Animals↗
PubMed1993

The SCL gene product is regulated by and differentially regulates cytokine responses during myeloid leukemic cell differentiation.

Differentiation induction in murine M1 leukemia cells by interleukin 6 (IL-6), leukemia inhibitory factor (LIF), and oncostatin M (OSM) is postulated to occur via a common receptor chain, gp130. In this study, growth factor-induced differentiation of M1 cells was accompanied by a late and persistent decrease in levels of mRNA and protein for a helix-loop-helix transcription factor, the SCL gene product. To evaluate whether reduced SCL expression was instrumental in monocyte differentiation, an SCL cDNA expression vector was introduced into M1 cells to obtain cell lines in which overexpression of SCL mRNA and protein was enforced. This resulted in a reduction in cells differentiating in response to LIF and OSM but not in response to IL-6. Scatchard analysis indicated that both parental and SCL-transfected cell lines exhibited similar receptor numbers and receptor affinities for LIF, OSM, and IL-6, suggesting that the differential responsiveness was not due to selective receptor down-modulation. Thus, these data implicate SCL in monocytic differentiation and provide evidence for differential receptor signaling pathways despite utilization of a common gp130 subunit by all three receptors.

Animals↗
PubMed1992

Leukemia inhibitory factor levels are elevated in septic shock and various inflammatory body fluids.

Leukemia inhibitory factor (LIF) has many biological actions which parallel those of IL-1, IL-6 and tumor necrosis factor-alpha, but its role in the pathogenesis of human disease is unknown. A specific radioreceptor competition assay capable of detecting LIF at concentrations above 1 ng/ml (45 pM) was developed. To identify disease states in which LIF might be involved, a cross-sectional survey of serum and body fluids from approximately 1,500 subjects with a variety of diseases was performed using the LIF radioreceptor competition assay. Serum LIF concentrations were transiently elevated (2-200 ng/ml) in six subjects with meningococcal or Gram-negative septic shock, and in a subject with idiopathic fulminant hepatic failure. Moderately elevated LIF concentrations (> 10 ng/ml) were detected in cerebrospinal fluid from subjects with bacterial meningitis, in effusions associated with pneumonia and peritonitis, and in amniotic fluid from a woman with chorioamnionitis. Low LIF concentrations (1-10 ng/ml) were present in synovial fluid from subjects with inflammatory arthritis, amniotic fluid from women in labor, and some reactive, chronic inflammatory and malignant effusions and cyst fluids, but rarely in transudates. These initial findings suggest that LIF might be involved in the pathogenesis of inflammation and septic shock.

Amniotic Fluid↗
PubMed1992

Affinity conversion of receptors for colony stimulating factors: properties of solubilized receptors.

Murine receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) and Multi-CSF (interleukin-3) can exist in both high- and low-affinity forms and demonstrate trans-modulation by several different ligands. In contrast the recently cloned human GM-CSF receptor and murine interleukin-3 (IL-3) receptor display only low-affinity binding. To begin to understand the molecular basis of the formation of high- and low-affinity receptors and their trans-modulation we have developed methods for the solubilization and assay of GM-CSF and interleukin-3 receptors so that their binding characteristics can be studied in cell-free solution. Both receptors displayed a single class of high-affinity binding on intact FDC-P1 cells and IL-3 receptors had unaltered binding characteristics in cells, membranes and in detergent solution. However, GM-CSF receptors were converted to a single class of low-affinity binding in detergent solution while both high- and low-affinity forms were evident in membranes. The basis of affinity conversion of GM-CSF receptors was exclusively a change in the kinetic dissociation rate of ligand. Cross-linking experiments suggested that high-affinity receptors for GM-CSF and IL-3 might consist of two different protein species and, if this is so, the data suggest that this association is more stable for IL-3 than for GM-CSF receptors.

Animals↗
PubMed1983

Further characterization of estrogen receptors in the human oviduct.

Estrogen binding in human oviducts was studied in vitro by the dextran-coated charcoal assay and sucrose density ultracentrifugation. Estrogen binds with high affinity and limited capacity to cytosol of the human oviduct. The concentration of competitive inhibitors to produce 50% reduction in estrogen binding was 8 x 10(-8) M for the antiestrogen CI-628, 8 x 10(-7) M for the progestogen norethynodrel, and 3 x 10(-6) M for the testosterone derivative danazol at the ligand concentration of 1 nM estradiol. Nuclear estrogen binding was not inhibited by a 100-fold excess of progesterone or by a 10-fold excess of norethynodrel. Estrogen-binding protein with a sedimentation coefficient of 4S was seen in oviductal cytosol of all three anatomic segments. The nuclear 4S peak of estrogen binding was demonstrated in the ampullary tubal segment.

Binding, Competitive↗
PubMed1982

Ovarian lipoid cell tumor. Steroid hormones and ultrastructure.

A virilizing, ovarian lipoid cell tumor was removed from a 19-year-old woman with amenorrhea. Light- and electron-microscopic studies of tumor morphology were combined with biochemical measurements of testosterone, dihydrotestosterone, estrone, estradiol, and progesterone. Electron microscopy demonstrated cells with the typical ultrastructural features of steroidogenesis. Analysis of extracts from tumor tissue showed high concentrations of progesterone, testosterone, dihydrotestosterone, estrone, and estradiol. These extracts from the ovarian lipoid cell tumor contained the following quantities of steroids: testosterone 450 ng/g tissue; dihydrotestosterone 56 ng/g tissue; estrone 233 pg/g tissue; estradiol 10896 pg/g tissue; and progesterone 512 ng/g tissue. Ovarian vein blood of the ovary with the lipoid cell tumor showed these results: testosterone 3276 ng/dl; dihydrotestosterone 311 ng/dl; estrone 69 pg/ml; estradiol 258 pg/ml; and progesterone 8.1 ng/ml. Because of the ultrastructural and biochemical similarities of this tumor to granulosa lutein cells it is concluded that this ovarian lipoid cell tumor probably originated from ovarian stromal cells.

Adrenal Rest Tumor↗
PubMed1981

Hormonal and cytogenetic studies in phenotypically female patients with gonadal dysgenesis.

In 4 cases of gonadal dysgenesis the clinical, hormonal, cytogenetic, and histological findings were correlated. There were 2 patients with 46,XY karyotype, one patient with 45,X Turner's syndrome and one patient with a 46,XX chromosome complement. All patients had streak gonads with ovarian stroma. In one phenotypically female 46,XY individual an involuted gonadoblastoma was found. Her testosterone was four-fold higher in gonadal vein blood compared to peripheral blood. Cytogenetic analysis of multiple tissues in both cases with the 46,XY karyotype greatly reduced the probability of mosaicism. In the patient with 45,X Turner's syndrome and in the one with 46,XX gonadal dysgenesis only peripheral blood cells were karyotyped and mosaicism was not further excluded by analysis of other tissues. The concentrations of steroid hormones in gonadal vein blood were low. The levels ranged as follows: estrone 41-98 pg/ml, estradiol 18-90 pg/ml, testosterone 37-294 ng/100 ml, dihydrotestosterone 13-22 ng/100 ml, and progesterone 0.3-1.5 ng/ml. It was concluded that gonadal streaks were similarly deficient in biosynthesis of steroid hormones despite different chromosomal complements.

Adolescent↗