Search PubMed⌕ Search

Biomedical subjects

D Gay

Publications and source records attributed to D Gay.

At least 19 recordsLinked to original sources

Natural variation of copper, zinc, cadmium and selenium concentrations in Bembicium nanum and their potential use as a biomonitor of trace metals.

Copper, zinc, cadmium and selenium were measured in the gastropod mollusc Bembicium nanum at two uncontaminated locations, Jervis Bay and Rosedale, NSW, to determine natural variability of metals associated with gender, mass, shore position and temporal variability. Trace metals were also measured in B. nanum at three industrialised locations to determine the accumulation of trace metals in contaminated environments.Copper, zinc, cadmium and selenium concentrations were not significantly different between male and female B. nanum. No significant relationships were found between zinc, cadmium and selenium concentrations and mass. There was a significant relationship between copper concentration and mass but only 19% of the variation was explained by mass. Generally inherent variability within samples had a greater influence than gender or variations in mass on trace metal concentrations. No trend was found in cadmium and selenium concentrations with variation in shoreline position. Copper and zinc concentrations increased further away from the low tide mark, with a decrease in metal concentrations at the furthest site from the water. Variability in metal concentrations is attributable to variations in food source, food availability and different immersion times.Copper, zinc, cadmium and selenium concentrations varied over a 12-month period. Copper, cadmium and selenium were taken up and lost over time, as metal body burden followed the same trend as metal concentrations. Zinc concentrations were influenced by mass. Copper and cadmium concentrations fluctuated throughout the 12-month period but with no clear seasonal trends. Selenium concentrations peaked in spring (October), with concentrations remaining uniform over the other months. These differences in mean concentrations between months were most likely due to inherent trace metal variability associated with differences in food availability and changes in metabolic rates associated with changes in temperature during the study period. Measurement of trace metals in B. nanum at contaminated sites showed that B. nanum accumulates metals in response to contamination.B. nanum meets most of the requirements to be a biomonitor of trace metal contamination as they are abundant, sedentary, easy to identify, provide sufficient tissue for analysis, tolerate high concentrations of pollutants and they accumulate trace metals in response to contamination. However, as trace metal concentration can vary with mass, shoreline position and temporally, care must be taken to collect individual organisms with similar mass from similar shoreline positions and times.

Animals↗

Two differing presentations of optic nerve head drusen.

BACKGROUND: Optic nerve head drusen was recognized histologically in 1858 by Heinrich Muller The majority of optic nerve head drusen cases have been benign in nature. However, optic nerve head drusen can be visually devastating. CASE REPORTS: Two patients were diagnosed with optic nerve head drusen. They were similar in age and each had a best-corrected visual acuity of 20/20 OU. Although the diagnosis was the same, the disease affected each person very differently. One is currently asymptomatic; the other is legally blind secondary to severely constricted visual fields. These cases demonstrate the diversity of visual effects produced by optic nerve head drusen. Appropriate ocular workup, including visual fields, B-scan ultrasonography, computed tomography, and other tests, are presented. CONCLUSION: There is no existing treatment for optic nerve head drusen. Proper diagnosis and patient education is the best-available modality of care. Patients need to be aware of potential complications which, while rare, can affect vision. Visual-field testing can aid in monitoring for subtle changes in vision.

Blindness↗

Cocaine-induced reflex sympathetic dystrophy.

Reflex sympathetic dystrophy (RSD) usually follows traumatic injuries or neurologic disorders. The authors report a rare case of RSD that followed intraarterial administration of cocaine in a patient with a history of intravenous drug abuse. The cocaine was self-administered inadvertently into the femoral artery rather than the femoral vein. Despite the intense pain, swelling, and dermatologic changes that followed, the diagnosis of RSD was not considered until scintigraphic studies suggested it. A combination of normal radiographs, a normal leukocyte study, and an abnormal bone scan in the region of tenderness and swelling excluded other possibilities and suggested RSD. In our patient, RSD was likely caused by an ischemic autonomic injury from the vasoconstrictor action of cocaine. Clinical follow-up and relief using phentolamine, an alpha-adrenergic blocker and vasodilator, made the diagnosis of RSD most likely.

Cocaine-Related Disorders↗

OlP-1, a novel protein that distinguishes early oligodendrocyte precursors.

Oligodendrocyte development may be divided into three distinct stages: I) commitment of neuroectoderm cells to the oligodendrocyte lineage, II) migration of precursors into the surrounding parenchyma concomitant with increased proliferation, and III) cessation of migration and proliferation and initiation of myelination. Stage II of development has remained enigmatic because of the paucity of known molecules that distinguish these immature migratory cells. We describe a novel surface protein, termed OlP-1, which is restricted in expression to this developmental stage in the mouse. Cytofluorographic comparisons with known developmental markers showed OlP-1 to be expressed primarily by stage II precursors in vitro. Histologic analyses supported this conclusion by showing co-localization of OlP-1 with stage II molecules in vivo. Two conclusions were drawn from these results. First, OlP-1 was a novel protein expressed by murine oligodendrocyte precursors at a point in development that suggested a role in migration or proliferation. Second, dispersal of OlP-1-positive cells throughout the developing brain did not correlate with the location of myelination which, observed days later, progressed in a caudal to rostral manner. These data supported the concept that the final steps of maturation and myelin gene expression may be dependent upon extrinsic factors located predominantly within white matter tracts.

Animals↗

Receptor editing: an approach by autoreactive B cells to escape tolerance.

To determine the fate of anti-DNA antibody-bearing B cells in normal mice, we generated transgenic mice bearing the heavy (H) and light (L) chain genes of a well-characterized anti-double-stranded DNA antibody. This antibody was originally isolated from a diseased MRL/lpr mouse and has characteristics common to spontaneously arising anti-DNA antibodies. Results show that the H/L transgene (tg) immunoglobulin receptor is not expressed by animals bearing both tgs, although single tg animals (H or L) express their transgenes. Young H/L tg animals express few B cells, whereas adult H/L tg animals maintain almost normal B cell numbers. Analysis of the immunoglobulin receptors used by adult B cells shows that all contain the tg H chain in association with endogenous L chains. These B cells transcribe the L tg as well as the rearranged endogenous L chain gene, and loss of endogenous L chain gene transcription results in resurrection of the 3H9 H/L tg product. Examination of the endogenous L chains used by these cells shows that they represent a highly restricted subset of V genes. Taken together, these data suggest that autoreactive transgenic B cells can rearrange endogenous L chain genes to alter surface receptors. Those L chains that compete successfully with the L tg for H chain binding, and that create a nonautoreactive receptor, allow the B cell to escape deletion. We suggest that this receptor editing is a mechanism used by immature autoreactive B cells to escape tolerance.

Animals↗

[Is it possible to individualize microvillous large-cell lymphoma among sinusoid lymphomas?].

Microvillous non-hodgkin lymphomas are large cell malignant lymphomas with a sinus growth pattern and the presence of cytoplasmic processes detected by electron microscopy. Microvillous non-hodgkin lymphomas appear to be of B cell lineage. Neoplasms considered in the differential diagnosis include anaplastic large cell Ki-1 lymphomas, malignant histiocytosis and metastatic carcinoma or malignant melanoma. A panel of markers are usually sufficient to recognize all of these neoplasms except microvillous lymphomas. We report a case of microvillous non-hodgkin lymphoma characterized by a histologic pattern mimicking those of anaplastic large cell Ki-1 lymphoma. However, immunohistochemistry study failed to demonstrate presence of activation antigen such as Ki-1, EMA, interleukin 2 receptor. Ultrastructural study showed that neoplastic cells exhibited filliform cytoplasmic processes. This report raise the possibility of an overlap between microvillous non-hodgkin lymphomas and anaplastic large cell Ki-1 lymphomas of B-cell lineage. It must be emphasized that, initially, these two kinds of lymphomas were defined with different morphologic technologies.

Biomarkers, Tumor↗

Blood-brain barrier damage in acute multiple sclerosis plaques. An immunocytological study.

To investigate blood-barrier leakage of plasma proteins in acute plaques of multiple sclerosis (MS) the authors used immunocytological methods to examine frozen tissue removed at autopsy from recently active cases. Annular patterns of protein-rich leakage were seen which may help to elucidate the patterns observed using gadolinium-enhanced nuclear magnetic resonance imaging. Vessel wall damage was found in all acute plaques examined and this was associated with the intramural deposition of complement on smooth muscle components and with an infiltration of HLA-DR +ve macrophages. In addition, all acute cases examined had small plaques which contained particulate material within macrophages and astrocytes, on which complement and immunoglobulins colocated. Attempts to find similar material in cases of chronic MS, subacute sclerosing panencephalitis and in perivenous encephalomyelitis were unsuccessful. These results suggest that the inflammatory changes in early MS plaques may have some specificity which could be related to the antigens whose presence is inferred by the colocation of complement and immunoglobulin on material within activated macrophages and astrocytes.

Acute Disease↗

Immunological and neuropathological significance of the Virchow-Robin space.

The anatomy of the Virchow-Robin space is reviewed and attention is drawn to its importance as a compartment which is in communication with lymphatic channels of the head and neck and in which local immunological reactions take place. Macrophages in the Virchow-Robin spaces express MHC class II antigens and are well placed to interact with lymphocytes derived from the blood in initiating and promoting immune response to foreign antigens in the brain. The immunological reactions taking place in the Virchow-Robin spaces in encephalitis, multiple sclerosis and human immunodeficiency virus encephalitis are examined for the light they may throw on the pathogenesis of these conditions.

AIDS Dementia Complex↗

Epitopic analysis by anti-I-Ak monoclonal antibodies of I-Ak-restricted presentation of lysozyme peptides.

Anti-I-A mAb were used as probes of functional epitopes for both the presentation of hen egg lysozyme (HEL) peptides to I-Ak-restricted T cell hybridomas and the direct binding of the HEL (46-61) peptide. When mAb directed to polymorphic regions of I-Ak were used as inhibitors of Ag presentation, several different patterns of inhibition were observed among T cells specific for the same HEL peptide as well as among T cells specific for different fragments of HEL. Although there appears to be a conserved usage of some TCR V beta gene segments among the T cell hybrids specific for the same HEL peptide, no correlation is evident between a single V gene usage and susceptibility to blocking of Ag presentation by a particular anti-I-Ak mAb. Several of the mAb demonstrated T cell "clonotypic blocking" of Ag presentation, whereas others blocked presentation to every T cell hybrid tested, regardless of the peptide specificity. When mAb directed to nonpolymorphic regions of the I-A molecule were tested for their ability to block Ag presentation, little or no inhibition was observed. In addition, Fab' fragments of inhibitory mAb functioned identically to their intact homologous counterparts in their ability to block Ag presentation indicating that "nonspecific" steric hindrance was not playing a major role in the inhibitions observed. When the polymorphic region-directed anti-I-A mAb were tested for their ability to block the direct binding of the lysozyme peptide HEL(46-61) to I-Ak, those mAb that block HEL presentation to all T cell hybrids were found to block the binding of this peptide. However, anti-I-A mAb that demonstrate selective inhibition of T cell hybrid stimulation during Ag presentation, i.e., those directed to polymorphic serologic specificities Ia.15 and Ia.19, do not block the binding of HEL(46-61) to I-Ak. These data indicate that functionally independent epitopes exist on the I-Ak molecule for the binding of antigenic peptides and for interaction with the TCR.

Animals↗

The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia.

The membrane protein CD4 is commonly found on mature T cells specific for antigen in association with class II major histocompatibility complex (MHC; Ia) proteins. This correlation has led to the suggestion that CD4 binds to a monomorphic region of the Ia molecule on the antigen-presenting cell (APC) and functions either by enhancing interaction between the T cell and the APC, or conversely, by transducing negative signals to the T cell. To address this hypothesis, we have made use of sublines from an unusual T hybrid that is class I MHC restricted but also CD4+. By incorporating purified MHC proteins into a planar membrane system, we show that different Ia molecules can greatly enhance the ability of a CD4+ but not a CD4- variant of this class I-restricted T hybrid to respond to isolated class I molecules. T-cell responses can be strongly augmented by the concurrent expression of CD4 on the T cell and any of four different Ia proteins on planar membranes, thus supporting the idea that CD4 binds to a monomorphic region of the Ia molecule and increases the avidity with which the T cell can interact with its target.

Animals↗

The T cell repertoire may be biased in favor of MHC recognition.

The receptors of two T cell hybridomas that recognize class I and class II major histocompatibility complex (MHC) molecules, respectively, have been compared. In both cases these receptors are hybrid molecules formed as a result of cellular fusion. The receptors contain the same alpha chain, contributed by the tumor cell fusion partner, and related beta chains, contributed by the normal T cell component. Thus, surprisingly, the same alpha chain can contribute to recognition of class I and class II MHC molecules. Moreover, the finding that in two independent examples hybrid receptor molecules created randomly by in vitro cell fusion recognize MHC supports the theory that the T cell repertoire has an intrinsic affinity for MHC.

Antibodies, Monoclonal↗