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Biomedical subjects

D Muir

Publications and source records attributed to D Muir.

At least 37 records · Page 2Linked to original sources
PubMed1998

Degradation of chondroitin sulfate proteoglycan enhances the neurite-promoting potential of spinal cord tissue.

The contribution of chondroitin sulfate proteoglycan (CSPG) in the suppression of axonal growth in rat spinal cord has been examined by means of an in vitro bioassay in which regenerating neurons are grown on tissue section substrata. Dissociated embryonic chick dorsal root ganglionic neurons were grown on normal and injured adult spinal cord tissue sections treated with chondroitinases. Neuritic growth on normal spinal cord tissue was meager. However, both the percentage of neurons with neurites and the average neurite length were substantially greater on sections treated with chondroitinase ABC. Enzymes that specifically degraded dermatan sulfate or hyaluronan were ineffective. Neuritic growth was significantly greater on injured (compared to normal) spinal cord and a further dramatic increase resulted from chondroitinase ABC treatment. Neurites grew equally within white and gray matter regions after chondroitinase treatment. Observed increases in neurite outgrowth on chondroitinase-treated tissues were largely inhibited in the presence of function-blocking laminin antibodies. These findings indicate that inhibitory CSPG is widely distributed and predominant in both normal and injured spinal cord tissues. Additionally, inhibitory CSPG is implicated in negating the potential stimulatory effects of laminin that might otherwise support spinal cord regeneration.

Animals↗
PubMed1998

Children's use of triadic eye gaze information for "mind reading".

Five experiments examined children's use of eye gaze information for "mind-reading" purposes, specifically, for inferring another person's desire. When presented with static displays in the first 3 experiments, only by 4 years of age did children use another person's eye direction to infer desires, although younger children could identify the person's focus of attention. Further, 3-year-olds were capable of inferring desire from other nonverbal cues, such as pointing (Experiment 3). When eye gaze was presented dynamically with several other scaffolding cues (Experiment 4), 2- and 3-year-olds successfully used eye gaze for desire inference. Scaffolding cues were removed in Experiment 5, and 2- and 3-year-olds still performed above chance in using eye gaze. Results suggest that 2-year-olds are capable of using eye gaze alone to infer about another's desire. The authors propose that the acquisition of the ability to use attentional cues to infer another's mental state may involve both an association process and a differentiation process.

Attention↗
PubMed1998

Characterization of a primary central nervous system atypical teratoid/rhabdoid tumor and derivative cell line: immunophenotype and neoplastic properties.

Primary central nervous system (CNS) atypical teratoid/malignant rhabdoid tumors (ATT/RhT) occur during early childhood and are almost invariably fatal. Expression of multiple phenotypes in ATT/RhT suggests the presence of an undifferentiated progenitor with the potential to differentiate along multiple lines. These properties have made it difficult to characterize the etiology and histogenesis of these tumors and complicate efforts to develop targeted therapies. This paper characterizes the immunophenotype of a human CNS ATT/RhT and describes the properties of a derivative cell line (Atrt95) which retained morphological and immunochemical characteristics of the parent tumor including diverse differentiation. Most tumor cells were strongly immunoreactive for glial fibrillary acidic protein, vimentin and A2B5. Scattered, large tumor cells that showed a rhabdoid phenotype were immunoreactive for synaptophysin. The morphology of cultured Atrt95 cells was heterogeneous, but often fit into 1 of 3 classes that appeared to correspond to cell populations observed within the parent tumor including: 1) tightly-packed small-cell colonies, 2) large, well-spread highly motile cells and 3) arrays of elongated cells. In vitro assays demonstrated that growth of the entire culture was anchorage-dependent but not serum-dependent. Transplantation of Atrt95 cells into the rat spinal cord resulted in tumor growth and CNS invasion. Preliminary cytogenetics study revealed complex aneuploidy but no apparent monosomy or deletions of chromosome 22. The immunophenotype of this neoplasm and derivative cell line is consistent with a primitive glioneuronal lineage and its in vitro characteristics are that of an invasive malignancy similar to the naturally occurring tumor. This unique cell line (Atrt95) provides a valuable model to study the biology and genetics of the CNS ATT/RhT.

Animals↗
PubMed1998

Disseminated invasive infection due to Metarrhizium anisopliae in an immunocompromised child.

The first reported human case of possible disseminated infection with the insect pathogen Metarrhizium anisopliae var. anisopliae, a fungus which has been used commercially for biocontrol of insects, is described. The patient, a 9-year-old boy, had a 5-year history of pre-B-cell acute lymphoblastic leukemia and had been on chemotherapy throughout this period. After 10 days of profound neutropenia, lesions consistent with ecthyma gangrenosum appeared on his arms and legs. M. anisopliae was grown from specimens from three separate sites, collected at different times over a period of 1 month: a skin biopsy, a swab from the base of a lesion, and the core of another skin lesion which spontaneously discharged. The initial skin biopsy also showed histological evidence of epidermal necrosis and dermal invasion with fungal hyphae. A computed-tomography (CT) scan of the chest demonstrated a lesion in the superior segment of the lower lobe of the left lung. A CT scan of the brain revealed a lesion in the left temporoparietal region of the brain, consistent with an abscess. Despite antifungal treatment including liposomal amphotericin and 5-flucytosine, the patient eventually died. The initial portal of entry is unknown, but hematogenous dissemination to the skin appears likely because of the multiple ecthymic lesions, and the appearances of the brain lesion on the CT scan are consistent with a hematogenous fungal abscess.

Child↗
PubMed1998

Chondroitin sulfate proteoglycan with neurite-inhibiting activity is up-regulated following peripheral nerve injury.

Numerous findings support the possibility that highly sulfated proteoglycans are inhibitory molecules which, at high concentration relative to growth-promoting signals, may regulate or guide axonal growth. Although most studies implicate sulfated proteoglycans in the poor regenerative capacity of the central nervous system, inhibitory proteoglycans also may play an important role in the successful regeneration of axons within peripheral nerve. Cultured rat schwannoma and Schwann cells produce chondroitin sulfate proteoglycan (CSPG) which binds to and inhibits the neurite-promoting activity of laminin [Muir et al. (1989) J. Cell Biol. 109:2353]. In the present study, we found a similar neurite-inhibiting activity associated with CSPG isolated from normal adult rat sciatic nerve. Following nerve crush injury, this inhibitory activity was increased sevenfold in regenerating nerve distal to the injury. This increase was largely attenuated by in vivo administration of the proteoglycan synthesis inhibitor beta-D-xyloside. In normal adult nerve, immunolabeling for CSPG core protein was concentrated in slender bands surrounding axon-Schwann cell units and within nodes of Ranvier. Following nerve crush injury, immunolabeling of CSPG and laminin became more intense in distal nerve and CSPG increased within endoneurium and surrounding nerve sheaths. Embryonic dorsal root ganglionic neurons cultured on longitudinal nerve sections extended neurites along the exposed surfaces of Schwann cell basal lamina. The length of neurites was increased 58% on normal nerve sections pretreated with chondroitinase. Even though laminin levels were elevated in basal lamina of injured nerve, neuritic growth on sections of injured nerve was not significant increased unless sections were pretreated with chondroitinase. These results indicate that inhibitory CSPG is up-regulated in injured nerve and plays a role in regulating axonal regeneration.

Animals↗
PubMed1998

Invasive hyphomycotic rhinitis in a cat due to Metarhizium anisopliae.

Invasive mycotic rhinitis was diagnosed in a cat with a 4-month history of stertor, nasal discharge and subcutaneous swelling of the nasal bridge. Histology demonstrated fungal hyphae in representative biopsies of the nasal cavity and subcutaneous mass. Mycological culture demonstrated a pure growth of Metarhizium anisopliae var. anisopliae. The infection was treated with orally administered itraconazole. This is the first well documented case of infection by M. anisopliae in a mammalian host.

Animals↗
PubMed1997

Glial lineages and myelination in the central nervous system.

Oligodendrocytes, derived from stem cell precursors which arise in subventricular zones of the developing central nervous system, have as their specialist role the synthesis and maintenance of myelin. Astrocytes contribute to the cellular architecture of the central nervous system and act as a source of growth factors and cytokines; microglia are bone-marrow derived macrophages which function as primary immunocompetent cells in the central nervous system. Myelination depends on the establishment of stable relationships between each differentiated oligodendrocyte and short segments of several neighbouring axons. There is growing evidence, especially from studies of glial cell implantation, that oligodendrocyte precursors persist in the adult nervous system and provide a limited capacity for the restoration of structure and function in myelinated pathways damaged by injury or disease.

Adult↗
PubMed1997

Scytalidium dimidiatum and Lecythophora hoffmannii: unusual causes of fungal infections in a patient with AIDS.

Immunocompromised patients are susceptible to infections by fungi that seldom cause disease in humans. We describe a human immunodeficiency virus-infected patient who had simultaneous infections with two fungi which are rare causes of serious infection: Lecythophora hoffmannii, causing chronic sinusitis, and Scytalidium dimidiatum, causing skin lesions, lymphangitis, and lymphadenitis. The clinical and pathologic findings are discussed.

AIDS-Related Opportunistic Infections↗
PubMed1996

Leukemia and cumulative exposure to butadiene, styrene and benzene among workers in the synthetic rubber industry.

Retrospective, quantitative estimates of exposure to 1,3-butadiene, styrene and benzene were developed for a follow-up study of leukemia mortality among 16610 subjects employed at six North American styrene-butadiene rubber manufacturing plants (418846 person-years, 58 leukemia deaths). The estimation procedure entailed identifying work areas within each manufacturing process, historical changes in exposure potential and specific tasks involving exposure, and using mathematical models to calculate job- and time-period-specific average exposures. The resulting estimates were linked with the subjects' work histories to obtain cumulative exposure estimates, which were employed in stratified and Poisson regression analyses of mortality rates. Mantel-Haenszel rate ratios adjusted by race, age, and cumulative styrene exposure increase with cumulative butadiene exposure from 1 in the nonexposed category to 4.5 in the category of 80 ppm-years or more (P = 0.01). The risk pattern is less clear and statistically nonsignificant for styrene exposure. A trend of increasing risk with butadiene exposure is still present after exclusion of the nonexposed category (P = 0.03). A parsimonious interpretation of the findings presented here, in light of previous epidemiologic studies, is that exposure to butadiene in the synthetic rubber industry produces a dose-related increase in the occurrence of leukemia.

Benzene↗
PubMed1996

Assessment of laminin-mediated glioma invasion in vitro and by glioma tumors engrafted within rat spinal cord.

Cell motility within central nervous system (CNS) neuropil may be largely restricted yet infiltration by glioma cells is commonly observed. Glioma cells remodel nervous tissue and may assemble extracellular matrix in order to migrate. We examined the rat C6 glioma cell line for laminin expression and response in vitro and following engraftment into rat spinal cord. C6 cell cultures expressed laminin-2. C6 cells attached equally well to substrates of purified laminin-1 and laminin-2 and laminin-2-enriched C6 conditioned medium. In contrast, C6 cell migration was substantially greater on laminin-2 and C6-derived substrata than on laminin-1. Glioma cell attachment to laminin-1 and -2 was largely inhibited by antibody to the laminin receptor LBP110 and by an IKVAV peptide but not by YIGSR or control peptides. IKVAV peptide and anti-LBP110 antibodies also inhibited glioma cell invasion through synthetic basement membrane. Anti-beta 1 integrin antibody selectively inhibited cell migration and invasion on laminin-2 substrata without affecting percent cell attachment. These findings suggest C6 cell migration and invasion are promoted by autocrine release of laminin-2 and involve LPB110 and beta 1 integrin laminin receptors. A possible role for laminin-2 in CNS infiltration in vivo was examined following glioma engraftment into rat spinal cord. Engrafted C6 tumors share many histologic features of invasive human glioma. Engrafted glioma cells expressed laminin, LBP110 and beta 1 integrin antigens, indicating the molecular mechanisms of C6 motility observed in culture may contribute to glioma invasion in vivo. NMR and corroborative immunocytochemistry provided precise means to monitor tumor progression following glioma engraftment into rat spinal cord. Advantages of this glioma model are discussed regarding the assessment of anti-adhesive therapies in vivo.

Animals↗
PubMed1996

The opportunistic pathogen Nocardia farcinica is a foam-producing bacterium in activated sludge plants.

A Gram-positive unicellular coccal-diphtheroid rod causing foam in an activated sludge plant was successfully isolated by micromanipulation. Phenotypic characterization and 16S rDNA sequencing identified it as Nocardia farcinica. This is the first report that this opportunistic pathogen is a foam-causing bacterium in activated sludge, and the clinical implications of these observations are discussed.

DNA, Bacterial↗
PubMed1995

Differences in proliferation and invasion by normal, transformed and NF1 Schwann cell cultures are influenced by matrix metalloproteinase expression.

Loss of negative growth regulation and high invasive potential are neoplastic traits often associated with abnormal expression of matrix metalloproteinases (MMPs). We previously found MMP-3 (stromelysin/transin) was secreted by quiescent rat Schwann cell cultures and expressed potent antiproliferative activity. In the present study we observed that human Schwann cells and cutaneous neurofibroma Schwann cell cultures secreted abundant MMP-3 and their proliferation was inhibited by autologous and rat Schwann cell conditioned media. Antiproliferative activities were depleted by immunoadsorption with anti-stromelysin antibodies. In contrast, plexiform neurofibroma cultures did not secrete MMP-3 and failed to respond to Schwann cell antiproliferative activities associated with MMP-3. Quiescent Schwann cells constitutively secreted low levels of MMP-2 (gelatinase A) and showed a low invasion potential in filter-based assays of basement membrane invasion. Cyclic AMP elevation, which profoundly influences cell differentiation, increased the invasion potential of rat Schwann cells and caused a corresponding increase in secretion of MMP-2. Schwann cells immortalized by protracted elevation of cAMP, as well as a schwannoma cell line (D6P2T), also rapidly invaded a reconstituted basement membrane and over-expressed MMP-2. Similarly, neurofibroma Schwann cells were highly invasive and secreted up to 10-fold more MMP-2 than normal human Schwann cells. Additionally, only cutaneous neurofibroma Schwann cell cultures secreted MMP-9 (gelatinase B) and MMP-1 (interstitial collagenase) and also invaded native type I collagen barriers. Cultures of normal Schwann cells and plexiform neurofibroma tumor expressed little or no MMP-1 and did not invade type I collagen barriers. These results suggest a role for MMPs in the control of proliferation and invasion by Schwann cells and in the formation of peripheral nerve sheath tumors.

Amino Acid Sequence↗
PubMed1994

Metalloproteinase-dependent neurite outgrowth within a synthetic extracellular matrix is induced by nerve growth factor.

In order to assess the requirement for matrix metalloproteinases in neuronal regeneration, in vitro neurite outgrowth by chick dorsal root ganglionic neurons (DRGn) was examined within a reconstituted extracellular matrix. For these studies, cultured neurons were treated with a synthetic peptide inhibitor of metalloproteinases (spIMP), LMHKPRCGVPDVGG. spIMP inhibited all neuronal metalloproteinase activities in zymography and substrate-release assays and was used to examine the role of metalloproteinases in neurite outgrowth by DRGn. Cultures of dissociated DRGn rapidly extended neurites on planar extracellular matrix substrates and this rate of outgrowth was not affected by adding NGF or spIMP. In contrast, neurite extension within a three-dimensional gel of extracellular matrix increased nearly threefold after adding NGF. The NGF-induced neurite penetration was negated in the presence of spIMP but not by control peptide. Similar results were obtained using explanted dorsal root ganglia. These findings suggested that NGF-induced neurite outgrowth within an extracellular matrix involves metalloproteinase activity. Zymographic analysis of media conditioned by NGF-treated DRGn revealed a pair of gelatinolytic bands with apparent molecular masses 72 and 66 kDa, which comigrated as a single 66-kDa band after activation with an organomercurial agent. The gelatinase activities were calcium- and zinc-dependent and were absent from zymograms developed in the presence of spIMP, indicating that NGF-treated DRGn release and activate a 72-kDa metalloproteinase. Samples from DRGn cultures treated with low levels of NGF contained similar amounts of latent and activated metalloproteinase, while high levels of NGF induced an apparent increase in total metalloproteinase secretion and a substantially greater proportion of activated enzyme. Western blot analysis showed this metalloproteinase was immunologically similar to 72-kDa type IV collagenase and immunoassays revealed that this matrix metalloproteinase was increased threefold by high NGF. Furthermore, after high NGF treatment, DRGn media contained sixfold more metalloproteinase activity in assays of matrix degradation. In summary, these results indicate that NGF enhanced metalloproteinase-dependent neurite outgrowth of DRGn within a reconstituted extracellular matrix. Also, NGF increased the expression and activation of 72-kDa type IV collagenase, suggesting a role for this matrix-degrading metalloproteinase in neuronal regeneration.

Amino Acid Sequence↗
PubMed1994

Colored aftereffects contingent upon global transformations?

Dodwell and Humphrey (Psychol. Rev. 97, 78-79, 1990) have argued that colored aftereffects (CAEs) are contingent on the global geometries of local orientation and edge components in induction patterns. The spatiotopic dimensions underlying these geometries are derived from previous applications of the mathematics of continuous transformations (Lie groups) to the stimulus dynamics of perceptual invariance. In these terms, complementary CAEs induced by inspecting alternating colored bullseyes and spokes are attributed to the adaptation of orthogonal spatiotopic channels; the former characterized by vectorfields dealing with object invariance under rotation, and the latter by vectorfields dealing with object invariance under dilation. Importantly, the pattern-contingent CAEs induced in this pair of pattern channels are independent of CAEs induced in channels characterized by vectorfields dealing with object invariance under vertical and horizontal translations (e.g. vertical and horizontal gratings). The present investigation examined whether CAEs contingent on the stimulus dynamics originally used to define these spatiotopic channels exhibit comparable properties. It is confirmed that pairs of complementary CAEs can be induced simultaneously with radially expanding and contracting bullseyes, and clockwise- and counter-clockwise-rotating spokes (Experiment 1); and it is shown that these CAEs combine linearly in generalizing to and from the radial and rotational components of spiral motion (Experiments 2 and 3 respectively). In direct contrast to findings for CAEs induced with stationary versions of these patterns, however, it is demonstrated that complementary pairs of CAEs induced by expanding and contracting bullseyes interact with CAEs induced by left- and right-moving vertical gratings, suggesting that the components of motion underlying these contingent effects are locally and not globally determined (Experiment 4).

Color Perception↗
PubMed1993

Quantitative methods for scoring cell migration and invasion in filter-based assays.

The ability of cells to traverse pores in a biocompatible filter provides means for examining cell chemoattraction. Filter-based assays also permit rapid, quantitative assessment of the in vitro migratory and invasive potential of tumor cells. Scoring migration has relied on visual counting of stained cells which appear on the underside of the filter and determining a true percentage score involves arduous counting of cells on both filter surfaces. Visual counting of random fields may be unreliable, and counting all fields is laborious. In the present study we developed and compared two alternative methods for scoring cell numbers in filter-based assays, a colorimetric assay of toluidine blue binding, and a radioassay of cells prelabeled with [3H]thymidine. Each method was evaluated for sensitivity, variability, ease of use and efficiency, and suitability for use in assays of cell migration and invasion. The radiolabeling method proved to be sensitive and reliable and was the most efficient technique. Although less sensitive and specific, the colorimetric dye method offered a rapid and reliable, nonradioactive alternative with the distinct advantage of preserving intact cultures for follow-up visual assessments. We conclude that colorimetric and radiolabel scoring of filter-based assays are reliable and efficient semiautomated methods which provide means to obtain more complete assessments of cell migration and invasion.

Cell Count↗