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Biomedical subjects

C C Wilkinson

Publications and source records attributed to C C Wilkinson.

9 recordsLinked to original sources
PubMed2000

Hindbrain herniation develops in surgically created myelomeningocele but is absent after repair in fetal lambs.

OBJECTIVE: The purpose of our study was to determine whether prenatal repair of myelomeningocele prevents or reverses hindbrain herniation in the sheep model. STUDY DESIGN: A myelomeningocele was surgically created in fetal sheep. One group was repaired later in utero; the others were delivered without repair. After delivery, lambs were assessed for the presence of hindbrain herniation. RESULTS: In all lambs that had not undergone repair of the myelomeningocele, severe hindbrain herniation developed, whereas the brains of all lambs that had undergone fetal repair were normal. CONCLUSION: Prenatal repair of myelomeningocele prevents or reverses development of hindbrain herniation in the fetal lamb model.

Animals↗
PubMed1999

Fetal neurenteric cyst causing hydrops: case report and review of the literature.

Routine prenatal ultrasound revealed a unilocular cystic mass associated with upper thoracic hemivertebrae that grew to 6 cm at 28 weeks and was associated with hydrops. A thoraco-amniotic shunt decompressed the cyst and resolved the hydrops, but the shunt occluded 17 days later. Preterm labour led to vaginal delivery at 31 2/7 weeks. Postnatally, the cyst was decompressed by thoracentesis due to respiratory distress. It was resected on day four of life. Severe tracheobronchomalacia was present post-operatively, presumably due to prenatal mass effect of the cyst. At one year of age, the child has recovered completely without adverse respiratory or neurological sequelae.

Adult↗
PubMed1996

Urokinase is required for the pulmonary inflammatory response to Cryptococcus neoformans. A murine transgenic model.

Urokinase (uPA) is hypothesized to provide proteolytic activity enabling inflammatory cells to traverse tissues during recruitment, and it is implicated as a cytokine modulator. Definitive evaluation of these hypotheses in vivo has previously been impossible because uPA could not completely and irreversibly be eliminated. This limitation has been overcome through the development of uPA-deficient transgenic mice (uPA-/-). Using these mice, we evaluated the importance of uPA in the pulmonary inflammatory response to Cryptococcus neoformans (strain 52D). C. neoformans was inoculated into uPA-/- and control mice (uPA+/+), and cell recruitment to the lungs was quantitated. The number of CFU in lung, spleen and brain was determined to assess clearance, and survival curves were generated. By day 21 after inoculation, uPA-/- mice had markedly fewer pulmonary inflammatory (CD45+), CD4+, and CD11b/CD18+ cells compared with uPA+/+ controls (P<0.0007); pulmonary CFUs in the uPA-/- mice continued to increase, whereas CFUs diminished in uPA+/+ mice(P<0.005). In survival studies, only 3/19 uPA+/+ mice died, whereas 15/19 uPA-/- mice died (p<0.001). We have demonstrated that uPA is required for a pulmonary inflammatory response to C. neoformans. Lack of uPA results in inadequate cellular recruitment, uncontrolled infection, and death.

Animals↗
PubMed1994

The urokinase receptor is required for human monocyte chemotaxis in vitro.

Mononuclear phagocytes (Mphi) produce urokinase-type plasminogen activator (uPA) and also express a specific cell-surface receptor for urokinase, uPAR. The concomitant expression of these proteins provides a mechanism by which Mphi can degrade extracellular matrix proteins during directed cell migration. In this study, we sought to determine if uPAR plays a role in Mphi chemotaxis that is distinct from its role in matrix proteolysis. Exposing adherent monocytes to a chemotactic gradient causes plasma membrane uPAR to localize strongly to the leading edge of cell migration. Adherence alone or exposure to FMLP had no effect on uPAR expression. Using Boyden chamber chemotaxis assays, we demonstrate that treating mononuclear cells with an anti-uPAR mAb (either as an intact mAb or F[ab']2) ablates chemotaxis induced by FMLP and monocyte chemotactic peptide-1 (P < 0.001). Inactivating the catalytic activity of uPAR-bound uPA had no effect on chemotaxis. Similarly, blocking uPAR expression with an antisense oligonucleotide to uPAR completely ablates chemotaxis, but blocking uPA expression with an antisense oligonucleotide to uPA has a minimal effect. We therefore demonstrate that expression and unimpeded function of uPAR plays an obligate role in M phi chemotaxis by mechanisms that are largely independent of its ligand, uPA. Combined with its known role in mediating pericellular proteolysis, these observations demonstrate that uPAR is essential for both locomotion and traversing tissue barriers during M phi migration.

Antibodies, Monoclonal↗
PubMed1993

Monocyte urokinase expression: modulation by interleukins.

This study delineates the regulatory effect of interleukin-1 (IL-1) and interleukin-2 (IL-2) on monocyte plasminogen activator (PA) activity. Mononuclear phagocytes regulate net PA activity by modulating the expression of urokinase-type PA (uPA) and a specific plasminogen activator inhibitor, PAI-2. To understand the regulation of mononuclear phagocyte PA activity, it is important to compare the expression of uPA and PAI-2. In this study, we determined the relative abundance of secreted PA and PA inhibitor activity in human monocyte-conditioned medium after stimulation with human recombinant IL-1 or IL-2. In agreement with our previous description of tumor necrosis factor-alpha and interferon-gamma stimulation of mononuclear phagocytes, we found no detectable PA activity in conditioned medium. Both IL-1 and IL-2 had dose-dependent effects, significantly up-regulating PA inhibitor activity in monocyte-conditioned medium (up to 11-fold). To further investigate the mechanism underlying this effect, Northern blot analysis was done to measure steady-state mRNA for uPA and PAI-2. Consistent with the increase in secreted PA inhibitor activity, we found that both IL-1 and IL-2 significantly increased steady-state mRNA for PAI-2. In addition, however, both IL-1 and IL-2 increased steady-state mRNA for uPA. IL-1 appears to increase mRNA for uPA to a greater extent than does IL-2. We conclude that IL-1 and IL-2 modulate monocyte proteolytic activity by increasing expression of uPA and PAI-2 with a resultant predominance of PAI-2. We further conclude that cytokine-specific regulation of plasminogen activity is achieved partly by varying the proportionate expression of uPA and PAI-2.

Blotting, Northern↗
PubMed1993

Monocyte 1 alpha-hydroxylase regulation: induction by inflammatory cytokines and suppression by dexamethasone and uremia toxin.

Alveolar macrophages acquire 1 alpha-hydroxylase activity in inflammation, and thereby metabolize 25 hydroxyvitamin D3 (25 D3) to the active metabolite, 1 alpha,25-dihydroxyvitamin D3 (1,25 D3, calcitriol). Calcitriol is a potent differentiation agent that modulates mononuclear phagocyte activation and effector functions. The mediators that induce macrophage 1 alpha-hydroxylase activity are not well delineated. Furthermore, it is unclear whether calcitriol is a product only of terminally differentiated macrophages or whether less mature mononuclear phagocytes can produce it as well. The ability of newly recruited monocytes to produce calcitriol as an autocrine differentiation agent is particularly important in inflammation, as it may substantially expand the functional repertoire of these cells. To assess the effects of cytokines on 1 alpha-hydroxylase activity, blood monocytes were cultured in the presence and absence of human recombinant tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukins 1 and 2 and then incubated with 25 D3 substrate. The conditioned media were assayed for calcitriol by high-performance liquid chromatography and competitive receptor binding assay. No detectable calcitriol was produced by unstimulated monocytes. However, all the cytokines markedly increased monocyte calcitriol production (range 133-151 pg/mg protein; in all cases P < .001). We then determined whether calcitriol production was suppressed by preincubation with either dexamethasone or the putative uremia toxin guanidinosuccinic acid (GSA). Dexamethasone pretreatment significantly inhibited subsequent cytokine-induced calcitriol production by monocytes, as did GSA (average 69 and 63% of control, respectively).

Calcitriol↗
PubMed1978

Electrophoresis of avian muscle proteins.

1. The electrophoretic patterns of water-soluble proteins of avian muscle showed differences due both to species and to muscle type. 2. Each muscle pattern within a species showed a unique protein band which distinguished that species from other species.

Animals↗
PubMedDate not supplied

Chronic subdural hematoma presenting with symptoms of transient ischemic attack (TIA): a case report.

Rarely, chronic subdural hematomas (CSDH) will present with symptoms mimicking transient ischemic attacks (TIAs). We report the case of an elderly man who presented with intermittent numbness and weakness of his left upper extremity typical of symptoms arising from a right sensorimotor cortex TIA. He was treated with empiric antiplatelet therapy for several days before a head CT was performed. The head CT and a subsequent MRI showed a CSDH with an acute component and cortical compression. Upon evacuation of the hematoma, his symptoms resolved. In cases of suspected TIA, a head CT should always be performed before beginning antiplatelet therapy. If there is an underlying hematoma, such therapy is dangerous, as it can potentiate more bleeding and leave the true pathology unaddressed.

Aged↗