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Biomedical subjects

A Wood

Publications and source records attributed to A Wood.

At least 19 recordsLinked to original sources

Enhanced neuronal differentiation of NTera-2 cells expressing neuronally restricted beta2 adrenergic receptor.

NTera-2/D1 (NT2) is a human teratocarcinoma cell line which can be cultured as a dividing population of precursor cells that can be manipulated with retinoic acid (RA) to yield post-mitotic neurons. Precursor cells were transfected with the human beta2 adrenergic receptor, controlled by the neuronal cell specific rat synapsin-1 promoter. Transfected precursor cells did not display elevated expression of the beta2 adrenergic receptor. Upon differentiation to a neuronal phenotype with RA, betaSyn2 and betaSyn4 (beta2Syn-NT2; ATCC CRL-12356) displayed elevated beta2 adrenergic receptor levels, and an elevated coupling to cAMP production. It was also observed that the elevated expression of the beta2 adrenergic receptor in the neuronal NT2 cells resulted in an enhanced level of neuronal differentiation compared to the wild type cells. These results demonstrate that the neuronally restricted expression of the human beta2 adrenergic receptor in NT2 neurons results in increased receptor levels and receptor stimulated generation of cAMP, this may result in the observed improvement in neuronal differentiation.

Animals

Contagious bovine pleuropneumonia. The costs of control in Central/southern Africa.

Contagious bovine pleuropneumonia (CBPP) caused by Mycoplasma mycoides subspecies mycoides small colony (M. mycoides) has been endemic in many parts of Africa for the greater part of this century. Because of an international vaccination campaign the disease was almost eliminated from the continent. With the deteriorating economic situation of many countries, vaccination programs have been allowed to slip; drought conditions have resulted in great movements of livestock and the disease has spread rapidly to the east and south. For Government Veterinary Departments, the implications of this resurgence of CBPP, are serious. The costs threaten to overwhelm completely under-funded government, services. Where cost-recovery measures are introduced, the charging for vaccines may damage rapport with communities and erode the credibility of the government services. Farmers may find the loss of cattle and the costs of vaccine severe burdens which threaten their livelihoods and social well-being (Zambia) and even, in extreme cases, their survival (Botswana). Controlling the disease today presents new possibilities which include increased cross-border collaboration (Malawi/Tanzania), increased emphasis on monitoring (N. Zambia) and the greater involvement of communities in disease control (W. Zambia).

Abattoirs

Absent pulmonary valve syndrome with interrupted aortic arch.

A surgically treated case of absent pulmonary valve syndrome associated with type B interrupted aortic arch is presented. The presence of a restrictive ductus arteriosus promoted the development of a collateral circulation between ascending and descending thoracic aorta, allowing the child to remain clinically stable after birth.

Aorta, Thoracic

The action of three antiseptics/disinfectants against enveloped and non-enveloped viruses.

The antiviral action of chloroxylenol, benzalkonium chloride and cetrimide/chlorhexidine was assessed against a range of enveloped and non-enveloped human viruses using a suspension test method. Viral suspensions of 10(6)-10(7) pfu/TCID50 or sfu were prepared in each of the antiseptic/disinfectant solutions in the presence of a bovine serum/yeast extract mixture to simulate 'dirty conditions'. During incubation, aliquots were removed at predetermined timepoints up to 10 min to assess the kinetics of inactivation. Results indicate that all products were effective in inactivating the enveloped viruses herpes simplex virus type 1 and human immunodeficiency virus type 1, whilst being ineffective in inactivating human coronavirus, also enveloped, and the non-enveloped viruses. The exception to this was the benzalkonium chloride-based product (Dettol Hospital Concentrate) which was active against the non-enveloped human coxsackie virus. Four antiseptic/disinfectant solutions with chloroxylenol, benzalkonium chloride, cetrimide/chlorhexidine and povidone-iodine were also assessed for antiviral effect against human immunodeficiency virus in the presence of whole human blood. All four solutions proved to be effective within 1 min despite the cytotoxic nature of the compounds to the detection system.

Anti-Infective Agents, Local

Periaortic fat pad mimicking an intramural hematoma of the thoracic aorta: lessons for transesophageal echocardiography.

We report a patient whose clinical and echocardiographic findings were compatible with a diagnosis of aortic intramural hematoma, but magnetic resonance imaging demonstrated a prominent and localized periaortic deposit of fat as the cause of the transesophageal echocardiographic appearance. This is a significant caveat that must be borne in mind when interpreting echocardiographic images obtained in patients with suspected intramural aortic hematomas.

Adipose Tissue

The orf virus OV20.0L gene product is involved in interferon resistance and inhibits an interferon-inducible, double-stranded RNA-dependent kinase.

The parapoxvirus orf virus was resistant to type 1 (IFN-alpha) and type 2 (IFN-gamma) interferons in cultures of ovine cells. The recently identified orf virus OV20.0L gene exhibits 31% predicted amino acid identity to the vaccinia virus E3L interferon-resistance gene, and is referred to as the (putative) orf virus interferon-resistance gene (OVIFNR). The objective of this study was to determine whether OVIFNR was involved in interferon resistance. Recombinant OVIFNR as a thioredoxin fusion protein (OVIFNR-Tx) inhibited the activation (by autophosphorylation) of an interferon-inducible, double-stranded (ds) RNA-dependent kinase (PKR) of sheep, which was shown to bind dsRNA (poly I:C). PKR in other species is involved in the inhibition of protein synthesis as part of the antiviral state in infected cells. Virus-infected cell lysates, but not control lysates, from cells grown in the presence of cytosine arabinoside also contained PKR inhibitory activity, which indicated that the inhibitory activity was associated with early viral gene expression. Significantly, the OVIFNR gene expressed in interferon-treated ovine fibroblasts protected the unrelated Semliki Forest virus from the antiviral effect of both type 1 and type 2 interferons. Taken together, the results indicate that the OVIFNR gene functions as an interferon-resistance gene, the product of which inhibits PKR in a similar way to the vaccinia virus E3L gene product.

Animals

Changes in neuron size in cynomolgus macaques infected with various immunodeficiency viruses and poliovirus.

Human immunodeficiency virus (HIV) infection leads to clinically significant neuronal pathology, but the underlying mechanism remains unclear. Infection of rhesus macaques with the simian immunodeficiency virus SIVmac251 has been shown to cause atrophy of hippocampal pyramidal cells. The aim of the current investigation was to determine whether SIVmac251 and other viruses with differing abilities to cause immune suppression or encephalitis could cause neuronal atrophy in cynomolgus macaques. Animals infected with SIVmac251 (n = 22), HIV-2 (n = 6). SIVmac239 (n = 7) and poliovirus (n = 10) were investigated, together with 16 controls. Hippocampal pyramidal cell diameter, averaged across the four CA subfields, was reduced by 16.6% in the SIVmac251 group (P < 0.0001) and by 13.3% in the HIV-2 group (P < 0.001), even though the latter virus does not generally cause immunosuppression. Conversely, SIVmac239, which does cause immunosuppression, caused an average neuronal hypertrophy of 6.8% (P = 0.033). Of possible relevance to the different behaviour of the two SIVs is that SIVmac239 is lymphocyte tropic and does not infect CNS microglia in vivo whereas SIVmac251 does. Animals inoculated with poliovirus into the lumbar spinal cord for polio vaccine neurovirulence testing acted as positive controls for CNS inflammation and they also showed an increase in neuronal diameter (4.1%, P = 0.025). The atrophy seen with SIVmac251 and HIV-2 involved all CA subfields but the hypertrophy following SIVmac239 or poliovirus infection was restricted to CA1 and CA2. These observations show a dissociation between the ability of immunodeficiency viruses to cause immune suppression and neuronal pathology and demonstrate that CNS inflammation per se may cause neuronal hypertrophy.

Animals

Which depressed patients respond to cognitive-behavioral treatment?

OBJECTIVE: To identify predictors of remission from major depression in adolescent patients given cognitive-behavioral therapy (CBT). METHOD: The study was based on 50 patients aged between 10 and 17 years who were obtained from two studies of CBT. A wide range of possible predictors was examined. RESULTS: Sixty percent remitted by the end of treatment. In multivariate analyses remission was associated with younger age and less social impairment. CONCLUSIONS: Depressed patients who respond to CBT tend to be younger and less severely impaired than those who do not respond.

Adolescent

Alpha interferon gene deletions in post-transplant lymphoma.

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication of organ transplant and has been associated with high mortality using conventional chemotherapy. We have investigated 11 cases of PTLD for alterations to the interferon alpha (IFNA) and p16 genes on chromosome 9p using archival material. 4/9 (44%) cases had deletions of the IFNA genes, in contrast to 1/59 (1.7%) cases of intermediate/high-grade de novo NHL drawn from the same geographical region. PTLD may therefore represent a distinct NHL subgroup exhibiting distinct gene pathology.

Chromosomes, Human, Pair 9

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

Early high dose chemotherapy intensification with autologous bone marrow transplantation in lymphoma associated with retention of fertility and normal pregnancies in females. Scotland and Newcastle Lymphoma Group, UK.

As more centres consider autologous bone marrow and peripheral blood stem cell transplantation for patients with high risk Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) in first complete remission (CR1) the long term sequelae of such treatments have to be considered. One of the most important side effects of such intensive treatment is loss of fertility. Sperm banking before treatment commences is available for males but unfortunately cryopreservation of ova/ovarian tissue is not yet possible for females. We have transplanted 30 women, 23 were under 40 years and report ten females who have had successful pregnancies (including two twin pregnancies and one triplet pregnancy), leading to live births following autologous bone marrow transplantation (ABMT) for poor prognosis HD and NHL in first or second complete remission. None of these children have shown evidence of birth defects (median follow up of two years). Of the twenty one pregnancies reported to the European Bone Marrow Transplantation Registry (EBMTR) following ABMT for lymphoma, eight of the seventeen unassisted cases came from our centres. The Newcastle/SNLG autotransplant differs from the approach in many EBMTR centres in that it uses melphalan or melphalan/etoposide alone instead of the more common four drug containing regimens and yet sustained complete remission rates indicate that the non-ablative approach is equally effective as more aggressive regimens on the disease with the huge advantage of preserved fertility in females. This approach to conditioning for ABMT should be considered when treating women in the reproductive age group.

Adult

Exogenous glycosaminoglycans (GAG) differentially modulate GAG synthesis by anchorage-independent cultures of the outer cells from neonatal rat calvaria in the absence and presence of TGF-beta.

In anchorage-dependent (AD) cultures of the outer cell population (OCP) from neonatal rat calvaria, transforming growth factor-beta 1 (TGF-beta) specifically upregulated the synthesis of chondroitin sulfate (CS) proteoglycan (PG) and uncoupled the inhibitory effect of increasing cell density on CS PG synthesis (reference #30). Utilizing the same cell population, we have further examined the possibility that glycosaminoglycans (GAG) known to be synthesized and secreted by bone cells might exert feedback effects on GAG synthesis and/or its stimulation by TGF-beta. Although addition of TGF-beta alone stimulated net synthesis of HA and CS in both AD and anchorage-independent (AI) cultures, significant alterations of basal and TGF-beta-stimulated GAG synthesis by exogenous GAGs were observed only in AI cultures. In AI cultures exogenously added hyaluronic acid (HA) markedly enhanced the basal synthesis of HA and CS while heparin (H) suppressed the basal synthesis of HA, CS as well as dermatan sulfate (DS). Also, the addition of HA markedly potentiated the stimulation by TGF-beta of HA and CS synthesis as did heparan sulfate (HS) for CS and DS synthesis. H suppressed the stimulation of the synthesis of HA, CS and DS by TGF-beta. Overall, our results indicate specific effects of individual GAGs on basal and TGF-beta-stimulated GAG synthesis in OCP cultures. We suggest that some of the GAGs in the OCP microenvironment (which with the exception of HA are covalently linked to protein cores of secreted PGs), acting in concert with TGF-beta, may serve as an amplification system for upregulating GAG synthesis in the rapidly growing neonatal calvarium.

Animals

CD59 expression and complement susceptibility of human neuronal cell line (NTera2).

The present study analysed the susceptibility of neuronal cells to human complement. A human neuronal precursor cell line (NTera2) which can be induced to differentiate into post-mitotic neuronal cells was employed. Using immunocytochemistry, NTera2 neurones, but not their precursors (stem cells), were shown to activate complement in the absence of antibody and to lack CD59, an inhibitor of the terminal stages of the complement cascade. Following exposure to human serum, neurones but not stem cells were lysed by complement, as demonstrated by a cell viability assay and consistent rise in intracellular calcium. This response was abrogated when cells were treated with complement-depleted serum by heat inactivation or cobra venom factor. Protection from lysis was observed following incorporation of CD59 with its glycolipid anchor in the neuronal cell membrane.

CD59 Antigens

Clinical validity of major depression-endogenous subtype in adolescent patients.

This paper explored the validity of the distinction between endogenous and nonendogenous forms of major depression in a clinical sample of adolescents, average age 13.6 years. The criteria used to establish this distinction were features of the disorder itself and the external criteria of demography, family history and psychosocial stressors. Endogenous subjects had a more severe form of depressive disorder than nonendogenous subjects. However, there were no significant differences between the depressed groups on any of the external criteria. The distinction between endogenous and nonendogenous major depression in early and mid-adolescence appears therefore to be quantitative rather than qualitative.

Adolescent

Patterns of supradiaphragmatic metastases in testicular germ cell tumours.

The imaging and clinical findings of 31 patients with supradiaphragmatic nodal metastases from primary testicular germ cell cancers were reviewed. In 11 patients the primary testicular tumor was a seminoma, and in 20 a non-seminomatous germ cell tumour (NSGCT). The patterns of spread of these tumour types were compared. All patients had chest radiographs (CXR): 27 had chest computed tomography (CT). One patient with seminoma and eight with NSGCT (40%) had lung metastases. Mediastinal lymphadenopathy was seen on CT in seven patients with seminoma (64%) and in nine patients with NSGCT (45%). Neck lymphadenopathy was present in 10 of 11 (91%) patients with seminoma, and 13 of 20 (65%) patients with NSGCT. Neck disease co-existed with mediastinal disease in six of 11 (55%) patients with seminoma, but in only two of 20 (10%) patients with NSGCT (P=0.012). This study gives further supporting evidence for the relative importance of haematogenous spread in teratoma, and lymphatic spread in seminoma. The contiguous nature of disease spread from abdomen to chest and neck in seminoma is confirmed. In NSGCT, supradiaphragmatic spread is more random but tends to occur in the paraoesophageal and subcarinal groups.

Abdomen

Controlled trial of a brief cognitive-behavioural intervention in adolescent patients with depressive disorders.

Fifty-three child and adolescent psychiatric patients with depressive disorders were randomly allocated to brief cognitive-behaviour therapy (CBT) or to a control treatment, relaxation training. Forty-eight patients completed the treatment phase of the trial, which comprised 5-8 treatment sessions. Post-treatment assessments showed a clear advantage of CBT over relaxation on measures of both depression and overall outcome. However, there were no significant differences between the treatments on comorbid anxiety and conduct symptoms. At follow-up, the differences between the groups were reduced, partly because of a high relapse rate in the DTP group and partly because subjects in the relaxation group continued to recover.

Adolescent