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C W Roberts

Publications and source records attributed to C W Roberts.

At least 19 recordsLinked to original sources
PubMed1992

Kinetics of cytokine mRNA production in the brains of mice with progressive toxoplasmic encephalitis.

C57BL/10 ScSn (B10) mice infected orally with Toxoplasma gondii were killed on days 5, 10, 15, 20 and 30 post infection and their brains excised. These were either used to count total tissue cyst numbers or divided for RNA purification and histopathological studies. The first signs of inflammation were on day 10 post infection, before the appearance of cysts in the brain, and correlating with the appearance of activated astrocytes. These mice had a mild meningitis with areas of encephalitis. Small numbers of cyst stages were first observed in the brain on day 15 and by day 20 the cyst numbers had increased dramatically but were not always associated with inflammation. After this time point, total cyst numbers did not increase significantly though there developed a marked variation in tissue cyst size with larger cysts becoming more numerous. The use of the polymerase chain reaction to assist in the amplification of brain RNA allowed the characterization of the kinetics of cytokine production within the brains of these animals. Only IL-1 alpha was found to be expressed constitutively in control mice. Transcripts for other cytokines associated with activated monocytes, microglial cells and astrocytes [tumor necrosis factor (TNF)-alpha and interleukin (IL)-6] were present on day 10, (IL-6) and day 15 (TNF-alpha) post infection. Thereafter, these cytokines were present in all infected animals. Of the T cell-associated cytokines, IL-4, a characteristic product of the T helper (Th)2 cell subset, was detected on days 10 and 15, while granulocyte macrophage colony stimulating factor (GM-CSF) which can be produced not only by this cell type but also by Th1 cells and CD8+ T cells, was also present on day 15 but not thereafter. Transcripts for interferon (IFN)-gamma, present from day 15 post infection, were probably produced by CD8+ T cells, as IL-2 which would indicate Th1 cell involvement was only detected 30 days after infection. The continual presence of IFN-gamma and TNF-alpha, cytokines with reported anti-toxoplasmic activity, in the CNS of B10 mice throughout the latter half of the experimental period did not diminish the severity of infection. These results indicate that the CD4+ Th2 subset may allow a rapid rise in cyst numbers and so be important in determining susceptibility to toxoplasmic encephalitis.

Animals↗
PubMed1992

Studies on a murine model of congenital toxoplasmosis: vertical disease transmission only occurs in BALB/c mice infected for the first time during pregnancy.

The incidence of congenital toxoplasmosis was determined by an ELISA in the litters of BALB/c mice which had been infected 8 weeks before mating, on day 12 of pregnancy, or on both these occasions. Of those mice given the infection for the first time on day 12 of pregnancy, 5 out of 6 gave birth to infected litters with approximately 50% of the individuals in each litter being infected. BALB/c mice which had been infected 8 weeks before mating did not give birth to infected litters, even if they were reinfected on day 12 of pregnancy. Following infection BALB/c mice were found to harbour significantly fewer tissue cysts than the congenic H-2 derivative BALB/K strain. However, chronically infected BALB/K mice also failed to produce infected litters, indicating that tissue cyst burden in the dam did not influence congenital infection at least on the BALB background. This study demonstrates that BALB/c dams chronically infected with Toxoplasma gondii, have immunity capable of protecting their embryos from congenital infection, even if the dams are reinfected during pregnancy. Our results demonstrate that the BALB/c mouse can be used as a model of human or ovine congenital T. gondii infection suitable for testing putative vaccines.

Animals↗
PubMed1992

Detection of cytokine mRNA in the brains of mice with toxoplasmic encephalitis.

C57Bl/10 ScSn mice infected with Toxoplasma gondii developed a meningoencephalitis, characterized by areas of tissue destruction and cellular infiltration including foci of neutrophils. Large numbers of cyst stages were found throughout the brain but were not always associated with inflammation. The use of immunocytochemistry to detect glial fibrillary acidic protein, an astrocyte specific marker, showed a widespread astrocyte activation. This was particularly prominent in areas of intense inflammation but cysts were negative for glial fibrillary acidic protein, indicating that astrocytes were not host cells for the bradyzoites. The use of the polymerase chain reaction to assist in the amplification of total brain RNA allowed the characterization of the cytokines being produced locally within the brains of infected animals. beta-actin transcripts were detected in all of the uninfected and infected mice. In only one of the seven uninfected control mice were other transcripts found. Transcripts for tumour necrosis factor-alpha, interleukin-1 alpha and beta, interleukin-6, macrophage inflammatory protein-1 and interferon-gamma as well as the CD4 marker were detected in all of the infected mice. However, transcripts for IL-2 and IL-4 were not present. Several of the cytokines present are capable of initiating meningeal inflammation and may play a role in the immunopathogenesis of toxoplasmic encephalitis.

Animals↗
PubMed1991

Deregulation of a homeobox gene, HOX11, by the t(10;14) in T cell leukemia.

Molecular cloning of the t(10;14)(q24;q11) recurrent breakpoint of T cell acute lymphoblastic leukemia has demonstrated a transcript for the candidate gene TCL3. Characterization of this gene from chromosome segment 10q24 revealed it to be a new homeobox, HOX11. The HOX11 homeodomain is most similar to that of the murine gene Hlx and possesses a markedly glycine-rich variable region and an acidic carboxyl terminus. HOX11, while expressed in liver, was not detected in normal thymus or T cells. This lineage-restricted homeobox gene is deregulated upon translocation into the T cell receptor locus where it may act as an oncogene.

Amino Acid Sequence↗
PubMed1991

Cataract surgery in anticoagulated patients.

A prospective study was performed on 31 patients having planned extracapsular cataract extraction with posterior chamber intraocular lens implantation. The patients were considered to be anticoagulated because of the medications they were taking. The patients were instructed to continue their usual medications throughout the perioperative period including the day of surgery. All patients had routine narcoleptic sedation and retrobulbar anesthesia. The surgical technique was altered to use an inferior corneal traction suture and a single planed clear corneal incision. No intraoperative or postoperative anterior chamber bleeding was seen. The observed complications were increased awareness of corneal sutures, increased endothelial cell loss, delayed visual rehabilitation from with-the-rule astigmatism, and transient corneal edema. All patients achieved 20/40 or better visual acuity without corneal edema by three months post-surgery.

Aged↗
PubMed1991

CD8+ T cells are the major lymphocyte subpopulation involved in the protective immune response to Toxoplasma gondii in mice.

The ability of the major T cell subsets to adoptively transfer resistance to T. gondii infection was studied. Spleen cells harvested from mice with a 3-month T. gondii infection and cells from uninfected mice were enriched for T cells by nylon/wool purification. Adoptive transfer of these cells from both groups of donor mice led to a significant increase in the survival of syngeneic recipient mice infected intraperitoneally with 20 T. gondii cysts. Increased survival was mediated particularly by CD4-depleted but also, to a lesser extent, CD8-depleted subpopulations. These results were confirmed in T cell reconstituted athymic nude mice. Unfractionated T cells from chronically infected donors produced a significant inhibition of cyst formation in the brains of recipient mice measured 10 weeks after infection compared with control mice. The inhibition of cyst formation was ablated by pretreating T cells with anti-CD8 antibody and complement, but not anti-CD4 antibody and complement. Mice receiving cells from infected donors produced an early increase in their IgG1 and IgG2a antibody titres compared with mice given cells from uninfected animals. The depletion of either CD8+ or CD4+ immune cells appeared to have little effect on the antibody responses in recipient mice and there was no correlation between antibody levels and immunity. The results indicate that CD8+ T lymphocytes from convalescent T. gondii-infected BALB/c mice are the principal mediators of resistance to T. gondii, although CD4+ T cells appear to be involved during the acute phase of infection.

Animals↗
PubMed1990

The t(10;14)(q24;q11) of T-cell acute lymphoblastic leukemia juxtaposes the delta T-cell receptor with TCL3, a conserved and activated locus at 10q24.

We cloned the t(10;14) recurrent translocation from CD3-negative T-cell acute lymphoblastic leukemia cells. The breakpoint at 14q11 involved an intermediate rearrangement of the delta T-cell receptor locus, suggesting that the translocation arose at the time of antigen receptor assemblage. Translocation introduced chromosome segment 10q24 as proven by hybridization of a breakpoint-derived probe to flow-sorted chromosomes and metaphase chromosomes. Two t(10;14) breakpoints were clustered within a 600-base-pair region of 10q24 but no heptamer-spacer-nonamer motifs resembling T-cell receptor/immunoglobulin rearrangement signals were noted at the breakpoint. A locus distinct from terminal deoxynucleotidyltransferase was found at 10q24. Evolutionarily conserved regions surrounding the 10q24 breakpoint were examined for transcriptional activity. A region telomeric to the 10q24 breakpoint, expected to translocate to the der(14) chromosome, recognized an abundant 2.9-kilobase RNA in a t(10;14) T-cell leukemia. This locus was not active in a variety of other normal and neoplastic T cells, arguing that it was deregulated by the introduction of the T-cell receptor. This locus is a candidate for a putative protooncogene, TCL3, involved in T-cell neoplasia.

Alleles↗
PubMed1990

Production of corneal lesions using high-intensity focused ultrasound.

In order to study the potential use of ultrasound as a noninvasive system for altering corneal curvature, we used high-density focused ultrasound at a frequency of 4.8 MHz and 7.9 MHz to produce corneal lesions in the rabbit eye. Intensity and duration threshold exposure conditions were determined for the production of minimally visible lesions. Threshold lesions were initially apparent as discrete white opacities resulting from stromal edema and disruption. Light and scanning electron microscopy of higher-energy, suprathreshold lesions revealed more extensive disruption, including the formation of a superficial stromal depression and a larger zone of edema and disorganization surrounding each lesion. Posterior stromal lamellae, endothelium, and Descemet's membrane were intact. Healing and reepithelialization resulted in a smooth corneal surface with no residual opacification. Threshold determinations predict safe exposure levels to the cornea during insonification of other ocular structures. Selective heating of the peripheral cornea using focused ultrasound may be a useful technique for correcting astigmatism.

Animals↗
PubMed1988

Response of human immunodeficiency virus-associated uveitis to zidovudine.

A patient with human immunodeficiency virus (HIV) type 1 infection developed chronic iridocyclitis and anterior vitritis that were poorly responsive to topical and systemic corticosteroid therapy. Anterior chamber paracentesis was performed and HIV was isolated from culture of aqueous humor. Subsequent treatment with oral zidovudine resulted in resolution of the iridocyclitis and vitritis and full functional recovery of the eye. This case suggests that HIV may be a cause of uveitis responsive to systemic zidovudine therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Specific cross-gender behaviour in boyhood and later homosexual orientation.

Data from a group of males aged 13 to 23, who as children exhibited extensive cross-gender behaviour, was analysed. In boyhood they frequently played with dress-up dolls, role-played as females, dressed in girls' clothes, stated the wish to be girls, primarily had girls as friends, and avoided rough-and-tumble play. The majority of the group evolved a bisexual or homosexual orientation; two types of behaviour, boyhood doll play and female role-playing, were found to be associated with later homosexual orientation. The findings suggest developmental associations between specific types of boyhood cross-gender behaviour and the objects of later sexual arousal.

Child Behavior↗
PubMed1986

Ultrastructural correlation of specular microscopy in retinoblastoma.

A patient with monocular retinoblastoma was examined with the wide-field specular microscope before undergoing enucleation. An unusual image on the corneal endothelium consisted of irregular oval dark structures within which bright reflections formed a lacy network. Light and electron microscopy confirmed these structures to be clusters of retinoblastoma cells adherent to the endothelium. These findings suggest that the specular microscope may aid in the diagnosis of intraocular tumors.

Cornea↗