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Biomedical subjects

O Williams

Publications and source records attributed to O Williams.

At least 55 records · Page 3Linked to original sources
PubMed1995

Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk.

The tyrosine kinase Syk (relative molecular mass 72,000), which is widely expressed in haematopoietic cells, becomes associated with and activated by engagement of the B-cell antigen receptor. Furthermore, it has been implicated in signalling through the receptors for interleukin-2 (IL-2), granulocyte colony-stimulating factor (G-CSF) and Fc, the T cell receptor, as well as through receptors for several platelet agonists. A homologous kinase, ZAP-70, is crucial in signalling through the T-cell receptor and in T-cell development. Using homologous recombination in embryonic stem cells, we created mice null for the syk gene which showed petechiae in utero and died shortly after birth. Irradiated mice reconstituted with Syk-deficient fetal liver showed a block in B-cell development at the pro-B to pre-B cell transition, consistent with a key role for Syk in pre-B-cell receptor signalling. Despite the production of small numbers of immature B cells, Syk-deficient radiation chimaeras failed to accumulate mature B cells, indicating a possible role for this protein in the production or maintenance of mature B cells. In addition, whereas the development of alpha beta T cells proceeded normally, Syk-deficient mice showed impaired development of thymocytes using the V gamma 3 variable region gene (V gamma 3+ thymocytes). Finally, we show that Syk is not required for signalling through the IL-2 and G-CSF receptors.

Amino Acid Sequence↗
PubMed1995

Anti-gamma delta T cell antibody blocks the induction and maintenance of oral tolerance to ovalbumin in mice.

The oral administration of antigens is one of the means of inducing tolerance in adult mammals. In this report, the role of gamma delta T cells in the induction and maintenance of orally-induced tolerance to ovalbumin was investigated. The injection of a monoclonal anti-gamma delta T cell monoclonal antibody blocked the induction of oral tolerance, because the secondary immune responses to ovalbumin in these animals were comparable to the corresponding responses in ovalbumin-immunized control mice. Furthermore, depletion of gamma delta T cells either in vivo or in vitro abolished already established oral-tolerance. The fact that the state of tolerance could be adoptively transferred to naive recipients by CD3+ alpha beta- gamma delta + spleen cells from tolerant mice. These results suggest that systemic oral tolerance is induced and actively maintained by mechanisms involving gamma delta T cells.

Administration, Oral↗
PubMed1995

Younger-onset Alzheimer's disease: learning from the experience of one spouse carer.

There are estimated to be 17,000 younger sufferers of dementia currently living in the UK. At present, individualized service and practice initiatives for younger sufferers and their carers remain fragmented and poorly developed. This is despite potential additional caregiving stressors caused by the age of onset, such as financial difficulties due to disruption in the work pattern, children still living at home, and the sufferer's decreased life expectancy. Drawing on an individual carer's personal case history, this article details a spouse carer's individual experience of her husband's decline through the stages of younger-onset Alzheimer's disease. Pointers for policy and practice for younger sufferers and their carers are drawn from this case history and a role for the community psychiatric nurse is outlined.

Adaptation, Psychological↗
PubMed1995

T cell-dependent antibody response to staphylococcal enterotoxin B.

Treatment of mice with staphylococcal enterotoxin B (SEB) induces specific T-cell tolerance to this superantigen, characterized by partial deletion of V beta 8+ T cells in vivo and T cell anergy in vitro. In this study we examined the humoral response to SEB in BALB/c mice. Immunization of mice with SEB results in a detectable anti-SEB antibody response. Upon further treatment of mice with SEB, specific antibody levels increase significantly and the response is accelerated--characteristics of a secondary humoral response. The secondary antibody response is T cell dependent, can be transferred to T cell deficient mice with splenocytes and is composed mainly of IgM, IgG1 and IgG2b isotypes, suggesting that Th2 cells provide B cell help in this response. These data demonstrate that at the same time as inducing in vitro unresponsiveness, SEB primes SEB-specific T helper cells to provide help for B cells in a secondary antibody response.

Animals↗
PubMed1994

Absence of peripheral clonal deletion and anergy in immune responses of T cell-reconstituted athymic mice.

Superantigens induce clonal deletion of reactive T cells in the thymus and clonal deletion and anergy in the periphery of euthymic mice. In this report we have assessed the ability of Staphylococcal enterotoxin B (SEB) to induce peripheral tolerance in nude mice reconstituted with normal, syngeneic T cells. Immunization of reconstituted nude mice with SEB resulted in lethal toxic shock in a large fraction of the animals. Such lethality was never observed in the normal donor mouse strain. Analysis of lymphokine production in response to SEB showed that reconstituted nude mice produced higher levels of interleukin-2 and tumor necrosis factor-alpha, but lower levels of interleukin-4, than euthymic control mice. Furthermore, SEB was unable to promote either clonal elimination or induction of anergy in the SEB-responsive peripheral T cells, despite the fact that reconstituted nude mice did produce high levels of corticosterone upon treatment with SEB. These results imply a lack of control over immune responses to superantigen in T cell-reconstituted athymic mice.

Animals↗
PubMed1994

Age-dependent changes in the response to staphylococcal enterotoxin B.

In the present study we investigated the response of old mice to staphylococcal enterotoxin B (SEB) immunization. Old mice were susceptible to lethal toxic shock, probably mediated by tumor necrosis factor-alpha, although lethal toxic shock was not observed in young mice. Old mice were able to produce more IL-2 and IL-4 than young mice in response to in vivo immunization with SEB. V beta 8+CD4+ T cells of old mice expanded less in vivo and were not deleted in response to SEB. However, in spite of the absence of clonal deletion, SEB was found to induce energy of SEB reactive cells in old mice, as demonstrated by reduced in vitro T cell proliferation to SEB and reduced in vitro IL-2 and IL-4 production.

Aging↗
PubMed1994

Genetic heterogeneity in hereditary haemorrhagic telangiectasia.

A locus causing hereditary haemorrhagic telangiectasia (HHT) has recently been mapped to 9q34 in four families and designated HHT1. In this paper, the results of a linkage study showing genetic heterogeneity in four families in whom HHT is segregating are reported. All the previously reported 9q34 linked families contain at least one affected member with a symptomatic pulmonary arteriovenous malformation. We postulate that clinical heterogeneity may also be a feature of HHT with a significantly higher predisposition to symptomatic PAVMs associated with the HHT1 linked families.

Chromosome Mapping↗
PubMed1994

Treatment of bacterial vaginosis with a three day course of 2% clindamycin vaginal cream: a pilot study.

OBJECTIVE: To evaluate the efficacy and safety of a 3 day course of 2% clindamycin cream in the treatment of bacterial vaginosis. DESIGN: A prospective, randomised, double blind, placebo controlled study. SETTING: Department of Genitourinary Medicine, Royal Liverpool University Hospital. SUBJECTS: 55 female patients aged 18 years and over, and premenopausal, who spontaneously or after questioning complained of symptoms of bacterial vaginosis. RESULTS: 55 patients were enrolled. 44 patients were evaluable at Visit 1 when among the 23 who received clindamycin cream bacterial vaginosis was not present in 22 (95.6%) and only one failed treatment. Of the 21 patients in the placebo group only one (4.8%) patient was cured and 20 (95.2%) were failures. Of the 17 patients evaluable at Visit 2 in the clindamycin group, bacterial vaginosis was not present in 14 (82.4%) and had recurred in three. No serious adverse events were noted in either group. CONCLUSION: This pilot study provides encouraging evidence of the efficacy and safety of a 3 day course of 2% clindamycin cream in bacterial vaginosis.

Adolescent↗
PubMed1993

Neoplastic transformation of immortalized human epidermal keratinocytes by two HHV-6 DNA clones.

Human herpesvirus-6 (HHV-6) DNA and high antibody titers have been detected in some human malignancies. To understand the role of HHV-6 in human cancer, the ability of these DNA sequences to convert nontumorigenic human epidermal keratinocytes (RHEK-1) to the tumorigenic phenotype was examined. Of the three HHV-6 clones tested, pZVH14 (8.7-kb insert) and pZVB70 (21-kb insert) exhibited transforming activity in RHEK-1 cells, whereas the other clone pZVE50 (6-kb insert) did not show any activity. Transformed cells were morphologically altered, forming bundles or islets, and produced tumors when injected into nude mice. Southern blot analysis of the pZVH14 DNA-transformed and tumor cells revealed multiple bands hybridizing to the 8.7-kb DNA insert of pZVH14. Karyotype analysis identified the mouse tumor cells to be of human origin and these cells exhibited some chromosomal aberration compared to untransfected RHEK-1 cells. This study demonstrates that pZVH14 DNA detected in some human tumors, and pZVB70 DNA can transform human cells in vitro to tumorigenic phenotype. These data are consistent with the possibility that HHV-6 DNA sequences may have some role in the development of some human cancers.

Animals↗
PubMed1993

Perceptions of elder abuse and help-seeking patterns among African-American, Caucasian American, and Korean-American elderly women.

Thirteen scenarios were used to measure and compare the perceptions of elder abuse and help-seeking behaviors of African-American, Caucasian American, and Korean-American elderly women. Significant group differences existed in their perceptions of elder abuse with regard to six scenarios, and the Korean-American women were substantially less likely to perceive a given situation as abusive than the other groups. The three groups also showed significant differences in their intended use of formal and informal sources of help in the case of elder abuse.

Black or African American↗
PubMed1993

Staphylococcal enterotoxin B promotes deletion and functional inactivation of CD4V beta 8-positive cells in the absence of CD8 T cells.

The staphylococcal enterotoxins stimulate discrete subsets of T cells depending on their expression of particular V genes. Among these, staphylococcal enterotoxin B (SEB) vigorously stimulates V beta 8+ cells. This stimulation results in proliferation of both CD4+V beta 8+ and CD8+ T cells and eventually to anergy and clonal deletion in the former subset. We have examined the possible role of CD8+ T cells in the response of CD4+ cells to SEB, by in vivo CD8+ T-cell-depletion. We found no qualitative difference in the responses of untreated and CD8+ T-cell depleted mice to SEB; however, a small quantitative difference in deletion was observed. Thus it appears that on the whole the response of CD4+V beta 8+ T cells to SEB is independent of CD8+ T-cell effector function, although the latter may play a partial role.

Animals↗
PubMed1993

Two-step mucosal competitive exclusion flora treatment to diminish salmonellae in commercial broiler chickens.

There is a need to control the intestinal colonization of broiler chickens by salmonellae in order to reduce the contamination of poultry products. A two-step treatment of broiler chicks with a mucosal competitive exclusion culture (MCE) was tested, in which the MCE was first sprayed on chicks in the hatchery followed by administration in the first drinking water. Three commercial flocks were treated and compared with parallel, untreated control flocks. Customary husbandry practices were employed. Environmental, hatchery, skin with feathers, and cecal samples were analyzed at 3 and 7 wk for the presence of salmonellae. Carcass rinse samples of fully processed birds were analyzed similarly. The results indicated that initial feed, water, and litter contamination was at a low frequency (< 10%). Eggshell fragments and chick paper pads were frequently contaminated (> 50%). After 3 wk growth, contamination of litter, skin with feathers, and ceca were significantly (P < .05) reduced in treated flocks as compared with control flocks. Salmonellae prevalence in ceca and in processed carcass rinses was also significantly (P < .05) reduced from 41% in control flocks to 10% in treated flocks. The study showed that treatment of chickens in a commercial setting with MCE cultures can serve as a useful means to reduce salmonellae contamination.

Animals↗
PubMed1992

The gene for Aarskog syndrome is located between DXS255 and DXS566 (Xp11.2-Xq13).

Aarskog syndrome has been mapped to Xq13 on the basis of a patient carrying an Xq13:8p21.2 translocation. We have identified a new microsatellite marker in a clone mapping to this region (HX60;DXS566). Using primers flanking this microsatellite along with primers detecting a microsatellite at PGK1P1 and DXS255, and DXS72, we have performed a multipoint analysis in a large kindred with Aarskog syndrome. Our results suggest that the Aarskog locus lies proximal to Xq13. This is supported by the recent redefining of the breakpoint of the original translocation as between DXS14 (Xp11.21-p11.1) and DXS146 (Xp11.23-p11.22).

Abnormalities, Multiple↗
PubMed1992

Survey of colposcopy service provided by genito-urinary medicine in England and Wales.

OBJECTIVE: To investigate the expansion of colposcopy services within genito-urinary medicine (GUM) in England and Wales since 1985. DESIGN: Data collected by postal and verbal communication from 189 genito-urinary medicine clinics in England and Wales in January 1990. SUBJECTS: Consultant and junior genito-urinary physicians practising colposcopy. MAIN OUTCOME MEASURES: Number of clinics providing colposcopy service; indication for colposcopy, treatment facilities available, waiting lists and training opportunities, compared with that in 1985. RESULTS: Of the 189 genito-urinary medicine clinics contacted, 60 provided a colposcopy service and 55 of these returned completed questionnaires. There has been a 67% increase in the number of colposcopies in use and over 50% of clinics have the facilities to treat cervical pathology. Waiting lists were minimal for both examination and treatment. Both men and women are examined with the colposcope for a variety of indications. At present, 52% of career grade GUM physicians practise colposcopy compared to 24% in 1985 and 94% of senior registrars compared with 42% in 1985 were in training or trained in colposcopy.

Colposcopy↗
PubMed1992

Coevolution of hosts and microorganisms: an analysis of the involvement of cytokines in host-parasite interactions.

Parasites may employ particular strategies of eluding an immune response by taking advantage of those mechanisms that normally guarantee immunological self-tolerance. Much in the way as it occurs during the establishment of self-tolerance, live pathogens may induce clonal deletion, functional inactivation (anergy) and immunosuppression. At this latter level, it appears that certain pathogens produce immunosuppressive cytokine-like mediators or provoke the host to secrete cytokines that will compromise the anti-parasite immune response. It appears that immune responses that preferentially involve T helper 1 cells (secretors of interleukin-2-and interferon-gamma) tend to be protective, whereas T helper 2 cells (secretors of IL-4, IL-5, IL-6, and IL-10), a population that antagonizes T helper cells, mediate disease susceptibility and are involved in immunopathological reactions. Cytokines produced by T helper 2 cells mediate many symptoms of infection, including eosinophilia, mastocytosis, hyperimmunoglobulinemia, and elevated IgE levels. Administration of IL-2 and IFN-gamma has beneficial effects in many infections mediated by viruses, bacteria, and protozoa. The use of live vaccinia virus might be an avenue for the treatment of or the vaccination against infection. We have found that a vaccinia virus expressing the gene for human IL-2, though attenuated, precipitates autoimmune disease in immunodeficient, athymic mice. Thus, although T helper 1 cytokines may have desired immunostimulatory properties, they also may lead to unwarranted autoaggressive responses.

Animals↗