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Biomedical subjects

T Williams

Publications and source records attributed to T Williams.

At least 127 records · Page 7Linked to original sources
PubMed1997

Baculovirus-expressed nonstructural protein NS2 of bluetongue virus induces a cytotoxic T-cell response in mice which affords partial protection.

Virus-specific cytotoxic T lymphocytes were generated in two strains of mice (BALB/c and CBA/Ca) against baculovirus recombinant proteins (minor and nonstructural) derived from bluetongue virus serotype 10. Immunization of mice with recombinant baculovirus insect cell extracts expressing the nonstructural protein NS2 (Bac-NS2) conferred partial protection against infection with vaccinia virus expressing the NS2 protein. This protective immunity was mediated by CD8+ cells. In contrast, no protection was observed when mice were immunized with similarly expressed Bac-NS1 or -NS3 or the virion minor structural proteins (Bac-VP1, -VP4, or -VP6). Furthermore, the in vitro cytotoxicity activity of T cells derived from immunized animals did not correlate to the protective efficacy of baculovirus recombinant proteins. The implications of this work with regard to the design of noninfectious subunit vaccines are discussed.

Animals↗
PubMed1997

Evaluation of antimicrobial sensitivity patterns as markers of Pseudomonas aeruginosa cross-infection at a cystic fibrosis clinic.

Pseudomonas aeruginosa is one of the most important bacterial pathogens in cystic fibrosis-associated lung disease. The means by which the organism is acquired or nosocomially spread is uncertain, but person-to-person spread has been implicated. Therefore, typing of P. aeruginosa from cystic fibrosis patients is necessary to determine the source of infection. Although P. aeruginosa strains can be compared using a variety of nucleic acid typing methods, this is time-consuming, expensive and requires specialised equipment, and is better suited to large reference laboratories. In this study, the use of antimicrobial sensitivity patterns in the investigation of possible cross-infection at cystic fibrosis clinics was examined, and 496 P. aeruginosa isolates from 69 patients were analysed. Analysis of dates and times of hospital visits allowed the study to concentrate on specific contact episodes where cross-infection could have occurred. Genotypic analysis of a number of organisms allowed the value of the sensitivity patterns to be assessed. No evidence of cross-infection was found, but antimicrobial sensitivity patterns proved unreliable in detecting similarity among P. aeruginosa strains.

Bacterial Typing Techniques↗
PubMed1996

A family of AP-2 proteins regulates c-erbB-2 expression in mammary carcinoma.

The proto-oncogene c-erbB-2 is overexpressed in 25-30% of breast cancers through increased transcription and amplification of the gene. We have previously described a factor, OB2-1 which upregulates c-erbB-2 transcription and which is closely related to the developmentally regulated transcription factor, AP-2. Further analysis of affinity purified OB2-1 has now shown that it is in fact a combination of proteins from three AP-2-related genes, the previously described AP-2alpha gene and two new human family members, AP-2beta and AP-2gamma whose cloning and characterisation are described here. All three AP-2 proteins show a high degree of homology and are capable of binding to the c-erbB-2 promoter as homo- or heterodimers. The three proteins can also activate a c-erbB-2 reporter construct, but AP-2alpha and AP-2gamma are 3-4 times more active in this regard than AP-2beta. In addition both AP-2alpha and AP-2gamma are expressed at elevated levels in the majority of c-erbB-2 overexpressing mammary tumour lines examined. Mechanisms which may have led to the increased AP-2 levels in these cells are discussed.

Amino Acid Sequence↗
PubMed1996

Chromosomal mapping of the human and mouse homologues of two new members of the AP-2 family of transcription factors.

The AP-2 transcription factor has been shown to play an important role in the development of tissues of ectodermal origin and has also been implicated in mammary oncogenesis. It has recently been found that AP-2 is encoded by a family of related genes, AP-2alpha, AP-2beta, and AP-2gamma. As a further step in understanding the role each of these genes has in development, we have used fluorescence in situ hybridization to map the chromosomal locations of the mouse and human homologues of the newly isolated AP-2beta and AP-2gamma genes. Tcfap2b and Tcfap2c map to mouse chromosomes 1A2-4 and 2H3-4, respectively, while TFAP2B and TFAP2C map to human chromosomes 6p12 and 20q13.2, the latter being a region that is frequently amplified in breast carcinoma.

Animals↗
PubMed1996

Comparative and functional analysis of the AP2 promoter indicates that conserved octamer and initiator elements are critical for activity.

AP-2 is a developmentally-regulated transcription factor expressed in ectodermal cell lineages. The AP-2 protein is essential for neural tube, craniofacial and body wall morphogenesis and has been implicated in oncogenesis. Here we report the isolation of the AP-2 promoter from human, mouse and chicken. The initiation sites for the human gene have been mapped in a variety of cell lines, including several derived from breast tumours. Initiation occurs just upstream of an IR3-like repetitive element, present in the human and mouse genes, but absent in chicken. The cis-acting elements responsible for promoter activity in human HeLa cells have been mapped both in vivo and in vitro. The proximal promoter contains binding sites for transcription factors AP-2, NF-1 and octamer proteins, but lacks a TATA box motif. Functional analysis demonstrates that the octamer binding site is the critical component of basal promoter activity. In addition, the promoter relies on an initiator element for efficient start site utilization. There is an excellent correlation between the requirement for the initiator and octamer elements in transcription assays and the conservation of these cis-acting sequences between chicken, mouse and human.

Animals↗
PubMed1996

Neural tube, skeletal and body wall defects in mice lacking transcription factor AP-2.

The retinoic acid-inducible transcription factor AP-2 is expressed in epithelial and neural crest cell lineages during murine development. AP-2 can regulate neural and epithelial gene transcription, and is associated with overexpression of c-erbB-2 in human breast-cancer cell lines. To ascertain the importance of AP-2 for normal development, we have derived mice containing a homozygous disruption of the AP-2 gene. These AP-2-null mice have multiple congenital defects and die at birth. In particular, the AP-2 knockout mice exhibit anencephaly, craniofacial defects and thoraco-abdominoschisis. Skeletal defects occur in the head and trunk region, where many bones are deformed or absent. Analysis of these mice earlier in embryogenesis indicates a failure of cranial neural-tube closure and defects in cranial ganglia development. We have shown that AP-2 is a fundamental regulator of mammalian craniofacial development.

Animals↗
PubMed1996

Studies of the activation of factor VII bound to tissue factor.

Experiments were performed to evaluate activation of factor VII bound to relipidated tissue factor (TF) in suspension and to TF constitutively expressed on the surface of an ovarian carcinoma cell line (OC-2008). Activation was assessed by measuring cleavage of 125I-factor VII and by the ability of unlabeled factor VII to catalyze activation of a variant factor IX molecule that, after activation, cannot back-activate factor VII. Factor Xa was found to effectively activate factor VII bound to TF relipidated in either acidic or neutral phospholipid vesicles. Autoactivation of factor VII bound to TF in suspension was dependent on the preparation of TF apoprotein used and the technique of its relipidation. This highlights the need for caution in extrapolating data from TF in suspension to the activation of factor VII bound to cell surfaces during hemostasis. A relatively slow activation of factor VII bound to OC-2008 monolayers in the absence of added protease was observed consistently. Antithrombin in the presence or absence of heparin prevented this basal activation, whereas TF pathway inhibitor (TFPI/factor Xa complexes had only a limited inhibitory effect. Adding a substrate concentration of factor X markedly enhanced basal activation of factor VII, but both TFPI/factor Xa and antithrombin/heparin abolished this enhancement. Overall, our data are compatible with the hypothesis that not all factor VII/TF complexes formed at a site of tissue injury are readily activated to factor VIIa (VIIa)/TF complexes during hemostasis. The clinical significance of this is discussed.

Cell Membrane↗
PubMed1996

Repression of a matrix metalloprotease gene by E1A correlates with its ability to bind to cell type-specific transcription factor AP-2.

Adenovirus E1A 243-amino acid protein can repress a variety of enhancer -linked viral and cellular promoters. This repression is presumed to be mediated by its interaction with and sequestration of p3OO, a transcriptional coactivator. Type IV 72-kDa collagenase is one of the matrix metalloproteases that has been implicated in differentiation, development, angiogenesis, and tumor metastasis. We show here that the cell type-specific transcription factor AP-2 is an important transcription factor for the activation of the type IV 72-kDa collagenase promoter and that adenovirus E1A 243-amino acid protein represses this promoter by targeting AP-2. Glutathione S-transferase-affinity chromatography studies show that the E1A protein interacts with the DNA binding/dimerization region of AP-2 and that the N-terminal amino acids of E1A protein are required for this interaction. Further, E1A deletion mutants which do not bind to p3OO can repress this collagenase promoter as efficiently as the wildtype E1A protein. Because the AP-2 element is present in a variety of viral and cellular enhancers which are repressed by E1A, these studies suggest that E1A protein can repress cellular and viral promoter/enhancers by forming a complex with cellular transcription factors and that this repression mechanism may be independent of its interaction with p3OO.

Adenovirus E1A Proteins↗
PubMed1996

The private costs of HIV/AIDS.

AIM: To identify and, where possible, measure and value the private costs related to HIV/AIDS, that is, those costs that fall on the person with HIV/AIDS and the family/household/informal caregivers. METHOD: Twenty-five people living with HIV - ranging from asymptomatic seropositive people, to people with AIDS - were followed prospectively to obtain information concerning the private costs (broadly defined) incurred. The participants resided in the Auckland, Hamilton, Wellington and Christchurch areas. RESULTS: Private direct costs rise steeply as the illness progresses, from around $100 per month for asymptomatic people to around $400 per month for people with AIDS. Both indirect costs (foregone income) and intangibles (measured by a range of indicators) were also considerable. CONCLUSION: The private costs of HIV/AIDS, defined in terms of direct, indirect and intangible costs, are significant and burdensome. Costing studies which ignore them will conceal, confuse and mislead.

Adult↗
PubMed1996

Physical and genetic localization of the gene encoding the AP-2 transcription factor to mouse chromosome 13.

Transcription factors are a major determinant of developmental fate. The chromosomal localization of the genes encoding these proteins provides important information that can link them to known genetic abnormalities. Here, we report the mapping of the mouse gene for transcription factor AP-2, a protein that has been implicated in human oncogenesis. Using FISH, we have mapped the gene encoding the transcription factor AP-2, Tcfap2, to mouse Chromosome 13A5-B1. We have also extended this analysis by placing Tcfap2 on the mouse genetic map, and we discuss the candidate mouse mutations that map in the vicinity of this transcription factor.

Animals↗
PubMed1996

Intrusive thoughts in a non-clinical adolescent population.

The frequency and pattern of intrusive thoughts reported by 279 adolescent school pupils and the relation of these to self-reported anxiety, depression and obsessional ritualisation are examined. Similarities in the frequency and processing of intrusive thoughts were identified between this group and previously studied adult populations. Self-reported symptoms of anxiety, depression and obsessional ritualisation were associated with both discomfort and interference from intrusive thoughts. Factor analysis of the data produced a three-factor solution and the interpretation and implications of this result are discussed in terms of affectivity, ritualisation and superstitious or magical beliefs.

Adolescent↗
PubMed1996

Determination of tablet coating distribution by deconvolution of uncoated and coated tablet weight distributions.

PURPOSE: The purpose of this research is to obtain the tablet coating distribution from weight distributions of uncoated and coated tablets. METHODS: The method of deconvolution with digital smoothing was used to calculate the distribution of coating applied to a tablet population from separate random measurements of individual uncoated and coated tablets. RESULTS: It was demonstrated that the calculated coating weight distribution agrees well with the measured distribution. The effect of the smoothing factor on the solution is illustrated. CONCLUSIONS: This method can be used during development to facilitate process scale-up/optimization. In routine production, the method can assess the reproducibility and consistency of a coating process.

Chemistry, Pharmaceutical↗
PubMed1996

Cytomegalovirus pneumonia in adult nontransplantation patients with cancer: review of 20 cases occurring from 1964 through 1990.

The objectives of this study were to estimate the frequency of cytomegalovirus (CMV) pneumonia and describe its clinical and radiological presentation in adult nontransplantation patients with cancer. Of the 10,441 autopsies performed at M. D. Anderson Cancer Center (Houston) during the period of January 1964 through December 1990, 9,029 were evaluable. Twenty histopathologically confirmed cases of CMV pneumonia were found, representing a frequency of 2.2 cases per 1,000 autopsies. When the frequency of CMV pneumonia was compared for the periods 1964-1979 (1.5 cases per 1,000 autopsies) and 1980-1990 (4.6 cases per 1,000 autopsies), a statistically significant increase due to an increase in the number of patients with solid malignancies was observed (P < .05). CMV pneumonia is an uncommon diagnosis at autopsy for adult nontransplantation patients with cancer and is usually found in conjunction with a disseminated neoplastic process.

Adult↗
PubMed1996

Management of invasive candidal infections: results of a prospective, randomized, multicenter study of fluconazole versus amphotericin B and review of the literature.

We conducted a prospective, randomized, multicenter study comparing fluconazole and amphotericin B in the treatment of candidal infections. One hundred and sixty-four patients (60 of whom were neutropenic) with documented or presumed invasive candidiasis were assigned to treatment with either fluconazole (400 mg daily) or amphotericin B (25-50 mg daily; 0.67 mg/kg daily for neutropenic patients). Clinical response and survival rates were assessed at 48 hours, after 5 days, and at the end of therapy. Overall response rates to fluconazole and amphotericin B were similar (66% and 64%, respectively). There were no differences in response as related to site of infection, pathogen, time to defervescence, relapse, or survival rates between the groups. Adverse effects were more frequent with amphotericin B (35%) than with fluconazole (5%; P < .0001). The results of this study confirm that fluconazole is as effective as but better tolerated than amphotericin B in the treatment of candidal infections.

Adolescent↗