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Biomedical subjects

G Hollis

Publications and source records attributed to G Hollis.

8 recordsLinked to original sources
PubMed2000

Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy.

Efavirenz is a potent and selective nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Nucleotide sequence analyses of the protease and RT genes (coding region for amino acids 1 to 229) of multiple cloned HIV-1 genomes from virus found in the plasma of patients in phase II clinical studies of efavirenz combination therapy were undertaken in order to identify the spectrum of mutations in plasma-borne HIV-1 associated with virological treatment failure. A K103N substitution was the HIV-1 RT gene mutation most frequently observed among plasma samples from patients for whom combination therapy including efavirenz failed, occurring in at least 90% of cases of efavirenz-indinavir or efavirenz-zidovudine (ZDV)-lamivudine (3TC) treatment failure. V108I and P225H mutations were observed frequently, predominantly in viral genomes that also contained other nonnucleoside RT inhibitor (NNRTI) resistance mutations. L100I, K101E, K101Q, Y188H, Y188L, G190S, G190A, and G190E mutations were also observed. V106A, Y181C, and Y188C mutations, which have been associated with high levels of resistance to other NNRTIs, were rare in the patient samples in this study, both before and after exposure to efavirenz. The spectrum of mutations observed in cases of virological treatment failure was similar for patients initially dosed with efavirenz at 200, 400, or 600 mg once a day and for patients treated with efavirenz in combination with indinavir, stavudine, or ZDV-3TC. The proportion of patients carrying NNRTI resistance mutations, usually K103N, increased dramatically at the time of initial viral load rebound in cases of treatment failure after exposure to efavirenz. Viruses with multiple, linked NNRTI mutations, especially K103N-V108I and K103N-P225H double mutants, accumulated more slowly following the emergence of K103N mutant viruses.

Alkynes↗
PubMed1998

The development of a mental health service patient information management system.

In this paper we describe the development of the Mental Health-Patient Information Management System (MH-PIMS), which is an information management system designed for use in a modern, primarily community-based, mental health service. MH-PIMS is a computerised database which was designed by clinicians and is supported by a case management system and complementary patient record set-together called the Assessment and Care Evaluation (ACE) system. The paper also describes the ACE system. MH-PIMS can generate patient reports of use to case managers and teams in managing their caseloads and is of use to senior clinicians and service managers for audit and strategic planning purposes.

Case Management↗
PubMed1996

Affinity maturation of a high-affinity human monoclonal antibody against the third hypervariable loop of human immunodeficiency virus: use of phage display to improve affinity and broaden strain reactivity.

The present study set out to investigate whether phage display could be used to improve the properties of a high-affinity human monoclonal antibody directed against the third hypervariable loop (V3 loop) of human immunodeficiency virus (HIV). The aim was to increase affinity through slowing the dissociation rate (off-rate constant of koff), whilst retaining the ability of this antibody to bind diverse V3 loop sequences. When reformatted as a scFv, the antibody fragment retained the properties of the parental IgG, including the ability to neutralise virus. Heavy and light chains were sequentially replaced with repertoires of variable domains from non-immunised human donors followed by selection on biotinylated synthetic peptide. All selected variants derived from the same germline as the parental antibody. Variants of the light chain provided little if any improvement, whereas two residue changes in VHCDR2 and one in VHFR3 resulted in a reduced koff from gp120 protein of the MN strain (MNgp120) and synthetic V3 loop peptides as measured by surface plasmon resonance using the BIAcore instrument (Pharmacia Biosensor). VHCDR3 was modified using synthetic oligonucleotides and several clones with reduced koff identified, a number of different substitutions occurring at a single residue position. The residues in the heavy chain identified as reducing koff were simultaneously randomised by site-directed mutagenesis, resulting in scFv variants with koff slowed up to sevenfold. Far from compromising recognition of variant loops, binding to these sequences was improved; the koff from synthetic peptides modelled on V3 loop variants being slowed to a degree similar to that observed with MNgp120. All four changes were located towards either extremes of CDRs 2 and 3, suggesting that the mechanism of improvement may be one of alternation of loop conformation. This work illustrates that phage display can be used to tailor the properties of a therapeutic monoclonal antibody in a predefined fashion.

Amino Acid Sequence↗
PubMed1991

Salmonella in captive crocodiles (Crocodylus johnstoni and C. porosus).

The prevalence of salmonellas in captive Crocodylus porosus and C. johnstoni was investigated at 2 Northern Territory crocodile farms. Similar proportions of each species at one farm (20.0 and 27.8% for C. porosus and C. johnstoni, respectively) carried salmonellas, but at the other farm there was a significant difference between the 2 species (81.0 and 5.0%, respectively). Procedures for the slaughter of crocodiles and processing of crocodile flesh for human consumption are outlined and discussed from the viewpoint of minimising salmonella contamination. The prevalence of salmonellas on flesh for human consumption (16.0% of carcases) was higher than that reported for beef and mutton, but lower than that for poultry products (Murrell 1986). Serotypes most often isolated from cloacai and faecal swabs were S. cerro, S. singapore, S. enteritidis and S. arizonae. Of the 10 serotypes isolated from processed carcases, S. singapore was most frequently isolated (33.3% of serotypes identified).

Alligators and Crocodiles↗
PubMed1989

Antiimmunoglobulin inhibition of Burkitt's lymphoma cell proliferation and concurrent reduction of c-myc and mu heavy chain gene expression.

We have demonstrated that polyvalent antiimmunoglobulin antibodies directed at appropriate cell surface light (L) or heavy (H) immunoglobulin (Ig) chains will inhibit proliferation and the expression of c-myc and mu-Ig chain mRNA in Burkitt's lymphoma (BL) cell lines bearing 8;14 chromosomal translocations. This effect was not observed in BL cell lines bearing 8;22 translocations or in BL cell lines which did not express surface Ig or in karyotypically normal Epstein-Barr virus-transformed lymphoblastoid cell lines. The antiproliferative effect was reproducible and resulted in cell death in the most sensitive cell lines. The decrease in gene expression preceded the antiproliferative effect. The effect of anti-Ig on gene expression was relatively specific since the level of total (shown by Northern blots) and cytoplasmic (dot blots) mRNA of several other genes (beta-actin, G6PD, kappa-L chain) and the first exon of c-myc (in cell lines in which this exon is expressed separately from the second and third exons) was not changed in these same BL cell lines. Expression of both c-myc and mu was maximally inhibited between 3 and 6 h after the addition of anti-Ig. In the most sensitive BL cell line, concurrent reduction in c-myc and mu mRNA was noted as early as 1 h after anti-Ig and the nadir of expression of these genes occurred at 3 h. These results indicate that the deregulated high constitutive expression of c-myc in some BLs can be down-regulated by anti-Ig resulting in inhibition of proliferation and cell death. In addition these data are consistent with the possibility that in at least some 8;14 bearing BLs the malignant transformation occurs in an immature B-cell undergoing antigen-independent differentiation.

Antibodies↗
PubMed1985

T-cell receptor gene rearrangements as clinical markers of human T-cell lymphomas.

The ability to detect immunoglobulin-gene rearrangements has proved useful in confirming diagnoses of suspected B-cell lymphomas and in establishing their monoclonality. By analogy, we employed a cloned DNA probe for the beta chain of the T-cell receptor gene to determine whether gene rearrangements were present in human T-cell neoplasms representing various stages of T-cell development. Gene rearrangements were present in all cases of T-cell disorders except a single case of T gamma lymphocytosis, a disorder that has not been proved to be a clonal T-cell neoplasm. A germline gene configuration was present in all patients with non-T-cell neoplasms and in normal tissues from patients with T-cell lymphoma. The probe promises to be useful for confirming the pathological an immunologic diagnosis in difficult cases of T-cell disorders and for assessing the extent of disease.

B-Lymphocytes↗
PubMed1985

Erbb is linked to the alpha-globin locus on mouse chromosome 11.

A fragment of the human gene for c-erb-B was used to map homologous sequences in mice. Analysis of somatic cell hybrids and recombinant inbred and congenic mouse strains indicated that this gene, designated Erbb, is closely linked to the gene for alpha-globin on mouse chromosome 11. Several genes controlling hematopoietic differentiation map to mouse chromosome 11.

Animals↗