Search PubMed⌕ Search

Biomedical subjects

C Williamson

Publications and source records attributed to C Williamson.

At least 19 recordsLinked to original sources
PubMed2000

Influenza virus (A/HK/156/97) hemagglutinin expressed by an alphavirus replicon system protects chickens against lethal infection with Hong Kong-origin H5N1 viruses.

Venezuelan equine encephalitis virus replicon particles (VRP) containing the gene expressing hemagglutinin (HA) from the human Hong Kong Influenza A isolate (A/HK/156/97) were evaluated as vaccines in chicken embryos and young chicks. Expressed HA was readily detected in bird-tissue staining with anti-H5 HA antibody and in chicken cells infected with the replicon preparations following immunoprecipitation with monoclonal antibody. Birds challenged with a dose of the lethal parent virus were protected to different extents depending on the age of the bird. In ovo and 1-day-old inoculated animals that received no boost with the VRP were partially protected; birds 2 weeks of age were completely protected with a single dose of VRP.

Age Factors↗
PubMed2000

Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy: evidence for a defect in protein trafficking.

Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy with serious consequences for the mother and fetus. Two pedigrees have been reported with ICP in the mothers of children with a subtype of autosomal recessive progressive familial intrahepatic cholestasis (PFIC) with raised serum gamma-glutamyl transpeptidase (gamma-GT). Affected children have homozygous mutations in the MDR3 gene (also called ABCB4 ), and heterozygous mothers have ICP. More frequently, however, ICP occurs in women with no known family history of PFIC and the genetic basis of this disorder is unknown. We investigated eight women with ICP and raised serum gamma-GT, but with no known family history of PFIC. DNA sequence analysis revealed a C to A transversion in codon 546 in exon 14 of MDR3 in one patient, which results in the missense substitution of the wild-type alanine with an aspartic acid. We performed functional studies of this mutation introduced into MDR1, a closely related homologue of MDR3. Fluorescence activated cell sorting (FACS) and western analysis indicated that this missense mutation causes disruption of protein trafficking with a subsequent lack of functional protein at the cell surface. The demonstration of a heterozygous missense mutation in the MDR3 gene in a patient with ICP with no known family history of PFIC, analysed by functional studies, is a novel finding. This shows that MDR3 mutations are responsible for the additional phenotype of ICP in a subgroup of women with raised gamma-GT.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

Allelic frequencies of host genetic variants influencing susceptibility to HIV-1 infection and disease in South African populations.

OBJECTIVES: Limited information is available on the prevalence in African populations of host genetic polymorphisms conferring resistance to HIV-1 infection and disease. The objective of this study was to determine the allelic frequencies in South African populations of the chemokine receptor gene variants CCR5delta32, CCR5m303 and CCR2b-641 and the CXCR4 ligand gene variant SDF1-3'A. METHOD: Cross-sectional study to determine the prevalence of these gene variants in South African subjects of African and European descent. RESULTS: The CCR5delta32 genetic variant is rare in individuals of African origin, having an allelic frequency of 0.1% (n = 1247) compared with 9.8% (n = 144) in Caucasians. The CCR5m303 mutation was not detected in Africans (n = 687), whereas an allelic frequency of 0.9% (n = 145) was identified in Caucasians. The frequency of CCR2b-641 allele was 13.1% (n = 180) in Africans, which was significantly higher that the 7.2% (n = 146) detected in Caucasians. Finally the allelic frequency of the SDF1-3'A gene variant was only 1.0% (n = 198) in Africans compared with 19.8% (n = 145) in Caucasians. CONCLUSIONS: These results indicate that genetic polymorphisms conferring resistance to HIV-1 infection are rare in the South African Black population. Except for the CCR2b-641 gene variant, individuals of African origin also had a much lower prevalence of genetic variants associated with prolonged disease progression.

Alleles↗
PubMed2000

Consumer and professional standards: working towards consensus.

Standards of treatment and care should be acceptable to healthcare consumers as well as to healthcare professionals. A simple categorisation of standards according to their acceptability to consumers is outlined. Professional/consumer groups which review and set standards are discussed, with emphasis on the principles of partnership. Working together towards consensus can be difficult but is now an important way forward.

Community Participation↗
PubMed1999

Evidence for the involvement of the glutathione pathway in drug resistance in AML.

We have studied altered drug detoxification through the glutathione pathway as a possible mechanism of resistance in 38 patients with AML. GST alpha, mu and pi expressions were determined using immunocytochemistry, the median percentages of positive cells being 73% (range 0-98), 55% (range 0-99) and 97% (range 80-100) respectively. MRP expression was measured using MRPm6 MoAb and flow cytometry. Results were expressed as the ratio of fluorescence associated with MRP over that of an isotype matched control (median, 1.32; range 0.95-2.15). Statistical analyses showed a significant increase in GST alpha expression in blast cells showing in vitro resistance to doxorubicin, with a median value of 78% positive cells compared to 41% in the sensitive group (p < 0.02). There was a significant reduction, however, in GST mu expression from a median value of 60% in newly presenting patients to 40% in a group of patients who had received previous cytotoxic therapy (p < 0.02). Interestingly, patients with high GST mu expression appeared to co-express MRP (p < 0.05). In vitro drug modulation studies, comparing the cytotoxic effect of doxorubicin +/- ethacrynic acid at 6.5 microM resulted in only one significant increase in sensitivity (2.6-fold), out of 22 comparisons. These results support the theory that altered detoxification through the glutathione pathway contributes towards drug resistance in AML. Further studies using fresh blast cells are required to elucidate the importance of this mechanism for individual patients.

ATP-Binding Cassette Transporters↗
PubMed1999

Readmission after cardiac operations: prevalence, patterns, and predisposing factors.

OBJECTIVES: This study was undertaken (1) to determine the prevalence of hospital readmission within 1 month of discharge after cardiac operations, (2) to categorize diagnoses responsible for readmission, and (3) to examine predischarge patient factors that influenced readmission. METHODS: Data at 1 month after discharge were obtained for 1665 (98.4%) of 1692 patients who underwent cardiac operations between January 1996 and July 1998. RESULTS: Two hundred twenty-five patients (13.5%) were readmitted to a hospital within a 1-month period after discharge. Forty-eight percent of readmissions were to other hospitals. The most common readmission problems were congestive heart failure (15.6%), atrial fibrillation (12.9%), chest pain (12.0%), wound problems (10.2%), and gastrointestinal problems (8.0%). Hospital discharge on or before the fifth postoperative day was associated with a lower prevalence of subsequent readmission. The independent predictors of a readmission for congestive heart failure were postoperative stay longer than 5 days, diabetes, New York Heart Association functional class IV, preoperative congestive heart failure, total blood product use, the need for postoperative inotropes, body mass index greater than 28 kg/m(2), and reoperation for bleeding. CONCLUSIONS: The prevalence of rehospitalization during the first month after discharge is not trivial. Other than postoperative atrial fibrillation, readmission is probably the single most likely adverse event to befall a patient in the early postoperative period. Patients who are discharged early do not appear to be at increased risk. Patterns in readmission diagnoses suggest opportunities for preventive strategies.

Aged↗
PubMed1999

Restriction fragment length polymorphism analysis for rapid gag subtype determination of human immunodeficiency virus type 1 in South Africa.

A rapid method for identification of human immunodeficiency virus Type 1 (HIV-1) gag subtypes was developed based on restriction fragment length polymorphism (RFLP) analysis of 400 or 650 bp long polymerase chain reaction (PCR) fragments encompassing the start of the p17 (400 bp) and part of the p24 (650bp) regions. The consensus sequences of subtypes A-D, the only subtypes identified in South Africa, were analyzed to detect restriction endonucleases which generate unique patterns for each subtype. Four restriction endonucleases were identified: AluI, AccI, SwaI and XmnI. Digestion of a 400 bp fragment with AluI allowed identification of subtype C. Samples not identified were then reamplified, and a 650 bp fragment digested with AccI to identify subtype B, followed by SwaI and XmnI to distinguish between subtypes A and D. This strategy was applied to 87 samples previously subtyped by either sequence analysis of the gag p17 region (n = 33); or heteroduplex mobility assay (HMA) based on the env gene (n = 75); or both (n = 21). Out of the 87 samples, RFLP identified two samples as subtype A, 28 as subtype B, 56 as subtype C and one as a subtype D virus. No discrepancies were found between RFLP gag subtypes and gag sequence subtypes demonstrating the reliability of this method. There was also no discordance between gag RFLP subtypes and env HMA subtypes, suggesting that there were no recombinant viruses detected relating to the genomic regions analyzed. RFLP is an effective technique for the rapid screening in an HIV epidemic of limited diversity, such as in South Africa.

DNA, Viral↗
PubMed1999

Contraceptive use and pregnancy decision making among women with HIV.

HIV is a growing epidemic among women in the United States. This study seeks to determine if knowledge of HIV infection and of the benefits of prenatal zidovudine (ZDV) to decrease vertical HIV transmission is related to decisions about pregnancy planning, contraceptive and condom use, and pregnancy termination among noninjection drug using (IDU) women with HIV. Eighty-two HIV-infected women were interviewed about their pregnancy decisions, contraceptive and condom use, and pregnancy outcome. Data was verified by structured chart review where available. Awareness of HIV infection or knowledge of the benefits of prenatal ZDV use did not significantly influence pregnancy planning, contraceptive choice, use of contraception, or consideration of pregnancy termination. Condom use was extremely low (14.6% consistent use), the majority of pregnancies (68.0%) were unplanned, contraceptive use was low (50.9%), and few pregnancies were terminated (6.3%). Women on Medicaid were significantly less likely than women with private or no insurance to terminate their pregnancy (2/20, 10% vs. 3/5, 60%, p = 0.04, two-tailed Fisher's exact test). Most women (70.0%) reported the most important reason for carrying the pregnancy to term was the desire for a child. In conclusion, among women in this non-IDU, Midwestern cohort, knowledge of HIV infection was not associated with decisions to plan a pregnancy, use contraception if not planning pregnancy, or terminate an unplanned pregnancy.

Abortion, Therapeutic↗
PubMed1999

Mapping the gene causing hereditary primary hyperparathyroidism in a Portuguese kindred to chromosome 1q22-q31.

A Portuguese kindred with autosomal dominant isolated primary hyperparathyroidism (HPT) that was associated with parathyroid adenomas and carcinomas was investigated with the aim of determining the chromosomal location of this gene, designated HPTPort. Leukocyte DNA from 9 affected and 16 unaffected members and 7 parathyroid tumors from 4 patients was used in comparative genomic hybridization (CGH), tumor loss of heterozygosity (LOH), and family linkage studies. The CGH studies revealed abnormalities of chromosomes 1 and 13, and the results of LOH studies were consistent with the involvements of tumor suppressor genes from these regions. Family segregation studies mapped HPTPort to chromosome 1q22-q31 by establishing linkage with eight loci (D1S254, D1S222, D1S202, D1S238, D1S428, D1S2877, D1S422, and D1S412) (peak two-point LOD scores = 3. 46-5.14 at 0% recombination), and defined the location of HPT Port to a 21 cM region flanked centromerically by D1S215 and telomerically by D1S306. Thus, HPTPort has been mapped to chromosome 1q22-q31, and a characterization of this gene will help to elucidate further the mechanisms that are involved in the development of parathyroid tumors.

Adenoma↗
PubMed1998

Genetic characterization of HIV type 1 from migrant workers in three South African gold mines.

The phylogenetic relationships between 44 HIV-1 isolates from 43 infected subjects employed by three adjacent South African gold mines were investigated. The patients were migrant workers originating from rural areas of South Africa and the neighboring countries of Lesotho, Botswana, Swaziland, and Mozambique. Proviral HIV-1 DNA was subtyped using a heteroduplex mobility assay (HMA) based on the 700-bp V3-V5 region of the env gene. DNA sequence analysis was used to confirm the subtype designation and to determine phylogenetic relationships between isolates. All 44 HIV-1 isolates were identified as env subtype C using both HMA and phylogenetic analysis. These isolates did not show a distinct phylogenetic relatedness based on the geographic origins of the migrant workers or show close homology to other subtype C sequences from southern Africa or India. However, five clusters of closely related sequences were identified, mainly involving miners of disparate geographic origins, suggesting possible epidemiological linkage in these few cases. The characteristic tetrapeptide sequence, GPGQ, at the tip of the V3 loop of subtype C viruses was conserved in the predicted amino acid sequences of most isolates. The heterogeneity of HIV-1 sequences among migrant workers in a mining cohort suggests multiple introductions of HIV-1 subtype C into this population that are not apparently linked to the geographic origins of the patients.

Adolescent↗