Academic research and HIV/AIDS in South Africa.
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Academic Medical Centers↗
Biomedical subjects
B G Williams
Publications and source records attributed to B G Williams.
Occupational lung disease in ex-mineworkers--sound a further alarm!
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Gold↗
Measles vaccination policy.
Where immunization campaigns locally eliminate measles, it will be important to identify the vaccination policy most likely to prevent future epidemics. The optimum age for vaccination depends on the rate of decline of maternal antibody, because the presence of antibody reduces vaccine efficacy. The first part of this paper contains a quantitative reappraisal of the data on antibody decline and seroconversion rates by age. The decline in maternal antibody protection follows delayed exponentials, with delays of 2-4 months, and subsequent half-lives of 1-2 months. Using this result in an analytical mathematical model we find that the optimal age to administer a single dose of vaccine to children, which is independent of vaccine coverage, lies within the range 11-19 months. We also show that, where the optimal age cannot be met, it is better to err towards late rather than early vaccination. There are therefore two reasons why developing countries, which presently vaccinate during infancy because measles transmission rates are high should eventually switch to the second year of life. The possible gains from two-dose vaccination schedules are explored with respect to both coverage and efficacy. A two-dose schedule will be beneficial, in principle, only when there is a need to increase net vaccine efficacy, after coverage has been maximized with a one-dose schedule.
Antibodies, Viral↗
Interferon response in chronic myeloid leukaemia correlates with ABL/BCR expression: a preliminary study.
alpha-Interferon (IFN) has been used to induce cytogenetic remission in chronic myeloid leukaemia (CML), but there are few indicators to predict IFN response. The role of the chimaeric BCR/ABL gene in the malignant process is undisputed. There are, however, conflicting views as to whether the breakpoint site within the BCR gene, and the type of mRNA produced determine disease prognosis and progression. The function and clinical significance of the newly discovered ABL/BCR mRNA has not been investigated for a correlation with CML prognosis or response to therapy. We have used a two-step reverse transcriptase polymerase chain reaction (RT-PCR) to detect the transcripts of the chimaeric genes BCR/ABL, ABL/BCR, as well as the normal ABL and BCR genes in 24 CML patients treated with IFN. Because of the variable expression of the four transcripts at presentation, a correlation between gene expression, prognosis and clinical progression was examined. No correlation between prognosis and gene expression was seen. Also, no correlation was found between expression of BCR, ABL or BCR/ABL mRNA and response to treatment with IFN. However, 7/10 ABL/BCR mRNA positive patients achieved a major cytogenetic response to IFN; but of the 13 ABL/BCR mRNA negative patients, only two achieved a major cytogenetic response (P = 0.013). Further studies are required to confirm these findings.
Adolescent↗
A cost-benefit analysis of feeding in female tsetse.
Three models for feeding in female tsetse are considered. Model I: there is a prolonged non-feeding phase after each meal followed by feeding at a constant rate, with a constant probability of dying as a consequence of feeding. Model II: the feeding rate increases linearly after each meal. Model III: the feeding rate increases exponentially after each meal. In Models II and III the feeding hazard is a linear function of the probability of feeding. Production of viable female offspring is estimated under each model, making allowance for losses of adults due to starvation and to background and feeding mortality, losses of pupae due to predation and parasitization, and losses of young flies if their mothers take insufficient blood during pregnancy. Under Model I, if females require three meals to produce viable pupae in 9 days, then for a non-decreasing population with a background mortality of 1%/day, and 25% pupal losses due to predation and parasitism, the feeding risk must be < or = 5%/feed. At this maximum level the non-feeding phase should be 2-2.5 days for optimal productivity, with a mean feeding interval of 60-72 h. If the background mortality is 2%/day, feeding losses cannot exceed 1%/feed for a non-decreasing population. If four or five meals are required for the production of fully viable pupae, the optimal values of the non-feeding phase and mean feeding interval tend towards 1 and 2 days respectively. Under Models II and III the mean feeding interval is 50-60 h for optimal productivity (with variances 3 times as large as for Model I), in good agreement with estimates from recent models for feeding and digestion. Field evidence suggests that feeding tsetse take greater risks as their fat levels dwindle. This should result in feeding (and feeding mortality) rates which increase during the feeding phase--as assumed in Models II and III but not in Model I. These models allow greater flexibility than Model I, because flies can feed early in the hunger cycle, at low probability, as long as the feeding risk is also low.
Animals↗
Activated protein c resistance (APC) and inherited factor V (FV) mis-sense mutation in patients with venous and arterial thrombosis in a haematology clinic.
BACKGROUND: Inherited factor V (FV) mis-sense point mutation has recently been identified as a major cause of familial venous thrombosis. The incidence of this congenital haemostatic disorder in Australia is unknown. AIM: To examine the incidence of this congenital defect in patients with thrombosis attending a haematology clinic. METHODS: Individuals investigated or treated for venous and arterial thrombosis over a four month period, as well as those who were on anticoagulant for valvular replacement or arrhythmia were studied for the presence of FV mis-sense point mutation, FV Q506 (G to A at nucleotide position 1691) by a polymerase chain reaction based test, and activated protein C (APC) resistance using an APTT based coagulation assay. RESULTS: Forty-five patients with venous thromboembolism (VTE), 20 patients with coronary artery disease and 25 patients with valvular replacement or arrhythmia who were on anticoagulant were examined. The frequency of FV mis-sense point mutation in these three groups was 26.7%, 15% and 4% respectively. In this study, patients with FV Q506 were of a younger age and had a higher incidence of extensive thrombosis or recurrence as compared to those with the normal factor V gene. This mutation was found in a diverse group of people (four of the 12 patients were of non-European origin). Nearly 50% of these patients had other risk factors for VTE. The number of patients with a family history of VTE was similar for those with the FV mutation and the normal FV. CONCLUSION: This study confirms the high incidence of FV Q506 mutation in patients with VTE reported overseas. Several clinical features, i.e. young age of onset of VTE, high recurrence rate, diverse ethnic background and importance of associated risk factors are highlighted. The findings in this study also raise the possibility that this mutation may be a risk factor for arterial thrombosis. Large studies are required to substantiate these findings.
Adult↗
A measurement of self-esteem in pregnant teenagers.
Low self-esteem is often viewed as an important factor in unprotected sexual activity and pregnancy in adolescents. The purpose of this pilot study was to determine the level of self-esteem in single pregnant teenagers. The Culture-Free Self-Esteem Inventory (CFSEI) and a researcher-developed demographic questionnaire were used to measure self-esteem in 19 pregnant teenagers and to gather demographic information about them. The mean score for total self-esteem was 16.4, which is an intermediate level of self-esteem according to Battle's classification of scores. Mean scores for general self-esteem (6.31), academic self-esteem (3.68), parental self-esteem (3.37), and social self-esteem (3.15) were also at intermediate levels. The pregnant teenagers in this study did not have low self-esteem, according to Battle's general population norms. Suggestions for further research include replication of this study with a larger sample and comparison of self-esteem in pregnant and nonpregnant teenagers.
Adolescent↗
Influence of needle gauge in Mantoux skin testing.
STUDY OBJECTIVE: To determine the influence of needle gauge in Mantoux skin testing for tuberculosis. DESIGN: Randomized selection of either a 27- or 30-gauge needle for Mantoux skin test placement; observer-blinded. SETTING: Annual hospital employee screening. PARTICIPANTS: Six hundred twenty-five employees working in clinical and laboratory research environments. RESULTS: Blinded observers found that the use of 27-gauge needles caused increased bleeding and bruising compared with 30-gauge needles (p < or = 0.007 for each). However, the 27-gauge needle produced larger blebs and less leakage of tuberculin solution (p < or = 0.0003). CONCLUSION: Smaller gauge needles could potentially cause false-negative screening results because of decreased antigen delivery. Use of needle gauges smaller than 27 gauge should be avoided until their reliability is validated.
Evaluation Studies as Topic↗
A Ph+ acute myeloid leukaemia expressing both CML-type and ALL-type BCR/ABL mRNA transcripts.
This report describes a patient presenting with acute myeloid leukaemia (AML-FAB classification M2). Phenotypic markers were positive for cells of the myeloid lineage, but negative for monocyte/macrophage, megakaryocyte, and T-cell lineages. The occasional blast was positive for CALLA. All blasts carried the Philadelphia chromosome (Ph+), with 20% also harbouring a monosomy 7 (a cytogenetic marker for AML). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed the presence of two BCR/Abl mRNA transcripts; b2a2, the CML-type and E1a2, the ALL-type. Immunoglobulin (Ig) gene analysis demonstrated the presence of a small population of cells containing rearranged Ig genes. After a short remission, the patient relapsed. At relapse the leukaemia had undergone a major phenotypic switch from AML to ALL, with blasts bearing B-cell markers. Ig gene analysis confirmed a monoclonal population of B-cells. The Ph+ persisted, but the monosomy 7 had disappeared. The same two BCR/Abl mRNA transcripts were found at relapse as at presentation. To our knowledge, this is the first report of an AML simultaneously expressing BCR/Abl transcripts from both the minor and major BCR. The possible mechanisms of this dual expression are discussed.
Base Sequence↗
Malnutrition, age and the risk of parasitic disease: visceral leishmaniasis revisited.
Children are said to be at greater risk of developing visceral leishmaniasis (VL) when they are younger and more malnourished. If malnutrition really is associated with VL, this potentially fatal and visible disease may be a general indicator of community health among the rural and suburban poor. Previous conclusions reached about the roles of malnutrition and age in VL epidemiology are questionable because they may have been confounded by transmission rate, because they have not been able to distinguish between different mechanisms of acquiring immunity, and because empirical observations have not been compared with theoretical expectations. Here we offer a framework with which to investigate these questions quantitatively, and do so with published data from endemic areas of Brazil. We conclude that children are indeed more susceptible to VL when they are younger and more malnourished, but it remains unclear whether the immunity to VL acquired with age is always acquired as a result of infection. The significance for leishmaniasis control, and for the control of other diseases associated with malnutrition, will depend on underlying mechanisms, which are not yet understood.
Adolescent↗
Isolation of a tomato alcohol dehydrogenase 2-encoding cDNA using phage-promoted antibody screening of a plasmid cDNA library.
We describe the cloning of a cDNA encoding tomato alcohol dehydrogenase 2 (Adh2) by screening plasmid cDNA clones in phage plaques. A cDNA library constructed in a plasmid vector containing a unique SstI site at the 5' end of the cDNA insert was transferred into the SstI site of the lacZ gene of phage lambda Charon16, and screened by anti-Adh2 antibody to identify reactive plaques. Plasmid cDNA clones were recovered by SstI digestion, ligation, and transformation from phage minipreps for subsequent characterization. This system preserves the original plasmid library for subsequent screening with nucleic acid probes to identify full-length, multiple independent, or related cDNA clones not subject to the selection pressure of phage growth or lysogeny, or negative antibody reactivity. Thirty-two cDNA clones were identified with polyclonal antiserum to Adh2. Three of these reacted with monoclonal anti-Adh2 and only those three hybridized to maize adh1 sequence. One of these cDNAs, Adh31, was further characterized as encoding Adh2 by hybrid-selected translation and high sequence homology with the maize adh1 gene.
Alcohol Dehydrogenase↗
Monitoring trypanosomiasis in space and time.
The paper examines the possible contributions to be made by Geographic Information Systems (GIS) to studies on human and animal trypanosomiasis in Africa. The epidemiological characteristics of trypanosomiasis are reviewed in the light of the formula for the basic reproductive rate or number of vector-borne diseases. The paper then describes how important biological characteristics of the vectors of trypanosomiasis in West Africa may be monitored using data from the NOAA series of meteorological satellites. This will lead to an understanding of the spatial distribution of both vectors and disease. An alternative, statistical approach to understanding the spatial distribution of tsetse, based on linear discriminant analysis, is illustrated with the example of Glossina morsitans in Zimbabwe, Kenya and Tanzania. In the case of Zimbabwe, a single climatic variable, the maximum of the mean monthly temperature, correctly predicts the pre-rinderpest distribution of tsetse over 82% of the country; additional climatic and vegetation variables do not improve considerably on this figure. In the cases of Kenya and Tanzania, however, another variable, the maximum of the mean monthly Normalized Difference Vegetation Index, is the single most important variable, giving correct predictions over 69% of the area; the other climatic and vegetation variables improve this to 82% overall. Such statistical analyses can guide field work towards the correct biological interpretation of the distributional limits of vectors and may also be used to make predictions about the impact of global change on vector ranges. Examples are given of the areas of Zimbabwe which would become climatically suitable for tsetse given mean temperature increases of 1, 2 and 3 degrees Centigrade. Five possible causes for sleeping sickness outbreaks are given, illustrated by the analysis of field data or from the output of mathematical models. One cause is abiotic (variation in rainfall), three are biotic (variation in vectorial potential, host immunity, or parasite virulence) and one is historical (the impact of explorers, colonizers and dictators). The implications for disease monitoring, in order to anticipate sleeping sickness outbreaks, are briefly discussed. It is concluded that present data are inadequate to distinguish between these hypotheses. The idea that sleeping sickness outbreaks are periodic (i.e. cyclical) is only barely supported by hard data. Hence it is even difficult to conclude whether the major cause of sleeping sickness outbreaks is biotic (which, in model situations, tends to produce cyclical epidemics) or abiotic.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Aspergillus terreus during hospital renovation.
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Air Microbiology↗
Deletion of WT1 and WIT1 genes and loss of heterozygosity on chromosome 11p in Wilms tumors in Japan.
Six of 39 sporadic Wilms tumors had gross homozygous or hemizygous WT1 and WIT1 deletions. Two Wilms tumor-aniridia-genitourinary abnormalities-mental retardation syndrome patients had total hemizygous WT1 and WIT1 deletions in both constitutional and nonsporadic type tumor cells. Four of the 8 tumors with WT1 and WIT1 deletions showed loss of constitutional heterozygosity (LOH) for markers limited to the 11p13 region. Seven of 19 Wilms tumors with neither WT1 nor WIT1 deletions also had LOH on 11p; 4 in the 11p15-11p13 region, one in the 11p15 and possibly also 11p13 regions, and two solely in the 11p15 region. Thus, 15 of the 41 Wilms tumors (37%) had WT1 and WIT1 deletions or LOH on 11p, and only 2 of the 27 tumors whose nonneoplastic normal tissues were available for study showed LOH limited to the 11p15 region. None of the 7 non-Wilms childhood renal tumors showed WT1 or WIT1 deletions, or LOH on 11p. These data suggest that Japanese Wilms tumors may be characterized by a higher incidence of the gross WT1 deletion and a lower incidence of LOH limited to the 11p15 region than the Caucasian counterparts. These molecular-genetic features may be contributing to the lower incidence of Wilms tumors in Japanese children than in Caucasian ones.
Blotting, Southern↗
Modelling the effect of feeding-related mortality on the feeding strategy of tsetse (Diptera: Glossinidae).
Free-living haematophagous insects risk death through host grooming responses or through increased susceptibility to predation whenever they take a bloodmeal. In this paper we investigate the effects of these risks on the feeding strategy of tsetse. A model is presented that allows for death of tsetse by starvation if they do not succeed in feeding within a fixed time (set at 6 days in the first instance) and for mortality specifically associated with feeding. In addition there is background mortality that applies to all flies at all times. The model is used to compute the individual life-time fertility (number of female puparia per female) as a function of the probability of obtaining a meal (indicated by field data to be very high, usually > 0.85 per day) and the day on which flies start to search for a meal. We suggest that the feeding strategy that would be selected for is that which allows the maximum reproductive output. The model shows that this strategy involves making no attempts to feed for 3-4 days after the previous meal and then attempting to feed with the greatest possible probability until a meal is obtained. The predicted feeding interval, obtained independently of any trapping data, agrees closely with all previous estimates from field studies using a variety of methods. Preliminary results from a laboratory experiment reveal an increased risk of predation of recently fed as compared with hungry tsetse. The lower the actual feeding mortality the more frequently will flies be able to feed should conditions so demand. It is adaptive, however, for tsetse to delay attempting to feed for as long as they can, which is made possible by the near certainty of locating and feeding on a host within 1 day, using their sophisticated sensory systems.
Animals↗
Quantitative assessment of HIV-1 DNA load by coamplification of HIV-1 gag and HLA-DQ-alpha genes.
We developed an assay for simultaneous amplification, detection and quantitation of HIV-1 gag gene and the DQ-alpha locus of the histocompatibility (HLA) region of the human genome by polymerase chain reaction (PCR). Crude cell lysates from control cell lines and peripheral blood mononuclear cells (PBMC) from HIV-1-infected and control individuals were coamplified using optimized concentrations of primers directed at both loci, followed by simultaneous hybridization with radioactively labeled HIV-1-gag and HLA-DQ-alpha probes. Simultaneous quantitation of the 242-base-pair HLA and 115-base-pair HIV products was accomplished by both end-point dilution analysis and image analysis of autoradiographs relative to standard curves derived from infected cell lines. We observed good agreement between input cell counts on fresh samples and the HLA-DQ-alpha target copy number values determined by both end-point dilution analysis and comparison of band intensities with standard curves. HIV-1 proviral load in symptomatic patients ranged from 200 to 4000 HIV-PCR-units per 1 x 10(6) PBMC (mean of 1245 copies), whereas asymptomatic patients had levels ranging from two to 1000 HIV-PCR-units per 1 x 10(6) PBMC (mean of 213 copies). This HIV/HLA coamplification approach should be particularly useful for analysis of frozen repository samples from natural history studies, and may facilitate wider application of quantitative PCR analysis.
Base Sequence↗
An unusual cutaneous lymphoma with B and T cell characteristics showing gallium-67 positive benign thymic hyperplasia following intensive chemotherapy.
This case illustrates two interesting features. Firstly it describes an unusual cutaneous lymphoma in an adolescent girl. This lymphoma showed features of B and T cell lineages with rearrangements of both immunoglobulin heavy chain and T cell beta chain genes. Secondly it describes the development of gallium-67 citrate (67Ga) scan positive benign thymic hyperplasia, 15 months after diagnosis and three months after cessation of intensive chemotherapy.
Adolescent↗
Molecular and hematologic characterization of Scottish-Irish type (epsilon gamma delta beta)zero thalassemia.
The DNA deletion associated with an example of (epsilon gamma delta beta)zero thalassemia (Scottish-Irish type) was characterized. The deletion is approximately 205 kb in length and involves the epsilon, G gamma, A gamma, delta, and beta globin genes. The breakpoint is located 263 bp 3' to exon 3 of the beta globin gene. An LI (KpnI) repeat element approximately 320 bp in size is found at the 3' end of the novel DNA sequence. Different clinical phenotypes for three heterozygous neonates suggest that the deletion alone does not predict severity of (epsilon gamma delta beta)zero thalassemia at this age.
Adolescent↗