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Biomedical subjects

J B Wilson

Publications and source records attributed to J B Wilson.

At least 55 records · Page 3Linked to original sources
PubMed1996

A model for the mechanism of precise integration of a microinjected transgene.

A unique transgenic mouse line has undergone transgene integration in a very precise fashion. The phenotype displayed by mice of the line followed the predicted inheritance patterns for X-linked transgene insertion which has been confirmed. In order to investigate the mechanism of integration the DNA sequence of the transgene and cellular junctions have been determined. A comparison between wild type and transgenic mutant sequences at the site of insertion revealed that there was no loss or rearrangement of cellular DNA upon integration of the transgene. The cellular sequences at the transgene 5' and 3' joins are contiguous in the wild type. The integrant exists as a head to tail tandem dimer with minimal loss of sequence compared with the injected monomer. Analysis of the site of insertion has revealed a 5 bp homology between the 5' end of the transgene and the cellular sequences. In addition, adjacent to the site of insertion within the cellular sequences, there are several sequence motifs implicated in recombination events including a clustering of strong consensus sites of DNA topoisomerase type I and a region of homology to the human minisatellite consensus core sequence, the Escherichia coli Chi site and the meiotic recombination hotspot within the E beta gene of the murine major histocompatibility complex. This clustering of features is likely to have been factorial in the integrity of the insertion event. A model depicting the mechanism of this precise integration is proposed.

Animals↗
PubMed1996

Vero cytotoxigenic Escherichia coli infection in dairy farm families.

Fecal samples from 335 dairy farm residents and 1458 cattle on 80 farms were tested for Vero cytotoxin (VT)-producing Escherichia coli (VTEC). Residents were also tested for antibodies to VT1 and O157 lipopolysaccharide (LPS). Residents and cattle on farms with VTEC-positive persons or E. coli O157:H7-positive cattle were retested. Twenty-one persons (6.3%) on 16 farms (20.8%) and 46% of cattle on 100% of the farms had VTEC in fecal samples. Human VTEC isolates included E. coli O157:H7 and 8 other serotypes, 4 of which were present in cattle on the same farms. More persons had antibodies to VT1 (41%) than to O157 LPS (12.5%). Seropositivity to O157 LPS was associated with isolation of E. coli O157:H7 on the farm (P = .022). Human VTEC infection was negatively associated with age (P < .05) and was not associated with clinical illness. Many dairy farm residents experience subclinical immunizing VTEC infections at a young age, which frequently involve non-O157 VTEC found in cattle.

Adolescent↗
PubMed1996

Comparison of Vero cell assay and PCR as indicators of the presence of verocytotoxigenic Escherichia coli in bovine and human fecal samples.

Comparisons were made between Vero cell assay (VCA) and PCR as indicators for the detection of verocytotoxigenic Escherichia coli (VTEC; also known as Shiga-like toxin-producing E. coli) and as predictors of VTEC isolation from bovine and human fecal samples. Fecal samples were collected as part of a survey on the prevalence of VTEC on dairy farms in southern Ontario (J. B. Wilson et al., J. Infect. Dis., 174:1021-1027, 1996). A total of 2,655 samples were examined by VCA and PCR, 2,153 originating from cattle and 502 originating from humans. Overall, 36.2% of the samples were positive in the VCA and 38.7% were positive by PCR. Of the VCA-positive samples screened, 41.6% yielded a VTEC isolate. For both human and bovine samples, a significant positive association between PCR result and VCA titer (P = 0.0001) was found. In addition, there was a significant positive association between the PCR result and VTEC isolation from VCA-positive samples for cattle (odds ratio = 9.1, P < 0.0001). For bovine samples positive in the VCA, VCA titer was significantly associated with the probability of obtaining a VTEC isolate. Agreement between VCA and PCR was good for both bovine and human samples (kappa = 0.69 and 0.64, respectively). The sensitivity and specificity of the PCR with respect to the VCA for bovine samples were 82.0 and 86.5%, respectively, and those for human samples were 59.3 and 98.1%, respectively. Although correlation between VCA and PCR results was not absolute, when used in conjunction, these tests complemented one another as predictors of VTEC isolation.

Animals↗
PubMed1996

Hb Costa Rica or alpha 2 beta 2 77(EF1)His --> Arg: the first example of a somatic cell mutation in a globin gene.

We have identified a minor hemoglobin component (approximately 5%) in the blood of a healthy Costa Rican female, but not in her mother and two brothers (father not studied), that has an His --> Arg replacement at position beta 77 (Hb Costa Rica). No other amino acid replacements were observed and no beta- or gamma-chain-like peptides were present. Hb Costa Rica has abnormal stability. Sequence analyses of numerous polymerase chain reaction (PCR)-amplified segments of DNA that contain exon 2 of the beta gene failed to identify a CAC --> CGC (His --> Arg) mutation. The same was the case when cDNA was sequenced, indicating that a beta-Costa Rica-mRNA could not be detected with this procedure. Gene mapping of genomic DNA with Bg/II, BamHI, and HindIII gave normal fragments only and with the same intensity as observed for the fragments of a normal control. The quantities of the beta chain variants Hb J-Iran and Hb Fukuyama with related mutations at beta 77 vary between 30% and 45% in heterozygotes, whereas that of Hb F-Kennestone with the same His --> Arg mutation but in the G gamma-globin gene, is a high 40%-45% (as percentage of total G gamma) in a heterozygous newborn. These different observations exclude a heterozygosity of the A --> G mutation at codon beta 77, as well as a deletion comparable to that of Hbs Lepore or Kenya, or a beta-globin gene duplication, and point to a nontraditional inheritance of Hb Costa Rica. Allele-specific amplification of cDNA with appropriate primers identified the presence of a low level of mutated mRNA in the reticulocytes of the patient, which was confirmed by dotblot analysis of the same material with 32P-labeled probes. Comparable amplification products were not observed in genomic DNA. The A --> G mutation apparently occurred in a somatic cell at a relatively early stage in the development of the hematopoietic cell system, and Hb Costa Rica accumulated through rapid cell divisions in patchy areas in the bone marrow (somatic mosaicism). An unequal distribution of Hb Costa Rica over the red cells supports this possibility.

Adult↗
PubMed1995

Innovative community-based postgraduate training for obstetrics and gynecology in west Africa.

OBJECTIVE: To describe a unique international effort to develop a training program in West Africa that would be of similar quality to any other in the world (but with sensitivity to cross-cultural needs) and would retain physicians in West Africa to improve women's health in that part of the world. METHODS: Step-by-step formulation of a program included initial trainee recruitment, the inclusion of foreign guest faculty, and the establishment of institutional libraries. This was followed by a phase of curriculum development, recruitment of West African faculty, and organization of an innovative, community-based fourth year. RESULTS: Between ten and 12 postgraduates will have completed the program by January 1996, and will be placed in Ghana. More than 60% of Ghanaian postgraduates have passed the relevant regional examinations, compared with less than 25% of candidates from other countries. Nine Ghanaian specialists have returned to Ghana to become faculty members in the program. Over 20 published peer-reviewed articles have resulted from this program since 1989. The number of residents being trained has increased from three to 28. Seven new residents joined the program in 1994. An early reduction in maternal mortality from 9.9 deaths per 1000 births in 1991 to 4.2 deaths per 1000 births in 1992 was noted when senior postgraduates took over labor and delivery at the teaching hospital in Accra, Ghana, where approximately 10,000 deliveries occur per year. CONCLUSION: Specialty training in obstetrics and gynecology that is specifically aimed at meeting the needs of West Africa has been initiated successfully. Long-range success will require support from regional governments and continued long-term commitments from the international community of obstetricians and gynecologists.

Africa↗
PubMed1995

Management of difficult intra operative bleeding by abdominal packing: report of four cases.

Difficult perioperative bleeding in four obstetric and gynaecology patients was managed with temporising abdominal packs left in place with abdominal closure for 48-72 hours in order to avoid deaths on the operating table when blood loss could not be adequately replaced and hemostasis could not be secured. Abdominal re-opening to remove the packs was undertaken. Three of the patients were eventually discharged home after satisfactory recovery. The fourth died of sepsis three weeks after the fourth re-operation and bilateral internal iliac artery ligation. Abdominal packing thus has a place in the management and salvage of patients with difficult obstetric and gynaecologic perioperative bleeding.

Adolescent↗
PubMed1994

A novel deletion of approximately 27 kb including the beta-globin gene and the locus control region 3'HS-1 regulatory sequence: beta zero-thalassemia or hereditary persistence of fetal hemoglobin?

A novel deletion of approximately 27 kb with the 5' breakpoint 1.5 to 2.2 kb upstream of the beta-globin gene, and the 3' breakpoint approximately 24 kb downstream of the beta-globin gene, has been found in five members of two families from Southeast Asia (Vietnam and Cambodia). Six members of another family from China, previously reported from our laboratory, have also been shown to carry this deletion. The patients presented with mild hypochromia and microcytosis, a hemoglobin (Hb) A2 level of approximately 4.0%, and a markedly increased, heterocellularly distributed, Hb F level (14.0 to 26.0%). In vitro globin-chain synthesis showed a mild imbalance with appreciable gamma-chain compensation (alpha/beta + gamma ratio of 1.46). The 3' end of this deletion includes the 3'HS-1, and we hypothesize that removal of this region results in the loss of its gamma-globin gene-silencing effect, which causes a markedly elevated Hb F level with a modest increase in Hb A2 levels, unlike the situation in other deletional beta zero-thalassemias. The possible influence of particular sequence variations in the locus control region 5'HS-2 and the G gamma promoter, present on the chromosome with this deletion, on the overall gamma-globin gene should also be considered.

Adolescent↗
PubMed1994

Quantities of alpha Q chain variants in heterozygotes with and without a concomitant beta-thalassemia trait.

We have analyzed the quantities of alpha x chain-containing hemoglobins (alpha 2 x beta 2 and alpha 2 x delta 2) in 14 heterozygotes for Hb Q-India [alpha 64(E13)Asp-->His] or Hb Q-Thailand [alpha 74(EF3)Asp-->His]; both amino acid replacements are the result of mutations in the alpha 1-globin gene. Five of these persons (three with Hb Q-India and two with Hb Q-Thailand) had an additional beta(0)-thalassemia heterozygosity. The average quantities for Hb Q + Hb Q2 in the four groups were 17.2% (alpha alpha Q/alpha alpha; beta A/beta A), 9.5% (alpha alpha Q/alpha alpha; beta A/beta(0) Th), 26.8% (-alpha Q/alpha alpha; beta A/beta A), and 16.95% (-alpha Q/alpha alpha; beta A/beta(0) Th). These variations can best be explained by a posttranslational control mechanism; an imbalance in the alpha A, alpha Q, and beta A chain ratio will favor the alpha 2 Q beta 2 formation when an alpha-thalassemia is present and will reduce its formation in the presence of a beta-thalassemia heterozygosity.

Adolescent↗
PubMed1994

Eclampsia: 134 consecutive cases.

OBJECTIVE: A retrospective analysis of all cases of eclampsia (134) at Korle Bu Teaching Hospital, Accra, Ghana, in 1991, was undertaken to determine future directions in prevention and management. METHODS: One hundred and thirty-four consecutive cases of eclampsia were reviewed to assess possible risk factors, associated medical impact, and the usefulness of prenatal care. RESULTS: Risk factors for the development of eclampsia include: young age, delivery in the rainy season, nulliparity, multiple pregnancy, prolonged labor, and lack of prenatal care. Eclampsia is associated with high maternal and perinatal mortality. CONCLUSIONS: Future emphasis on prenatal clinics, and earlier detection and management of pre-eclampsia should lessen the incidence of this severe obstetric emergency.

Adolescent↗
PubMed1994

Diagnosing unruptured ectopic pregnancy.

OBJECTIVE: A retrospective analysis of the management of ectopic pregnancy at Korle Bu Teaching Hospital in Accra, Ghana, to assess the impact of the introduction of ultrasonography as a diagnostic tool. METHODS: All charts of patients with ectopic pregnancies from 1 January 1986 to 31 December 1990 were analyzed. The management of those patients who had transabdominal ultrasonography was compared with those who had not. RESULTS: The use of ultrasonography increased the number of unruptured ectopic pregnancies from 0.3% to 8.5% (P < 0.001). This also reflected a reduction in misdiagnoses, blood transfusions, and maternal deaths. CONCLUSIONS: The reasonable use of modern technology can be of great assistance even in developing countries, as shown by the positive impact of the use of ultrasonography to aid in the diagnosis of ectopic pregnancy in Ghana, West Africa.

Developing Countries↗
PubMed1994

Generating colour and texture verniers.

This paper describes computer graphics techniques for presenting visual stimuli in a vernier format composed out of coloured texture patterns. Such stimuli can be used to investigate the performance at the task of localising boundaries mediated by changes in colour and/or texture. We summarise the contents as follows: (1) Techniques for presenting visual stimuli are reviewed with a view to how they might be used to present colour and texture verniers. (2) The design of the vernier stimuli for the localisation task is considered. (3) Significant elements of this design are: (a) the use of non-isoplanatic textures to avoid interference effects at boundaries, (b) the modulation of the texture patterns along axes in MacLeod-Boynton colour space so that relative retinal cone contributions are controlled, and (c) the use of double-buffering, colour map manipulation, and contrast randomisation techniques to avoid problems commonly encountered when presenting computer graphics stimuli on colour monitors. (4) Results of a psychophysical experiment that presents colour and texture verniers are reported elsewhere.

Color Perception Tests↗
PubMed1994

Hb Fannin-Lubbock in five Spanish families is characterized by two mutations: beta 111 GTC-->CTC (Val-->Leu) and beta 119 GGC-->GAC (Gly-->Asp).

We have sequenced the amplified beta-globin genes of five, apparently unrelated, Spanish adults with a fast-moving hemoglobin variant, and observed a GGC-->GAC mutation at codon 119 which identified the abnormality as Hb Fannin-Lubbock or alpha 2 beta (2)119(GH2)Gly-->Asp. In addition, we found a GTC-->CTC change at codon 111 which leads to a Val-->Leu replacement at this location. Protein analysis of the beta A and beta X chains from one of these individuals confirmed that both mutations are located on the same chromosome. It is hypothesized that some other known variants may carry an additional mutation in one of their exons, resulting in a silent amino acid substitution which may have an effect on some physicochemical property. In the case of Hb Fannin-Lubbock, it appears likely that the Val-->Leu replacement at beta 111, rather than the Gly-->Asp replacement of beta 119, is the cause of the instability of the variant. The Hb Fannin-Lubbock variant in these Spanish families had a normal oxygen affinity.

Adult↗