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Biomedical subjects

R Williamson

Publications and source records attributed to R Williamson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Chromosome analysis of blastomeres from human embryos by using comparative genomic hybridization.

Karyotypic studies of aborted fetuses have been used to draw the inference that the proportion of conceptuses with chromosome abnormalities is very high. Fluorescent in situ hybridization (FISH) studies of blastomeres from early cleavage embryos have provided some support for this inference but they are limited to the study of a few chromosomes. We describe the novel application of comparative genomic hybridization (CGH) to the study of numerical and structural abnormalities of single blastomeres from disaggregated 3-day-old human embryos. CGH results were obtained for 63 blastomeres from 12 embryos. Identification of all chromosomes with the exception of chromosomes 17, 19, 20 and 22 was possible. The embryos divided into four groups: (1) embryos with a normal CGH karyotype seen in all blastomeres; (2) embryos with consistent aneuploidy suggesting meiotic non-disjunction had occurred; (3) embryos that were mosaic generally with one or more cells showing aneuploidy for one or two chromosomes but some with cells showing extensive aneuploidy; and (4) one embryo with extensive aneuploidy in all blastomeres. The extensive aneuploidy in group 4 is interpreted as corresponding to the random aneuploidy seen in "chaotic" embryos reported by using interphase FISH. Partial chromosome loss and gain following chromosome breakage was observed in one embryo. Our analysis provides basic biological information on the occurrence of constitutional and post-zygotic chromosome abnormalities in early human embryos. Used in conjunction with embryo biopsy, diagnostic CGH should allow the exclusion of a proportion of embryos that appear normal but that have a poor probability of survival and, therefore, may improve the implantation rate after in vitro fertilization.

Base Sequence↗
PubMed2000

Sensor systems for lower limb functional electrical stimulation (FES) control.

Two sensor systems comprising clusters of accelerometers, magnetic sensors, a rate gyroscope, and a strain gauge were designed. For one system, the clusters were located at the belt and AFO. In the other system, the clusters were located at the AFO and the thigh. The maximum cluster size was 14 cm(3) and 75 g. The clusters of each sensor system were interconnected by a single flexible wire bus, which minimized the effects of cabling. The sensors detected five phases of normal gait to a resolution of 40 ms in an able bodied test. Using a threshold method, the sensor system repeatedly predicted an incipient knee buckle in a paraplegic individual by a minimum of 30 ms. One system detected knee flexion angle analytically to an accuracy of 3.2 degrees during sit to stand trials. The second system determined knee and hip flexion angle to an accuracy of 3.8 degrees during sit to stand trials through neural networks. The signal processing of the acquired sensor signals in each system was performed on a MC68332 microcomputer in conjunction with the data sampling, and suggested the possibility for each sensor system to be used in real time control of FES.

Adult↗
PubMed2000

Assessment of education and counselling offered by a familial colorectal cancer clinic.

We have evaluated whether or not client expectations, in terms of education and information needs, have been met by a multi-disciplinary familial colorectal cancer clinic. The study used a pre- and post-clinic questionnaire design and 126 (84 women, 42 men) clients of the clinic participated. The most common reason for coming to the clinic is to 'find out whether there is a gene for colorectal cancer in the family', followed by 'to reduce risk for bowel cancer' and 'concern for children's risk'. Clients would have preferred to receive more information before attendance at the clinic to help with preparation. Information given during the clinic increased knowledge of bowel cancer genetics and had a positive effect on the accuracy of some clients' perceptions of their risk of developing cancer. In multivariate analysis, higher risk perceptions, higher education level and greater baseline knowledge predicted post-clinic knowledge of bowel cancer genetics and an increase in knowledge. Client reports of the presence of a genetic counsellor or medical geneticist in the session also predicted post-clinic knowledge and an increase in knowledge. Most participants felt they received enough information during the clinic session on various aspects of familial colorectal cancer, but the desire for more written information on prevention, including lifestyle actions, was expressed by many.

Adult↗
PubMed2000

Cancer worries, risk perceptions and associations with interest in DNA testing and clinic satisfaction in a familial colorectal cancer clinic.

Multi-disciplinary familial cancer clinics are becoming an integral part of cancer services. It is, therefore, important to assess how attendance at these clinics impacts on cancer-related concerns, risk perceptions and behavioural intentions, and how the clinic services are being received by those using them. This study has assessed a familial colorectal cancer clinic with respect to cancer-related worries and risk perceptions and their impact on interest in DNA testing and overall satisfaction with the clinic. Pre- and post-clinic questionnaires were completed by 127 patients and relatives attending the clinic. After attending the clinic, the proportion of people 'very' or 'extremely' worried about developing bowel cancer reduced from 49 (pre-clinic) to 34% (p = 0.002). Worry about bowel cancer was positively associated with younger age, higher education level and higher perceived risk of developing cancer. A reduction in level of risk perception correlated with a lower likelihood of feeling 'very worried' about developing bowel cancer. Of those intending to go ahead with DNA testing, 58% were 'very worried' about bowel cancer compared with 15% of those not intending to proceed with testing, suggesting that worry was a motivation for interest in DNA testing. One-third of participants indicated another session of genetic counselling would be helpful. Within this group, a higher proportion was very worried about bowel cancer (43%) than for those who did not want another session (17%). Attendance at this familial colorectal cancer clinic alleviated worry for many individuals, partly due to improved information about risk of colorectal cancer.

Adult↗
PubMed2000

Ranitidine bismuth citrate can help to overcome Helicobacter pylori resistance to clarithromycin in vivo.

BACKGROUND: Helicobacter pylori eradication usually fails when clarithromycin is used against resistant strains. OBJECTIVE: The objective of this study was to test whether the apparent synergy found in vitro between ranitidine bismuth citrate (RBC) and clarithromycin also exists in vivo against resistant strains. METHODS: H. pylori was cultured and clarithromycin susceptibility was determined before and after treatment, from duodenal ulcer patients receiving RBC and clarithromycin or omeprazole and clarithromycin for 2 weeks in a multicenter randomized clinical trial. RESULTS: The overall eradication rate was 88.7% in the RBC group (71 patients) and 52.7% in the omeprazole group (74 patients). The demographic characteristics of the two groups were not different. Clarithromycin-resistant strains were isolated in 22 cases (15.1%). A difference between the eradication rates of susceptible and resistant strains was found in the omeprazole group but not in the RBC group. After treatment, resistance to clarithromycin developed in three of the seven strains (42.3%) cultured from the patients of the RBC group, compared with 11 of the 26 strains (42%) of the omeprazole group. That is, clarithromycin-resistant strains were found in 6% and 27% in the RBC group and the omeprazole group, respectively, on considering the global results. CONCLUSION: A synergy between RBC and clarithromycin may exist in vivo and, while clarithromycin resistance is increasing, it is an argument for using RBC in triple therapies.

Adult↗
PubMed2000

Gait event detection for FES using accelerometers and supervised machine learning.

Rule based detectors were used with a single cluster of accelerometers attached to the shank for the real time detection of the main phases of normal gait during walking. The gait phase detectors were synthesized from two rule induction algorithms, Rough Sets (RS) and Adaptive Logic Networks (ALNs), and compared with to a previously reported stance/swing detector based on a hand crafted, rule based algorithm. Data was sampled at 100 Hz and the detection errors determined at each sample for 50 steps. For three able bodied subjects, the sample by sample accuracy of stance/swing detection ranged within 94-97%, 87-94%, and 87-95% for the RS, ALN, and the handcrafted methods, respectively. A heuristically formulated postdetector filter improved the RS and ALN detectors' accuracy to 98%. RS and ALN also detected five gait phases to an overall accuracy of 82-89% and 86-91%, respectively. The postdetector filter localized the errors to the phase transitions, but did not change the detection accuracy. The average duration of the error at each transition was 40 ms and 23 ms for RS and ALN, respectively. When implemented on a microcontroller, the RS-based detector executed ten times faster and required one tenth of the memory than the ALN-based detector.

Acceleration↗
PubMed2000

Friedreich ataxia: an overview.

Friedreich ataxia, an autosomal recessive neurodegenerative disease, is the most common of the inherited ataxias. The recent discovery of the gene that is mutated in this condition, FRDA, has led to rapid advances in the understanding of the pathogenesis of Friedreich ataxia. About 98% of mutant alleles have an expansion of a GAA trinucleotide repeat in intron 1 of the gene. This leads to reduced levels of the protein, frataxin. There is mounting evidence to suggest that Friedreich ataxia is the result of accumulation of iron in mitochondria leading to excess production of free radicals, which then results in cellular damage and death. Currently there is no known treatment that alters the natural course of the disease. The discovery of the FRDA gene and its possible function has raised hope that rational therapeutic strategies will be developed.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Conditionally immortalized mouse hepatocytes for use in liver gene therapy.

BACKGROUND AND AIMS: The use of hepatocytes for gene therapy is limited by the difficulty of maintaining and altering primary liver cells in culture. A conditionally immortalized mouse hepatocyte cell line has been developed which can be passaged indefinitely at the permissive temperature (33 degrees C), but fails to proliferate and dies at the non-permissive temperature (39 degrees C) in vitro. METHODS: Hepatocytes were harvested from a 6 week-old male transgenic mouse ('immortomouse') carrying a thermolabile SV40 Large T gene, using a modified two-step collagenase perfusion method, and serially passaged at 33 degrees C for more than 1 year. To assess the ability of immortohepatocytes to engraft and populate mouse liver, cells were infused into partially hepatectomized congenic mice via the portal vein (n = 10) or the spleen with (n = 2) and without (n = 2) partial hepatectomy. The ability to transfect immortohepatocytes was assessed using the reporter gene enhanced green fluorescent protein (EGFP). RESULTS: All immortohepatocytes in culture stained positive by immunohistochemistry for the hepatocyte markers albumin, AFP, CK8 and CK18. In early cultures a proportion of cells also stained strongly for the biliary epithelial markers CK7 and CK19. Late cell cultures were negative for M2PK and CK7 and stained variably with anti-CK19 antibodies. Cells transferred to the non-permissive temperature of 39 degrees C ceased proliferation and died within 1 week in vitro. Large T DNA was detected in the liver of all postoperative mice up to 2 weeks post-hepatocellular transplantation via PCR and Southern blot analysis. The immortohepatocytes were easily transfected with a reporter gene. CONCLUSIONS: Immortohepatocytes can survive in vivo after transfer to liver, and will be useful as a model for hepatic gene therapy.

Animals↗
PubMed1999

Clinical and genetic study of Friedreich ataxia in an Australian population.

Friedreich ataxia is an autosomal recessive disorder caused by mutations in the FRDA gene that encodes a 210-amino acid protein called frataxin. An expansion of a GAA trinucleotide repeat in intron 1 of the gene is present in more than 95% of mutant alleles. Of the 83 people we studied who have mutations in FRDA, 78 are homozygous for an expanded GAA repeat; the other five patients have an expansion in one allele and a point mutation in the other. Here we present a detailed clinical and genetic study of a subset of 51 patients homozygous for an expansion of the GAA repeat. We found a correlation between the size of the smaller of the two expanded alleles and age at onset, age into wheelchair, scoliosis, impaired vibration sense, and the presence of foot deformity. There was no significant correlation between the size of the smaller allele and cardiomyopathy, diabetes mellitus, loss of proprioception, or bladder symptoms. The larger allele size correlated with bladder symptoms and the presence of foot deformity. The duration of disease is correlated with wheelchair use and the presence of diabetes, scoliosis, bladder symptoms and impaired proprioception, and vibration sense but no other complications studied.

Adolescent↗
PubMed1999

Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy.

To investigate mechanisms in the pathogenesis of cardiomyopathy associated with mutations of the dystrophin-glycoprotein complex, we analyzed genetically engineered mice deficient for either alpha-sarcoglycan (Sgca) or delta-sarcoglycan (Sgcd). We found that only Sgcd null mice developed cardiomyopathy with focal areas of necrosis as the histological hallmark in cardiac and skeletal muscle. Absence of the sarcoglycan-sarcospan (SG-SSPN) complex in skeletal and cardiac membranes was observed in both animal models. Loss of vascular smooth muscle SG-SSPN complex was only detected in Sgcd null mice and associated with irregularities of the coronary vasculature. Administration of a vascular smooth muscle relaxant prevented onset of myocardial necrosis. Our data indicate that disruption of the SG-SSPN complex in vascular smooth muscle perturbs vascular function, which initiates cardiomyopathy and exacerbates muscular dystrophy.

Animals↗
PubMed1999

Kallmann syndrome gene (KAL-X) is not mutated in schizophrenia.

Kallmann syndrome and schizophrenia share several clinical features, including dysfunctional olfactory ability, hypogonadotrophic hypogonadism, an excess of affected males, and psychiatric presentation. Because of this congruence, it has been proposed that up to 70% of male schizophrenics might have mutations affecting the function or expression of the gene mutated in Kallmann syndrome, KAL-X. We identified and studied 9 unrelated males with schizophrenia (as defined by DSM-IIIR criteria) who also have severe anosmia (first percentile of normal range) and low sex drive (seventh percentile of the normal range), and we sequenced the exons and the intron-exon junctions of the KAL-X gene for each. We found no mutations, and conclude that schizophrenia is rarely, if ever, due to a mutation in the coding sequence or splice junctions of KAL-X.

Extracellular Matrix Proteins↗
PubMed1999

Phenotypic variability of Filipino beta(o)-thalassemia/HbE patients in Indonesia.

Three Indonesian patients with identical genotypes, each compound heterozygotes for Filipino beta(o)-thalassemia/HbE, expressed different clinical severities. One patient has mild disease and is transfusion independent, while the other two are severely affected and transfusion dependent. The size of the Filipino beta(o)-globin gene deletion was confirmed to be 45 kb, resolving conflicting values given in the literature. Neither ameliorating genetic factors such as alpha-globin gene deletions or the XmnI restriction site polymorphism at position -158 upstream of the (G)gamma-globin gene, nor differences in beta-globin gene haplotype, explain the phenotypic variation. These observations have implications for the development of antenatal diagnosis in Indonesia, as at present it is not possible to give an accurate prediction of severity of phenotype for this common genotype.

Child↗