Search PubMed⌕ Search

Biomedical subjects

J Goldblatt

Publications and source records attributed to J Goldblatt.

At least 37 records · Page 2Linked to original sources
PubMed2000

Population screening for cystic fibrosis in Western Australia: community response.

We measured acceptance of carrier testing for cystic fibrosis in the community when offered in a primary care setting, determined variables influencing acceptance, and assessed knowledge of cystic fibrosis 3-6 months later. A total of 5,102 individuals age 18-50 years attending general practices or a family planning clinic in Western Australia completed questionnaires about knowledge of cystic fibrosis and the State Anxiety Inventory. Testing for the delta F508 gene was offered. After 3-6 months, carriers, a sample of consenting participants who were not tested, and a sample of test-negative participants were sent a further questionnaire; 43.5% of participants chose to be tested for cystic fibrosis carrier status. Women, younger people, people with higher education, people without children, and people planning to have children were more likely to be tested. After 3-6 months, carriers gave correct responses to questions about cystic fibrosis more frequently than those who tested negative or were not tested; 82.2% of carriers knew that they were definitely a carrier and 31.1% of test-negative individuals believed they were definitely not carriers. Thus, population carrier screening for cystic fibrosis offered in a community setting in Western Australia was acceptable to almost half of those offered testing, particularly younger people and those planning to have children, for whom knowledge of carrier status could be useful in making reproductive decisions. There was evidence that tested individuals recalled information in a way that minimised their risk of being a carrier.

Adolescent↗
PubMed2000

Evolutionary adaptation of inflammatory immune responses in human beings.

Modern man's ancestors lived in an environment where infectious, tropical diseases would have been endemic. We postulate that this relatively hostile environment would have caused genetic selection for increased proinflammatory immune responses. On migrating to temperate regions, pronounced proinflammatory responses would have been less important and selected against due to increased mortality from overly vigorous responses to harmless environmental agents. This hypothesis is supported by the observation that proinflammatory alleles in several genes involved in inflammation are more prevalent in populations with long-term tropical ancestry than those with long-term residence in temperate regions. In addition, when the former populations relocate from a tropical to a temperate region, they have a higher incidence of allergic inflammatory diseases than the latter populations. These observations suggest that there may be general patterns of recent evolutionary adaptation of the human immune system to particular regions and that these adaptations can produce differences in disease susceptibility.

Adaptation, Physiological↗
PubMed2000

Genetic testing for Alzheimer's disease.

Genetic factors are important in the development of Alzheimer's disease (AD). Familial AD can result from rare mutations in some genes. Other genes, such as the apolipoprotein E gene (APOE), operate as risk factors for late-onset sporadic AD. On a background of advances in the genetics of AD we suggest a way in which genetic information may be used in the diagnosis of AD. If there is a positive family history of early-onset dementia and the clinical features suggest AD, patients may be tested for presenilin and amyloid precursor protein gene mutations with appropriate pretest and post-test counselling. Predictive testing should be performed under guidelines developed by the World Federation of Neurology and the Human Genetics Society of Australasia. The usefulness of APOE genotyping as an adjunct to conventional diagnostic tests is unknown; data suggest it has low sensitivity and specificity and may have little predictive value in an individual patient. APOE genotyping should not be performed in asymptomatic individuals, except as part of an ethically approved research project; this recommendation is supported by a number of international consensus statements. APOE testing should not be used as a diagnostic test without adequate pretest and post-test counselling, education and support. APOE testing should not be used as a sole diagnostic test in the work-up of patients with AD. Genetic risk factors other than APOE require validation and should not be used routinely, except as part of an ethically approved research protocol.

Aged↗
PubMed2000

Identification of a novel deletion of the entire OCRL1 gene detected by FISH analysis in a family with Lowe syndrome.

The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked multisystem disorder affecting the lens, kidney and brain. The gene involved (OCRL1) has been identified and is known to encode a phosphatidylinositol 4,5-bisphosphate 5-phosphatase. Mutations in OCRL1 have been shown to be causative of OCRL. To date, most of the mutations identified have consisted of simple or point mutations and there is one report of a 1.4-kb deletion. We investigated the OCRL1 gene in a male patient with OCRL by the polymerase chain reaction and found that the entire OCRL1 gene was deleted. Fluorescence in situ hybridisation analysis (FISH), with cosmid probes that span the entire OCRL1 gene, was used to confirm this deletion and subsequently identify it in the proband's mother. This is the first report of a whole gene deletion of OCRL1 and thus expands the range of mutations that give rise to OCRL. The use of the FISH technique facilitated carrier and prenatal testing for the deletion in the family.

Child↗
PubMed2000

Tibial aplasia--VACTERL association, a new syndrome?

We report on a male infant, born to nonconsanguineous parents, with a vertebral anomaly, cardiac defect, tracheo-oesophageal fistula and hypospadias (VACTERL association) together with bilateral tibial aplasia. This pattern of abnormalities appears to represent a unique syndrome.

Abnormalities, Multiple↗
PubMed2000

Association between plasma CC16 levels, the A38G polymorphism, and asthma.

The effect of the A38G polymorphism on Clara cell secretory protein (CC16) gene expression and asthma was investigated by measuring plasma CC16 levels in 100 asthmatic and nonasthmatic children. Restriction digestion determined the A38G genotype and plasma CC16 levels were analyzed using a sensitive latex immunoassay. Asthmatics had lower mean plasma CC16 levels adjusted for age and gender (7.96 microg/L; 95% confidence interval [CI] = 6.79 to 9.31) than nonasthmatic subjects (9.98 microg/L; 95% CI = 8.83 to 11.26) (p = 0. 006). Similarly adjusted, mean plasma CC16 levels were also lower in 38A/38A (6.79 microg/L; 95% CI = 4.56 to 9.02) than 38G/38G subjects (10.01 microg/L; 95% CI = 7.90 to 12.12; p = 0.003). The odds ratio for asthma diagnosis of 38A/38A subjects was 4.78 (95% CI = 1.08 to 21.18; p = 0.04) compared with 38G/38G subjects. However, this was reduced when corrected from plasma CC16 level, suggesting that the odds of asthma was largely mediated through altered plasma CC16 levels. The 38A sequence was associated with reduced plasma CC16 levels and individuals with lower plasma CC16 levels were more likely to have asthma. This provides further evidence for a significant role of the CC16 gene, 38A allele in the development of asthma.

Adolescent↗
PubMed2000

Complexed prostate specific antigen provides significant enhancement of specificity compared with total prostate specific antigen for detecting prostate cancer.

PURPOSE: Determining serum total prostate specific antigen (PSA) has proved to be a valuable diagnostic aid for detecting prostatic carcinoma, although the lack of specificity has limited its usefulness. Studies indicate that the use of percent free PSA would improve specificity while maintaining sensitivity. Since complexed PSA represents the major proportion of measurable PSA in serum, we determined whether it represents a single test alternative to the use of percent free PSA for the early detection of prostate cancer. MATERIALS AND METHODS: Archival serum was obtained from 385 men with no evidence of malignancy on biopsy and 272 with biopsy confirmed prostate cancer. We determined the concentration and proportion of total, complexed and free PSA. RESULTS: Receiver operating characteristics analysis using total PSA results from all samples (range 0.32 to 117 ng./ml.) indicated that the areas under the curve for complexed PSA alone as well as the free-to-total and complexed-to-total PSA ratios were similar and significantly greater than those for total PSA alone. Within the range of 85% to 95% sensitivity receiver operating characteristics analysis revealed that the specificity of complexed PSA was higher than that of total PSA and equivalent to that of the free-to-total PSA ratio. We noted a similar improvement in specificity in the 4 to 10 ng./ml. total PSA range. Using published cutoff values for complexed, total and percent free PSA when total PSA was in the 4 to 10 ng./ml. range the sensitivity and specificity of complexed and percent free PSA were similar. Within the 4 to 10 ng./ml. total PSA range the population of patients with no evidence of malignancy and complexed PSA below the upper limit was different with respect to total PSA from that with no evidence of malignancy and free PSA greater than 25%. CONCLUSIONS: The measurement of complexed PSA represents an alternative to the use of percent free PSA, although the patient populations identified by the 2 tests are different.

Humans↗
PubMed1999

Craniosynostosis in Western Australia, 1980-1994: a population-based study.

A craniomaxillofacial unit was established recently in Western Australia, and a study was carried out to provide some baseline characteristics of primary craniosynostosis in Western Australia and to investigate whether there has been any significant temporal change in birth prevalence. A case control study was conducted, using cases identified from a population-based register of birth defects, and a random sample of all births without a birth defect formed the control group. All subjects were born in Western Australia over the period 1980-1994 inclusive. The prevalence of craniosynostosis over the period 1980-1994 in Western Australia was 5.06 per 10,000 births. There was a significant linear increase in lambdoid synostosis over this period of 15.7% per year. Craniosynostosis was significantly more common among male infants, infants born preterm (<37 weeks gestation), breech presentation or presentations other than vertex, and infants born to fathers 40 years of age or older, even after accounting for known autosomal dominant syndromes. Other major birth defects were found in 11.2% of children with nonsyndromic craniosynostosis. Only 43 children (25.3%) with craniosynostosis were reported to have been seen by a geneticist. Thus, the prevalence of craniosynostosis in Western Australia is among the lowest reported. There is no current explanation for the increase in lambdoid synostosis. The increased risk of so-called nonsyndromic craniosynostosis with paternal age raises the possibility of undiagnosed new dominant mutations. This, along with the excess of other birth defects in children with craniosynostosis emphasises the need to ensure that these families are offered genetic counseling.

Adult↗
PubMed1999

Association of polymorphisms in the beta2-adrenoreceptor gene with higher levels of parasitic infection.

The diminishing incidence of parasitic infection in westernised societies has been suggested to result in an increased prevalance of asthma. Asthma is a polygenic disease and genome screens have shown that genes on chromosome 5q31-33 are strongly linked to the disease. The gene for the beta2-adrenoreceptor is located in this region and two polymorphisms have been identified that result in amino acid changes at positions 16 (ArgGly) and 27 (GlnGlu). To determine whether these polymorphisms influence asthma and parasitic infection, a genotype/phenotype study has been performed on a cohort of 126 children from Coche Island in Venezuela. There is a high incidence of asthma on the island and intestinal helminthiasis is endemic. Genotyping for both polymorphisms was carried out by using the polymerase chain reaction and allele-specific oligonucleotide hybridisation. Genotype frequencies in this cohort were consistent with other studies and both polymorphisms were in significant linkage disequilibrium. Individuals who were homozygous for Arg16 had significantly higher levels of specific IgE to Ascaris lumbricoides (P=0.002), significantly higher A. lumbricoides egg counts (P<0.001) and significantly larger wheal sizes following skin-prick testing with A. lumbricoides allergen (P=0.008). There was no association between either polymorphism and total serum IgE or asthma in this population. A combination of mast cell degranulation and the lung migratory phase of A. lumbricoides larvae may result in bronchoconstriction in infected individuals. These results suggest that the Gly 16 allele confers resistance to high levels of parasitic infection in this population. An alternative explanation for the association is that it may be the result of linkage disequilibrium with other genes in the chromosome 5q31-33 region.

Adolescent↗
PubMed1999

Polymorphisms in the beta2-adrenoreceptor gene are associated with decreased airway responsiveness.

BACKGROUND: There are a number of candidate genes thought to play a role in the development of asthma. Polymorphisms at amino acid positions 16 (arginine to glycine) and 27 (glutamine to glutamic acid) of the beta2-adrenoreceptor (B2AR) gene are known to be functionally relevant and have been associated with more severe forms of asthma, nocturnal asthma and decreased airway responsiveness in asthmatic subjects. OBJECTIVE: To determine if these polymorphisms contribute to the development of asthma by investigating the associations between the polymorphisms at amino acid positions 16 and 27 of the B2AR gene and asthma-related parameters in a large, phenotypically well-characterized population which was unselected for asthma. METHODS: Subjects (n = 332) were characterized using physiological assessments, immuno-logical data and information obtained from questionnaire. PCR was used to generate a 229 base pair fragment spanning the mutations of interest. Genotype was determined using allele-specific oligonucleotide hybridization and confirmed in 10% of the samples by direct sequencing. Multivariate analysis of the association between genotype and phenotype was then undertaken. RESULTS: Homozygotes for Glu27 were significantly less responsive to histamine than Gln27 homozygotes. In addition, Arg16 homozygotes were more likely to 'wheeze during a cold', in comparison with Gly16 homozygotes. However, there was no association between either polymorphism and physician-diagnosed asthma, eczema, skin reactivity to common allergens or total and specific serum IgE levels. The two polymorphisms were found to be in significant linkage disequilibrium. CONCLUSION: The polymorphism at position 27 was associated with decreased airway responsiveness in the study population and the polymorphism at position 16 was associated with increased wheeze during respiratory infection, but neither was associated with physician-diagnosed asthma or any of the other variables considered.

Adolescent↗
PubMed1999

Association of FcepsilonR1-beta polymorphisms with asthma and associated traits in Australian asthmatic families.

BACKGROUND: Asthma is a genetically complex disease, and is characterized by elevated serum immunoglobulin E (IgE) levels, elevated blood eosinophil counts and increased airway responsiveness. Polymorphisms in the beta subunit of the high affinity receptor for IgE (FcepsilonR1-beta) have been previously associated with these phenotypes and with an increased risk of asthma. OBJECTIVE: To investigate the association of all known bi-allelic polymorphisms in FcepsilonR1-beta to asthma and quantitative traits associated with asthma in a selected sample of Australian asthmatic children and their nuclear families. METHODS: Australian Caucasian nuclear families (n = 134 subjects) were recruited on the basis of a child proband with current, severe, symptomatic asthma. The quantitative traits assessed included serum levels of total IgE and specific IgE to house dust mite and mixed grass, blood eosinophil counts and the dose-response slope of the forced expiratory volume in 1 s to histamine provocation. RESULTS: Neither the Leu181 nor the E237G mutations were detected in this population. Allele B of RsaI intron 2 (RsaI_in2*B) was significantly associated with physician-diagnosed asthma (ever) (P = 0.002). Alleles of both the RsaI_in2 and RsaI exon 7 (RsaI_ex7) polymorphisms were significantly associated with loge total serum IgE levels and the combined RAST index. RsaI_ex7 was also associated with loge blood eosinophil counts. These associations were independent of age, sex and familial correlations. CONCLUSION: This study supports a role for the FcepsilonR1-beta gene or a nearby gene in the pathogenesis of asthma.

Adolescent↗
PubMed1999

Expanding the phenotype of Filippi syndrome: a report of three cases.

This report is of two brothers and a male singleton with clinical characteristics of Filippi syndrome, born to young, healthy, non-consanguineous parents. Their features, which include borderline to milder developmental delay, particularly of speech and language, primary microdontia and previously unreported radiological findings are described to further delineate and expand the clinical spectrum of the condition.

Abnormalities, Multiple↗
PubMed1999

Genome screen and candidate gene studies in parasitized populations.

The immunoglobulin E (IgE) antibody system is important in the genesis of asthma, but it appears to have originally evolved for defence against parasite infection. In order to study how IgE contributes to asthma, there are advantages in studying parasitized populations. Firstly, the IgE system can be studied when it is operating in a more natural state, and this could allow new insight into basic immune function. Secondly, the genetic susceptibility to produce high levels of IgE is more likely to be expressed, as the most intense IgE responses in nature are those found in the presence of parasitic infection. These more intense IgE responses should facilitate finding new 'asthma genes', assist in investigating how the DNA variations in candidate genes affect gene function and provide the possibility of developing new approaches to the treatment of asthma.

Asthma↗
PubMed1998

Efficacy of gene testing for von Hippel-Lindau disease.

OBJECTIVE: To determine the efficacy of genetic testing of individuals presenting with features possibly indicative of von Hippel-Lindau (VHL) disease, regardless of other relevant family and clinical details. SETTING AND PARTICIPANTS: Between September 1994 and December 1997, 16 unrelated individuals were referred to Genetic Services of Western Australia by local clinicians and by similar genetic services in other States, for VHL gene mutation analysis because of clinical manifestations suggestive of the diagnosis. METHODS: The subjects were investigated by screening for mutations in the polymerase chain reaction products of the three VHL gene exons using single-stranded conformational polymorphism analysis (SSCP). If no mutations were detected the exons were sequenced, and if no variations were found DNA was examined by Southern analysis for germinal rearrangements. RESULTS: Mutations in the VHL gene were detected in eight of 16 individuals (50%), including 3 individuals with no family history suggestive of VHL disease. Five mutations were detected by SSCP, two by gene sequencing and one by Southern analysis. Each mutation occurred only in a single family and three had not been previously reported. CONCLUSION: Genetic screening of individuals presenting with clinical features suggestive of VHL facilitates confirmation of the diagnosis, accurate genetic counselling and surveillance of at-risk family members. The necessity for costly and time-consuming screening programs can be reduced and screening directed at those carrying the mutation. Our low stringency criteria are justified for screening for VHL mutations.

Genetic Testing↗
PubMed1998

Mutation analysis of interleukin-5 in an asthmatic cohort.

Interleukin-5 (IL-5) is a potential candidate gene in the pathogenesis of asthma, as it is the main cytokine controlling eosinophil activity and eosinophils are pivotal in the development of airway inflammation. Mutation detection studies were performed on the IL-5 gene and the alpha-chain of its receptor in 30 asthmatic and 30 nonasthmatic subjects. Single-strand conformational polymorphism (SSCP) and heteroduplex analysis (HA) did not reveal any change from the reported normal sequence in all 4 exons of IL-5 as well as the promoter and 3'-untranslated regions of the gene. No SSCP variations were seen within the complete coding sequence of the IL-5 receptor alpha-chain. Mutations of the IL-5 gene coding region, its promoter and receptor are unlikely to be common causes of an inherited predisposition to asthma.

Asthma↗