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Biomedical subjects

A Sand

Publications and source records attributed to A Sand.

At least 19 recordsLinked to original sources
PubMed2001

Population-based risk estimates of Wilms tumor in sporadic aniridia. A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia.

Aniridia is a severe eye disease characterized by iris hypoplasia; both sporadic cases and familial cases with an autosomal dominant inheritance exist. Mutations in the PAX6 gene have been shown to be the genetic cause of the disease. Some of the sporadic cases are caused by large chromosomal deletions, some of which also include the Wilms tumor gene (WAGR syndrome), resulting in an increased risk of developing Wilms tumor. Based on the unique registration of both cancer and aniridia cases in Denmark, we have made the most accurate risk estimate to date for Wilms tumor in sporadic aniridia. We have found that patients with sporadic aniridia have a relative risk of 67 (confidence interval: 8.1-241) of developing Wilms tumor. Among patients investigated for mutations, Wilms tumor developed in only two patients out of 5 with the Wilms tumor gene (WT1) deleted. None of the patients with smaller chromosomal deletions or intragenic mutations were found to develop Wilms tumor. Our observations suggest a smaller risk for Wilms tumor than previous estimates, and that tumor development requires deletion of WT1. We report a strategy for the mutational analysis of aniridia cases resulting in the detection of mutations in 68% of sporadic cases and 89% of familial cases. We also report four novel mutations in PAX6, and furthermore, we have discovered a new alternatively spliced form of PAX6.

Alternative Splicing↗
PubMed2000

Mutation analysis of the GJB2 (connexin 26) gene by DGGE in Greek patients with sensorineural deafness.

The GJB2 (connexin 26) gene, one of the major genes responsible for autosomal recessive deafness, has been investigated previously by a variety of techniques, including PCR-SSCP and sequencing of the entire gene for screening of unknown mutations, and allele-specific PCR, ASO, and PCR-mediated site-directed mutagenesis for the detection of the common mutation 35delG. Here, we present the development of a DGGE method for the characterization of the full spectrum of mutations in the GJB2 gene. The GJB2 cDNA and flanking sequences were amplified in three overlapping segments. We screened 26 Greek patients with prelingual, sensorineural deafness, where syndromic forms and environmental causes of deafness had been excluded. The 35delG mutation was detected in 28 chromosomes (53.8%), while another three sequence variations accounted for 7.6% of the alleles. The sequence variation R127H, previously described in a few Spanish and Balkan patients, was detected in two patients as the sole mutation. A novel sequence variation, K224Q, was identified as the sole mutation in one patient. Use of this approach may contribute to the full description of mutations in this important deafness gene.

Alleles↗
PubMed1999

Mutational analysis of PAX6: 16 novel mutations including 5 missense mutations with a mild aniridia phenotype.

Mutations in the developmental control gene PAX6 have been shown to be the genetic cause of aniridia, which is a severe panocular eye disease characterised by iris hypoplasia. The inheritance is autosomal dominant with high penetrance but variable expressivity. Here we describe a mutational analysis of 27 Danish patients using a dideoxy fingerprinting method, which identified PAX6 mutations in 18 individuals with aniridia. A thorough phenotype description was made for the 18 patients. A total of 19 mutations, of which 16 were novel, are described. Among these were five missense mutations which tended to be associated with a milder aniridia phenotype, and in fact one of them seemed to be non-penetrant. Four of the five missense mutations were located in the paired domain. We also describe a third alternative spliced PAX6 isoform in which two of the four missense mutations would be spliced out. Our observations support the concept of dosage effects of PAX6 mutations as well as presenting evidence for variable expressivity and gonadal mosaicism.

Alternative Splicing↗
PubMed1997

Investigation of deletions at 7q11.23 in 44 patients referred for Williams-Beuren syndrome, using FISH and four DNA polymorphisms.

Williams syndrome (WS) is associated with a submicroscopic deletion of the elastin gene (ELN) at 7q11.23. The deletion encompasses closely linked DNA markers. We have investigated 44 patients referred for possible WS using fluorescence in situ hybridization (FISH) analysis with a P1 clone containing an insert from the ELN, as well as performing genotype analysis of patients and parents with four DNA polymorphisms. Twenty-four patients were found to have deletions, 19 of whom were found clinically to have typical WS. The facial features were especially characteristic. None of the patients without detectable deletions was reported to have typical WS features, although one had supravalvular aortic stenosis, hypercalcemia, and mental retardation. No evidence was found in this material for variability of the size of the deletion. Our study supports the usefulness of analysis of ELN deletion in WS patients, both for confirmation of diagnosis and for genetic counselling.

Adolescent↗
PubMed1996

Physical and clinical evaluation of high-resolution thyroid pinhole tomography.

UNLABELLED: High-resolution pinhole-SPECT (PSPECT) is a new method for examining the thyroid gland. METHODS: The camera is tilted slightly so that it is as close to the thyroid as possible. Patients are injected with 185-260 MBq (5-7 mCi) of [99mTc]pertechnetate and examined for 20 min. The reconstruction algorithm is based on filtered back-projection. RESULTS: We performed static scintigraphy on the thyroids of 114 patients, followed by PSPECT. The major advantage of P SPECT is high resolution. Three- and 4-mm-pinholes produce resolutions of 6 mm and 7 mm, respectively, while resolutions obtained with a parallel collimator are always above 15 mm. The second advantage associated with this method is the good visualization of the cold nodules surrounded by higher activity. Finally, the reconstruction program provides exact sizes of thyroids. CONCLUSION: SPECT is a powerful tool for examining the thyroid.

Adolescent↗
PubMed1992

Involvement of the renal parenchyma in acute urinary tract infection: the contribution of 99mTc dimercaptosuccinic acid scan.

We performed 99mTc dimercaptosuccinic acid (DMSA) scan and ultrasonography in 146 children during the acute phase of a proven urinary tract infection (UTI). In 99 a micturating cysto-urethrography and in 83 an intravenous urography was also done. The occurrence of fever and increased WBC count, CRP and ESR were also studied. It appeared from this retrospective study that 47% of the kidneys had a cortical or patchy pattern of decreased uptake of 99mTc DMSA, as compared to 23% with abnormal findings on US. Vesico-ureteral reflux was present in 38% of the kidneys with parenchymal involvement on 99mTc DMSA scan. Although fever, leucocytosis and elevated CRP and ESR were significantly correlated with abnormal 99mTc DMSA scan, they were also observed in children without renal parenchymal involvement. Our results suggest that 99mTc DMSA scan is a sensitive method for the detection of parenchymal involvement during acute UTI. The exact nature of these lesions and their relation with scars need, however, to be defined.

Acute Disease↗
PubMed1991

Hypofixation on bone scintigraphy in reflex sympathetic dystrophy syndrome.

We report an adult case of reflex sympathetic dystrophy. In contrast to the usual findings in adults, three phase bone scintigraphy showed decreased bloodflow and bloodpool with hypofixation on delayed steady state bone scan of the affected lower limb. In spite of various therapeutic attempts severe dystrophy developed.

Adult↗
PubMed1986

Production and characterization of monoclonal antibodies against recombinant human tumor necrosis factor/cachectin.

Tumor necrosis factor is a monokine, which causes cytolysis of many transformed cells. In this study we have found that in addition to cytotoxicity recombinant Escherichia coli-derived human tumor necrosis factor, like cachectin, inhibited the lipoprotein lipase of 3T3-L1 preadipocytes. Both effects were inhibited by monoclonal anti-tumor necrosis factor antibodies. Monoclonal antibodies against recombinant human tumor necrosis factor were produced by fusing splenocytes of immune mice with P3X63Ag8 653 myeloma cells. The monoclonal antibodies, namely BG 2-4, were of IgG2a, IgG, and IgG2a subclasses. These monoclonal antibodies neutralized the cytotoxicity of natural and recombinant human tumor necrosis factor but not that of rabbit or mouse tumor necrosis factor. They also neutralized the cachectin activity of human tumor necrosis factor in the 3T3-L1 embryonic cell assay. These results indicate that the functional structure(s) of human tumor necrosis factor responsible for the cytotoxicity and cachectin activities are likely to be closely related.

Adipose Tissue↗
PubMed1986

Oesophageal transit patterns in healthy subjects.

Oesophageal transit was studied in 49 healthy volunteers. When a good quality bolus was reached, the tracer passed through the oesophagus leaving no residual activity. The mean time of transit of the total oesophagus was 4.5 +/- 1.3 s. In cases of fragmented bolus, residual activity was found in about 80% of the cases giving rise to a prolonged transit time. When using 81Krm, artefacts due to fragmented bolus can easily be overcome by repeating the test as often as necessary.

Adult↗
PubMed1986

[Risk-taking behavior and accidents in adolescence in developed countries].

Injuries due to accidents are the primary cause of fatalities among adolescents. Between the ages of 10 and 19, mortality caused by accidents augments significantly, and there is an excess of male mortality, increasing with age. This mortality has remained virtually unchanged over the past 25 years, except for a small narrowing of rate differences by sex. Traffic accidents, particularly those involving motorcycles, are the leading cause of accident fatalities. Though not easily assessed, morbidity due to accidents is probably very high, especially among males. Sports accidents are the most frequent. Adolescents appear to be particularly exposed to some risks, but also tend to be careless about safety. Risk-taking is a source of rewards: pleasure, self-affirmation, sense of independence; but it is described by some authors as self-destructiveness, death from accidents reflecting suicidal tendencies. Paradoxical results of prevention have been observed in this age group.

Accident Prevention↗
PubMed1985

Study of antigenic epitopes recognized by monoclonal antibodies to recombinant interferon-gamma.

Seven hybridomas (BG 1-7) which secreted monoclonal antibodies against recombinant interferon-gamma were produced. The ascites fluids containing four of the seven monoclonal antibodies (BG 1-4) neutralized the antiviral activity of both natural and recombinant interferon-gamma. Competition between labeled and unlabeled monoclonal antibodies for interferon-gamma in a solid phase immunoassay showed that BG 1 was competed by both BG 3 and BG 4 but not by BG 2; BG 2 was competed by BG 3 but not by BG 1 nor by BG 4. These results suggest that human interferon-gamma has at least two antigenic epitopes; one of the epitopes reacted with BG 1 & BG 4 while the other reacted with BG 2; BG 3 either binds to a region overlapping with the other two epitopes or reacts with both epitopes. The antigenic epitopes recognized by these four neutralizing monoclonal antibodies are likely at or closely related to the active sites of interferon-gamma.

Antibodies, Monoclonal↗