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A Dalton

Publications and source records attributed to A Dalton.

33 records · Page 2Linked to original sources
PubMed1995

Detecting deletions in the critical region for lissencephaly on 17p13.3 using fluorescent in situ hybridisation and a PCR assay identifying a dinucleotide repeat polymorphism.

During a study of lissencephaly in England and Wales, 23 children were identified with this diagnosis. They were classified as follows: three children had Miller-Dieker syndrome (MDS), 13 had isolated lissencephaly sequence (ILS), two had type II lissencephaly, and five children were reclassified as focal or diffuse cortical dysplasia. Microdeletions of chromosome 17p13.3, also known as the Miller-Dieker critical region, have been associated with both MDS and ILS. We used the commercially available Oncor probe for fluorescent in situ hybridisation (FISH) studies on 14 patients and a further four were studied elsewhere. Deletions were identified in all three MDS patients and two of the ILS patients. These results are consistent with previously reported data. No deletions were found in those patients with focal or diffuse cortical dysplasia. In addition, a CA repeat polymorphism which maps to the Miller-Dieker critical region was studied in 12 families and was informative in nine; the results were consistent with the FISH data. We conclude that FISH is a reliable method to detect deletions in patients with MDS and ILS and also useful to identify chromosome rearrangements in their parents which are not detected by conventional cytogenetic analysis. The PCR assay, if informative, is also reliable and a useful alternative if only DNA is available. None of the five children with atypical radiological features had a deletion. We therefore suggest that as well as looking for other aetiologies a careful review of the diagnosis should be made of the MDS or ILS cases in whom a deletion is not found.

Brain↗
PubMed1992

Characterization and purification of a novel dATP-binding protein in eukaryotes.

We characterized and purified an acidic dATP-binding protein, which, in its active form, resides in the nuclear fraction of a range of cells from mammals (including pig liver) and baker's yeast (Saccharomyces cerevisiae). This protein exhibits a high degree of specificity for the deoxy form of the naturally occurring nucleoside triphosphates and shows a marked preference for the purine deoxynucleoside triphosphates dATP and dGTP. The protein cleaves the terminal phosphate of dATP and appears to retain the dADP moiety of the nucleotide in a reaction that is resistant to both SDS and 8 M-urea. Fractionation of the nuclear preparation followed by non-denaturing PAGE and SDS/PAGE electrophoresis was sufficient to produce pure protein. The occurrence of this activity in all nuclei tested suggests that it plays an important role in nuclear metabolism. The specificity of the enzyme for deoxynucleoside triphosphates further suggests a role for this enzyme in DNA replication or repair, but the acidity of the protein argues against a direct interaction with DNA, and, indeed, the catalytic activity is not modulated by the inclusion of DNA in a variety of physical forms.

Adenosine Triphosphatases↗
PubMed1990

Synergistic effects of azathioprine and ultraviolet light detected by sister chromatid exchange analysis.

The immunosuppressant azathioprine and longwave ultraviolet (UV) light have been postulated to have a synergistic effect on DNA resulting in carcinogenic change. This study investigated the in vitro effect of UV light on renal transplant recipients (RTRs) immunosuppressed with azathioprine and prednisolone to prevent rejection and patients on azathioprine for skin conditions and normal controls on no drug therapy. The results show clearly that there is an increase in sister chromatid exchanges (SCEs) in both patient groups in response to UV light with the greatest increase shown by the RTRs. Both patient groups without exposure to UV also showed a significant increase, as compared with normal controls, with the RTRs again showing the highest level. Both patient groups also showed disruption of the cell cycle in response to UV light as measured by the proliferative rate index (PRI) but the controls did not. These findings support the hypothesis of a synergistic effect between azathioprine and UV light and correlate well with the clinical pattern of carcinogenesis observed in these patients, with RTRs having a well-documented increased risk of neoplasia, particularly skin carcinomas in light-exposed areas.

Adult↗
PubMed1990

A comparison of four staging systems for localized and regional neuroblastoma: a report from the Childrens Cancer Study Group.

Four major staging systems have been used to estimate the prognosis for children with local and regional neuroblastoma (NBL). Data obtained at diagnosis for 251 neuroblastoma patients from two Childrens Cancer Study Group (CCSG) studies were analyzed according to staging systems of the CCSG, St Jude Children's Research Hospital, the Pediatric Oncology Group (POG), and the Union Internationale Contre le Cancer (UICC) tumor-nodes-metastasis (TNM) system. The most significant variables were found to be age, tumor stage, extent of tumor removal, transgression of the midline by tumor infiltration, and site of primary tumor. Involvement of lymph nodes per se was not a bad prognostic sign unless associated with extension beyond the midline, the latter being the single most important prognostic variable. All four staging systems had value for prognostication and all identified with accuracy the low stage patient (stage I, stage A) who fares well (greater than or equal to 87% survival). The CCSG definition of stages II and III disease discriminated prognostic groups best among the remaining patients, and was able to identify the child with local-regional NBL with poor survival. The estimated 5-year survival rates for children with regional tumor (stage III, IIIA[N]), according to the four systems were 44%, 74%, 74%, and 74% for the CCSG, St Jude, POG, and UICC methods, respectively. We conclude that all four staging systems effectively define good-prognosis patients with localized disease but that the CCSG staging system most accurately identifies patients with regional tumor who have a poor outcome.

Child↗
PubMed1988

Epidural granulocytic sarcoma in acute myeloid leukemia with 8;21 translocation.

Three patients with M2 acute myeloid leukemia (AML) in whom cord compression developed due to epidural granulocytic sarcoma are reported and compared with six similar patients described previously. These three cases had 8;21 translocation, t (8;21), in the marrow karyotype and also in the karyotype of granulocytic sarcoma tissue obtained from two of the cases. Treatment with chemotherapy and radiotherapy can be effective, but an emergency laminectomy should be performed if there is rapid neurologic progression.

Adolescent↗
PubMed1986

Clinical implications of oncogene activation in human neuroblastomas.

Amplification of the oncogene N-myc has been identified in almost all human neuroblastoma cell lines tested. Eighty-nine primary neuroblastomas from untreated patients were studied to determine the frequency and clinical significance of N-myc amplification. Tumor DNA was analyzed by hybridization with the radiolabeled probe pNB-1 for N-myc. Amplification (3-300 copies) of the N-myc gene was found in 34 of the 89 tumors (38%). Amplification was not found in 8 Stage I or 5 Stage IV-S tumors, but it was found in 2 of 16 with Stage II, 13 of 20 with Stage III, and 19 of 40 with Stage IV tumors (P less than 0.01). Correlation of N-myc amplification with progression-free survival (PFS) indicated that N-myc amplification was associated with a worse prognosis (P less than 0.0001). The PFS at 18 months was 70%, 30%, and 5% for patients whose tumors had 1, 3-10, and more than 10 copies, respectively. Even within individual stages, the presence of N-myc amplification correlated with rapid progression. For instance, of 16 patients with Stage II disease, the 2 with N-myc amplification developed progressive disease rapidly, whereas only 1 of 14 without amplification progressed (P = 0.03). Similarly, those with Stage III and IV disease whose tumors have multiple copies of N-myc had a substantially worse prognosis. The correlation between N-myc amplification and age at diagnosis was also analyzed. Although N-myc amplification was detected in only 4 of 28 infants less than 1 year of age, compared to 30 of 61 older patients (P less than 0.005), this difference disappeared when corrected for disease stage. The results suggest that N-myc amplification is a powerful prognostic indicator, and that this gene may play an important role in the progression of certain neuroblastomas.

Age Factors↗
PubMed1985

Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas.

Eighty-nine patients with untreated primary neuroblastomas were studied to determine the relation between the number of copies of the N-myc oncogene and survival without disease progression. Genomic amplification (3 to 300 copies) of N-myc was detected in 2 of 16 tumors in Stage II, 13 of 20 in Stage III, and 19 of 40 in Stage IV; in contrast, 8 Stage I and 5 Stage IV-S tumors all had 1 copy of the gene (P less than 0.01). Analysis of progression-free survival in all patients revealed that amplification of N-myc was associated with the worst prognosis (P less than 0.0001); the estimated progression-free survival at 18 months was 70 per cent, 30 per cent, and 5 per cent for patients whose tumors had 1, 3 to 10, or more than 10 N-myc copies, respectively. Of 16 Stage II tumors, 2 with amplification metastasized, whereas only 1 of 14 without amplification did so (P = 0.03). Stage IV tumors with amplification progressed most rapidly: nine months after diagnosis the estimated progression-free survival was 61 per cent, 47 per cent, and 0 per cent in patients whose tumors had 1, 3 to 10, or more than 10 copies, respectively (P less than 0.0001). These results suggest that genomic amplification of N-myc may have a key role in determining the aggressiveness of neuroblastomas.

Adolescent↗
PubMed1985

Prognostic importance of serum ferritin in patients with Stages III and IV neuroblastoma: the Childrens Cancer Study Group experience.

Ferritin was measured in sera obtained at diagnosis from 241 patients with neuroblastoma to determine (a) the incidence of elevated ferritin and (b) the relationship between ferritin level and outcome. Ferritin was infrequently elevated in sera from patients with Stages I and II disease but was abnormally elevated in 37 and 54% of those with Stages III and IV neuroblastoma, respectively. The mean and median levels for each stage were compared and were highest for Stages III and IV disease. Analysis of progression-free survival for children with Stages III and IV disease indicated that elevated ferritin was associated with a significantly poorer prognosis than was normal ferritin and that this correlation was independent of stage and age at diagnosis. Progression-free survival at 24 months of follow-up for patients with Stage III disease with normal ferritin was 76% and with elevated ferritin was 23%. For those with Stage IV disease, progression-free survival was 27 and 3% with normal and elevated ferritin, respectively. We conclude that determination of the level of ferritin in serum at diagnosis is useful for selecting appropriate therapy for patients with Stage III neuroblastoma. Those with normal ferritin (63% of patients) have a good outcome with current therapy, but those with elevated ferritin (37%) do poorly and require more effective therapy. Although ferritin defines subgroups with Stage IV disease, the outcome of all groups must be improved.

Adolescent↗
PubMed1983

Raised neuron-specific enolase in serum of children with metastatic neuroblastoma. A report from the Children's Cancer Study Group.

Serum levels of neuron-specific enolase (NSE) were measured by radioimmunoassay at diagnosis in 122 children with widespread metastatic neuroblastoma (clinical stage IV). 96% of these patients had NSE levels more than three standard deviations above the mean for age-matched normal children. Mean serum NSE was 207 +/- SD257 ng/ml (range 10-1240 ng/ml), whereas that in normal age-matched children was 7.5 +/- 2.1 ng/ml (range 5.4-12.9 ng/ml). Analysis of survival in relation to the level of NSE at diagnosis suggested that serum levels greater than 100 ng/ml were associated with a poor outcome. This relation was highly significant in the subgroup of infants less than 1 year old at diagnosis; all 7 with serum NSE below 100 ng/ml were alive up to 36 months after diagnosis, whereas 7 of 8 with serum NSE above 100 ng/ml died within 12 months of diagnosis. Serum NSE may be a useful disease marker and a prognostic indicator in children with metastatic neuroblastoma.

Child↗
PubMed1981

Scoliosis screening: results of a community project.

From 1973 to 1977, 7,642 girls and 751 boys were screened for spinal deformity in a Wisconsin County with a population of approximately 100,000. Of 243 girls and 30 boys found to have scoliosis, 155 girls and 13 boys had curves 10 degrees or greater. The most common location and curve direction was right thoracic; 98% of those with scoliosis were classified as idiopathic. Eighteen girls required treatment when initially seen: ten with a Milwaukee brace and eight with spine fusion. Of those not treated and followed for six months or longer, 24 girls and one boy had a decrease in their curve of at least 5 degrees, and 21 girls and one boy had an increase in their curve of at least 5 degrees. Determination of which curves would progress was unpredictable and identification of progression was possible only by repeated examinations.

Adolescent↗
PubMedDate not supplied

Elevated alpha 1-antichymotrypsin serum levels in a subset of nondemented first-degree relatives of Alzheimer's disease patients.

A portion of Alzheimer's disease (AD) patients have elevated serum levels of the acute phase reactant alpha 1-antichymotrypsin (A1ACT) compared to age-matched controls. We measured serum levels of A1ACT in AD patients, age-matched controls, Down's syndrome patients, and nondemented first-degree relatives of AD patients. Significantly elevated levels of A1ACT were found in both AD patients and first-degree-relatives. In AD patients, serum A1ACT concentrations decreased with increasing severity of cognitive impairment. These results may suggest that inflammatory phenomena may be an early component of AD pathophysiology.

Age Factors↗