In order to evaluate the incidence and prognostic significance of gene amplification in primary brain neoplasms we measured the number of gene copies per cell of three oncogenes (epidermal growth factor receptor [EGFR] gene, N-myc, C-myc) and syntenic control genes in 40 specimens using quantitative DNA dot blots. We observed EGFR gene amplification in astrocytomas and anaplastic astrocytomas with approximately the same incidence as in glioblastoma multiforme (33%), although large amplifications were only seen in glioblastoma multiforme. Fourteen patients had a supratentorial glioblastoma multiforme; six had EGFR gene amplification and eight had either normal EGFR gene copy number or elevated EGFR copy number attributable to extra copies of chromosome 7. Patients with gene amplification had shorter survival than patients without gene amplification (p = 0.01). The observed difference in survival was not likely to be due to group differences in age, sex, treatment, or histopathology.

No abstract

Crouzon craniofacial dysostosis (CFD) is an autosomal dominant craniofacial disorder characterized by premature craniosynostosis, shallow orbits and hypoplastic maxilla. To map the gene responsible, we have used a mapping strategy of testing for linkage to known developmental genes. Analysis of a large kindred established linkage between CFD and three loci (D10S190, D10S209 and D10S216) that span a 13 cM region on chromosome 10q. A maximum pairwise lod score of 4.42 (theta = 0) at D10S190 was obtained and the addition of a second kindred produced a combined pairwise lod score of 5.32 (theta = 0) at the same locus. The developmental gene, PAX2, located within this region, is an attractive candidate gene.

As the initial step in a systematic genome survey, 16 simple sequence tandem repeat polymorphisms that span the X chromosome at an average spacing of 10 cM were examined for allelic associations with typical-onset Alzheimer's disease (AD). The efficiency of this survey was substantially enhanced by genotyping pools of genomic DNA from 50 autopsy-confirmed AD cases and 50 autopsied controls who were similar in sex ratio, race, and age at death. The frequency of the DXS1047 202-bp allele was twice as common among AD cases (0.45+/-S.E. 0.06) than controls (0.22+/-S.E. 0.05), a finding that was reproduced in an independent and geographically disparate sample. Consistent with Hardy-Weinberg equilibrium, the proportion of women with AD who carried the 202-bp allele, 73% was nearly double that observed for men with AD, 38%. However, the frequency of the 202-bp allele was similar for men and women and the presence of this allele did not affect the age at onset of dementia in either sex. Furthermore, the frequency of the DXS1047 202-bp allele in AD cases and controls was unaffected by the APOE genotype, indicating that these two loci modulate AD risk independently. Finally, the frequency of the 202-bp allele among 50 autopsy-confirmed cases of Parkinson's disease (0.29+/-S.E. 0.06) was indistinguishable from the control value, reflecting relative specificity for this allelic association with AD.

A 66-year-old woman had several episodes of aseptic meningitis associated with exposure to cephalexin, cefazolin, and ceftazidime. The cerebrospinal fluid IgG index was elevated, specific IgG-ceftazidime binding was shown, and skin allergy testing with cefazolin provoked a recurrence of meningitis. We postulate an acute hypersensitivity reaction involving an antigen-specific humoral immune response.