Spectral differences in real-space electronic structure calculations.

Real-space grids for electronic structure calculations are efficient because the potential is diagonal while the second derivative in the kinetic energy may be sparsely evaluated with finite differences or finite elements. In applications to vibrational problems in chemical physics a family of methods known as spectral differences has improved finite differences by several orders of magnitude. In this paper the use of spectral differences for electronic structure is studied. Spectral differences are implemented in two electronic structure programs PARSEC and HARES which currently employ finite differences. Applications to silicon clusters and lattices indicate that spectral differences achieve the same accuracy as finite differences with less computational work.

Variability in expression of common fragile sites: in search of a new criterion.

Fragile sites are nonrandom, heritable sites on chromosomes that can be induced to form gaps, breaks, and rearrangements under specific conditions. There is currently no established criterion to define a common fragile site. We applied seven published criteria to our data from three groups of subjects: (1) three pairs of like-sexed twins, (2) four unaffected von Hippel-Lindau (VHL) family members, and (3) six patients affected with VHL disease. Substantial differences were present in the numbers of sites considered positive by these criteria. While some of this variability can be attributed to technical factors, our data illustrate the problems in comparing results from different studies to assess the significance of fragile sites. A recently published criterion is based upon the Poisson distribution. We found this criterion to be flawed in its presentation, and furthermore, the Poisson distribution did not provide an adequate approximation to our data. We propose here an alternative approach based upon the negative binomial distribution.

Cytogenetic abnormalities in tumors of patients with von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that causes the development of benign and malignant tumors in several organ systems. Tumors causing significant morbidity include retinal angioma, cerebellar hemangioblastoma (CH), renal cell carcinoma (RCC), and pheochromocytoma (Pheo). Cytogenetic studies of tumors in VHL patients are rare. Cytogenetic findings in tumors from 12 patients with VHL disease, including four RCCs, three CHs, and five Pheos are presented. Three of the four RCC cases were abnormal. Monosomy 3 or a deletion of 3p was present in all three abnormal cases. Complete or partial trisomy of chromosome 5 was present in two cases. A deletion of 14q, trisomy 7, and a missing Y were each observed in one case. These findings indicate that a deletion of 3p may be a primary cytogenetic change in RCCs associated with VHL disease in addition to playing a role in sporadic RCC. Duplications of 5q and deletions of 14q may be important secondary changes in the progression of the malignant phenotype. No visible cytogenetic abnormalities were observed in the three CHs, or in four of the Pheos. One of the five Pheos was found to exhibit mosaic trisomy 7; its significance is unclear at the present time.

Fragile site expression in families with von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that predisposes to diverse tumors including renal cell carcinoma. Six affected and four unaffected subjects from five families were studied to determine the frequency of fragile site expression. Peripheral lymphocyte cultures from each subject were treated with low folate, 5-fluorodeoxyuridine (FUdR), and FUdR plus caffeine for fragile site induction. A site was considered to be fragile if it was expressed at least two times in half of the affected or unaffected subjects. Of the established sites, four were expressed in the unaffected group (3p14, 6p22, 8q22, and Xp22) and six were expressed in the affected group (3p14, 4q31, 5q31, 7q32, Xp22, and Xq22). Only 3p14 and Xp22 were expressed in both groups. There were four new sites: three (3q26, 6p21, 7p15) in the unaffected group and one (16q24) in the affected group. The 3p14 site was expressed twice as frequently in affected versus unaffected subjects. This finding is of interest because of reports of the involvement of 3p14 in hereditary renal cell carcinoma and in VHL.

Sister chromatid exchange analysis in nurses handling antineoplastic drugs.

Sister chromatid exchange (SCE) analyses were carried out in hospital nurses to determine whether an increased frequency of SCE may be used as an indicator of occupational exposure to potentially harmful antineoplastic drugs. In our study of 18 oncology nurses who handled these agents for an average of three days per week, we found no increase in mean SCE frequency (9.3 +/- 1.7 SCEs/cell) and no difference in the distribution of individual mean SCE frequencies compared to a group of 18 nurses who did not handle these drugs (9.5 +/- 1.5 SCEs/cell). There was a great deal of individual variation in mean SCE frequency as well as in SCE values in individual cells. No relationship with SCE frequency was found in terms of a subject's age, or the number of days of exposure to the drugs. Since conflicting results have been reported in persons handling antineoplastic drugs, SCE analysis alone is probably not a reliable indicator of exposure to possible mutagenic/carcinogenic effects of these drugs. SCE analysis may be helpful in conjunction with other studies, such as an analysis of urinary mutagens, or in studies of occupational exposure to agents other than antineoplastic drugs which may have a more noticeable effect on SCE frequency.

Familial pericentric inversion 19.

Several members in two families were found to have a pericentric inversion of chromosome 19. A review of four previous cases, together with those reported here, suggests that inversion of chromosome 19 is not related to the phenotypic features of the probands. Furthermore, there has been no report of an affected subject resulting from a duplication deficiency product of inverted chromosome 19 among the offspring of inversion heterozygotes. The suggested association of aneuploidy in the inversion carriers is also discussed.

Partial duplication of the long arm of chromosome 5: a case due to balanced paternal translocation and review of the literature.

A partial duplication of the distal segment of the long arm of chromosome 5 (q31 leads to qter) was observed in an infant with congenital malformations and dysmorphic features. The phenotypically normal father had a balanced translocation between the long arm of chromosome 5 and the short arm of chromosome 9: 46,XY,t(5;9)(q31;p24). The clinical and cytogenetic data obtained from six patients with partial duplications of two different long arm segments of chromosome 5 suggest that partial duplication of the distal long arm of chromosome 5 is associated with microcephaly, hypertelorism, epicanthus, strabismus, large upper lip, low-set, dysplastic ears, in addition to growth and psychomotor retardation. Partial duplication of the proximal part of the long arm of chromosome 5, on the other hand, is associated mainly with musculoskeletal abnormalities including muscle hypotrophy and hypotonia, scoliosis, lordosis, pectus carinatum, cubitus valgus, and genu valgum, in addition to psychomotor retardation. The dysmorphic features in this latter group include a bulging forehead, short nose, thick upper lip, low-set protruding ears and tapering, thin fingers.