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Biomedical subjects

B Vogelstein

Publications and source records attributed to B Vogelstein.

298 records · Page 17Linked to original sources
PubMed1977

Continuous sampling as a pharmacokinetic tool.

Continuous sampling (CS) of blood through a nonthrombogenic catheter is presented as a tool for determining various pharmacokinetic parameters after a single injection of a drug. In addition to defining many of the usual parameters used in pharmacokinetic analyses, CS provides an accurate and direct determination of the total area under the plasma concentration curve. The theoretic background underlying the CS method is derived, and a practical formulation for its use in a clinical setting is described. The aminoglycoside antibiotic, amikacin, was chosen to exemplify the use of this technique. The drug was administered to 6 children, and CS was used to define plasma and single organ (kidney) clearance, volume of distribution, half-life during the final elimination phase, the shape of the plasma concentration curve, and the exponential factorization of this curve for multicompartmental analysis. The CS method has several theoretical and practical advantages over the usual technique of intermittent blood sampling; such as accuracy in the determination of the plasma concentration-time curve integral, relative model independence, requirement for few samples, and ease in obtaining samples.

Adolescent↗
PubMed1976

Molecular determinants of immunogenicity: the immunon model of immune response.

The immunological response in vivo to a series of size-fractionated linear polymers of acrylamide substituted with hapten has been measured in mice. A sharp threshold was observed in immunogenic response elicited by various polymer preparations. All polymers with less than 12 to 16 appropriately spaced hapten groups per molecule were nonimmunogenic, while those polymers with greater than this number were fully immunogenic. The results lead to the conclusion that the immunological response at its most elementary level is quantized, i.e., a minimum specific number of antigen receptors (approximately 12 to 16) must be connected together as a spatially continuous cluster, an immunon, before an immunogenic signal is delivered to the responding cell.

Acrylamides↗
PubMedDate not supplied

Somatic deletion and duplication of genes on chromosome 11 in Wilms' tumours.

One of the most provocative findings in tumour biology is the relationship between chromosomal changes and embryonal cancers in children. For example, children with the rare paediatric syndrome AGR triad (aniridia, genito-urinary abnormalities and mental retardation) often develop Wilms' tumours at a very early age and carry a germ-line deletion on the short arm of chromosome 11 (11p13). It has been suggested that the germ-line deletion 11p is the first of two or more steps to cancer in AGR children. If this were true, one might expect a similar deletion to arise somatically in the far more common isolated Wilms' tumours of children without AGR, as suggested by Knudson from epidemiological data. However, a chromosomal deletion on 11p was observed in only two of five such cases, while it was absent or seen inconsistently in others. We have now used a molecular genetic approach to determine whether Wilms' tumour cells possess somatic alterations at 11p loci. We have found somatic deletions of specific genes in four of six Wilms' tumours. Surprisingly, in all four cases, the deletions were associated with duplications leading to homozygosity of the non-deleted alleles in the tumour cells. As analogous observations were recently reported in retinoblastoma, the genetic events reported here may underlie the development of many such embryonal tumours in children.

Alleles↗
PubMedDate not supplied

Loss of genes on the short arm of chromosome 11 in bladder cancer.

Recent studies have shown that normal cellular sequences on chromosome 13 are lost during the development of retinoblastomas and that sequences on chromosome 11 are similarly lost during the development of Wilms' kidney tumours and embryonal tumours. Cells from these tumors have been found to contain either the paternal or maternal copies of loci on the affected chromosome, but not both. Thus, the somatic loss of heterozygosity for sequences on chromosome 13 or 11 is hypothesized to result in homozygosity for a recessive mutant allele on these chromosomes, and in this way the chromosomal loss may contribute to the development of these tumours. We sought to investigate whether similar losses of heterozygosity for chromosome 11 sequences occurred in a common adult tumour. We chose to analyse bladder cancers, since such cancers are common in the adult population and are derived from urogenital tissue, as are Wilms' tumours. We examined constitutional and tumour genotypes at loci on the short arm of chromosome 11 (11p) in 12 patients with transitional cell carcinomas. In five tumours, we observed the somatic loss of genes on 11p resulting in homozygosity or hemizygosity of the non-deleted alleles in the tumour cells. Our results show that the frequency of loss of 11p sequences in bladder cancer approaches that seen in Wilms' tumour (42% compared with 55%), and suggest that recessive genetic changes involving sequences on 11p may contribute to the development of bladder neoplasms.

Aged↗
PubMedDate not supplied

Prevalence of ras gene mutations in human colorectal cancers.

A combination of DNA hybridization analyses and tissue sectioning techniques demonstrate that ras gene mutations occur in over a third of human colorectal cancers, that most of the mutations are at codon 12 of the c-Ki-ras gene and that the mutations usually precede the development of malignancy.

Adenoma↗