Survival of patients with malignancy-associated effusions

For a better understanding of the prognosis after the onset of a malignancy-associated effusion in patients known or subsequently shown to have cancer, survival time was compared with the findings and the date of the first cytologic diagnosis of an effusion. The number of patients studied was 254; 171 had a pleural and 83 a peritoneal effusion. The average survival time was 25.5 weeks, which was about equal for both sites of effusions. After two years, only 6% of all patients were alive. When the cytologic diagnosis of the effusion was "malignant," only 4% survived after two years; when the cytologic diagnosis was "suspicious for malignancy" and "nonmalignant," these figures were 5% and 7%, respectively. This indicates that a cytologic diagnosis of benign or nonmalignant is not a good indicator of a better prognosis in cancer patients for whom benign causes of the effusion have been excluded. There appeared to be a prognostic relationship between the length of the interval from the initial diagnosis of cancer to the time of examination of the first sample of the effusion: a longer interval was correlated with a better survival. When survival time was viewed in relation to therapy, patients whose pleural effusions were only treated by aspiration were found to have a particularly short average survival (13.9 weeks).     

Linkage analysis of families with hereditary retinoblastoma: nonpenetrance of mutation, revealed by combined use of markers within and flanking the RB1 gene.

Nonpenetrance of the inherited mutation responsible for retinoblastoma has been reported. By DNA analysis in families with hereditary retinoblastoma, it is possible to identify healthy individuals in whom the mutation is nonpenetrant. This requires the use of DNA markers both within and flanking the retinoblastoma gene. We have analyzed the segregation of several markers in 19 families (69 meioses) with hereditary retinoblastoma. In two families a carrier was identified who showed nonpenetrance of the mutation predisposing to retinoblastoma. The intragenic markers were informative in 15 pedigrees. The use of flanking markers from the same chromosomal region caused an increase of the number of informative families to 18. No crossing-over within the gene was observed. In one family an inherited deletion involving one of the RB1 alleles was detected. Our findings emphasize the use of a combination of both intragenic and flanking markers to obtain both the highest reliability of carrier detection in families with hereditary retinoblastoma and an accurate estimate of the frequency of nonpenetrance.     

Effect of anticancer drugs on the release of interferon γ in vitro

Summary Some conventional and experimental anticancer drugs were tested for their effect on concanavalin-A-induced interferon release from rat splenocytes in vitro. When 2.5 × 10⁶ rat splenocytes/ml, stimulated with 1 µg/ml concanavalin A, were incubated with various non-cytotoxic doses of the vinca alkaloid vincristine, there was an inhibition of the release of interferon in culture supernatants. The antitumour antibiotics bleomycin and Adriamycin, alkylating agents 4-hydroperoxycyclophosphamide and mafosfamide, and the immunoactive peptides FK 156 and FK565 did not affect the release of interferon under similar conditions. However, cyclosporin A, in similar experiments, markedly inhibited the release of interferon .     

Improved separation of chromosome-sized DNA from Trypanosoma brucei, stock 427-60.

Separation of chromosome-sized DNA from the parasitic protozoan Trypanosoma brucei had previously resulted in the fractionation of DNA molecules that ranged in size from 50 kb up to roughly 1.5 Mb. The number of larger chromosomes and their size, accounting for 80% of the DNA of T. brucei remained unclear. We have now size separated these larger DNA molecules by pulsed field gel electrophoresis (PFG) and resolve a total of 20 bands, accounting for roughly 120 chromosomes, ranging in size from 50 kb up to the size of the largest, 5.7 Mb chromosome of Schizosaccharomyces pombe. Three different VSG gene expression sites were located to chromosomes of 430 kb, 1.5 Mb and 3 Mb, respectively. We have not been able to identify additional, previously cryptic DNA rearrangements, that could explain the activation or inactivation of the expression sites.     

High resolution deletion breakpoint mapping in the DMD gene by whole cosmid hybridization.

The locus DXS269 (P20) defines a deletion hotspot in the distal part of the Duchenne Muscular Dystrophy gene. We have cloned over 90 kilobase-pairs of genomic DNA from this region in overlapping cosmids. The use of whole cosmids as probes in a competitive DNA hybridization analysis proves a fast and convenient method for identifying rearrangements in this region. A rapid survey of P20-deletion patients is carried out to elucidate the nature of the propensity to deletions in this region. Using this technique, deletion breakpoints are pinpointed to individual restriction fragments in patient DNAs without the need for tedious isolation of single copy sequences. Simultaneously, the deletion data yield a consistent restriction map of the region and permit detection of several RFLPs. A 176 bp exon was identified within the cloned DNA, located 3' of an intron exceeding 150 Kb in length. Its deletion causes a frameshift in the dystrophin reading frame and produces the DMD phenotype. This exon is one of the most frequently deleted exons in BMD/DMD patients and its sequence is applied in a pilot study for diagnostic deletion screening using Polymerase Chain Reaction amplification.     

Assignment of the gene(s) involved in the expression of the proliferation-related Ki-67 antigen to human chromosome 10

Summary The antigen recognized by the monoclonal antibody Ki-67 is a proliferation-related nucleolus-associated constituent used as a marker for cycling cells in tumor diagnosis. Antibody Ki-67 reacts with human proliferating cells, but not with hamster and mouse cells. Expression of the Ki-67 antigen was studied in a panel of human-rodent somatic cell hybrids. The results indicate that a gene involved in the expression of the antigen is located on chromosome 10.     

Cloning and molecular characterization of the chalcone synthase multigene family of Petunia hybrida

Chalcone synthase-encoding genes (chs) in Petunia hybrida comprise a multigene family. Some of the chs genes have been grouped into a subfamily, based upon their strong cross-hybridization and tight genomic linkage. From genomic libraries eight 'complete' chs genes, two chs gene 5'-fragments and two chs gene 3'-fragments have been isolated. The nucleotide sequence of six complete chs genes is presented and discussed in relation to their evolutionary origin and expression in different tissues. Each member of the family consists of two exons separated by an intron of variable size and sequence, which is located at a conserved position. The chs gene fragments represent single exons. Homology between non-linked chs genes is approx. 80% at the DNA level and restricted to protein-coding sequences. Homology between subfamily members (which are tightly linked) is higher (90-99%) and extends into untranslated regions of the gene, strengthening the view that they arose by recent gene duplications. The chsD gene contains a mutated translation stop codon, suggesting that this is an inactive (pseudo)gene. None of the other members of the gene family exhibits characteristics of a pseudogene, indicating that if gene inactivation has occurred during their evolution, it must characteristics of a pseudogene, indicating that if gene inactivation has occurred during their evolution, it must have been a recent event. Homology at the protein level between some (expressed) chs genes is surprisingly low. The possibility that these genes encode proteins with slightly different enzymatic activities is discussed.