Decrease in the phagocytic activity of peripheral monocytes in patients treated with human interferon-α

Summary The influence of daily intramuscular injections of 3×10⁶ units of interferon- (IFN-) on the phagocytic activity of peripheral monocytes was studied in 28 tumor patients. One day after initiation of IFN therapy no major change in the capacity of monocytes to ingest yeast particles was observed. After 1 week, 3 months, 6 months, and 9 months of treatment, monocyte phagocytosis had decreased in the majority of the patients tested. In patients where natural killer (NK) cell activity was measured simultaneously with monocyte phagocytosis, a correlation between the degree of enhancement of NK activity and the degree of decrease in monocyte phagocytosis was observed.     

Tobamovirus evolution: gene overlaps, recombination, and taxonomic implications

Tobamoviruses, mostly isolated from solanaceous plants, may represent ancient virus lineages that have codiverged with their hosts. Recently completed nucleotide sequences of six nonsolanaceous tobamoviruses allowed assessment of the codivergence hypothesis and support a third subgroup within tobamoviruses. The genomic sequences of 12 tobamoviruses and the partial sequences of 11 others have been analyzed. Comparisons of the predicted protein sequences revealed three clusters of tobamoviruses, corresponding to those infecting solanaceous species (subgroup 1), those infecting cucurbits and legumes (subgroup 2), and those infecting crucifers. The orchid-infecting odontoglossum ringspot tobamovirus was associated with subgroup 1 genomes by its coat and movement protein sequences, but with the crucifer-pathogenic tobamoviruses by the remainder of its genome, suggesting that it is the progeny of a recombinant. For four of five genomic regions, subgroup 1 and 3 genomes were equidistant from a subgroup 2 genome chosen for comparison, suggesting uniform rates of evolution. A phylogenetic tree of plant families based on the tobamoviruses they harbor was congruent with that based on rubisco sequences but had a different root, suggesting that codivergence was tempered by rare events of viruses of one family colonizing another family. The proposed subgroup 3 viruses probably have an origin of virion assembly in the movement protein gene, a large (25-codon) overlap of movement and coat protein open reading frames, and a comparably shorter genome. Codon-position- dependent base compositions and codon prevalences suggested that the coat protein frame of the overlap region was ancestral. Bootstrapped parsimony analysis of the nucleotides in the overlap region and of the sequences translated from the -1 frame (the subgroup 3 movement protein frame) of this region produced trees inconsistent with those deduced from other regions. The results are consistent with a model in which a no or short overlap organization was ancestral. Despite encoding of subgroup 2 and 3 movement protein C-termini by nonhomologous nucleotides, weak similarities between their amino acid sequences suggested convergent sequence evolution.      

Hprt mutations and karyotype abnormalities in T-cell clones from healthy subjects and melphalan-treated ovarian carcinoma patients

In vivo mutations at the locus for hypoxanthine phosphoribosyl transferase (hprt) were studied in 6-thioguanine (TG)-resistant T-lymphocytes clones from healthy male and female subjects and ovarian carcinoma patients treated with melphalan. Southern blot analysis of 108 clones showed alterations in 14% (4/29) of the colnes from healthy males, 4.3% (2/47) of the clones from healthy females and 3.1% (1/32) of the clones from melphalan-treated patients. 2 of the 7 abnormal clones had a total deletion of the hprt gene; the others had partial deletions. Karyotype analysis of 82 clones revealed 1 clonal abnormality in 29 mutant clones from healthy males (3.6%). Loss or structural aberration of 1 X-chromosome occurred in 6% of the clones from healthy females. The frequency of karyotypic abnormalities (excluding those affecting one of the X-chromosomes) was significantly higher in clones from patients (37%) as compared to healthy females (5.9%). No aberration was found to affect the hprt locus at Xq27 in any of the 82 clones studied.     

Cis ε-viniferin: A New Antifungal Resveratrol Dehydrodimer from Cyphostemma crotalarioides Roots

Six antifungal constituents were isolated from the roots of Cyphostemma crotalarioides (Vitaceae): a new product, Cis‐ε‐viniferin 3, along with five known compounds: trans‐resveratrol I and its oligomers: trans ε‐viniferin 2, gnetin C 4, pallidol 5 and gnetin E 6. It is the first time such compounds have been reported in this plant species. The roots tissues were found to be rich in other resveratrol oligomers, however, the available amounts of the other purified products did not allow structure investigations. No fungicidal activity was detected in the leaves of this plant.     

Molecular analysis of the human chromosome 5q13.3 region in patients with hairy cell leukemia and identification of tumor suppressor gene candidates.

The pathogenesis of hairy cell leukemia (HCL) remains largely unknown since no specific genetic lesion has been identified in this disease. Previous cytogenetic analysis from our group has shown that chromosome abnormalities involving the 5q13 band are common in HCL, occurring in approximately 1/3 of patients. The data suggest that the 5q13.3 band is likely to harbor a gene involved in the transformational events of this disease. We have recently found two cosmids flanking the 5q13.3 breakpoint in patients with HCL, and the distance between them is approximately 35 kb, as analyzed by fiber-FISH. The two cosmids have been located between the markers SGC34998 and WI-15505/WI-6897 by radiation hybrid mapping. Five of 11 patients with HCL had a hemizygous deletion of the two cosmids, indicating that the function of a tumor suppressor gene may be lost. With the aim of delineating the critical region of 5q13.3 loss in patients with HCL, we have constructed an integrated contig of YAC, BAC, PAC, P1, and cosmid clones that covers the region. Within this area, three expressed sequences were identified as candidates for the putative 5q13.3 tumor suppressor gene involved in the pathogenesis of HCL.     

Biological control of Chenopodium album L. in Europe

Ascochyta caulina (P. Karst) v.d. Aa and v. Kest is aplant pathogenic fungus which is specific to Chenopodium albumL. It has been suggested as a potential mycoherbicide to this weed,which is important and wide spread in arable crops throughout Europe. Toinvestigate its potential as a biocontrol agent, the fungus has beentested in glasshouse and field experiments. Formulations containingdifferent combinations of A. caulina conidia, the phytotoxinsfrom the fungus and low doses of herbicides have been tested.Significant improvement in the efficacy of the fungus was achieved inglasshouse trials with an aqueous formulation containing PVA(0.1% v/v), Psyllium (0.4% w/v), Sylgard 309(0.1% v/v), nutrients and conidia (5 ×10⁶/ml). The extracellular, hydrophilic phytotoxinsproduced by A. caulina were purified and their structuresdetermined. The main toxin, named ascaulitoxin, was characterised as theN²--D-glucopyranoside of the unusual bis-aminoacid2,4,7-triamino-5-hydroxyoctandioic acid. Two other toxins proved to betrans-4-amino-D-proline and the aglycone of ascaulitoxin. Thesetoxins have shown promising herbicidal properties. Field trials haveinvestigated the performance of A. caulina conidia applied atdifferent developmental stages of C. album either as a singletreatment or combined with sub-lethal doses of herbicides or with thefungal phytotoxins. With the available formulation, favourable weatherconditions are needed to obtain infection in the field. The efficacy ofthe strain of A. caulina used so far has proved to beinadequate to justify its development as a bioherbicide. This isprobably due to its low virulence.     

Three-dimensional reconstruction of fracture callus morphogenesis.

Rat and mouse femur and tibia fracture calluses were collected over various time increments of healing. Serial sections were produced at spatial segments across the fracture callus. Standard histological methods and in situ hybridization to col1a1 and col2a1 mRNAs were used to define areas of cartilage and bone formation as well as tissue areas undergoing remodeling. Computer-assisted reconstructions of histological sections were used to generate three-dimensional images of the spatial morphogenesis of the fracture calluses. Endochondral bone formation occurred in an asymmetrical manner in both the femur and tibia, with cartilage tissues seen primarily proximal or distal to the fractures in the respective calluses of these bones. Remodeling of the calcified cartilage proceeded from the edges of the callus inward toward the fracture producing an inner-supporting trabecular structure over which a thin outer cortical shell forms. These data suggest that the specific developmental mechanisms that control the asymmetrical pattern of endochondral bone formation in fracture healing recapitulated the original asymmetry of development of a given bone because femur and tibia grow predominantly from their respective distal and proximal physis. These data further show that remodeling of the calcified cartilage produces a trabecular bone structure unique to fracture healing that provides the rapid regain in weight-bearing capacity to the injured bone.