Prolonged remission maintenance in acute myeloid leukaemia.

Twenty-five patients with acute myeloid leukaemia were treated with three quadruple drug combinations in predetermined rotation: TRAP (thioguanine, daunorubicin, cytarabine, prednisolone); COAP (cyclophosphamide, vincristine, cytarabine, prednisolone); and POMP (prednisolone, vincristine, methotrexate, mercaptopurine). Fifteen patients (60%) achieved complete remission and five (20%) partial remission. For maintenance, five-day courses of drugs were administered every 14 to 21 days and doses were increased to tolerance. The median length of complete remission was 66 weeks. In eight patients remission maintenance treatment was discontinued and some remained in complete remission for over two years. In this series the remission induction rate was comparable with that reported for other regimens and complete remission lasted longer with this intensive maintenance regimen than with others. Nevertheless, the TRAP programme must still be regarded as only palliative treatment for acute myeloid leukaemia.     

Enhanced virulence effect of K1 polysaccharide in neonatal rats challenged withE. coli

Purified K1 polysaccharide enhanced the virulence of non-K1Escherichia coli species when given by orogastric feeding to neonatal rats. Neonatal rats developedE. coli bacteremia when K1 polysaccharide was given concomitantly with non-K1E. coli, whereasE. coli bacteremia did not develop when non-K1E. coli was given alone.E. coli K1 species did cause bacteremia and meningitis when fed to neonatal rats. The mechanism by which k1 polysaccharide enhances virulence can be studied with this model of bacteremia development in neonatal rats.     

Free Ammonia Inhibition of Algal Photosynthesis in Intensive Cultures

The effect of free NH₃ inhibition on short-term photosynthesis was investigated in three microalgal species: the freshwater chlorophyte Scenedesmus obliquus, the marine diatom Phaeodactylum tricornutum and the marine chlorophyte Dunaliella tertiolecta. By performing a series of assays at various concentrations of added NH₄Cl and culture pH, we demonstrated that the inhibitory compound was free NH₃ and that pH played no role in determining the magnitude of inhibition, other than in establishing the degree of dissociation of nontoxic NH₄⁺ to toxic NH₃. When corrections were made for pH, all three species displayed the same sigmoidal response curve to free NH₃ concentration; 1.2 mM NH₃ led to 50% reduction in photoassimilation of ¹⁴C. Based on literature values, some marine phytoplankton appear to be significantly more sensitive to free NH₃ than were the test species, which are noted for their excellent growth characteristics. However, the combination of low algal biomass and strong pH buffering commonly found in most marine and many freshwater environments probably limits the possibilities for NH₃ toxicity to low alkalinity freshwaters and intensive algal cultures in which NH₄⁺ is the main source of N. Such conditions occur commonly in algal wastewater treatment systems.     

Cowpea Rhizobia Producing Dark Nodules: Use in Competition Studies

During a program of screening rhizobia from West Africa, it was found that some strains produced nodules of unusually dark appearance on cowpeas, but not on peanuts, soybeans, pigeon peas, or mung beans. The dark pigmentation was in the bacteroid zone, was not correlated with nodule effectiveness, and was additional to the leghemoglobin pigment. Only rhizobial strains with a nongummy (“dry”) colony morphology produced dark nodules. Visually distinguishable pink and dark nodules formed on the same root when a mixture of pink and dark strains was applied as inoculum. The dark-nodule phenotype was therefore appraised as a marker and found to be useful for studying nodulation competition with strains of the orthodox pink-nodule type. The competitiveness of 10 pink-nodule strains was examined relative to a black-nodule strain, IRc 256; a range of competitiveness was obtained of less competitive than, equally competitive to, or more competitive than IRc 256. Patterns of primary (early) nodulation were generally the same as patterns of secondary (later) nodulation. Mixed infections by dark and pink strains produced piebald nodules, the frequency of occurrence of which was much greater among primary than among secondary nodules.     

The regulation of intermediate filament reorganization in mitosis. p34cdc2 phosphorylates vimentin at a unique N-terminal site

The disassembly of vimentin-containing intermediate filament (IF) networks during mitosis in BHK-21 cells is accompanied by increased phosphorylation of vimentin (Chou, Y.-H., Rosevear, E., and Goldman, R. D. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 1885-1889). We have recently identified p34cdc2 as the catalytic subunit of one of the two endogenous vimentin kinases in mitotic baby hamster kidney cells (Chou, Y.-H., Bischoff, J. R., Beach, D., and Goldman, R. D. (1990) Cell 62, 1063-1071). To begin to characterize the biochemical basis of the p34cdc2-mediated IF disassembly process, we have purified and sequenced the 32P-labeled tryptic peptides derived from in vitro-phosphorylated vimentin. The results demonstrate that Ser-55, in the N-terminal non-alpha-helical domain of vimentin, is the most favored phosphorylation site. This finding supports the idea that the N-terminal domain of type III IF protein plays a crucial role in regulating IF structure and supramolecular organization.     

Structural basis of a conserved idiotope expressed by an autoreactive human B cell lymphoma. Evidence that a VH CDR3 mutation alters idiotypy and specificity

Our laboratory has previously investigated the relationship of autoimmune disease and B cell neoplasia in a patient with a diffuse, well differentiated splenic B cell lymphoma and associated autoimmune hemolysis due to an anti-Pr2 antibody. EBV-immortalized B cell clones, established from this lymphoma, were shown to secrete the same pathologic anti-Pr2 antibody. The antiidiotypic mAb, RI.1, defined a private Id (IdRI.1) of the anti-Pr2 antibody that was related to the Ag-binding site and was expressed by both the lymphoma and derived cell lines. This unique Id was expressed by the majority of splenic tumor B cells and also was conserved over a period of 4 yr. In this report, the structural basis of IdRI.1 expression was investigated by analysis of Id- variants isolated by flow microfluorimetry using RI.1. Six Id- cell lines that secrete IgM kappa but lack Pr2 specificity were generated from an Id+ cell line, LS2. These lines were shown to be related to LS2 and the lymphoma by karyotype and by restriction fragment analysis of Ig gene rearrangements. Shared and unshared nucleotide substitutions in the VH and VL regions of the six independent clones were used to construct a genealogic tree relating the Id- clonal members to a common Id+ precursor. The tree illustrates that the base changes occurred sequentially, suggesting that they were introduced by somatic point mutation. Only one VH CDR3 bp difference from the LS2 nucleic acid sequence is common to all Id- sequences, resulting in an amino acid substitution of cysteine 108 to tyrosine. Taken together, these findings suggest that both the expression of IdRI.1 and Ag binding are affected by a single mutation localized to the D region of the anti-Pr2 antibody.     

Trend,seasonality, cycle,and irregular fluctuations in primary productivity at Lake Tahoe,California-Nevada,USA

Primary productivity has been measured routinely at Lake Tahoe since 1967, and a number of mechanisms underlying variability in the productivity record have now been identified. A long-term trend due to nutrient loading dominates the series. Seasonality also is prominent, apparently controlled by direct physical factors unrelated to the trophic cascade. A 3-yr cycle has been detected and several possible mechanisms are considered. Irregular fluctuations also are present, caused in part by isolated events (a forest fire) and recurring but variable phenomena (spring mixing). Except possibly for the 3-yr cycle, the known sources of variability appear to operate bottom-up through direct physical and chemical effects on the phytoplankton.