Leucostasis, an underestimated cause of death in leukaemia

Massive sludging of leukaemic cells in blood vessels is a frequent and often lethal complication of leukaemia. In a retrospective clinicopathological study on the causes of death in 52 patients with acute myeloid leukaemia and myeloproliferative disease, pulmonary leucostasis was found in 40% of the patients. In many of these patients the vessels of the heart, brain and testes were also involved. In search for signs and symptoms specific for leucostasis, the clinical records of the 21 patients with leucostasis (the study group) were compared to those of 20 patients without leucostasis (the control group). Dysfunction of the organs most affected by leucostasis, namely lungs, heart and brain, was found more often in the study group than in the controls, but the combination of unexplained fever with cardiopulmonary and/or central nervous system failure occurred almost exclusively and in half of the patients with leucostasis. Leucostasis occurs predominantly, but not exclusively, in patients with high leucocyte counts, and especially, but again not exclusively, when the leucocyte counts rise sharply.     

Changes in fiber composition of soleus muscle during rat hindlimb suspension

Chronic reduction of gravitational load in the rear limbs of rats to simulate the influence of near-zero gravity in skeletal muscles has been shown previously to elicit atrophy in the soleus muscle. Use of this model by the present investigation indicates that soleus atrophy was characterized by a decline in the number of fibers in groups that contained the slow isoenzyme of myosin and which were classified as type I from intensity of staining to myofibrillar actomyosin adenosinetriphosphatase (ATPase) and to NADH tetrazolium reductase. Furthermore total fiber number was not changed, whereas fibers containing the intermediate isoenzyme and those classified as type IIa increased. There results could be explained by either a change in the composition within existing fibers or a simultaneous loss of slow fibers and de novo synthesis of intermediate and fast fibers. Evidence for transformation included an absence of embryonic or neonatal myosin in muscles from suspended rats and the constant fiber number that was unchanged by 4 wk of suspension. Furthermore although fiber areas of both groups of type I and IIa fibers declined during suspension, variability of the fiber areas within each group did not increase.     

The immunobiology of T cell responses to Mls-locus-disparate stimulator cells. II. Effects of Mls-locus-disparate stimulator cells on cloned, protein antigen-specific, Ia-restricted T cell lines

Cloned, protein antigen-specific, Ia-restricted T cell lines frequently (approximately 20%) also respond strongly to stimulator cells from strains expressing stimulatory alleles at the chromosome 1-encoded Mls-locus. Furthermore, such responses are blocked by monoclonal antibodies specific for Ia antigens expressed by the stimulator rather than the responder cells. However, such responses show no specificity for polymorphic determinants on Ia molecules, although in such responses, as in primary and secondary T cell responses to stimulating Mls-locus alleles, I-E molecules appear to play a central role. These results, combined with the unique immunobiology of the primary T cell proliferative response to Mls-locus-disparate stimulator cells, suggest to us that this response involves the interaction of the receptor on T cells for antigen:self Ia with a relatively nonpolymorphic region of Ia glycoproteins. This hypothesis is supported by the observation that a monoclonal antibody to the T cell receptor will inhibit both responses, although the response to Mls-locus-disparate stimulators appears to be more sensitive to these antibodies. We propose that the interaction of the T cell receptor with Ia is stabilized by a cell interaction molecule encoded or regulated by the Mls-locus gene product permitting the T cell receptor:Ia glycoprotein interaction to lead to T cell activation.     

Primary structures of the mRNAs encoding the rat precursors for bradykinin and T-kinin. Structural relationship of kininogens with major acute phase protein and alpha 1-cysteine proteinase inhibitor

Three types of cloned cDNA sequences for rat low molecular weight prekininogens were isolated and determined by molecular cloning and sequence analysis. The deduced amino acid sequences indicated that one, termed K-prekininogen, represents the counterpart of the known low molecular weight prekininogen present in other mammals, while the other two, called T-prekininogens, contain a novel T-kinin sequence which was recently identified from rat plasma. Although T- and K-prekininogens are highly homologous with each other, both of the T-prekininogens contain methionine, instead of arginine or lysine, as an amino acid preceding T-kinin and exhibit two consecutive amino acid deletions in the preceding region of T-kinin as compared with K-prekininogen. The former finding accounts for the previous observation of strong resistance of T-kininogens to cleavage with trypsin or kallikreins, while the latter finding has been explained by the structural analysis of genomic clones in which T-kinin-coding exon is contracted at its intron junction. A partial nucleotide sequence reported recently for the rat major acute phase protein (alpha 1-MAP) mRNA was found to be extremely related to the corresponding portion of the rat T-prekininogen mRNA. Furthermore, consistent with the previous report of the structural identity of major acute phase protein and alpha 1-cysteine proteinase inhibitor, kininogen closely resembles not only the former but also the latter in the amino acid compositions. The interrelationship among the triad of these proteins has been discussed.     

Translational discrimination between the four RNAs of alfalfa mosaic virus. A quantitative evaluation

In an attempt to relate the translational characteristics of alfalfa mosaic virus (A1MV) RNAs to their structure [Ravelonandro et al. (1983) Nucleic Acids Res. 11, 2815-2826; Gehrke et al. (1983) Biochemistry 22, 5157-5164] we measured the relative affinities (discrimination ratios) of these RNAs for the initiation complex, in the wheat germ extract and in the nuclease-treated reticulocyte lysate, using a competition method designed by Brendler et al. [(1981) J. Biol. Chem. 256, 11747-11754]. As a prerequisite of this study we ascertained that the molecular mass distribution of the translation products was independent of RNA concentration in both translation systems. In the wheat germ extract the discrimination ratios are very similar for two strains of A1MV (S and B) which differ mainly by the presence (strain S) or absence (strain B) of a stable 5'-proximal hairpin. Hence this structure has no bearing on discrimination. Taking the affinity of RNA 3 as reference, the following orders of magnitude are found for the affinities of the different RNAs in the wheat germ: RNA 3, 1.0; RNA 1, 10; RNA 2, 60; RNA 4, 150. In the reticulocyte lysate the discrimination ratios are not significantly different from the wheat germ. Thus it seems that the mechanism of discrimination is essentially the same in the two translation systems, despite a difference in rate-limitation.     

Escherichia coli RecBC pseudorevertants lacking chi recombinational hotspot activity

Pseudorevertants of an Escherichia coli exonuclease V (RecBC enzyme)-negative mutant have been isolated after ethyl methane sulfonate mutagenesis of a recC73 (presumed missense) mutant. The remedial mutations in each of the four pseudorevertants studied in detail map and complement as recC mutations. By several criteria, such as recombination proficiency, support of phage growth, RecBC nuclease activity, and cell viability, the pseudorevertants appear to have regained partially or completely various aspects of RecBC activity. However, chi recombinational hotspots, which stimulate exclusively the RecBC pathway of recombination, have no detectable activity in lambda vegetative crosses in the pseudorevertants. The properties of these mutants, in which the RecBC pathway of recombination is active yet in which chi is not active, are consistent with the hypothesis that wild-type RecBC enzyme directly interacts with chi sites; alternatively, the mutants may block or bypass the productive interaction of another recombinational enzyme with chi.