Management of localized non-Hodgkin's lymphoma

Non-Hodgkin''s lymphomas (NHLs) are a heterogeneous group of disorders that vary widely in response to therapy. In Canada the modified Rappaport classification is used to categorize NHL. To facilitate the reporting and comparison of treatment results all cases should also be categorized in the terminology of the National Cancer Institute''s working formulation. The choice of therapy should be guided by specific prognostic factors: stage and bulk of the disease, patient''s age, presence of systemic symptoms and histologic subtype. Of these, the last appears to be the most important. Radiotherapy (RT) is the treatment of choice in localized low-grade lymphomas with favourable prognoses, while bimodal therapy (RT and chemotherapy [CT]) is warranted in presentations with unfavourable prognoses. Regional irradiation alone is indicated in intermediate-grade lymphomas with good prognoses (i.e., pathological stage I or II or clinical stage IA or IIA localized disease of small bulk in young patients). All other patients require CT followed by RT. The results of CT alone are encouraging but remain experimental. Aggressive therapy with multidrug regimens that include central nervous system prophylaxis is the foundation for successful treatment of high-grade NHL such as lymphoblastic lymphoma and diffuse small-noncleaved-cell lymphomas. Low-dose RT should be given to sites of bulky disease.     

A new spring for plant cell biology: microtubules as dynamic helices

Cortical microtubules wind around plant cells describing flat, medium or steeply pitched helices. Experiments now suggest that these arrays are dynamically interconvertible — providing a spring-like device that is sensitive to environmental cues and shifts the axis of cell expansion through 90°.     

Characteristics of bacterium GB-2, a presumptiveCytophaga species with novel immunoregulatory properties

A Gram-negative, psychrophilic bacterium, designated GB-2, was isolated from fetal calf serum and analyzed for its morphological, physiological, and biochemical characteristics. Gliding motility, sensitivity to actinomycin D, the presence of the pigment flexirubin and cytochrome c, growth on a variety of carbohydrates, the production of acid fermentation products, and a 34.9 mol% guanine+cytosine (G+C) content of bacterial DNA indicate GB-2 to be a member either of the generaCytophaga orFlexibacter. Growth of GB-2 was optimized in a simple defined medium to facilitate isolation and characterization of bacterial products. Liquid growth of GB-2 resulted in the release of significant quantities of a macromolecule free of both endotoxin and protein into the growth supernatant, which activated the proliferation of murine lymphocytes. The relationship between this bacterium and its end-products to other species of theCytophaga/Flexibacter group is discussed.     

Effects of fructose on human fibroblast metabolism: the application of DNA measurements as a basis for interpretation

Summary A fluorometric procedure for measuring DNA was used to study growth and metabolic responses of eight cell strains of human foreskin fibroblasts. In preliminary studies this procedure gave more precise specific activity changes inN-acetyl-β-d-glucosaminidase (NAG) than did a protein activity basis, when changes in this enzyme's specific activity were investigated as a function of experimental cell manipulation. When fibroblast growth in eight cell strains was compared in 134 mM d-fructose vs. 13.4 mM glucose-supplemented minimum essential media, a significant increase in cellular DNA (50%) and protein (45%) occurred over an 11-d period. No significant differences in media pH change, lactate production, or carbohydrate uptake occurred on a DNA basis when cell metabolism was compared over the last 24 h of culture in the two media. Cells grown in fructose-containing media tended to show a reduction in NAG specific activity when compared with those grown in glucose-containing media.     

The diets of Hispaniolan colubrid snakes

Summary Approximately 1590 Hispaniolan colubrid snakes representing six genera and eight species were examined for prey remains (Alsophis cantherigerus, Antillophis parvifrons, Darlingtonia haetiana, Hypsirhynchus ferox, Ialtris dorsalis, Uromacer catesbyi, U. frenatus, and U. oxyrhynchus). The snakes were collected at many localities over a span of 80 years.Of 426 prey items, 77.9% were lizards (of which 69.6% were anoles), 19% frogs, 2.6% birds and mammals, and 0.5% other snakes. Darlingtonia was the only snake that did not exploit lizards; it fed exclusively on Eleutherodactylus frogs, including egg clutches. Disregarding Darlingtonia, there is no size class of Hispaniolan colubrids between 20–90 cm SVL that does not prey primarily on Anolis. Certain prey genera are added to, or deleted from, diets depending on snake size, but the data suggest that snake SVL alone does little to dictate what prey genera (or groups) are eaten. Shannon-Wiener values (H') indicate that Darlingtonia has the narrowest trophic niche, while Alsophis and Ialtris have the widest. Values of H' are not correlated with snake SVL, but highly significant (P<0.001) correlations exist between H' and mid-body circumference, head width, and snout width, and these characters may be indicators of trophic generalists and specialists. Anolis lizards are the most ubiquitous and conspicuous vertebrates on Hispaniola, and it is not surprising that they are widely exploited as a food source. Although as some snake species grow larger, anoles play a decreasingly important role in their diets, there is no evidence to suggest that they are ever abandoned as a food source by any Hispaniolan colubrid of any size.Secretive lizards of low vagility are eaten almost exclusively by wide ranging foragers (Alsophis, Antillophis); very active prey (Ameiva) is taken by sit-and-wait strategists (Hysirhynchus, U. frenatus). Those snakes which exploit the most prey groups are active foragers. Uromacer catesbyi exhibits both foraging modes, and predictably, eats diurnally active (anoles) and diurnally quiescent (hylid frogs) prey with almost equal frequency.Within Maglio's cantherigerus species assemblage, in which an Alsophis cantherigerus-like snake was ancestral to the other species, and in which longsnouted Uromacer are the most morphologically derived, there is an obvious trend toward trophic specialization on Hispaniola. The West Indies have provided an ideal natural laboratory for the investigation of many aspects of vertebrate ecology, and an arena in which to test theories of island biogeography. The most extensively studied West Indian vertebrates have been the lizards of the iguanid genus Anolis. Conversely, the ecology of West Indian snakes has been largely ignored. This is surprising in light of the fact that much has been written about Anolis predation, but little has been written about predators of Anolis; snakes may be important, frequent consumers of anoles.Hispaniola is physiographically and ecologically the most diverse of the Greater Antilles and, concomitantly, it has the most diverse snake fauna, including six colubrid genera containing 11 described species. It has rich frog and lizard faunas, but only two endemic mammals. Study of the diets of Hispaniola's colubrid snakes was undertaken to gain initial insights into the ecology of the snakes and to determine 1) what the snakes eat; 2) what relationships exist between snake diet and snake size as well as head and body proportions; 3) what relationships exist between snake foraging mode and prey type and size; 4) if anoles, as the most ubiquitous and conspicuous vertebrates on Hispaniola, comprise an important source of food; 5) if significant geographical differences in diet exist, expecially on satellite islands; 6) if north island and south island (sensu Williams 1961) Anolis ecomorphs are preyed upon by the same snake species in similar proportions; 7) if snakes are selective or opportunistic predators.This paper, the first in a series that will address all of the above topics, will briefly describe methods, snake species and prey genera. Prey genera are analyzed in terms of what snake taxa prey upon them, what size classes of snakes prey upon them, and prey genera diversity versus snake size and proportions.     

Phospholipid Biosynthesis in Myelin: Presence of CTP: Phosphoethanolamine Cytidylyltransferase in Purified Myelin of Rat Brain

Highly purified myelin from rat brain was previously shown to contain the ethanolaminephosphotransferase which completes the synthesis of phosphatidyl ethanolamine. We have now obtained evidence for the presence in myelin of CTP:phosphoethanolamine cytidylyltransferase, the enzyme catalyzing formation of CDP-ethanolamine. Myelin was isolated by two different procedures, one based on the Norton-Poduslo method and the other involving repetitive gradients with osmotic shocking deferred to the end. The fact that activity remained constant through all but the earliest steps suggested that the enzyme is intrinsic to myelin. Comparison of subcellular fractions revealed that approximately half the total activity was in the supernatant, the remainder being distributed among the particulate fractions. Relative specific activity of myelin was 27-31% that of microsomes, thus eliminating the possibility of appreciable contamination by the latter. The possibility of adsorption of the soluble enzyme by myelin was rendered unlikely by retention of activity after washing the myelin with buffered sodium chloride or sodium taurocholate. Furthermore, relative specific activity of the cytidylyltransferase was 10-fold higher than that of lactate dehydrogenase (a cytosolic marker) in myelin. The apparent Km for CTP was approximately the same for myelin and microsomes, but that for phosphoethanolamine was significantly higher for myelin.     

Decreased High-Affinity Binding of [3H]Muscimol to Cerebral Synaptic Membranes of Scrapie-Infected Mice

Scrapie is a transmissible disease that results in progressive degeneration of the central nervous system and death. Although scrapie has been studied histopathologically, relatively little is known concerning neurotransmitter alterations. Specific [3H]muscimol binding to whole brain crude synaptic membranes (CSM) from mice clinically affected with scrapie was significantly (p less than 0.01) reduced, to approximately 73% of that of the controls. Of the brain regions examined, binding to only cerebral CSM was significantly (p less than 0.0001) decreased. Scatchard analyses of saturation curves revealed that the high-affinity (KD = 8 +/- 3 nM) site for muscimol was abolished in cerebral CSM from scrapie-infected mice, while the low-affinity site was unaffected. Binding of [3H]flunitrazepam to cerebral CSM was unaffected by scrapie and was stimulated by GABA to the same extent in both scrapie and control mice. These results suggest that scrapie agent 139A in C57BL/6J mice manifests a portion of its CNS pathology via a high-affinity GABA binding site that is unassociated with the benzodiazepine receptor.     

Organization of the ribosomal ribonucleic acid genes in various wild-type strains and wild-collected strains of Neurospora

Summary The organization of the ribosomal DNA (rDNA) repcat unit in the standard wild-type strain of Neurospora crassa, 74-OR23-1A, and in 30 other wild-type strains and wild-collected strains of N. crassa, N. tetrasperma, N. sitophila, N. intermedia, and N. discreta isolated from nature, was investigated by restriction enzyme digestion of genomic DNA, and probing of the Southern-blotted DNA fragments with specific cloned pieces of the rDNA unit from 74-OR23-1A. The size of the rDNA unit in 74-OR23-1A was shown to be 9.20 kilobase pairs (kb) from blotting data, and the average for all strains was 9.11+0.21 kb; standard error=0.038; coefficient of variation (C.V.)=2.34%. These data indicate that the rDNA repeat unit size has been highly conserved among the Neurospora strains investigated. However, while all strains have a conserved HindIII site near the 5 end of the 25 S rDNA coding sequence, a polymorphism in the number and/or position of HindIII sites in the nontranscribed spacer region was found between strains. The 74-OR23-1A strain has two HindIII sites in the spacer, while others have from 0 to at least 3. This restriction site polymorphism is strain-specific and not species-specific. It was confirmed for some strains by restriction analysis of clones containing most of the rDNA repeat unit. The current restriction map of the 74-OR23-1A rDNA repeat unit is presented.     

The effect of ethanol on arachidonic acid metabolism in the murine peritoneal macrophage

Exposure to ethanol in man has been linked to an alteration of the immune surveillance system and reduced ability of the macrophage to undergo phagocytosis. Since ethanol has been suggested to alter membrane function and inhibit the production of calcium ionophore stimulated synthesis of prostaglandins and leukotrienes by the human neutrophil and transformed murine mast cell, the dose response effect of ethanol on the biosynthesis of icosanoids by the peritoneal macrophage during zymosan phagocytosis was studied. Peritoneal macrophages from two inbred strains of mice derived from a common stock (HS) and selected for sensitivity to ethanol (shoprt sleep [SS]/long sleep [LS]) were studies. Zymosan phagocytosis was found to lead to synthesis of LTC₄ (70 ng/10⁶ cells), 6-keto-PGF_1a (5 ng/10⁶ (3 ng/10⁶ cells). For the HS macrophage, ethanol caused a dose dependent inhibition of these lipid mediators as well as inhibition of phagocytosis and release of beta-hexosaminidase. However, a difference was observed in arachidonate metabolism stimulated by phagocytosis between the LS and SS mice below 100 mM ethanol. The SS mouse had a 50% inhibition of cyclooxygenase products at 86 mM ethanol with no inhibition of lipoxygenase metabolites. The LS mice had a trend suggesting increased lipoxygenase metabolites below 100 mM ethanol. At these levels of ethanol which can be found in man, these results suggest there may be differential production of lipid mediators under genetic control.