Burkitt's lymphoma - a human tumor model system for immunological studies.

Burkitt's lymphoma occurs mainly in parts of tropical Africa and has attracted the attention of experimental workers due to its epidemiological and clinical features, which indicate a viral etiology and a host immune response to the tumor. As a result of virological studies, Epstein-Barr virus (EBV) DNA has been demonstrated in almost all tested biopsies of African BL. This contrasts to the absence of EBV in all, or almost all, of the non-African Burkitt's lymphoma-like tumors, even though the number of tested tumors in this group is small, and to the lack of EBV in all other types of lymphoma or leukemia. Immunological studies have revealed the presence of antibodies to different EBV-associated antigens in all African patients with Burkitt's lymphoma. However the antibodies are not specific for Burkitt's lymphoma but are found in most adults all over the world, although at lower levels. They cannot therefore serve diagnostic purposes, but they can give prognostic information and occasionally give clues to the mechanisms behind late tumor recurrences, and possibly guide so-called immunotherapy. Burkitt's lymphoma patients contrast to appropriate control groups where some of the persons are anti-EBV seronegative, and this, together with the presence of EBV in Burkitt's lymphoma biopsies and the absence of EBV in other lymphomas, even though the cell type involved may be infectable by EBV in vitro and the tumor may arise in an EBV-carrying person, favors an etiological role in EBV in Burkitt's lymphoma and speaks against the "passenger" hypothesis, according to which EBV is picked up by the Burkitt's lymphoma cell which happens to be particularly suitable for EBV persistence. To explain the geographical distribution, a cofactor, such as certain forms of malaria, has been implied.     

Derepression and repression of the histidine operon: role of the feedback site of the first enzyme.

Thiazolealanine, a false feedback inhibitor, causes transient repression of the his operon previously derepressed by a severe histidine limitation in strains with a wild-type or feedback-hypersensitive first enzyme but not in feedback-resistant mutants. Since experiments reported here clearly demonstrate that thiazolealanine is not transferred to tRNAHis, it is proposed that this "transient repression" is effected through the interaction of thiazolealanine with the feedback site of the enzyme. Experiments in the presence of rifampin indicate that this thiazolealanine-mediated effect is exerted at the level of translation. We conclude that histidine (free), in addition to forming co-repressor, also represses the operon at the level of translation through feedback interaction with the first enzyme of the pathway (adenosine 5'-triphosphate phosphoribosyltransferase). Rates of derepression in feedback-resistant strains are roughly half of those observed in controls, suggesting a positive role played by a first enzyme with a normal but unoccupied feedback site. Some feedback-resistant mutants, in contrast to the wild type, were unable to exhibit derepression under histidine limitation caused by aminotriazole.     

Viererbruten des Kaiseradlers(Aquila heliaca)

Ohne Zusammenfassung     

Incorporation of (3H)-arachidonic acid into cattle retina lipids: high uptake in triacylglycerols, diacylglycerols, phosphatidylcholine and phosphatidylinositol.

The incubation of (³H)-arachidonic acid-prelabeled cattle retinas for 20 min in the presence of glucose under a gas phase of 5% carbon dioxide in oxygen showed uneven labeling in lipid classes. Total phospholipids, acylglycerides and free fatty acids contained 35, 37 and 31 per cent of the total radioactivity. In phosphatidylinositol and phosphatidylcholine almost 70% of the polar lipid (³H)-arachidonate was recovered. About 70% of the total fatty acid esterified in retina lipids was found in diacylglycerols, triacylglycerols, phosphatidylinositol and phosphatidylcholine. It is concluded that the cattle retina “in vitro” takes up free arachidonic acid and that this fatty acid is further unevenly acylated into lipids.The apolar fatty acyl residues of lipids display an independent turnover and their composition may be modified by acylation-deacylation reactions. In several cellular lipids, a differential turnover of the fatty acids as compared with other lipid moieties has been indicated, such as the case of phosphatidylinositol (1–3) and cardiolipin (4). The latter is enriched in the inner mitochondrial membrane where energy conservation processes take place and the former has been implicated in synaptic transmission (5) and related with a protein identified as the acetylcholine receptor (6). In brain phosphoinositides tetraenoic molecular species are by far the largest (2) and an active acylation-deacylation cycle of arachidonic acid occurs (7). However data regarding retina phosphoinositides composition and metabolism is limited to: fatty acid distribution (8), to some studies on the phosphodiester metabolism by ³²p (9) and to a study reporting that in frog rod outer segments and retina, polyphosphoinositides are undetectable (10). The purpose of the present investigation was to observe the (³H)-arachidonic acid labeling of acylglycerides and of phosphoglyceride classes of cattle retina.     

Properties of spinach chloroplast fructose-1,6-diphosphatase

Photosynthetic fructose-1,6-diphosphatase (FDPase) fractions I and II, earlier purified from spinach leaves, show a similar amino acid composition, with the exception of a higher glutamic acid content in the latter. In both fractions glutamic and aspartic acids are the main amino acids. pH activity profiles of fractions I and II are similar, with optima at 8·65–8·70, both showing a high specificity for fructose- 1,6-diphosphate. These two fractions are Mg²⁺-dependent for activity, with an Optimum Mg²⁺ concentration of 10 mM in standard conditions, which shifts to 5 mM when the MG²⁺/EDTA ratio is increased to 10; Mn²⁺ and Co²⁺ are slightly active. EDTA enhances FDPase activity slightly, with an optimum at 0·4–0·8 mM. Cysteine has no activating effect, and acts as an inhibitor above 10 mM. Both I and II have an optimum substrate concentration of 4 mM, and the substrate inhibits at concns above this value. Kinetic velocity curves are sigmoidal, with the concave zone located in the range of physiological substrate concns. (Hill coefficient 1·75 for both). This suggests a strong regulatory role of fructose-1,6-diphosphate. K_m values are 1·4 × 10⁻³ M (fraction I) and 1·1 × 10⁻³ M (fraction II). The highest activity rate occurs at 60°, in accordance with the high thermostability of both fractions; the activation energies are 14·3 kcal/mol (fraction I) and 13·0 kcal/mol (fraction II).     

Neutral currents in weak interactions and molecular asymmetry

Weak interactions are parity violating forces, i.e. they differentiate between mirror images. Therefore it is a very attractive hypothesis to invoke weak interactions in explaining the origin of molecular asymmetry. It is, however, not clear whether weak interactions may operate between electrons and/or between electrons and protons? For these types of interactions so called neutral currents are needed. Recent experiments with muon neutrinos at CERN gave some evidence for the existence of neutral currents. Thus we may suppose that parity violating forces are active in molecules. In the first part of this paper a very elementary theory of weak interactions is outlined with special reference to the discovery of neutral currents. In the second part we show how weak interactions may differentiate between mirror image molecules. The asymmetrically distributed static charges in chiral molecules represent a helical potential field. This potential field may exert an effect on the orbital electrons and therefore coupling of spins and momenta occurs. Thus the enantiomers are parity transformed images not only as geometrical bodies, but their orbital electrons are parity transformed too as "a helical electron gas". Weak interactions will differentiate between L and D forms because their orbital electrons have a nonzero spin polarization with respect to their velocity.     

On the possible role of organic melanoidin polymers as matrices for prebiotic activity

Summary One of the major diagenetic pathways of organic matter in recent sediments involves the condensation of cellular constituents, particularly amino acids and sugars, into insoluble melanoidin-type polymers. These polymers consist mainly of humic and fulvic acids and make up the major part of the organic carbon reservoir in recent sediments. We suggest that a similar set of reactions between abiotically formed amino acids and sugars, and more generally between aldehydes and amines, occurred on a large scale in the prebiotic hydrosphere. The rapid formation of this insoluble polymeric material would have removed the bulk of the dissolved organic carbon from the primitive oceans and would thus have prevented the formation of an "organic soup".Melanoidin polymers have several properties which make them attractive hypothetical precursors of contemporary oxidation-reduction coenzymes: 1. they contain heterocyclic nitrogen compounds similar to the nitrogenous bases; 2. they contain a high concentration of stable free radicals; and 3. they tend to concentrate those heavy metals which play prominent roles in contemporary enzymic redox processes. The prebiotic formation of similar polymers could, therefore, have provided the starting point for a basic class of biochemical reactions.We suggest that the prebiotic scenario involved chemical and protoenzymic reactions at the sediment-ocean interface in relatively shallow waters and under conditions not much different from those of the recent environment.On leave from the Isotope Department, Weizmann Institute of Sciences, Rehovot, Israel. This is the address for reprint requests.On leave from the Department of Cell and Molecular Biology, San Francisco State University, San Francisco, California.On leave from the Department of Biophysics, University of Houston, Houston, Texas.     

Effect of p-chlorophenylalanine on the reproduction of the rat (author's transl)]

The effect of p-chlorophenylalanie (p-CPA) --300 mg/kg-- on reproduction has been studied in the female rat. Groups of animals were injected with a dose of 300 mg/kg of p-CPA 48 hours before proper copulation conditions at different moments along the ovarian cycle. Presence of spermatozoa in the vaginal frotis was negative in treated rats; in the control groups however, positivity was found in variable proportions according to the phase of the ovarian cycle: 30 ad 90% in diestrus and proestrus respectively. Treated animals showed continuous diestrus phases and diffuse luteinitation of the ovary. The results may indicate that a decrease of cerebral 5-HT, caused by p-CPA, lessens the reproductive behaviour of the female rat through mechanisms depending probably on the liberation of gonadrotrophins.     

Uric acid as electronic acceptor of chicken liver's XDH (author's transl)]

Uric acid seems to act as an electronic acceptor in the dehydrogenation of hypoxanthine catalyzed by chicken liver's xanthinedehydrogenase (XDH). Oxidation was observed in crude homogenates under anaerobic conditions, although dialyzed homogenates or purified hepatic XDH also induce a similar action either in aerobic or anaerobic conditions. The reaction pH optimum is about 6.0. Xanthine appears to be the only inhibited product of the reaction when its concentration is greater than 1 X 10(-4) M. When hypoxanthine and uric acid concentrations exceed 2 X 10(-3) M and 1 X 10(-4) M, respectively, they induce inhibition by substrate. Purine is a fairly good substrate of XDH when uric acid acts as acceptor. Allopurinol inhibits hypoxanthine oxidation by uric acid in the presence of XDH. XDH also catalyzes the dismutation of xanthine to hypoxanthine and uric acid.