Tissue-specific expression of three types of beta-protein precursor mRNA: enhancement of protease inhibitor-harboring types in Alzheimer's disease brain

Expression of three types of mRNA encoding amyloid beta-protein precursor (APP) in various tissues was analysed, using a ribonuclease protection assay, with special reference to Alzheimer's disease (AD). The total content and the proportion of APP mRNAs were specific to each tissue. Among eight tissues examined, the brain was distinct in that the expression level was highest and APP695 mRNA was expressed in abundance. The ratio of APP770/APP751/APP695 mRNAs was approximately 1:10:20 in the cerebral cortex of control brain. The proportions of APP770 mRNA and APP770-plus-APP751 mRNAs increased up to 2.6- and 1.4-fold, respectively, in various regions of AD brain compared with control. The enhanced expression of protease inhibitor-harboring types (APP770 and APP751) may disturb the balance between biosynthesis and degradation of APPs and ultimately lead to accumulation of beta-protein as amyloid.     

2-(p-Nitrophenyl)-2''-deoxyadenosine, a new type of mutagenic nucleoside.

A crude preparation of 2-phenyladenosine was found to be mutagenic in the Ames Salmonella assay. In the purification of this preparation, it was revealed that 2-phenyladenosine itself was nonmutagenic but that 2-(m- and p-nitrophenyl)-adenosines (5m,p) contaminating the sample were the mutagenic principles. A structure-activity relationship study was carried out, and it was found that 5p, 2-(p-nitrophenyl)-adenine (7p), and 2-(p-nitrophenyl)-2'-deoxyadenosine (15p) were strongly mutagenic toward S. typhimurium TA98 and TA100 without metabolic activation, the potency being in the order 15p greater than 7p greater than 5p. The potency of 15p in TA98 was one order of magnitude greater than that of 4-nitroquinoline N-oxide. 15p also showed mutagenicity in the mouse cell line FM3A in culture.     

Lidocaine inhibits stimulation-coupled responses of neutrophils and protein kinase C activity

The effects of lidocaine, a local anesthetic, on various stimulation-coupled responses of neutrophils were studied. Superoxide generation, generation of chemiluminescence, depolarization of membrane potential and transitional increase in intracellular Ca2+ were inhibited by lidocaine in a concentration dependent manner. Lidocaine also inhibited Ca(2+)-activated phospholipid-dependent protein kinase (PKC) in the presence of various concentrations of Ca2+, phosphatidylserine and dioleoylglycerol. For the inhibition of all these stimulation-coupled responses, a similar order of the lidocaine concentration was needed. As in the case of dibucaine (Mori, T., Takai, Y., Minakuchi, R., Yu, B. and Nishizuka, Y., J. Biol. Chem. 255:8378-8380, 1980), lidocaine inhibited PKC activity in a manner competitive with phosphatidylserine. Lidocaine also inhibited the phosphorylation of 47 kDa neutrophil cytosplasmic protein, a phosphorylated protein required for NADPH oxidase activation. Thus, the cellular membrane phospholipid may be one of the target sites of lidocaine for the inhibitory action on the various stimulation-coupled responses of neutrophils, and these effects of lidocaine may correlate with its inhibitory action on PKC activity.     

Effect of adsorption of an inhibitory factor on raw starch hydrolysis by glucoamylase

An inhibitory factor (IF) produced byAspergillus niger strain 19, and which inhibits the action of glucoamylase on starch, has the ability to be tightly adsorbed on to various raw starches, though the amount differs from starch to starch. Based on the hydrolysis of the IF-starch complex by glucoamylase, the inhibitions per unit IF adsorbed are similar for some varieties of starch. The effectiveness ratio of IF (% hydrolysis inhibition per % IF adsorbed on raw starch) for corn, sweet potato, waxy rice and waxy corn starches are 1.1, 1.0, 0.85 and 0.96, respectively. These results support the hypothesis that both glucoamylase and IF are adsorbed on to a common binding site on raw starch. However, the effectiveness ratio of IF for cassava and wheat starches are 0.71 and 1.65, respectively, which differ significantly from other varieties of starch.

---

Résumé Un inhibiteur (facieur IF) produit par la souche 19 d'Aspergillus niger et qui inhibe l'action de la glucoamylase sur l'amidon a la propriété d'être fortement adsorbé sur dives amidons, bien que la quantité varie d'amidon à amidon. Sur la base de l'hydrolyse du complexe amidon-IF par la glucoamylase, les inhibitions par unité d'IF adsorbé sont sembiables pour quelques variétés d'amidon. Le rapport d'efficience de IF (% d'inhibition de l'hydrolyse par % de IF adsorbé sur l'amidon cru), pour le maïs, la patate douce, et les amidons de riz cireux et de maîs cireux vaut respectivement 1.1, 1.0, 0.85 et 0.96. Ces résultats soutiennent l'hypothèse que tant la glucoamylase que le lacteur IF sont adsorbés sur un site commun de liaison de l'amidon cru. Toutefois, le rapport d'efficience du facteur IF pour les amidons de manioc et de froment valent respectivement 0.71 et 1.65, valeurs significativement différentes de celles pour les aufres variétés d'amidon.

     

T cells subsets responsible for clearance of Sendai virus from infected mouse lungs

T cell subsets responsible for clearance of Sendai virus from mouse lungs determined by adoptive transfer of immune spleen cell fractions to infected nude mice. T cells with antiviral activity developed in spleens by 7 days after intranasal infection. Spleen cell fractions depleted of Lyt-2+, Lyt-1+, or L3T4+ cells showed antiviral activity in vivo, although the degree of the activity was lower than that of control whole spleen cells. The antiviral activity of the Lyt-2+ cell-depleted fraction was consistently higher than that of L3T4+ (Lyt-1+)-depleted cells. In vitro cytotoxic activity against Sendai virus-associated, syngeneic lipopolysaccharide-blast cells was detected in stimulated cells from intraperitoneally immunized mice but was lost after depletion of Lyt-2+ cells. Multiple injection of anti-Sendai virus antibody into infected nude mice had no effect on lung virus titer. These results indicate that L3T4+ (Lyt-1+) and Lyt-2+ subsets are cooperatively responsible for efficient clearance of Sendai virus from the mouse lung.     

Some characteristics of a raw starch digestion inhibitory factor fromAspergillus niger

Summary The effect of an inhibitory factor (IF) fromAspergillus niger 19 on raw starch digestion by pure glucoamylase I of blackAspergillus, pure glucoamylae ofRhizopus niveus, bacterial -amylase, fungal -amylase and various combination was investigated. The IF caused higher inhibition of raw starch hydrolysis by the combined action of glucoamylase and fungal -amylase than of hydrolysis by the individual enzymes. A protein moiety of IF might play an active part in this inhibition phenomenon. The IF was bound to starch granules, preventing hydrolysis by the enzymes, and caused decreased raw starch hydrolysis yields.     

Serodiagnosis of Streptococcus pneumoniae infection in guinea pigs by an enzyme-linked immunosorbent assay

Guineapig antibodies to Streptococcus pneumoniae (SPN) serotype 19F were detected by an enzyme-linked immunosorbent assay using a simple procedure. In experimentally infected hosts, antibody was detectable as early as 2 to 3 weeks after infection, and high titres were maintained for a long period. Antibodies higher than 1:64 were regarded as specific. In a field study, high antibody titres were shown in SPN enzootic colonies in contrast to negative or low antibody titres in a majority of the animals from non-enzootic and SPF colonies.