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PubMed1998

TRAM regulates the exposure of nascent secretory proteins to the cytosol during translocation into the endoplasmic reticulum.

Translocational pausing is a mechanism used by certain specialized secretory proteins whereby discrete domains of a nascent chain destined for the endoplasmic reticulum lumen are transiently exposed to the cytosol. Proteoliposomes reconstituted from total endoplasmic reticulum proteins properly assemble translocationally paused intermediates. The capacity of the translocon to correctly pause the nascent chain is dependent on a glycoprotein fraction whose active component is TRAM. In the absence of TRAM, the normally sealed ribosome-membrane junction still opens in response to a pause transfer sequence. However, nascent chain domains that are not exposed to the cytosol in the presence of TRAM are so exposed in its absence. Thus, TRAM regulates which domains of the nascent chain are visible to the cytosol during a translocational pause.

Animals↗
PubMed1986

Effects of intrahippocampal injections of the cholinergic neurotoxin AF64A on open-field activity and avoidance learning in the rat.

The effects of direct intrahippocampal administration of the cholinergic neurotoxin, AF64A, were investigated in male rats. Bilateral injections of AF64A (5 nmole/2 microliters) produced a significant decrease in choline acetyltransferase (CAT) activity in the dorsal hippocampus (25%) and overlying frontoparietal cortex (30%) but no changes in the striatum. Rats lesioned with AF64A exhibited increased levels of open-field activity, which was most marked at 1 week after the lesion; however, the rates of intrasession habituation were similar in lesioned and control rats. Lesioned rats also displayed deficits in acquisition and retention of a passive avoidance task and less dramatic deficits in acquisition of two-way shuttle box avoidance. These findings indicate that lesioning of cholinergic terminals in the hippocampus and/or cerebral cortex with AF64A leads to long-term deficits in learning and memory as well as increases in open-field activity.

Animals↗
PubMed1981

Influence of the immunomodulating compound BM 12.531 (azimexone) on radioresistance and granulopoietic colony forming units in mice.

BM 12.531 (azimexone) increases the survival of mice exposed to 650 rad. Levamisole, isoprenosine or aristolochia acid have no effects in this system. After administration of 25 mg/kg azimexone to C57 Bl/6-mice a statistically significant increase in CFUc was found. Maybe this increase in CFUc can explain the radioprotective effect of azimexone.

Adjuvants, Immunologic↗
PubMed2000

Structural differences between foot-and-mouth disease and poliomyelitis viruses influence their inactivation by aziridines.

Inactivation of foot-and-mouth disease virus (FMDV) and poliovirus by ethyleneimine (EI) and N-acetylethyleneimine (AEI) has been studied at 25 degrees and at 37 degrees C and in different ionic conditions. FMDV is inactivated rapidly in 100 mM Tris pH 7.6 by each reagent at both temperatures. Poliovirus is also inactivated rapidly in 100 mM Tris by EI at both temperatures and by AEI at 37 degrees C. However, it is inactivated much more slowly by AEI at 25 degrees C; but if the virus is first incubated overnight at 2 degrees C with AEI before transferring to 25 degrees C inactivation then proceeds rapidly. Moreover, the rate of inactivation at 25 degrees C is markedly increased if the virus is suspended in 1 mM Tris. We had interpreted these differences as being due to the greater penetrability of poliovirus (i) in 100 mM Tris at 37 degrees C compared with 25 degrees C and (ii) at lower ionic strength. This interpretation has been confirmed by electron microscopy of FMDV and poliovirus particles stained with phosphotungstic acid. At the elevated temperature, poliovirus had an average diameter of 34+/-0. 21 nm and the stain outlined the nucleic acid core and the individual subunits, whereas at 25 degrees C it averaged 28+/-0.13 nm and the stain did not penetrate the particle. This study also showed that the particle diameter alters with changes in buffer concentration, being 28+/-0.13 nm in 100 mM Tris, 31+/-0.16 nm in 10 mM Tris and 34+/-0.21 nm in 1 mM Tris. The changes in poliovirus are reversible as addition of 1/10 volume of 1 M Tris to the virus in 1 mM Tris resulted in the return of the diameter to 28+/-0.13 nm. FMDV, on the other hand, was less sensitive to osmotic differences as its particle diameter only varied by 7% over the 100-fold change in buffer concentration compared with the 22% change observed for poliovirus.

Animals↗
PubMed1978

Interaction of endosulfan and metepa in rats.

Repeated administration of endosulfan or metepa or their mixture did not induce any significant histological changes in the organs examined in male rats. Similarly, the activity of different enzymes assayed here showed no significant alterations. The level of endosulfan did not differ significantly in presence or absence of metepa in the samples of blood, brain, fatty tissue, kidney, liver and testis. The observations do not suggest any kind of additive or antagonistic effects or potentiation of each compound in presence of the other, at the doses and duration studied in male rats.

Animals↗
PubMed1985

In the search for new anticancer drugs XI. Anticancer activity of nitroxyl labeled phosphoric N,N;N',N';N",N"-tris[1,2-ethanediyl]triamide(TEPA) and phosphorothioic N,N;N',N';N",N"-tris[1,2-ethanediyl]triamide(thio-TEPA) derivatives.

In order to further evaluate the effect of the nitroxyl moiety on the anticancer activity of nitroxyl labeled analogues of phosphoric N,N;N',N';N",N"-tris[1,2-ethanediyl]triamide (TEPA) and phosphorothioic N,N;N',N';N",N"-tris[1,2-ethanediyl]triamide (thio-TEPA), the activity of these compounds was compared in vivo, using murine lymphoid leukemia L1210, with the reduced forms of the drugs, i.e. the hydroxylamines and amine congeners. At optimum dose, all compounds were active. However, the nitroxyl containing compounds were more active than the corresponding reduced forms. An admixture of 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl had no effect on the activity of thio-TEPA. Consequently, the nitroxyl moiety must be an integral part of the anticancer drug's structure in order to influence that drug's performance.

Animals↗
PubMedDate not supplied

[Preliminary study of the comparative action of 1 methyl-2 (2 naphtyl) aziridine on kindling effect and on paradoxical sleep (author's transl)].

Methyl-2 (2 Naphtyl) Aziridine (MNA) is a new agent which has been demonstrated to have effects on paradoxical sleep (PS) and on the levels of cerebral noradrenaline (Yamamoto, 1975). It has been tried on a experimental model of epilepsy, the kindling effect, produced in the cat by repetitive stimulation of the amygdala. The results obtained in the cat confirmed blockage of paradoxical sleep (PS) and revealed a marked reduction in the number of stimuli required to produce the effect. The shortening of the time before the first generalised seizure did not seem attributable to privation of paradoxical sleep. The role of cerebral catecholamine reduction, however, is discussed.

Animals↗