Pharmacokinetic disposition of pethidine under tolerance

Under tolerance, evoked by multiple doses of pethidine (PD), the serum and brain tissue content of PD was related to diminished analgesic activity. Even though in tolerant rats no enhancement of PD biotransformation in the liver could be recognized (as followed by the measurement of hepatic esterase and N-demethylase activity), the amounts of both PD and nor-PD excreted in urine were increased under tolerance. The authors conclude that the faster disposition of PD may contribute to the development of tolerance.     

Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130

Interleukin-6 mediates pleiotropic functions in various types of cells through its specific receptor (IL-6-R), the cDNA of which has already been cloned. We report here that an 80 kd single polypeptide chain (IL-6-R) is involved in IL-6 binding and that IL-6 triggers the association of this receptor with a non-ligand-binding membrane glycoprotein, gp130. The association takes place at 37 degrees C within 5 min and is stable for at least 40 min in the presence of IL-6, but does not occur at 0 degree C. Human IL-6-R can associate with a murine gp130 homolog and is functional in murine cells. Mutant IL-6-R lacking the intracytoplasmic portion is functional, suggesting that the two polypeptide chains interact to involve their extracellular portion. In fact, a soluble IL-6-R lacking the transmembrane and intracytoplasmic domains can associate with gp130 in the presence of IL-6 and mediate its function. These findings indicate that the complex of IL-6 and IL-6-R can interact with a non-ligand-binding membrane glycoprotein, gp130, extracellularly and can provide the IL-6 signal.     

Reciprocal unconditional-conditional organization of the fundamental emotions and paraadaptive personality reactions

Paraadaptive personality reactions (PPR) are modes of behavior and experience on the borderline of normal psychology and psychopathology. In them the thinking is overdetermined or obsessive. Overdetermined PPR are well illustrated in common proverbs. The people's wisdom has also knowledge of the obsessive (or "magic") paraadaptive rituals for prevention of possible misfortunes (such as touching wood, keeping away from a black cat, etc.). One part of the PPR is described in the psychoanalytical literature as defense mechanisms. The analysis of thought dissociation in schizophrenia shows that the reciprocal relations could be considered as a basic principle of functional organization on all levels of nervous and psychic activity. Proceeding from this assumption, the author proposes the conception of a reciprocal neuropsychological unconditional-conditional affect-behavioral system (ABS). It consists of ten subsystems corresponding to the basic emotions. Each subsystem stimulates the personality toward predetermined forms of thinking and behavior. In adequate conditions the reciprocal processes in the ABS are well counterweighted and integrated. In some persons and in situations of greater affective "loading" this reciprocal balance is disorganized, which leads to PPR. In this paper a neuropsychological analysis is made of the overdetermined PPR, reflected in such proverbs as "Not being able to beat the donkey, he beats the packsaddle" and "The thief cries catch the thief."     

Antigenic similarity between cytoplasmic tetrodotoxin-sensitive protein and neuronal membrane proteins

Membrane proteins with a molecular weight of 290, 180, and 55 kDa were isolated using immunosorbent attached to sepharose and rabbit antibodies to cytoplasmic tetrodotoxin-sensitive protein from beef brain gray matter. A technique used for research into voltage-dependent sodium channels was applied to reconstruction of these proteins and investigation of toxin-dependent sodium flows through the lipoprotein membrane. Findings are interpreted as evidence of the similarity between cytoplasmic tetrodotoxin-sensitive protein and that of sodium channels at the cell membrane.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev; A. V. Palladin Institute of Biochemistry, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 4, pp. 485–489, July–August, 1989.     

Spread of fast thermowaves through the cerebral cortex produced by visual stimulation

Thermowaves spreading through the cerebral cortex were observed and investigated during acute experiments on white rats using a new technique — that of thermoencephaloscopy (TES) through the intact skull. These waves were induced by regular visual stimulation (at intervals of 1.5–3 min) or by initiating one of the flashes and spread through the cortex along trajectories of five basic types; amplitude of thermowaves: 0.005–0.1°C; length: 10–15 mm; duration 1.2–11.4 sec; velocity: 1–33 mm/sec; extent of pathway: 2–56 mm. They appeared with a high degree of probability (of 0.92) during the interval between 15 sec before and 26 sec after the flash. Numbers of moving waves declined by the point of stimulus application and rose by 7–8 sec after the flash. Waves arose in 50% of cases in the contralateral visual cortex (areas 17 and 18a), spreading to the midline and crossing to the ipsilateral hemisphere (areas 17, 18a, and 7). Local waves moving along a circular trajectory were also discovered in the contralateral visual cortex. Several types of wave, differing in trajectory, also arose in the ipsilateral visual cortex. Mechanisms and possible significance of this effect are examined.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 21, No. 4, pp. 467–475, July–August, 1989.     

Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein

To study the putative precursor proteins (PreA4(695), PreA4(751), and PreA4(770] of Alzheimer's disease A4 amyloid protein, polyclonal and monoclonal antibodies were raised against a recombinant bacterial PreA4(695) fusion protein. These antibodies were used to identify the precursors in different cell lines as well as in human brain homogenates and cerebrospinal fluid (CSF). The precursors are tyrosine-sulfated, O- and N-glycosylated membrane proteins and have half-lives of 20-30 min in cells. Cells express the polypeptides at their surface but also secrete C-terminal truncated proteins into the medium. These proteins are also found in CSF of both Alzheimer's disease patients and normal individuals. The proteins are derived from their cognate membrane-associated forms by proteolysis and have apparently lost the cytoplasmic and the transmembrane domains. Since the latter contributes to the A4 amyloid sequence, it seems possible that this proteolytic cleavage represents the first step in the formation of A4 amyloid deposits.     

Production of trichothecene and non-trichothecene mycotoxins by Fusarium species isolated from maize in Minnesota

Eighty-two cultures of Fusarium species isolated in 1986 from moldy maize in Minnesota were each cultured on rice for 4 weeks and found to produce the following mycotoxins: F. graminearum isolates, deoxynivalenol (DON, 4–225 g/g), 3-acetyldeoxynivalenol (3-ADON, 2–4g/g), 15-acetyldeoxynivalenol (15-ADON, 1–35 g/g) and zearalenone (ZEA, 5–4350 g/g); F. moniliforme, fusarin C (detectable amounts to 1000 g/g); F. mòniliforme, F. oxysporum, F. proliferatum and F. subglutinans isolates, moniliformin (15–6775 g/g); F. moniliforme, F. proliferatum, and F. subglutinans isolates, fusaric acid (detectable amounts). Other mycotoxins screened for in each rice sample and not detected were T-2 toxin, HT-2 toxin, neosolaniol, T-2 tetraol, nivalenol, fusarenon-X, scirpenols, alpha and beta trans-zearalenols, wortmannin, and fusarochromanone. The rat feeding bioassay indicated that other, unidentified toxins may be present.     

Two distinct O-methyltransferases in aflatoxin biosynthesis

The substances belonging to the sterigmatocystin group bear a close structural relationship to aflatoxins. When demethylsterigmatocystin (DMST) was fed to Aspergillus parasiticus NIAH-26, which endogenously produces neither aflatoxins nor precursors in YES medium, aflatoxins B1 and G1 were produced. When dihydrodemethylsterigmatocystin (DHDMST) was fed to this mutant, aflatoxins B2 and G2 were produced. Results of the cell-free experiment with S-adenosyl-[methyl-3H]methionine showed that first the C-6-OH groups of DMST and DHDMST are methylated to produce sterigmatocystin and dihydrosterigmatocystin (O-methyltransferase I) and then the C-7-OH groups are methylated to produce O-methylsterigmatocystin (OMST) and dihydro-O-methylsterigmatocystin (DHOMST) (O-methyltransferase II). However, no methyltransferase activity was observed when either OMST, DHOMST, 5,6-dimethoxysterigmatocystin, 5-methoxysterigmatocystin, or sterigmatin was incubated with the cell extract. Treatment of the cell extract with N-ethylmaleimide inhibited O-methyltransferase I activity but not that of O-methyltransferase II. Furthermore, these O-methyltransferases were different in their protein molecules and were involved in both the reactions from DMST to OMST and DHDMST to DHOMST. The reactions described in this paper were not observed when the same mold had been cultured in YEP medium.     

Cyclic analogs of des-Arg9-[Leu8]bradykinin

Four cyclic derivatives of des-Arg9[Leu8]bradykinin have been obtained by classical methods of peptide chemistry. They are cyclo-(-X-Arg-Pro-Pro-Gly-Phe-Gly-Pro-Leu-), where X=Lys or none, and cyclo-(Y-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Leu-), where Y= Lys or Orn. Peptide bonds have been formed by the pentafluorophenylester method, and cyclization has been carried out in a diluted dioxane solution with 40% yield. Subsequent cleavage of protecting groups was made by treatment with hydrogen fluoride. The products obtained were purified by droplet counter-current chromatography. These substances liberate histamine from the rat mast cells comparably to bradykinin and fail to produce myotripic and vascular effects.     

Specificity of deletion events in pBR322

The reversion of mutations due to inserts of identical palindromic DNAs just 1-bp apart in the amp gene of plasmid pBR322 varied up to 3000-fold (U. DasGupta, K. Weston-Hafer, and D.E. Berg (1987) Genetics 115, 41-49). The experiments reported here show that the intrinsic frequencies of deletion from these sites are truly very different. Deletions were selected by the joint loss of sacB (sucrose sensitivity) and lacZ alpa genes cloned together at these sites, without requiring restoration of the ampr allele. We found that greater than 90% of deletions at each of these sites do restore the ampr allele. This result reinforces the view that the probability of forming a particular deletion depends strongly on the DNA sequence at its prospective endpoints.