Reactions of polycyclic hydrocarbon epoxides with RNA and polyribonucleotides

RNA, poly(G) and poly(A) were reacted with benz[a]anthracene 5,6-oxide or with 7,12-dimethylbenz[a]anthracene 5,6-oxide and hydrolysates of the alkylated polymers examined using a combination of Sephadex LH20 column chromatography and thin-layer chromatography on silica gel. The results show that two RNA products are formed in reactions with benz[a]anthracene 5,6-oxide, one resulting from reaction with guanine and the other from reaction with adenine. With 7,12-dimethylbenz[a]anthracene 5,6-oxide, six RNA products appeared to be formed, two resulting from reactions with guanine and three from alkylation of adenine; the other product has not been identified.     

Plasma 11-Hydroxycorticoid Levels after Carbenoxolone Sodium

A definite rise in plasma 11-hydroxycorticoid levels has been shown in eight patients with duodenal ulcer following the oral administration of carbenoxolone sodium. A similar rise was seen in one patient with sarcoidosis whose pituitary A.C.T.H. secretion had been acutely suppressed with dexamethasone. No such rise, however, was seen in three patients suffering from adrenal insufficiency. It is suggested that carbenoxolone acts directly on the adrenal cortex, causing an increased production of corticosteroids.     

Terminal Disinfection in Hospitals with Quaternary Ammonium Compounds by Use of a Spray-Fog Technique

Spray-fogging of hospital rooms with a quarternary ammonium disinfectant was found to be an effective means of reducing the number of detectable airborne and surface bacteria. The level of bacterial contamination in hospital rooms was determined before and after fogging by means of the gravitational fallout method, the petri dish swab technique, and volumetric air-sampling procedures. Rooms vacated by patients infected with staphylococci, streptococci, pseudomonads, and salmonellae were tested and found to be effectively decontaminated of most of the detectable organisms by the fogging procedure.     

THE INCORPORATION AND FATE OF H3-TYROSINE IN THE HAIR CORTEX OF RATS OBSERVED BY RADIOAUTOGRAPHY

The incorporation of H³-tyrosine into the protein of the cells in the cortex of rat hair has been investigated by radioautography. In growing hairs, radioactivity is found in the matrix, the upper bulb, and the whole of the keratogenous zone up to the fully keratinized part of the shaft, 10 and 30 minutes after an injection of labelled tyrosine. This is unequivocal evidence of protein synthesis at these sites. There is a very precise relationship between the end of protein synthesis and the hardening of the cortical cells at the top of the keratogenous zone. The way in which the silver grains of the radioautographs are clustered indicates that at 30 minutes after the injection the isotope is distributed more evenly in the matrix and upper bulb than in the top of the keratogenous zone. Possibly this reflects a difference, at these sites, in the cell components engaged in protein synthesis, or in the proteins being synthesized. The fully keratinized and hardened part of the hair was not radioactive at 10 and 30 minutes after the injection of H³-tyrosine. The rate at which the radioactivity moves into this region shows that the hair of rats grows 0.9 mm/24 hours. Comparison of the degree of radioactivity along the growing hair in the 30-minute, 12-hour, and 36-hour materials shows conclusively that protein accumulates in the cortical cells during their keratinization. An injection of a labelled amino acid does not behave as an ideal pulse dose; consequently, the grain density over the hair cortex at 36 hours is 100 per cent larger than would be expected if an ideal pulse dose situation existed.     

A convenient pH-gradient method for the determination of the maximum and minimum pH for microbial growth

Previously existing methods for determining the pH limits for the growth of microorganisms have involved (1), the setting up of individual cultures, each having a specific pH; (2), the pH gradient plate technique devised by Sacks (1956) in which a continuous pH gradient is established in a Petri dish by means of a buffer system; and (3), the pH gradient plate technique of Zak (unpublished), in which a continuous pH gradient is established by means of an electric current. The discontinuous pH gradient technique described here provides a convenient method of determining the maximum and minimum pH at which a microorganism can grow. The technique can be used aerobically or anaerobically, and has a precision of about ± 0.1 pH unit. Data are given for several yeasts and forSerratia marcescens. In all cases, the organisms tested continued to metabolize at pH values beyond those representing the limits for growth, sometimes by as much as 0.5 pH unit. The results suggest that pH limits are unsuitable criteria in microbial classification.     

Conjugations with glutathione. The enzymic conjugation of some chlorocyclohexenes

1. α-3,4,5,6-Tetrachlorocyclohex-1-ene and γ-2,3,4,5,6-pentachlorocyclohex-1-ene are conjugated with glutathione in vitro by a rat-liver enzyme that is probably glutathione S-aryltransferase. 2. Chlorocyclohexane and the α-, β-, γ- and δ-isomers of hexachlorocyclohexane were not substrates for rat-liver glutathione S-aryltransferase. 3. Glutathione-S-aryltransferase activity was present in tissue preparations of houseflies of insecticide-resistant and -susceptible strains. More activity was found in a dieldrin-resistant strain of houseflies fed on dieldrin than in either a dieldrin-resistant strain not fed on dieldrin or a control strain of dieldrin-susceptible houseflies. 4. Housefly soluble supernatant preparations converted S-(2-chloro-4-nitrophenyl)glutathione into the corresponding cysteine and mercapturic acid derivatives.     

Evidence of a Monoaminergic-Cholinergic Imbalance Related to Visual Hallucinations in Lewy Body Dementia

Senile dementia of Lewy body type is characterized clinically by a relatively acute onset of fluctuating memory loss and confusion, frequently accompanied by visual hallucinations. Neurochemical analyses of temporal cortex has revealed a distinction between hallucinating and nonhallucinating patients in both cholinergic and monaminergic transmitter activities. In contrast with the cholinergic enzyme choline acetyltransferase, which was more extensively reduced in hallucinating individuals, serotonergic S2 receptor binding and both dopamine and serotonin metabolites were significantly decreased in nonhallucinating cases. These results suggest that an imbalance between monaminergic and cholinergic transmitters is involved in hallucinogenesis in the human brain.     

Complement proteins C5b-9 induce secretion of high molecular weight multimers of endothelial von Willebrand factor and translocation of granule membrane protein GMP-140 to the cell surface

The effect of immune activation of the serum complement system on the secretory response of human endothelial cells was examined. Exposure of antibody sensitized cultured umbilical vein endothelial cells to human serum resulted in secretion of very high molecular weight multimers of von Willebrand factor which coincided with new surface expression of the intracellular granule membrane protein GMP-140. This response required complement activation through deposition of C5b-9 and was not observed with cells exposed to antibody plus C8-deficient serum or to membrane C5b-8 (in the absence of C9). This C5b-9-induced secretion was observed with minimal cell lysis, as assessed by the release of lactic dehydrogenase. Delayed addition of C8 and C9 to cells exposed to antibody plus C8-deficient serum revealed a rapid decay of membrane C8 binding sites accompanied by loss of the secretory response, suggesting a process of removal or inactivation of nascent C5b67 complexes deposited on the endothelial surface. Membrane assembly of C5b-9 complexes caused an increase in endothelial cytosolic [Ca2+], due to influx across the plasma membrane. This C5b-9-dependent increase in cytosolic [Ca2+] and concomitant von Willebrand factor secretion were both abolished by removal of external calcium. In addition to being linked to the level of external Ca2+, the C5b-9-induced secretory response was partially inhibited by the protein kinase inhibitor, sphingosine. The capacity of the C5b-9 proteins to stimulate endothelial cells to secrete a platelet adhesive protein provides one mechanism for increased platelet deposition at sites of inflammation, and suggests the potential for other functional changes in endothelium exposed to C5b-9 during intravascular complement activation.