Effect of ay-9944 on sterol biosynthesis in Chlorella sorokiniana

When Chlorella sorokiniana was grown in the presence of 4 ppm AY-9944 total sterol production was unaltered in comparison to control cultures. However, inhibition of sterol biosynthesis was shown by the accumulation of a number of sterols which were considered to be intermediates in sterol biosynthesis. The sterols which were found in treated cultures were identified as cyclolaudenol, 4α,14α-dimethyl-9β,19-cyclo-5α-ergost-25-en-3β-ol, 4α,14α-dimethyl -5α-ergosta-8,25-dien-3β-ol, 14α-methyl-9β,19-cyclo-5α-ergost-25-en-3β-ol, 24-methylpollinastanol, 14α-methyl-5α-ergost-8-en-3β-ol, 5α-ergost -8(14)-enol, 5α-ergost-8-enol, 5α-ergosta-8(14),22-dienol, 5α-ergosta-8,22-dienol, 5α-ergosta-8,14-dienol, and 5α-ergosta-7,22-dienol, in addition to the normally occurring sterols which are ergosterol, 5α-ergost-7-enol, and ergosta-5,7-dienol.The occurrence of these sterols in the treated culture indicates that AY-9944 is an effective inhibitor of the Δ⁸ → Δ⁷ isomerase and Δ¹⁴-reductase, and also inhibits introduction of the Δ²²-double bond. The occurrence of 14α-dimethyl-5α-ergosta-8,25-dien-3β-ol and 14α-methyl-9β,19-cyclo-5α-ergost -25-en-3β-ol is reported for the first time in living organisms. The presence of 25-methylene sterols suggests that they, and not 24-methylene derivatives, are intermediates in the biosynthesis of sterols in C. sorokiniana.     

Do antibody binding techniques identify polysomes synthesizing a specific protein?

Specific binding of antibody directed against MOPC-21 myeloma protein to MOPC-21 polysomes has been demonstrated. It was also shown that this same antibody bound specifically to the ribosomal subunits of these polysomes, suggesting that the antibody is not binding exclusively to the nascent polypeptide chains on the polysomes. The antibody was bound specifically to polysomes of a nonproducing variant XC1 which had been isolated in the presence of MOPC-21 myeloma protein while the antibody was not bound to XC1 polysomes isolated in the absence of myeloma protein. This suggests that the myeloma protein is adsorbed to the polysomes during the isolation procedure.     

Circulatory effects of prolonged hypoxia before and during antihistamine.

Five chronically instrumented healthy dogs were exposed to a 5-day period of breathing 10% oxygen in a chamber. The response to hypoxia was found to be time dependent. During the first 24 h of hypoxia the circulatory response was characterized by increases in cardiac output, heart rate, pulmonary and systemic arterial blood pressures, and pulmonary vascular resistance. Systemic vascular resistance increased; left atrial pressure decreased. During the early part of hypoxia the animals became hypocapnic; the arterial blood pH rose significantly. During the rest of the hypoxic period cardiac output, heart rate, and arterial blood pH returned to the control values; pulmonary and systemic arterial pressures and pulmonary vascular resistance remained significantly elevated. Systemic vascular resistance rose; left atrial pressure remained below control. This response to hypoxia was not substantially modified when the experiment was repeated during the administration of the antihistamine promethazine, an H1-receptor blocking agent, in a dose which blocked the pulmonary vasoconstrictor response to small doses of exogenous histamine. The circulatory response to acute hypoxia in five anesthetized dogs was not modified by intravenous administration of metiamide, an H2-receptor blocking agent.     

Componental analysis of the ocellar electroretinogram of the locust, Schistocerca gregaria

Ruck's componental analysis of the ocellar electroretinogram (ERG) has been reappraised using techniques of signal averaging and waveform subtraction. Components (1), (3), and (4) can readily be isolated in the locust ocellus but component (2) as recorded in the locust ocellus is probably an artefact. Component (1), produced by the receptor cells, only contributes significantly to the total ERG at higher light intensities and it is this contribution which changes most with the degree of light and dark adaptation employed in these experiments. Component (3), the response of the second-order neurones, indicates that the majority of second-order neurones hyperpolarize on illumination of the ocellus. Component (4), the afferent activity of the second-order cells, indicates that more than one afferent axon is involved in the production of off spikes in the locust ocellus.     

SPINAL CORD LIPIDS AND MYELIN COMPOSITION IN BORDER DISEASE (HYPOMYELINOGENESIS CONGENITA) OF LAMBS

Spinal cords from clinically affected newborn lambs, each with muscular spasms (‘shaking’) and a ‘hairy’ birth coat, were found to be deficient in DNA and to contain less myelin and various lipid components, suggesting retarded CNS development equivalent to about 124 days conceptual age. Cerebrosides were notably deficient in whole cord and isolated myelin and contained more saturated and less unsaturated fatty acids than normal. The rate of cerebroside synthesis assayed in vitro was enhanced and taken with the very low tissue concentrations this indicated faster cerebroside turnover and a less stable myelin in the spinal cords of lambs affected with Border Disease. Marked decreases in plasmalogen concentrations, the redistribution of phospholipid fractions, the presence of about 8 per cent cholesterol in the esterified form and the characteristic fatty acid composition of these esters strongly suggest that degeneration is concomitant with myelin immaturity. Hypocupraemia, low concentrations of copper in the cerebrum and increased concentrations in spinal cord myelin are additional features of the clinical disease. The latter result may be related to myelin immaturity.     

Role for protein kinase C in the modulation of glomerular PGE2 production by angiotensin II

Angiotensin II increased PGE2 release from superfused glomeruli, and stimulated labeled inositol phosphate production. 12-O-Tetradecanoyl phorbol -13-acetate (TPA, 10(-7) M), which stimulates protein kinase C activity in soluble fractions of glomerular homogenates, suppressed angiotensin II actions on inositol phosphate production and PGE2. By contrast, 4a phorbol 12,13 di-decanoate and phorbol had no effect on protein kinase C activity or angiotensin II induced increases in inositol phosphate or PGE2. 1-(5-Isoquinolinyl)-2-methylpiperazine (H-7), which inhibits protein kinase C activity in soluble fractions of glomerular homogenates, prevented TPA induced suppression of angiotensin II actions on inositol phosphate production and PGE2. Moreover H-7 prolonged the time course of angiotensin II induced inositol phosphate production and enhanced angiotensin II actions on glomerular PGE2 production. The results support a role for inositol phospholipid hydrolysis through the phospholipase C pathway in the mediation of angiotensin II actions on PGE2 in glomeruli and are consistent with negative modulation of these actions by protein kinase C.