Inhibition of herpes simplex virus replication by retinoic acid.

The retinoic acid (RA) isomers all-trans-RA, 9-cis-RA and 13-cis-RA as well as other retinoids were tested for their ability to reduce the yield of herpes simplex virus-1 (HSV-1). RA isomers reduced HSV-1 replication whereas the other retinoids, retinol, retinal, beta-carotene and amide derivatives of RA were not inhibitory. All-trans-RA reduced the yield of HSV-1 by 100-fold at 5 micrograms/ml but 9-cis-RA and 13-cis-RA reduced viral replication by 10-fold. At a concentration of 10 micrograms/ml all-trans-RA and 9-cis-RA reduced virus yield by 1000-fold while 13-cis-RA decreased HSV-1 production by 100-fold. RA isomers at a concentration of 10 micrograms/ml were not cytotoxic for the Vero cells used in these studies. Immunofluorescence studies showed that all-trans-RA treated cell cultures exhibited small foci of virus specific immunostaining while untreated cultures displayed intense HSV-1 immunoreactivity in virtually the entire cell population. RA-dependent inhibition of HSV-1 replication required the presence of RA with the virus. HSV-1 replication proceeded when RA was removed from infected cells. Treatment of cell cultures with RA did not induce gene expression for type-1 interferon (IFN) or for the type-1 IFN inducible genes studied suggesting that RA inhibition of HSV-1 replication is not mediated by IFN. These studies have established the ability of RA to reduce the replication of HSV-1 in vitro.

Taurine uptake by cultured human lymphoblastoid cells.

Cultured human lymphoblastoid cells take up taurine from the medium by two processes: 1) a temperature-dependent, Na+-dependent, saturable "active"-transport system and 2) diffusion. The active transport has properties similar to those reported for taurine transport by other tissues. Apparent Km is about 25 microM and Vmax about 7.2 pmol/min/10(6) cells; saturation occurs at 100 microM taurine. Uptake is competitively inhibited by the beta-amino acids hypotaurine (50% inhibition at 44 microM) and beta-alanine (50% at 152 microM), as measured at 50 microM taurine. Taurocyamine inhibits 50% at 260 microM. Chlorpromazine and imipramine are strong uncompetitive inhibitors, giving 50% inhibition at 26 microM and 115 microM, respectively; at these concentrations cellular viability per se is not affected. Ouabain inhibits 40-50% over a concentration range of 4-500 microM. Diffusion of taurine into the cells is proportional to concentration up to 20 mM. However, at the concentration of taurine in human plasma, 40-100 microM, active transport would provide 90% of the taurine taken up.

Ornithine carbamoyltransferase deficiency in an adult male patient: significance of hepatic ultrastructure in clinical diagnosis.

Ornithine carbamoyltransferase (OCT) activity was deficient (8% of control) in the liver of a 21-year-old man who died after suddenly becoming comatose. Activities of other enzymes of the urea cycle in the liver were normal. There was no known prior illness or injury; the patient, however, had been taking liquid protein supplements to his diet. Hyperammonemia and orotic aciduria were present, and the concentration of lysine in the plasma was elevated. Survey of earlier reports indicates that neither the specific deficiency of hepatic OCT nor the urine and plasma findings provide a basis for definitive diagnosis of the patient's illness as primary OCT deficiency or as Reye's syndrome. Indeed, the age of the patient at onset of symptoms and the absence of any prodromal infection argue against the OCT deficiency being either primary or a sequel to Reye's syndrome. We suggest that it was secondary to mitochondrial injury caused by an unknown agent. Electron microscopic study of hepatocyte ultrastructure lends support to this view; abnormalities of the patient's mitochondria (bizarre, elongated shapes) do not resemble those seen in Reye's syndrome, nor have abnormalities been found in primary OCT deficiency.