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Biomedical subjects

H R MORGAN

Publications and source records attributed to H R MORGAN.

At least 55 records · Page 3Linked to original sources

Latent viral infection of cells in tissue culture. II. Relationship of cell nutrition to initiation of growth of psittacosis virus.

When chick embryo tissues cultivated for 13 days in Hanks's balanced salt solution (BSS) were infected with psittacosis virus (6BC), they did not support active viral multiplication until synthetic medium 199 of Parker (3) was added. By testing various combinations of the substances in this and other synthetic media, it was found that the minimum number of compounds required to effectively stimulate virus growth in the presence of BSS comprised the amino acids and water-soluble vitamins found in medium 199. Addition of either amino acids or water-soluble vitamins alone to BSS resulted in only slight stimulation of viral proliferation. Many constituents of the synthetic media were found not to be essential to the stimulation of viral multiplication. The following substances added to a medium containing amino acids and water-soluble vitamins in BSS failed to increase the quantity of virus produced: diphosphopyridine nucleotide (DPN), triphosphopyridine nucleotide (TPN), coenzyme A, the fat-soluble vitamins, ribose sugars, and three biological reducing agents: cysteine, glutathione, and ascorbic acid. Among other substances that proved to be not essential a group of purines and pyrimidines present in medium 199 were found to be probably toxic to cells in the concentrations used, since virus titers were lower in media containing these compounds than in those from which they were absent. A change in the nutritional status of these cells involving amino acids and water-soluble vitamins has thus permitted to transform a latent, undetectable viral infection to an inactive infection in vitro.

Amino Acids↗

Latent viral infection of cells in tissue culture. I. Studies on latent infection of chick embryo tissues with psittacosis virus.

Chick embryo tissues maintained for from 11 to 28 days in Hank's balanced salt solution lost their capacity to support the multiplication of psittacosis virus. The virus however infected such cells, as active multiplication of the virus occurred on the addition of beef embryo extract to this nutritionally poor medium at any period up to 28 days of cultivation in balanced salt solution. The virus remained in a state of latency for as long as 15 days in these starved cells in a non-infectious phase. These results obtained in this in vitro model system for the investigation of latent infections of cells with psittacosis virus suggest that cell nutrition as well as an alteration in the immunological defenses of the host may prove to be an important factor in the activation of latent viral infections.

Chlamydophila psittaci↗

Studies on hypersensitivity of human tissues in vitro. I. Tuberculin hypersensitivity.

A new simple method of evaluating specific cytotoxicity to tuberculoprotein in the study of tuberculin hypersensitivity in vitro by comparing cell populations is presented. Utilizing this technic it was possible to reproduce Rich's results (1, 2) using human tissues of reticuloendothelial origin. The demonstration of the specific cytotoxic phenomenon in tuberculin-sensitive human tissues indicates that the principle elaborated by Rich (2) of specific changes in the individual fixed tissue cells in tuberculin hypersensitivity, possibly related to cellular antibodies, applies to human subjects as well as to the animals heretofore studied. Preliminary observations suggest that macrophages from donors with clinically active tuberculosis are more sensitive to tuberculoprotein than macrophages from tuberculin-positive donors without clinically active disease. Macrophages from tuberculin-positive donors appeared to be more sensitive to tuberculoprotein than fibroblasts derived from the same tissue. An inhibition of cell proliferation was seen when both cell types were exposed to PPD. In addition macrophages responded to tuberculoprotein with gross morphological changes and eventual cytolysis.

Animals↗

Factors related to the growth of psittacosis virus (strain 6BC). IV. Certain amino acids, vitamins, and other substances.

The analogues of amino acids, beta-2-thienylalanine, ethionine, and 6-methyltryptophane, inhibited the growth of psittacosis virus (6BC) in tissue culture without evidence of serious toxicity for the host cells. Of a number of vitamin analogues tested, only salicyl-beta-alanide inhibited viral multiplication in the absence of toxic effects on the host cells. 6,7-Diethylriboflavin, desoxypyridoxine, and oxythiamine reduced viral growth in concentrations that possessed some toxicity for host tissue. In tolerated amounts, 3-acetylpyridine, pyridine-3-sulfonic acid, pantoyl sulfanilamide, and desthiobiotin did not effect viral multiplication. Sodium malonate inhibited psittacosis virus growth in non-toxic amounts, whereas sodium monofluoroacetate was ineffective. Colchicine suppressed multiplication of virus only after a prolonged period of exposure and subsequent delay before producing inhibition, suggesting that the effect was secondary to its antimitotic action which suppressed multiplication of the host cells.

Alanine↗

Studies on the factors essential to the initiation and maintenance of multiplication of psittacosis virus (6BC strain) in deficient cells in tissue culture.

The growth of psittacosis virus (6BC) was studied in cultures of minced whole chick embryo tissue maintained in either Hanks-Simms solution or Hanks's balanced salt solution (BSS), and in neither medium could sustained, long-term virus growth take place. Addition of beef embryo extract (BEE) to cultures at a time when virus multiplication was declining reversed this general trend and resulted in greater virus growth. This virus-stimulating action of BEE was only partially diminished by colchicine, a mitotic inhibitor, indicating that the action of BEE was not due entirely to the development of a larger population of cells as a result of its enhancement of cell proliferation. Chick embryo tissue cultivated for 13 days in BSS prior to infection lost its ability to support the growth of psittacosis virus, but this capacity could be restored by the addition of BEE, alone or with colchicine, at the time of infection. A significant amount of virus was adsorbed to tissue in BSS alone, indicating that the failure of virus to grow in depleted tissue maintained only in BSS after infection was not due entirely to failure of virus to attach to and invade the cells. It was found that an ultrafiltrate and a dialysate of BEE contained the major part of the stimulating capacity of the whole extract, indicating that the active materials were substances of low molecular weights. Autoclaved lactalbumin hydrolysate was an active stimulator, suggesting that the materials responsible for its activity were relatively heat-stable. Since a chemically defined medium (Parker 199) was equally effective in stimulating viral growth, it should be possible eventually to define the chemical nature of the virus stimulators. The implications of the findings are discussed with special reference to their application in the study of tissue tropisms and of latency in viral infections of cells.

Chlamydophila psittaci↗

Factors related to the growth of psittacosis virus (strain 6BC). I. Pteroylglutamic acid, vitamin B12, and citrovorum factor.

The inhibitory action of sodium sulfadiazine on the growth of psittacosis virus (6BC) in embryonated eggs is readily reversed by citrovorum factor but not by small amounts of vitamin B(12). In embryonated eggs, the pteroylglutamic acid analogues, 9-methylpteroylglutamic acid and 4-aminopteroylaspartic acid, produced some suppression of the growth of psittacosis virus (6BC). 4-Aminopteroylglutamic add, 4-amino-N(10)-methylpteroylglutamic acid, and 4-aminopteroylaspartic acid inhibited the growth of this virus in tissue cultures at concentrations which were not toxic for the host tissue. The inhibitory action of 4-amino-N(10)-methylpteroylglutamic acid and 4-aminopteroylaspartic acid was readily overcome by addition of citrovorum factor. Growth of meningopneumonitis virus in embryonated eggs or tissue culture is suppressed by 4-aminopteroylaspartic acid. The advantages of the tissue culture technic for studies on the growth of viruses are discussed.

Chlamydophila psittaci↗

Factors related to the growth of psittacosis virus (strain 6BC) II. Purines, pyrimidines, and other components related to nucleic acid.

In various amounts and mixtures, adenine, guanine, xanthine, hypoxanthine, thymine, thymidine, cytidylic acid, and an enzymatic digest of desoxyribonucleic acid all failed to influence the inhibition by sulfadiazine of the growth of psittacosis virus (6BC) in embryonated eggs. A number of purine analogues, including benzimidazole, 2,6-diaminopurine, and 8-azaguanine, inhibited the growth of psittacosis virus (6BC) in tissue cultures at concentrations which had no obvious toxic effects on the host tissues. The virus inhibitory action of 2,6-diaminopurine was reversed by addition of adenine and that of 8-azaguanine by guanine. The growth of psittacosis virus (6BC) was inhibited by the pteridine compounds 2-ammo-4-hydroxy-6-formylpteridine and xanthopterin, while other related substances had little or no inhibitory activity. Xanthine reversed the inhibitory effects of 2-amino-4-hydroxy-6-formylpteridine. There was no correlation between the inhibitory activity of the pteridines on xanthine oxidase and multiplication of the virus.

2-Aminopurine↗