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Biomedical subjects

G C GODMAN

Publications and source records attributed to G C GODMAN.

35 records · Page 2Linked to original sources

A cytological and cytochemical investigation of the development of the viral papilloma of human skin.

The morphological appearances and some tinctorial properties of the cells of the infectious (viral) papilloma of human skin are described. Pathological alterations of the nuclei of affected cells occur in a definite sequence of stages. In the earliest, and acidophilic Feulgen-negative intranuclear inclusion body is recognizable. Subsequently the inclusion body and nucleus enlarge, there is progressive disorganization of nuclear structure, and the inclusion body then becomes basophilic and stains with the Feulgen reaction. The nucleus finally disappears, leaving the inclusion body in the cell remnant. The relative amounts of Feulgen-colored DNA per cell at each stage in the evolution of the lesion in the infected cells, as well as in normal appearing and hypertrophic cells of the papilloma, were measured microphotometrically in Feulgen preparations. Determinations were made using the "plug" and "two wave length" methods. These are compared with measurements of DNA in cells of the basal and spinous layers of normal human skin. The frequency distribution curves of relative amount of DNA in cells of normal skin, and normal-appearing cells in hyperplastic epithelium, show the bimodal diploid and tetraploid peaks characteristic of growing tissues. Infection of the epidermal cell entails prompt synthesis of DNA in the nucleus. Increased amounts of DNA (tetraploid to 16 ploid levels) are found in the earliest recognizable cytopathological stages of infection and do not increase appreciably during the subsequent evolution of the cellular lesion. At a relatively late stage, all the cellular DNA is relocated ("transferred" or "reassembled") in the inclusion body, and is not further significantly increased in amount. Active formation of DNA in affected cells appears, from these measurements, to occur only in relatively intact nuclei. The inclusion bodies of infected cells are found to contain a relatively basic protein which stains with the alkaline-fast green method for histone.

Cell Nucleus↗

A correlated histochemical and electron microscopic study of the intranuclear crystalline aggregates of adenovirus (RI-APC virus) in HeLa cells.

HeLa cells in tissue cultures infected with types 3, 4, or 7 of adenovirus (RI-APC virus) were studied in order to correlate certain histochemical and electron microscopic findings. Adjacent thin (ca. 0.05 micro) and thick (2-4 micro) sections of osmium-fixed, methacrylate-embedded cells were cut; by mapping the sections the same cells could be identified with both the electron and the light microscope. Intranuclear crystalline aggregates seen with the electron microscope to be composed of ordered arrays of viral particles were found by means of the Feulgen reaction to contain DNA. DNA is therefore assumed to be a constituent of the viral particle. The virus appeared to develop from an osmiophilic Feulgen-negative matrix. Displacement of nuclear chromatin occurred during this process. A Feulgen-azure staining method was found to permit clear distinction between viral and nuclear (host) DNA in thick sections.

Adenoviridae↗

Evidence of differences in the desoxyribonucleoprotein complex of rapidly proliferating and non-dividing cells.

1. Quantitative cytophotometric analysis of the interphase cells of a rapidly proliferating differentiated tissue such as liver of new born rat, indicates that these cells can be separated into two groups on the basis of their staining characteristics after methanol fixation. 2. These groups are thought to correspond to two stages of interphase. The first, called "autosynthetic interphase," comprises cells which are duplicating chromosomal material in preparation for mitosis, and shows parallel increases in the methyl green and Feulgen staining of DNA and the fast green staining of histone from the diploid (2 C) to double these values (4 C). 3. The second group is designated the "heterosynthetic interphase," during which the cell ceases proliferating and functions in a manner commensurate with its state of differentiation. In this stage Feulgen staining indicates the diploid chromosomal complement, but there is a decreased capacity of the DNA to bind methyl green and of the histone to bind fast green. 4. The difference between the methyl green binding of the heterosynthetic and autosynthetic 2 C cells is due to the presence of a protein in the former which presumably inhibits staining by competing with the dye for binding sites on the DNA. The effect of this inhibition can be removed by extracting the protein, or by blocking the protein basic groups. 5. The decreased fast green staining of histone in the heterosynthetic cells can be minimized by prolonged fixation with formaldehyde. It is thought to stem either from a similar type of inhibition, or from an increased susceptibility of the histone to loss from the cell during this stage. 6. While histone inhibits methyl green staining of DNA in all cells, the differences between the staining properties of the autosynthetic and heterosynthetic interphase cells are believed to be due to another protein, whose properties appear similar to those of the chromosomal "residual protein." It is concluded that a complex of DNA and residual protein existing during the heterosynthetic interphase is dissociated during the autosynthetic interphase.

Animals↗

A microphotometric study of the syntheses of desoxyribonucleic acid and nuclear histone.

1. The fast green stain of Alfert and Geschwind for nuclear basic protein is shown to obey the Beer-Lambert laws when used on purified histone. Interference from acid substances other than nucleic acids as a possible source of error is indicated. 2. Use of this technique after a modified Feulgen stain enables determination of relative amounts of desoxyribonucleic acid and histone in the same individual cells. 3. DNA and histone are shown to have the same distribution in formalin-fixed nuclei. 4. The syntheses of DNA and histone proceed simultaneously resulting in the doubling of both these substances prior to cell division. 5. The standard error for histone values is greater than that for DNA; however, the source of this variability is not known.

Cell Nucleus↗

Pathogenesis of coxsackie virus infection; multiplication of virus and evolution of the muscle lesion in mice.

The quantitative distribution of the Conn.-5 strain of Coxsackie virus in different tissues was determined by serial titration at intervals after inoculation of 4 to 5 day old mice. High titers were reached by the 2nd day in blood, heart, liver, muscle, intestine, and its contents, and these were maintained through the 8th day, except for the blood, in which the virus level fell earlier. In paralyzed mice, muscle and brain attained the highest titers and it was in these tissues alone that virus persisted through the 9th day of illness. The pathology of the infection has been briefly described. In particular, the evolution of morbid changes in striated muscle was correlated with the concentrations of virus in muscle. Acute muscle necrosis first occurred when there was a peak viral concentration (4th day), and reached maximal intensity on the 8th day. Scattered acute lesions continued to appear while the virus titer remained above 10(-4), from the 9th to 12th day. With the decrease in the myositis, there was a concomitant decrease in the incidence of perceptible disease. Inflammation was found to follow upon the development of necrosis, and subsided slowly. Regeneration began very early, became exuberant, and led finally to restitution of the muscle.

Animals↗