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Biomedical subjects

R T Johnson

Publications and source records attributed to R T Johnson.

At least 235 records · Page 13Linked to original sources
PubMed1977

The inhibition of repair in UV irradiated human cells.

We have used three different assay procedures to determine the effects of hydroxyurea on excision repair in UV-irradiated HeLa cells. The results were as follows. (a) At the cytological level, incubation of UV-irradiated metaphase cells with hydroxyurea caused chromosome decondensation. (b) Using a modified alkaline sucrose gradient sedimentation technique involving minimal lysis before centrifugation, we found a marked retardation in the sedimentation of DNA from UV-irradiated cells incubated for a short period with hydroxyurea. (c) The effect of hydroxyurea on the incorporation of[3H]thymidine by UV-irradiated G1 cells was found to depend on the concentration of thymidine present in the medium. Normal primary human cells resemble HeLa cells in the response of chromosomes and DNA to UV plus hydroxyurea. Xeroderma pigmentosum cells, deficient in excision repair, are not sensitive to hydroxyurea in our assays. Chromosome decondensation and retarded DNA sedimentation occur also after incubation of irradiated HeLa cells with deoxyadenosine, but not thymidine, at concentrations which inhibit semiconservative DNA synthesis. The effects of hydroxyurea or deoxyadenosine on chromosomes and DNA are not seen if all four deoxyribonucleoside precursors of DNA are supplied exogenously. These results point to an inhibition of repair DNA synthesis by hydroxyurea (or deoxyadenosine), at the level of the supply of DNA precursors, i.e. in the same way that these agents inhibit semiconservative DNA synthesis. In the presence of these inhibitors, single-strand gaps accumulate in the DNA.

Cell Division↗
PubMed1977

Effects of ultraviolet light on synchronized Chinese hamster ovary cells; potentiation by hydroxyurea.

We have examined the effects of hydroxyurea on u.v.-irradiated Chinese hamster CHO-KI cells. Ultraviolet irradiation followed by incubation with hydroxyurea causes only slight disruption of DNA and chromosome structure in CHO-KI cells compared with HeLa cells. There is, however, a clear potentiation by hydroxyurea of the u.v. killing of CHO-KI cells, which is most pronounced at those points in the cycle which are reported to have small DNA precursor pools. This potentiation is reduced when DNA precursors are provided together with hydroxyurea. These data are discussed in terms of an uncoupling of excision and repair DNA synthesis.

Animals↗
PubMed1977

Induction of brain tumors in hamsters with BK virus, a human papovavirus.

The oncogenicity of BK virus for the central nervous system was studied in newborn hamsters. The virus was weakly oncogenic after intracerebral inoculation. Two of 45 hamsters treated with antithymocyte serum developed tumors whereas no untreated hamsters developed tumors. Both tumors were choroid plexus papillomas by histologic and electron microscopic examination. Cells cultured from one tumor had growth characteristics of transformed cells and had intranuclear T antigen; but infectious virus could not be rescued. Cultured tumor cells were weakly oncogenic for hamsters, but theoncogenicity of these cells was enhanced when the recipient animals were treated with antithymocyte serum. The possible role of host immune response as a basis for the weak oncogenicity of BK virus is discussed.

Animals↗
PubMed1977

Role of the immune response in recovery from Sindbis virus encephalitis in mice.

The role of the immune response in recovery from acute encephalitis was studied by using a neuroadapted strain of Sindbis virus. Intracerebral inoculation of this virus caused fatal disease in weanling mice. Passive transfer of homologous immune serum protected mice, but transfer of immune spleen cells and lymph node cells failed to alter mortality. Transfers were made 24 hr after intracerebral infection of the recipient, when central nervous system infection was established. The protective factor in serum was present 7 days after donor infection, was specific for Sindbis virus, and appeared to be IgG; however, the protection did not correlate with virus-neutralizing activity.

Animals↗
PubMed1976

Studies of human papovavirus tumor antigen in experimental and human cerebral neoplasms.

Three types of papovaviruses (JC, BK, and SV40) have been isolated from man. All three are oncogenic in hamsters, cause frequent infection of man, and share a common T antigen. Augmentation of the expression of T antigen by in vitro cultivation of SV40-induced tumors of hamsters suggested that growing human brain tumors in vitro might provide an effective screening technique for the SV40 virus. In a series of human brain tumors examined in cryostat sections and in tissue culture, T antigen could not be demonstrated, suggesting that by this immunofluorescent technique SV40 was not implicated in the etiology of these tumors.

Animals↗
PubMed1976

Acute encephalopathy caused by defective virus infection. I. Studies of Newcastle disease virus infections in newborn and adult mice.

An acute encephalopathy caused by a defective paramyxovirus infection was studied. Newcastle disease virus (ndv), given intracerebrally, caused neurologic disease and death in mice. Infected newborn mice died by the fourth day after inoculation, and abundant amounts of virus were recovered from their brains. Infected 4-week-old mice died by the eighth day, but only minimal amounts of virus, if any, were recovered. The brains of many moribund 4-week-old mice were histologically normal and contained no NDV antigen on fluorescent antibody staining. No serum antibody to NDV was detected. These features make this infection difficult to distinguish from a metabolic encephalopathy.

Age Factors↗
PubMed1976

Perturbation of mammalian cell division. III. The topography and kinetics of extrusion subdivision.

If mitotic-arrested, cold-stored HeLa cells are incubated at 37 degrees C a proportion of the population divides by an aberrant process which we have called subdivision by extrusion. This process has been studied by time-lapse photography and shown to differ from normal cleavage in several respects. The cell surface becomes more generally mobile and, instead of producing the precisely localized furrowing activity of cytokinesis, gives rise to multiple surface protrusions. These protrusions enlarge at the expense of the parent cell and develop into a cluster of small daughter cells (mini segregants). The surface structure of the cell, as seen by scanning electron microscopy, also changes; the microvilli characteristic of interphase, metaphase and cleaving HeLa cells are lost during extrusion and the cell surface becomes smooth. Extrusion activity is much more variable than division by cleavage in terms of both topography and kinetics, and in general takes longer to complete. Some cells in the cold-treated populations divide by mixtures of cleavage and extrusion or by cleavage alone. The relative numbers of cells dividing in different ways vary with the conditions of pretreatment and incubation of the mitotic cells. The greater the perturbation (e.g. longer cold storage), the greater the proportion of extruding rather than cleaving cells. Human diploid cells can also be induced to subdivide by extrusion. Possible mechanisms underlying the different types of division activity are discussed.

Cell Division↗
PubMed1976

Experimental viral infections of the inner ear. I. Acute infections of the newborn hamster labyrinth.

Acute viral infections of the inner ear were produced in neonatal hamsters. Viruses were inoculated percutaneously through the temporal cartilage into the endolymphatic and perilymphatic spaces of the labyrinth or were inoculated intracerebrally to reach the perilymphatic spaces via the cochlear aqueduct. Selective vulnerability of inner ear structures was demonstrated using a variety of viruses. Influenza virus infected only the mesenchymal cells of the perilymphatic channels of the cochlea; mumps virus infected principally endolymphatic structures; herpes simplex virus infected primarily the sensory cells of the labyrinth; and rubeola and vaccinia viruses infected both perilymphatic and endolymphatic cells.

Acute Disease↗
PubMed1975

Changes in the organization of chromosomes during the cell cycle: response to ultraviolet light.

Fusion between mitotic and interphase cells results in the premature condensation of the interphase chromosomes into a morphology related to the position in the cell cycle at the time of fusion. These prematurely condensed chromosomes (PCC) have been used in conjunction with u.v. irradiation to examine the interphase chromosome condensation cycle of HeLa cells. The following observations have been made: (I) There is a progressive decondensation of the chromosomes during G1 which is accentuated by u.v. irradiation: (2) The chromosomes become more resistant to u.v.-induced decondensation during G2 and mitosis. (3) There is a close correlation between the degree of chromosome decondensation and the amount of unscheduled DNA synthesis induced by u.v. irradiation during G1 and mitosis: (4) Hydroxyurea enhances the ability of u.v. irradiation to promote the decondensation of chromosomes during G1, G2 and mitosis. Hydroxyurea also potentiates the lethal action of u.v. irradiation during mitosis and G1. These data are discussed in relation to the suggestion that chromosomes undergo a progressive decondensation during G1 and condensation during G2.

Autoradiography↗