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Biomedical subjects

R T Johnson

Publications and source records attributed to R T Johnson.

At least 199 records · Page 11Linked to original sources
PubMed1980

Pathogenesis of human poliovirus infection in mice. I. Clinical and pathological studies.

Human poliovirus infection in mice was studied to determine the similarities to human poliomyelitis, the selective vulnerability of neurons to infection, the role of the immune response in age-dependent susceptibility, and possible viral persistence. Mice inoculated intracerebrally (ic) with the Lansing type 2 poliovirus developed a disease with clinical, pathological, and age-dependent features resembling human poliomyelitis. Adult mice had a shorter incubation period (50% paralysis, Day 8 vs. Day 13) and a higher incidence of paralysis (97% vs. 79%) than newborns. Only paralyzed animals had pathologic changes in the spinal cord, and these corresponded to the degree of paralysis. Fluorescent antibody staining showed that selective infection of neurons was most intense in the anterior horn motor neurons of the spinal cord. There was no extraneural virus replication and no systemic neutralizing antibody response. Cyclophosphamide immunosuppression enhanced rather than diminished disease, indicating that maturation of immune responses did not explain the relative resistance of newborns to paralysis.

Animals↗
PubMed1980

Pathogenesis of human poliovirus infection in mice. II. Age-dependency of paralysis.

The mechanism of resistance of newborn mice to poliovirus-induced paralysis was studied by comparing regional virus replication in the adult and in the newborn central nervous systems (CNS) after intracerebral (ic) and intraspinal inoculation. Initial virus replication in the brains was similar in both age groups. Paralysis correlated with replication of virus in the spinal cord to a constant threshold, and this replication in newborns was delayed. Intraspinal inoculation of newborns eliminated the delay, indicating that neonatal anterior horn motor neurons were fully susceptible to infection. Cordectomy prevented the spread of virus, despite patent cerebrospinal fluid (CSF) pathways. Thus, poliovirus appeared to spread within the CNS via an axonal transport system. Known maturational changes in the fast transport system may explain the relative resistance of immature mice to poliovirus-induced paralysis.

Age Factors↗
PubMed1980

A comparison of the structural polypeptides of five strains of mumps virus.

The polypeptide patterns of five strains of mumps virus have been compared under uniform electrophoresis conditions. These strains included the MJ and RW strains, recently isolated from human cerebrospinal fluid, the neuro-adapted Kilham strain and the chick embryo-adapted Enders and Jeryl Lynn strains. A similar pattern of polypeptides, featuring six common and virus-specific species, was obtained with purified virus grown in ovo, in hick embryo fibroblasts (CEF) or in Vero cells. These polypeptides have been designated VP1 (mol. wt. 200000), VP2 (mol. wt. 80000 or 75000), VP3 (mol. wt. 68000), VP4 (mol. wt. 58000), VP5 (mol. wt. 45000), VP6 (mol. wt. 39000). The virus glycoproteins were identified as VP2 and VP4; the nucleocapsid-associated proteins as VP1, VP3 and VP5. Additional polypeptides occurring both in uninfected Vero cells and in uninfected CEFs appeared in polypeptide profiles of purified mumps virus preparations, and could not be designated virus-specific polypeptides. Alhtough strain differences were minimal, we did observe (1) an extra protein, nucleocapsidassociated, in patterns from the chick-adapted Enders strain of mumps virus and (2) strain-dependent variability in the size of VP2.

Animals↗
PubMed1980

Morphological heterogeneity in relation to structural and functional properties of mumps virus.

The morphological heterogeneity of the chick embryo-adampted Enders strain of mumps virus was examined in relation to biological and biochemical properties of the virus. The range of virion sizes increased as multiplicity of infection (m.o.i.) increased, with virions of 800 to 1000 nm in diam. occurring in preparations grown at the higher multiplicities. There was no evidence for a distinct class of noninfectious haemagglutinating particles. Dense fractions from isopycnic gradients of virus were enriched in larger virions, but virus RNA was predominantly a single 50S species. Despite evidence that many virions were multiploid, u.v. inactivation kinetics were single-hit, suggesting only a single biologically active genome per virion.

Centrifugation, Isopycnic↗
PubMed1980

Packing DNA into chromosomes.

Electron microscopy of HeLa metaphase nucleoids (i.e. whole metaphase cells exposed to 2 M salt and non-ionic detergent) spread by the Kleinschmidt technique, reveals a variety of protein-depleted structures (spreads) derived from chromosomes. Spreads vary in size and shape. At one extreme are oval structures with one or more cores surrounded by a network of supercoiled fibres. These fibres are probably arranged as loops and we estimate that 600-1000 may emerge from a single, large core region. At the other extreme are chromosome-shaped spreads with an elongated core which takes the form of a multifibred axis. At intervals groups of lateral fibres appear to emerge from each axis to produce the network. Spreads intermediate between these extremes occur in which axial fibres can be resolved in only part of the elongated core. Similar structures are observed in chromosomes deproteinized and spread after isolation by a procedure which preserves high molecular weight DNA. The appearance of chromosomes isolated by the Wray-Stubblefield hexylene glycol procedure agrees in general with previous findings of others, except that in some more extended spreads axial fibres are visible. We believe our observations are consistent with the idea that the chromonema of each metaphase chromatid contains regions of multistranded DNA. We do not propose, however, that the chromatid is functionally multineme, but rather that axial fibre folding either within or between chromomere regions contributes to packing of DNA in the metaphase chromosome. These regions of constraint re also postulated as the locations of emergence of lateral loops. In spread preparations the axial fibres are seen clearly only when chromatids have been elongated beyond the contracted metaphase length. Elongation would be produced both by relaxation of chromosomal coils (gyres) and by extension of the chromonema upon deproteinization and spreading. Whereas in deproteinized nucleoids the long axis is liable to elongate, fragment or collapse, the chromomena of Wray-Stubblefield chromosomes is locked at the metaphase (gyred) length and axial fibres are generally not visible. We propose that the assembly of the complex DNA axis of the metaphase chromosome from its extended interphase counterpart plays a major part in increasing the DNA packing ratio in the mitotic cell.

Cell Nucleus↗
PubMed1980

Producing positive interaction among Down syndrome and nonhandicapped teenagers through cooperative goal structuring.

Effects of cooperative, competitive, and individualistic goal structures compared on the dimensions of interpersonal interaction and attraction. Subjects were nonhandicapped and Down syndrome junior high school students who participated in eight weekly sessions of recreational bowling. Results indicated that significantly more positive interactions and evidence of greater interpersonal attraction took place between the nonhandicapped students and the Down syndrome students in the cooperative condition than in the competitive and individualistic conditions. .

Adolescent↗
PubMed1979

Ultraviolet-induced DNA excision repair in human B and T lymphocytes. II. Effect of inhibitors and DNA precursors.

Despite their great sensitivity to ultraviolet light purified human B and T lymphocytes are capable of complete repair provided that the ultraviolet dose does not exceed 0.5 Jm-2. Their capacity to repair, as measured by the restoration of DNA supercoiling in preparations of nucleoids, and their survival are significantly increased in the presence of deoxyribonucleosides. Certain agents which inhibit semi-conservative DNA synthesis (hydroxyurea, 1-beta-D-arabinofuranosylcytosine (arafCyt) either stop or delay the repair process in lymphocytes. The effect of hydroxyurea is eventually overcome spontaneously, but changes in the sedimentation behaviour of ultraviolet-irradiated nucleoids caused by arafCyt can only be neutralized by addition of deoxycytidine. The effective inhibition of repair by arafCyt permits the detection of extremely small amounts of ultraviolet damage and also the estimation of when repair is complete.

Animals↗
PubMed1979

Repair and survival after UV in quiescent and proliferating Microtus agrestis cells: different rates of incision and different dependence on DNA precursor supply.

Cultured cells of Microtus agrestis, the common field vole, perform unscheduled DNA synthesis after UV irradiation. They respond to incubation with a DNA synthesis inhibitor (1-beta-D-arabinofuranosylcytosine) following UV in ways typical of cells capable of excision repair, with reduced survival and an accumulation of breaks in pre-existing DNA. Microtus cells irradiated with UV in a quiescent pre-S-phase state are more sensitive to UV than are proliferating cells, in terms of survival. Adding DNA precursors (deoxyribonucleosides), and--in case of proliferating cells--growing in complete rather than dialysed serum, enhance UV survival. Quiescent cells show a higher rate of endonucleolytic incision of DNA after UV than do proliferating cells. The balance between incision (producing single-strand DNA breaks) and repair DNA synthesis (leading to rejoining of breaks) is shifted by the addition of deoxyribonucleosides, which suggests that DNA precursor supply is a rate-limiting factor in repair. The lower survival of quiescent cells (in the absence of added deoxyribonucleosides) may be due to insufficient precursor supply to meet the demands of the high incision rate.

Animals↗
PubMed1979

DNA damage in synchronized HeLa cells irradiated with ultraviolet.

The lethal effect of UV radiation of HeLa cells is least in mitosis and greatest in late G1-early S. Photochemical damage to HeLa DNA, as measured by thymine-containing dimer formation and by alkaline sucrose sedimentation, also increases from mitosis towards early S phase. Computer simulations of UV absorption by an idealized HeLa cell at different stages of the cell cycle indicate that changes in damage could be due solely to changes in chromatin geometry. But survival is not exclusively a function of damage.

Cell Division↗
PubMed1979

Detection of polyoma virus DNA in PML-brain tissue by (in situ) hybridization.

The human papova (JC) virus was extracted from brain of a patient with progressive multifocal leukoencephalopathy. A single band of virus was obtained at a density of 1.345 g/ml CsCl.JC virus DNA was purified and a highly specific cRNA was generated in vitro. In situ hybridization with JC virus cRNA and autoradiography on sections of the same brain revealed silver grains over oligodendrocytes, astrocytes and possible vascular endothelial cells, indicating the presence of JC virus DNA in these different cell classes.

Astrocytes↗
PubMed1979

Interactions between immune cells and antibody in protection from fatal Sindbis virus encephalitis.

Transfer of anti-Sindbis virus serum, obtained from peripherally inoculated donors, protected mice from an otherwise fatal intracerebral infection with neuroadapted Sindbis virus (NSV). F(ab)'2 preparations of serum were not protective, indicating that the Fc piece of immunoglobulin G was important. Complement-depleted animals were protected with anti-NSV serum, ruling out as essential the complement-fixing function of the Fc piece. The presence of protective antibody correlated with the ability of serum to inhibit T-cell cytotoxicity. However, experiments using athymic nude mice showed that T cells played no role in killing the mice since the 50% lethal dose was the same as that in normal BALB/c mice, and that T cells were not required for protection since athymic nude mice were protected with antibody alone. Cyclophosphamide treatment of NSV-infected mice ablated the protective capacity of anti-NSV serum. Therefore, a non-T cell, cyclophosphamide-sensitive cell was required for antibody-mediated protection.

Animals↗