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Biomedical subjects

T C Johnson

Publications and source records attributed to T C Johnson.

At least 145 records · Page 8Linked to original sources
PubMed1976

Comparison of central nervous system disease produced by wild-type and temperature-sensitive mutants of vesicular stomatitis virus.

The pathogenicity of infection produced following intracerebral (i.c.) inoculation of wild-type vesicular stomatitis virus (VSV) or temperature-sensitive (ts) mutants of VSV was compared. ts mutants used were ts 31 (VSV complementation group II) and ts 41 (VSV complementation group IV). The i.c. injection of wild-type VSV in weanling Swiss mice produced a rapidly fatal encephalitis with death of mice in 2 to 3 days. Histopathologically, such mice exhibited minimal changes of encephalitis on light microscopy. In contrast to the highly virulent, rapidly fatal central nervous system (CNS) infection seen after i.c. inoculation of wild-type VSV, infection with ts 31 VSV produced a more slowly progressive CNS infection characterized by hind limb paralysis and death 6 to 9 days after infection. Histopathologically, CNS infection with ts 31 is associated with previously unreported extensive spongiform changes in the gray matter of the spinal cord. The inoculation of ts 41 i.c., on the other hand, did not result in either clinical illness or histopathological changes in the spinal cords or brains of infected mice. The absence of clinical and histopathological lesions following i.c. infection of ts 41 VSV suggests that the capacity to alter the pathogenesis of VSV CNS infection may be a function of only certain ts mutants of VSV.

Animals↗
PubMed1976

Spectral density analysis of the effects of barbiturates and benzodiazepines on the electrocorticogram of the squirrel monkey.

The effects of pentobarbital and diazepam were compared in a series of tests in squirrel monkeys; the effects of phenobarbital and flurazepam were compared in a second series. Observations were made of gross behavior and on the ECoG; the latter was analyzed by the spectral density technique. The two barbiturates induced sedation,which was occasionally so deep that the monkeys could not be readily aroused. The benzodiazepines induced sedation in some monkeys, but others showed signs of restlessness. The ECoG showed general slowing with the barbiturates, whereas the benzodiazepines produced mixed fast and slow patterns. Spectral density analysis showed that pentobarbital increased activity at frequencies below 40 Hz, with the largest increases occurring below 8 Hz. Phenobarbital increased activity below 8 Hz, but differed from pentobarbital by decreasing activity above 13 Hz. The benzodiazepines increased activity below 8 Hz, decreased it between 8 and 20 Hz, and increased it between 20 and 50 Hz.

Animals↗
PubMed1976

Status spongiousus resulting from intracerebral infection of mice with temperature-sensitive mutants of vesicular stomatitis virus.

Mice infected intracerebrally (i.c.) with wild-type (wt) VSV or temperature-sensitive (ts) mutants, ts 11, ts 22, ts 31 and ts 41, were studied for the development of histopathological lesions in the central nervous system (CNS). Mice infected i.c. with wt VSV exhibited histopathological lesions consisting principally of occasional foci of perivascular mononuclear cell infiltration and rare foci of necrosis. All wt VSV infected mice died within 2 days of i.c. inoculation. In contrast, mice infected i.c. with ts 22 and ts 31 developed spongiform lesions limited to the grey matter of the spinal cord beginning 4 days after inoculation. The spongiform lesions rapidly spread to involve the entire grey matter of the spinal cord by 5-7 days after infection. Vacuolar changes were restricted principally to neuronal processes and astrocytes. Ts 22 and ts 31 infected mice developed neurological illness beginning 4 days after infection and the majority of mice died by 7 days after infection. Mice infected with ts 11 and ts 41, on the other hand, remained clinically well and were devoid of neuro-pathological lesions at 4 and 8 days after infection.

Animals↗
PubMed1976

An ultrastructural study of central nervous system disease produced by wild-type and temperature-sensitive mutants of vesicular stomatitis virus.

Outbred Swiss mice 3 to 4 weeks of age were injected intracerebrally with wild-type vesicular stomatitis virus or its temperature-sensitive (ts) mutants ts 11, ts 22, ts 31, and ts 41. Brain and spinal cord were then studied for pathologic changes by electron microscopy. All mice infected with wild-type vesicular stomatitis virus died within 2 days of inoculation. Diffuse ependymal alterations often culminating in necrosis in brain and especially spinal cord and rare foci of necrosis and mononuclear cell infiltration in the injected hemisphere were the main pathologic changes in these animals. In contrast, mice infected intracerebrally with ts 22 and ts 31 showed their first clinical signs, consisting of hind limb paralysis, on day 4 and did not die until day 7 or 8 after inoculation. Ependymal alterations were of less severe degree in these animals, whereas the most striking changes were those of status spongiosus limited to the gray matter of the spinal cord. Such status spongiosus was mainly due to ballooning of dendrites and astrocytic processes, although myelin and neurons were also occasionally involved. Mice infected with ts 11 and ts 41, on the other hand, remained clinically well and failed to show significant pathologic features at 4 and 8 days after intracerebral inoculation. This study would indicate that some ts mutants of vesicular stomatitis virus are capable of altering the fulminating disease produced by the parent virus and of producing strikingly different pathologic changes.

Animals↗
PubMed1976

In vivo assembly and maturation of vesicular stomatitis virus.

Previous studies on vesicular stomatitis virus (VSV) maturation in infected cells have utilized in vitro cell cultures. The present study is, to our knowledge, the first in vivo analysis of VSV-cell interaction in the central nervous system of weaning outbred Swiss mice. Intracerebral inoculation of wild-type VSV resulted in rapid viral replication in brain and spinal cord. By immunoflourescence, viral antigens were first seen in ependymal cells of brain and spinal cord and soon thereafter in surrounding neurons. The large anterior horn neurons of spinal cord appeared to be in the most heavily infected. Ultrastructurally, VSV-neuron interaction evolved in three phases. The first phase consisted of viral entry into the cell by fusion and viropexis. The second phase was characterized by nucleocapsid accumulation and resulted in the appearance of large cytoplasmic inclusions. The third phase was maturation and release from the infected cell and was accomplished by viral budding from plasma membranes. Degenerative changes in infected neurons were generally absent. Cells in the area of the central canal seemed to present a different pattern of virus-cell interaction especially at the level of maturation and release. Some of these cells in advanced stages of degeneration showed viral particles free in nucleocapsid material with no virus-membrane association. Viral budding was not observed and, because these cells do eventually die, it is possible that virus was released in the intercellular space at the moment of cellular disruption. These results suggest that VSV-cell interactions may vary depending upon the nature of the infected cells.

Animals↗
PubMed1975

The mechanism of polyribosome disaggregation in brain tissue by phenylalanine.

The injection of neonatal mice with phenylalanine resulted in a rapid decrease in brain polyribosomes and a concomitant increase in monomeric ribosomes. Animals of 1-16 days of age were equally affected by phenylalanine, although the brain polyribosomes of 60-day-old mice were relatively resistant to the effects of phenylalanine. The population of free polyribosomes appeared to be more sensitive to phenylalanine treatment than bound polyribosomes, which were somewhat more resistant to disruption by high concentrations of the amino acid. The effects of phenylalanine were more pronounced with polyribosomes in the cerebral cortex than with those in the cerebellar tissue. The mechanism of polyribosome disruption was shown to be independent of hydrolysis mediated by ribonuclease. Virtually all of the monomeric ribosomes that resulted from phenylalanine treatment were shown to be inactive with regard to endogenous protein synthesis and were present in the cell cytoplasm as vacant couples. These ribosomes were readily dissociated by treatment with 0.5 M-KCl and subsequent ultracentrifugation. These results are discussed in the light of the possibility that high concentrations of phenylalanine disrupt brain protein synthesis by a molecular mechanism that is associated with initiation events.

Aging↗
PubMed1974

Thermostability of mammalian brain ribosomes and the effects of nucleoside triphosphates on their heat-sensitivity.

Mammalian brain ribosomes were found to be heat-labile. On preincubation of the ribosomes at 37 degrees C, their ability to participate in polypeptide-synthesis reactions was substantially diminished. Despite the sensitivity of ribosomal protein synthesis to heat-inactivation, preincubation resulted in no significant alterations in ribosomal sedimentation profiles or changes in the integrity of the ribosomal RNA. The thermolability of brain ribosomes was shown to be associated with their inability to bind both template RNA and aminoacyl-tRNA. Similar experiments with brain ribosomal subunits demonstrated that the small (40S) subunit was more sensitive to heat-inactivation than the large (60S) subunit. The presence of ATP (1mm) protected ribosomes from thermal inactivation, although this protection was shown to be temporary. The protection appeared to be specific to nucleoside triphosphates, since GTP and UTP also stabilized ribosomes to thermal denaturation whereas nucleoside diphosphates (ADP) and nucleoside monophosphates (AMP and cyclic AMP) did not alter ribosomal sensitivity to heat. Although 1mm concentrations of nucleoside triphosphates protected ribosomes from heat-inactivation, the presence of higher concentrations resulted in complete inactivation of ribosomal activity.

Adenosine Triphosphate↗
PubMed1974

The role of ribosomal ribonucleic acid in the structure and function of mammalian brain ribosomes.

In order to resolve the functional role of intact rRNA in polypeptide chain elongation mouse brain ribosomes were treated with dilute pancreatic or T(1) RNAase (ribonuclease). After RNAase treatment, several physical-chemical properties as well as the functional activity of the ribosomes were measured. RNAase treatment resulted in the extensive hydrolysis of both 18S and 28S rRNA; however, the sedimentation properties of mono-ribosomes were unaltered and more than 90% of the relatively low-molecular-weight RNA fragments remained associated with ribosome particles. Analysis of the ability of RNAase-treated ribosomes to participate in cell-free protein synthesis showed that ribosomes with less than 2% intact rRNA retained more than 85% of their activity in polyphenylalanine incorporation. Proof that the incorporation of phenylalanine by ribosomes with hydrolysed rRNA actually represented active translocation was obtained by the effective inhibition of incorporation by diphtheria toxin. In addition, the oligopeptide products of protein synthesis could be identified by BD (benzoylated diethylaminoethyl)-cellulose column chromatography. Analysis of the size distribution of oligopeptides synthesized by normal and RNAase-treated ribosomes showed no significant differences which indicated that there was no change in the proportion of ribosomes engaged in protein synthesis. Thus strong RNA-protein and protein-protein interactions must serve to maintain the functional integrity of ribosomes even when the rRNA is extensively degraded. The ability of the enzyme-treated ribosomes to efficiently incorporate amino acids clearly demonstrated that ;intact' rRNA is not required for protein-synthetic activity.

Animals↗
PubMed1973

Synthesis of RNA-polyadenylic acid by isolated brain nuclei.

Nuclei, isolated from mouse brain tissue at various stages of postnatal development and incubated under cell-free conditions, synthesized RNA molecules that were associated with polyadenylic acid [poly(A)]. The RNA synthesized by these nuclei was similar to the poly(A)-associated products described for intact eukaryotic cells. The brain nuclei synthesized a similar proportion of RNA-poly(A) in the presence either of Mg(2+) or of Mn(2+) with (NH(4))(2)So(4). The RNA from neonatal brain nuclei appeared to have a greater proportion of poly(A)-containing RNA than nuclear products obtained from more mature neural tissue.

Adenine Nucleotides↗