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Biomedical subjects

R T Johnson

Publications and source records attributed to R T Johnson.

At least 145 records · Page 8Linked to original sources
PubMed1985

A quantitation of myelin-associated glycoprotein and myelin basic protein loss in different demyelinating diseases.

The loss of myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) was compared by quantitative immunocytochemistry in demyelinating lesions of measles encephalomyelitis (ME), multiple sclerosis (MS), and progressive multifocal leukoencephalopathy (PML). Serial sections from paraffin-embedded tissue were reacted with antisera for MAG and MBP, and areas of staining loss were compared morphometrically. Lesions in ME showed MAG loss equal to that of MBP, lesions of PML showed MAG loss greater than that of MBP, and MS lesions showed a mixture of patterns. These data demonstrate distinctive patterns of MAG and MBP loss in these three diseases.

Central Nervous System↗
PubMed1985

Japanese encephalitis: immunocytochemical studies of viral antigen and inflammatory cells in fatal cases.

The distribution of virus and the composition of the mononuclear inflammatory response were studied in the brains of 7 children who died with Japanese encephalitis. Viral antigen was localized to neurons, with greatest involvement in the thalamus and brainstem. Quantitation of perivascular inflammatory responses showed a preponderance of T cells, but only 7 to 30% of these cells were T suppressor/cytotoxic cells. Inflammatory cells invading the parenchyma were predominantly macrophages with small numbers of T cells. B cells remained localized to perivascular cuffs. Viral antigen was progressively cleared in patients with survival of 6 days or more.

Antibodies, Viral↗
PubMed1985

Changes in plasma IgE levels during complicated and uncomplicated measles virus infections.

Plasma IgE levels were measured in 214 samples from 182 Peruvian patients with acute measles virus infections. Plasma IgE levels were significantly elevated early in infection compared to later time points. Plasma levels of IgG from the same patients rose during the same time period, whereas levels of IgA and IgM did not change. In patients with postmeasles encephalomyelitis, IgE remained elevated longer than it did in patients either with uncomplicated measles or measles complicated by pneumonia. It is proposed that the elevation of IgE is another manifestation of the altered immunoregulatory function in patients with measles.

Adolescent↗
PubMed1985

DNA repair in mouse embryo fibroblasts. II. Responses of nontransformed, preneoplastic and tumorigenic cells to ultraviolet irradiation.

Ultraviolet light-induced excision repair, as measured by single-strand DNA-break accumulation in the presence of hydroxyurea and 1-beta-D-arabinofuranosylcytosine, undergoes an apparent decline concomitant with spontaneous transformation of mouse cells in vitro. This decline is seen in preneoplastic transformed cells as well as tumorigenic cells, suggesting that it is an early event in transformation. The difference between nontransformed and transformed mouse cells in apparent incision rates is greatest at short times after irradiation when nontransformed cells show a transient phase of rapid incision. No gross differences in the effects of UV on replicative DNA synthesis, bulk RNA synthesis, cell proliferation or clonal survival in nontransformed and transformed cells were seen, in spite of the reduced incision capacity of the latter. Taken together the results suggest that transformed cells are capable of growth in the presence of significantly increased amounts of DNA damage. A decreased ability of nontumorigenic cells to remove DNA lesions, coupled with unrestricted growth, may be responsible for genetic alterations which increase the probability of a cell becoming tumorigenic.

Animals↗
PubMed1985

Mainstreaming hearing-impaired students: the effect of effort in communicating on cooperation and interpersonal attraction.

Cooperative and individualistic learning experiences were compared in terms of their effects on interaction and relationships between hearing and hearing-impaired students. Two contradictory hypotheses were tested--one stating that the effort required for hearing and hearing-impaired students to communicate would lead to frustration, withdrawal, exclusion, and rejection; the other stating that cooperative learning experiences would lead to cross-handicap interpersonal attraction regardless of communication difficulties. Thirty 3rd-grade students (20 hearing and 10 hearing impaired) were assigned to conditions on a stratified, random basis controlling for handicap, sex, and ability level. They participated in the study for 55 min a day for 15 instructional days. The results indicate that subjects involved in cooperative learning experiences performed higher on measures of interaction and interpersonal attraction between hearing and hearing-impaired students than did subjects involved in individualistic learning experiences.

Achievement↗
PubMed1985

Oral interaction in cooperative learning groups: speaking, listening, and the nature of statements made by high-, medium-, and low-achieving students.

Oral interaction within cooperative learning groups was observed for high-, medium-, and low-achieving students. Initially, cooperative and individualistic learning situations were compared on achievement and attitudes. Forty-eight 4th-grade American students were assigned to learning situations on a stratified random basis controlling for ability and sex. They participated in the study for 55 min a day for 15 instructional days. Two observation schemes were used. The results for the cooperative situation were factor analyzed to determine the basic dimensions of oral interaction within cooperative learning groups. Five orthogonal factors were identified: Exchanging Task-Related Information, Elaborating on the Information, Encouraging Each Other to Learn, Disagreeing With Each Other's Conclusions, and Making Nontask Comments and Sharing Personal Feelings. The oral participation of students from different achievement levels was differentially related to achievement. Vocalizing was found to be more strongly related to achievement than was listening to other group members vocalize. Medium and low achievers especially benefited from cooperative learning experiences.

Achievement↗
PubMed1985

Novobiocin inhibition of DNA excision repair may occur through effects on mitochondrial structure and ATP metabolism, not on repair topoisomerases.

Novobiocin inhibits DNA topoisomerases. It also inhibits excision repair of DNA photodamage, blocking both repair synthesis and the earlier step of incision at u.v. damage sites (as measured by the accumulation of DNA strand breaks in u.v.-irradiated interphase cells treated with DNA synthesis inhibitors such as hydroxyurea or cytosine arabinoside). It has been supposed, therefore, that novobiocin affects repair by blocking a putative topoisomerase step prior to incision. But we find that novobiocin also has a marked dose- and time-dependent effect on mitochondria: in cells exposed to novobiocin, mitochondria swell and their cristae become disrupted, and the intracellular ATP:ADP ratio is lowered, though the membrane potential is maintained as judged by rhodamine 123 fluorescence. Mitotic cells are more resistant to mitochondrial disruption by novobiocin than are interphase cells. This correlates with a relative resistance of u.v.-irradiated mitotic cells to the inhibition of incision by novobiocin. The chromosomal decondensation that results from the accumulation of DNA breaks due to incision when u.v.-irradiated mitotic cells are treated with hydroxyurea and cytosine arabinoside is largely suppressed by novobiocin. Furthermore, the suppression of induced strand break accumulation is partly due to a suppression by novobiocin of the uptake and phosphorylation of cytosine arabinoside; breaks accumulated in u.v.-irradiated cells in the presence of aphidicolin, an inhibitor of DNA polymerase alpha that does not require phosphorylation, are less novobiocin-sensitive. We conclude that the effects of novobiocin on excision repair are more likely to be due to a non-specific effect on ATP metabolism than to a specific effect on a repair-related topoisomerase.

Adenosine Triphosphate↗
PubMed1985

Manipulating chromosome structure and metaphase status with ultraviolet light and repair synthesis inhibitors.

DNA repair occurs in metaphase-arrested cells in response to ultraviolet irradiation. In the presence of the repair synthesis inhibitors hydroxyurea and 1-beta-D-arabinofuranosylcytosine the chromosomes of such cells, as seen in Carnoy-fixed preparations, are decondensed. The extent of decondensation is related to both the u.v. dose and the duration of incubation in the presence of inhibitors. For any particular cell type there is a reasonable correlation between the amount of decondensation and the number of single-strand DNA breaks generated by the repair process under the same inhibitory conditions, though the chromosome changes continue after the number of single-strand breaks has reached a plateau. The dose response of chromosome decondensation varies between different cell types but is in general correlated with differences in levels of single-strand breaks accumulated under comparable inhibitory conditions. Decondensation can be detected after 0.5 Jm-2 in repair-competent human cells. In human cells defective in excision repair there is much less chromosome decondensation in response to the same u.v. dose and time of repair inhibition. However, a simian virus 40-transformed muntjac cell displays pronounced chromosome decondensation but has limited incision ability. Both chromosome decondensation and single-strand break accumulation in the presence of inhibitors are reversed when DNA precursors are provided, but reversal after higher u.v. doses and longer periods of incubation leads to recondensed chromosomes that are fragmented. Elution of the DNA from such cells through polycarbonate filters under non-denaturing conditions reveals that double-strand DNA breaks are generated during the period of incubation with inhibitors. Although the chromosomes of repair-inhibited metaphase cells are decondensed in fixed preparations, their morphology appears normal in intact cells. The cells also retain a capacity to induce prematurely condensed chromosomes (PCC) when fused with interphase cells: compared with control mitotic cells, the speed of induction is sometimes reduced but the final amount of PCC produced is similar.

Animals↗
PubMed1985

Xeroderma pigmentosum D-HeLa hybrids with low and high ultraviolet sensitivity associated with normal and diminished DNA repair ability, respectively.

Fusion between HeLa and fibroblasts from complementation group D xeroderma pigmentosum (XPD) followed by challenge with small doses of ultraviolet light (u.v.) results in the production of hybrid cells expressing either HeLa (HD1) or XPD-like (HD2) sensitivity to u.v. and related repair capacity. Assays used included unscheduled DNA synthesis (UDS), DNA break accumulation in the presence of inhibitors of DNA repair synthesis and host cell reactivation of irradiated adenovirus. Complementation assay in heterokaryons reveals limited ability of HD2 to restore UDS in XPD nuclei. We believe this complementation is more apparent than real since proliferating hybrids of HD2 and XPD parentage are without exception u.v.-sensitive and express limited excision repair. On the other hand hybrids between HD2 and XPC, XPE or XPF fibroblasts show true complementation resulting in a return to normal u.v. sensitivity and elevated repair ability.

Cells, Cultured↗
PubMed1984

Measles encephalomyelitis--clinical and immunologic studies.

We studied 19 patients with postinfectious encephalomyelitis complicating natural measles-virus infections, and our results support the hypothesis that this demyelinating disease has a pathogenesis similar to that of experimental allergic encephalomyelitis. Early myelin destruction was demonstrated by the presence of myelin basic protein in cerebrospinal fluid, and lymphocyte proliferative responses to myelin basic protein were found in 8 of 17 patients tested. A lack of intrathecal synthesis of antibody against measles virus suggests that measles encephalomyelitis may not be dependent on virus replication within the central nervous system. Similar lymphoproliferative responses to myelin basic protein of lymphocytes from single patients with encephalomyelitis after rabies vaccine or after varicella or rubella virus infections suggest a common immune-mediated pathogenesis for the perivenular demyelinating disease that can follow the injection of neural tissues or infection by a variety of viruses.

Adolescent↗
PubMed1984

Measles encephalomyelitis: lack of evidence of viral invasion of the central nervous system and quantitative study of the nature of demyelination.

Measles encephalomyelitis appears to be an immune-mediated parainfectious disorder, but it is unclear whether viral invasion of brain is an obligate step in its development. Immunocytochemical methods were used to search for virus antigen in formalin-fixed, paraffin-embedded central nervous system (CNS) tissues from 10 patients with measles encephalomyelitis and 12 patients who had died of measles without CNS involvement. All the CNS tissues studied were viral antigen negative. Similarly fixed CNS tissues from all of 6 patients with subacute sclerosing panencephalitis were viral antigen positive and served as controls. The pattern of perivenular demyelination was also determined in 4 cases of measles encephalomyelitis using antibodies to myelin associated glycoprotein and myelin basic protein and a Luxol fast blue stain. Areas of demyelination in serial sections were quantitated, and no morphometrical differences were found among tissues stained with the three stains. The data suggest the lack of virus replication in the CNS during encephalomyelitis or fatal measles without CNS symptoms. The pattern of loss of myelin associated glycoprotein and myelin basic protein in regions of perivenular demyelination resembles that reported in experimental allergic encephalomyelitis. This pattern of demyelination has been proposed to result from a primary attack on the myelin sheath rather than from direct involvement of the oligodendroglial cell.

Adolescent↗
PubMed1984

Cellular immune responses during complicated and uncomplicated measles virus infections of man.

Lymphocytes from patients with measles showed profound and prolonged suppression of proliferative responses to mitogens. The degree of suppression was similar in patients with uncomplicated measles virus infection and in those with pneumonia or postinfectious encephalitis. Despite this suppression, lymphocyte responses to measles antigen and PPD were demonstrated in patients with encephalitis and uncomplicated disease, even early in infection. Most patients with pneumonia did not have demonstrable antigen-specific responses. The proportions of T helper (OKT 4) and T suppressor (OKT 8) cells and functional tests of Con A suppressor cell activity showed no significant difference between control and measles patients but, in contrast to controls, cells from measles patients cultured in the absence of any stimulant significantly suppressed the proliferation of allogeneic responder cells. Nine of 20 supernatant fluids from these cultures possessed a soluble suppressor factor. These studies indicate varied disruptions of immune reactivity during measles.

Adolescent↗
PubMed1984

Development of antibody to measles virus polypeptides during complicated and uncomplicated measles virus infections.

Immune precipitation of 181 sera from 152 patients with natural measles was studied to determine the temporal course and frequency of antibody responses to nucleocapsid, fusion, hemagglutinin, and matrix proteins of measles virus. Large amounts of antibody to nucleocapsid protein developed in all patients by day one of the rash. Antibody to hemagglutinin and fusion proteins developed in all patients over the next 3 weeks, the former to high levels and the latter to low levels. Antibody to matrix protein developed to very low levels and was detectable in only 41% of the patients; this poor response to matrix protein was not correlated with the age of the patient or the acute neurological complications of measles.

Adolescent↗