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Biomedical subjects

R T Johnson

Publications and source records attributed to R T Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1987

In vitro studies of the role of monocytes in the immunosuppression associated with natural measles virus infections.

Measles is associated with suppression of mitogen-induced proliferative responses. The role of monocytes in depressed responses to phytohemagglutinin during measles was assessed. Depleting peripheral blood mononuclear cells of adherent cells decreased, increased, and did not change proliferative responses in essentially equal numbers of individuals. Inhibition of prostaglandin synthesis by indomethacin significantly increased proliferation (P = 0.009) but often not to normal values. Addition of supplemental interleukin 1 had little effect. Addition of supplemental natural interleukin 2 significantly increased proliferation (P = 0.002) even in patients with very low responses. These data suggest that monocyte function is abnormal in some individuals with measles, that the abnormality is variable, and that lymphocyte response to monocyte signals is probably suboptimal as well.

Biomechanical Phenomena↗
PubMed1987

Abnormal mutation frequencies in human repair-defective hybrid cell lines.

Two intraspecific human cell hybrids, HD2 and HD1A, produced from fusion between HeLa cells and xeroderma pigmentosum fibroblasts, express XPD-like rates of excision repair and hypersensitivity to UV-radiation. In the present paper we describe unusual patterns of UV-induced mutation in both cell lines. Though HD2 very closely resembles XPD both phenotypically and genetically, in UV-dose response it is hypomutable at the loci for ouabain and diphtheria toxin resistance. At equitoxic dose, however, it shows normal mutability, HD1A, by contrast, is hypermutable as a function either of UV dose or in terms of equitoxicity for these genes. HD1A's mutator phenotype is a dominant characteristic and is not associated with grossly abnormal DNA precursor pool imbalance. The possibility remains that DNA polymerase infidelity underlies its hypermutability.

Cell Division↗
PubMed1987

Action of etoposide (VP-16-123) on human cells: no evidence for topoisomerase II involvement in excision repair of u.v.-induced DNA damage, nor for mitochondrial hypersensitivity in ataxia telangiectasia.

The excision repair of u.v. damage has been supposed to involve an initial action of DNA topoisomerase II, since some pre-incision step is sensitive to novobiocin, a topoisomerase II inhibitor. But novobiocin also affects mitochondrial structure and ATP metabolism, and this may account for its apparent inhibition of energy-dependent excision repair. We have investigated the effects of etoposide, another inhibitor of topoisomerase II, on u.v.-irradiated human cells: it is a more specific agent with no immediate side-effects on mitochondria. But etoposide is without effect on cellular excision repair, at the pre-incision stage or at the later stages of either DNA resynthesis or strand break ligation; nor does it potentiate cell killing after u.v. irradiation. The chromosome decondensation that accompanies incomplete excision repair in mitotic cells is likewise not greatly affected by etoposide. Therefore, if topoisomerase II is involved in excision repair or its regulation, it acts through a process that in whole cells is insensitive to etoposide. In ataxia telangiectasia cells, which are known to be hypersensitive to etoposide, the mitochondrial activities are not abnormally affected.

Ataxia Telangiectasia↗
PubMed1987

The pathogenesis of acute viral encephalitis and postinfectious encephalomyelitis.

Japanese encephalitis and postmeasles encephalomyelitis represent two important forms of acute encephalitis in the developing world. Japanese encephalitis accounts for 20,000 acute illnesses per year, and measles encephalomyelitis accounts for as many as 100,000. Both are accompanied by mortalities of 20%-30%, and in both forms, approximately one-half of the survivors have neurological sequelae. Therefore, these two diseases are responsible for a considerable proportion of worldwide mental and motor disabilities. Furthermore, both diseases are preventable with use of safe vaccines. Despite these similarities, their very different pathologies appear to be based on different mechanisms of pathogenesis (table 2). In Japanese encephalitis there is direct invasion of the virus into the nervous system, selective infection and destruction of neurons, and evidence that both humoral and cellular immune responses attenuate the infection. In measles encephalomyelitis there is little evidence that the virus invades the nervous system. Rather, measles virus infects lymphoid cells and causes abnormalities in immune regulation. Humoral immune responses are not found within the nervous system, and the cellular immune response may be inappropriately directed against host antigens. In measles encephalomyelitis, the inflammatory cells entering the nervous system may be the effector cells of autoimmune disease.

Animals↗
PubMed1987

Cytomegalovirus encephalitis associated with episodic neurologic deficits and OKT-8+ pleocytosis.

After 3 days of symptoms suggesting a viral illness, a 35-year-old man experienced three episodes of aphasia, right-sided sensory symptoms, and bifrontal headache. Each lasted several hours. CSF examination revealed a moderate lymphocytosis consisting of 80% OKT-8+ cells. Serum anti-cytomegalovirus (anti-CMV) antibody titer was elevated at 1:1,024 and subsequently fell to 1:64. Episodic symptoms recurred 5 months later, at which time the anti-CMV titer peaked at 1:8,192. A trial of inhaled oxygen aborted two episodes after several minutes each.

Adult↗
PubMed1987

Neurologic complications of Semple-type rabies vaccine: clinical and immunologic studies.

We studied 61 patients with complications of Semple-type postexposure rabies immunization. Thirty-six had neurologic signs, and 25 had only fever, headache, or myalgia. Thirty-two patients had CNS complications, and 4 had an acute peripheral neuropathy. Disease was acute and monophasic in 33, but 3 patients had progressive disease, including 1 patient with a relapsing-remitting course. No clinical features, including CSF content of myelin basic protein, were prognostic indicators. In three of six patients with encephalomyelitis, lymphocytes showed a proliferative response to myelin.

Central Nervous System Diseases↗
PubMed1987

DNA repair under stress.

When the excision repair process of eukaryote cells is arrested by inhibitors of repair synthesis including hydroxyurea (HU), 1-beta-D-arabinofuranosylcytosine (araC) or aphidicolin, major cellular changes follow the accumulation of repair-associated DNA breaks. These changes, each of which reflects more or less severe cellular stress, include cycle delay, chromosome behaviour, fall in NAD level, the development of double-stranded DNA breaks, rapid chromosome fragmentation and cell killing. Disruption of the repair process by agents such as araC after therapeutic DNA damage may, therefore, have some potential value in cancer treatment. The extreme cellular problems associated with the artificial arrest of repair may have their subtler counterparts elsewhere, and we discuss several systems where delays in the completion of excision repair in the absence of repair synthesis inhibitors have marked repercussions on cell viability. We also show that the average completion time of an excision repair patch varies according to the state of cell culture, and that completion time is extended after treatment with insulin or following trypsin detachment. Under certain growth conditions ultraviolet irradiation followed by mitogenic stimulation results in double-stranded DNA breakage and additional cell killing, and we discuss these data in the light of protocols that have been used successfully to transform human or rodent cells in vitro. Finally, we consider whether the rejoining of DNA breaks accumulated by repair synthesis inhibitors is a valid model system for studying ligation, and show that this protocol provides an extremely sensitive assay for most incision events and, thereby, a means for discriminating between normal human cells on the one hand, and Cockayne's Syndrome cells and their heterozygotes on the other.

Aphidicolin↗
PubMed1987

DNA repair mutants in higher eukaryotes.

Over the past ten years or so, we have seen a proliferation of reports of new cell lines of various vertebrate species, showing hypersensitivity to killing by DNA damaging agents. Regrettably, but predictably, there is no standard terminology to describe the mutants, and as a result the literature is liberally scattered with fragments of individualistic nomenclature. There is no way of imposing order at this stage, but it may be helpful to bring together in this chapter as much information as possible on the mutants now available. As well as being an aid for reference, this should serve as a pointer towards further investigation--either in characterizing the mutants we have, or in developing new ones to fill gaps in our knowledge.

Animals↗
PubMed1987

Disassembly of the mammalian metaphase chromosome into its subunits: studies with ultraviolet light and repair synthesis inhibitors.

Metaphase chromosomes of a simian virus-transformed Indian muntjac cell line have been examined by scanning electron microscopy of material in which the fully packed metaphase structure is progressively relaxed. Such chromosomes are seen in standard, spread preparations of ultraviolet light-irradiated, metaphase-arrested cells, which have been incubated in the presence of inhibitors of DNA synthesis; they are processed for electron microscopy by trypsinization, further fixation and osmium impregnation. Decondensation is initially associated with a gradual elongation and loosening of the chromosome axis and, as loosening proceeds, the appearance of unexpected higher order structures--clusters of 20-40 nm diameter fibres. The arrangement of the clusters shows much variation between spreads. In the most fully extended chromosomes clusters are arranged in two longitudinal series with pairing between sister chromatids; the diameter of the majority of clusters in such chromosomes is in the range 0.4-0.6 micron. In the final stages of decondensation, clusters separate and individual chromosomes are no longer recognizable. Similar fibre clusters are found in interphase nuclei prepared by the same method. We suggest that the clusters of chromatin fibres may assemble as intermediates in the construction of an axial structure, which is further compacted in the fully condensed metaphase chromosome.

Animals↗
PubMed1987

The pathogenesis of spinal cord involvement in the encephalomyelitis of mice caused by neuroadapted Sindbis virus infection.

Weanling mice develop an acute encephalomyelitis with high mortality after intracerebral inoculation of neuroadapted Sindbis virus. The mice develop kyphoscoliosis and hindlimb paralysis. Immunohistochemical and in situ hybridization studies have demonstrated virus in the gray matter of the brain and spinal cord. Ventral horn cells are prominently infected, providing an anatomical basis for the clinical poliomyelitis. A novel route of spread of inoculated virus within the central nervous system has been found. The virus enters the ventricular system, and then travels caudally in the central canal of the spinal cord where ependymal cells are infected. The virus subsequently spreads into the gray matter. The distribution of virus in the spinal cord is likely dependent both on variations in the susceptibility of neural cells and on this route of entry and subsequent spread.

Animals↗
PubMed1987

Using cooperative learning strategies to teach nutrition.

There are three ways in which student-student interaction may be organized for nutrition education. Of the three, cooperation is the only instructional strategy congruent with the goals of nutrition education. The essential elements of cooperative learning and the specific actions teachers need to take to implement it are presented. When cooperative learning is implemented effectively, long-term modifications of nutrition knowledge, attitudes and behavior result. Nutrition education classes will more successfully fulfill their purposes when cooperative learning is primarily used.

Adolescent↗
PubMed1986

Japanese encephalitis: identification of inflammatory cells in cerebrospinal fluid.

Fifteen patients with acute encephalitis were studied during the epidemic season of Japanese encephalitis (JE) in Northern Thailand; 13 of 15 proved to have the encephalitis. In serial cerebrospinal fluids and blood samples, mononuclear cells were identified using monoclonal antibodies. In cerebrospinal fluid from the patients with Japanese encephalitis, T cells predominated with a 4.2:1 ratio of T helper/inducer cells to T suppressor/cytotoxic cells; B cells and macrophages were often present but in small numbers compared to their presence in blood. Distribution of cell types did not vary between the first and fifth day of hospitalization, were similar in fatal and nonfatal cases, and were unaffected by administration of steroids.

Acute Disease↗
PubMed1986

Peripheral blood mononuclear cells during natural measles virus infection: cell surface phenotypes and evidence for activation.

Peripheral blood mononuclear cells from 25 patients with measles and 13 patients with other diseases from Lima, Peru, were studied by immunocytochemical staining for cell surface antigens indicating the type of cell (Leu 4, Leu 3, T8, B1, M1, or esterase) and the state of cell activation (T10 and IL-2 receptor). Measles patients were studied during the first 2 weeks of disease and had no alteration in the proportion of cells which were positive for any subset marker or in the ratio of helper/inducer to cytotoxic/suppressor T cells compared to controls. Measles patients, however, had a greater number of cells expressing the activation antigens T10 and IL-2 receptor than controls. Incorporation of [3H]thymidine was also higher in measles patients when exogenous natural or recombinant IL-2 was added to unstimulated cultured cells. We conclude that the peripheral blood mononuclear leukocytes of patients with measles have normal proportions of helper/inducer and cytotoxic/suppressor T lymphocytes, B lymphocytes, and monocytes but that an increased number of these cells are in an activated state.

Adolescent↗
PubMed1986

Excessive chromosome fragility and abundance of sister-chromatid exchanges induced by UV in an Indian muntjac cell line defective in postreplication (daughter strand) repair.

Two UV-hypersensitive animal cell mutants defective in postreplication recovery (daughter strand synthesis) display quite different patterns of induced sister-chromatid exchange (SCE). One, an SV40-transformed Indian muntjac cell (SVM), shows extremely high frequencies of SCE after UV; induced exchanges can be measured after UV doses as low as 0.01 J/m2. This cell also displays exaggerated levels of induced and spontaneous chromosome aberrations. By contrast SCE rates in the Chinese hamster cell mutant, UV-1, are essentially normal. In both SVM and UV-1, however, there is a clear correlation between the cell density and spontaneous frequencies of SCE, a feature which could be related to the observed density-dependent rate of DNA maturation.

Animals↗
PubMed1986

Defective post-replication recovery and u.v. sensitivity in a simian virus 40-transformed Indian muntjac cell line.

The responses to u.v. of two cell lines derived from the Indian muntjac are described. The u.v. sensitivity of the diploid cell falls within the range of most normal mammalian cells while the other, a heteroploid cell, transformed by SV40, is much more sensitive to killing. This hypersensitivity cannot be explained by defective excision repair: the two cell types are indistinguishable in this activity as judged by inhibitor-associated DNA break accumulation and unscheduled DNA synthesis. Rather, the SV40 transformed cells have a pronounced inability to recover normal DNA replication after u.v. These cells are, therefore, defective in a post-replication recovery mechanism and in this respect resemble the behaviour of the variant form of xeroderma pigmentosum. Their limited ability to recover normal levels of RNA synthesis after u.v. hints at the complexity of the phenotype.

Animals↗
PubMed1986

Analysis of DNA repair in XP-HeLa hybrids; lack of correlation between excision repair of u.v. damage and adenovirus reactivation in an XP(D)-like cell line.

Hybrids formed between HeLa cells and fibroblasts from xeroderma pigmentosum group D show either HeLa sensitivity or XPD-like hypersensitivity to u.v. radiation and corresponding high or low excision repair capability. Hybrids with low repair are presumed to have lost, via chromosome segregation, the HeLa wild type D alleles. In this paper we analyse the u.v. sensitivity and excision repair capability of another hybrid, HD1A, derived spontaneously from the normally sensitive hybrid HD1. While HD1A closely resembles the XPD phenotype in terms of u.v. sensitivity and excision repair it differs from XPD because of its ability to reactivate u.v.-irradiated adenovirus 2 to an extent similar to that of its HeLa parent. This capacity functionally dissociates excision repair of chromatin-based damage from damage in a viral environment. Moreover, on the basis of complementation studies the excision repair of genomic damage by HD1A is subtly different from that of a true XPD-like hybrid, HD2. The data are discussed in terms of a second change in the defective D allele of the HD1A cell.

Adenoviridae↗