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R Warren

Publications and source records attributed to R Warren.

At least 181 records · Page 10Linked to original sources

The effects of strychnine on neurons in cat somatosensory cortex and its interaction with the inhibitory amino acids, glycine, taurine and beta-alanine.

In area 3b of primary somatosensory cortex, neurons may be classified as either rapidly adapting or slowly adapting to sustained stimuli and may be differentiated further by the presence or absence of a receptive field and by their threshold of activation. It is also possible to use the rate of adaptation of the background activity to a sustained stimulus to divide the cortex into slowly adapting regions or rapidly adapting regions. By blocking GABA-mediated inhibition with iontophoretically administered bicuculline methiodide, others have observed an increase in receptive field size in rapidly adapting regions but not in slowly adapting regions. The present study was designed to look for a different inhibitory transmitter which might control receptive field size in slowly adapting regions. Iontophoretically delivered strychnine was employed as an antagonist because it interferes with glycine-like inhibitory transmitters such as glycine, taurine and beta-alanine. Pharmacological tests were performed on 157 neurons in two series of experiments. In the first series three effects were documented. (i) In rapidly adapting regions, the size of the receptive field increased in 11 out of 25 cases whereas none of the 20 receptive fields tested in slowly adapting regions enlarged. (ii) In 13 of 24 cases a receptive field was revealed for previously unresponsive neurons in rapidly adapting regions whereas only 5 of 22 unresponsive cells tested in slowly adapting regions developed a receptive field. (iii) In 15 of 25 cells with receptive fields tested in rapidly adapting zones, strychnine reduced the threshold for somatic stimuli but only 8 of 20 cells isolated in slowly adapting zones showed this effect. In a second series of experiments, the effect of beta-alanine, glycine and taurine was examined on neurons of the rapidly adapting regions. beta-Alanine and taurine reduced the excitability of all neurons tested. Glycine inhibited most neurons. However, strychnine only antagonized the inhibitory effects of beta-alanine on responses to peripheral stimuli (9 of 11 cases). When neurons could not be driven by peripheral stimuli, the inhibition of spontaneous or glutamate-induced activity could not be blocked by strychnine (0 of 18 cases). We suggest that glycine-like amino acids contribute to the control of receptive field size and the control of neuronal excitability in rapidly adapting regions but not in slowly adapting regions. Our data suggest that strychnine-sensitive synapses are limited only to a subset of cortical neurons driven by somatic inputs.

Alanine↗

Transfer of murine host protection by using interleukin-2-dependent T-lymphocyte lines.

We have demonstrated in this study that long-term, interleukin-2 (IL-2)-dependent, salmonella antigen-specific T-lymphocyte lines, as well as peritoneal exudate-enriched T cells, could be developed from both the antigen-sensitized inguinal and periaortic lymph nodes. Only those lines (salmonella-specific lymph node cells or peritoneal exudate T cells) were capable of adoptively transferring significant host protection (P less than 0.01) compared with the immune reactions of lethally challenged naive controls or of mice that had ovalbumin-specific T-cell lines transferred. Of particular interest was the finding that IL-2-dependent T-cell lines derived from the lymph nodes could only confer host protection to naive mice when both the transfer and challenge dose were administered via the intravenous route. Likewise, those T-cell lines derived from the peritoneal exudate were only capable of adoptively transferring significant protection when the cells and challenge dose of salmonellae were administered intraperitoneally. These studies indicate that systemic host protection can be transferred to naive mice, but depending on the source, the IL-2-dependent T-cell lines (lymph node or peritoneally isolated) functioned differentially upon challenge. Also, the results of this study indicate that the administration of greater numbers of IL-2-specific T cells may result in decreased, rather than enhanced, host protection. This may be due to the fact that the IL-2-dependent T-cell population consisted of 20 to 25% Lyt-2,3+ cells, indicating that cells of the suppressor/cytotoxic phenotype were present. Thus, increasing the number of cells transferred may result in an abrogation of protection.

Animals↗

Visual perception in high-speed low-altitude flight.

An ongoing exploratory development program on visual perception and control in high-speed low-altitude flight is being conducted by the Human Engineering Division of the Armstrong Aerospace Medical Research Laboratory. This paper begins with a discussion of the necessity of vision for low-altitude flight; proceeds to an analysis of objectives, strategies, and issues in designing a comprehensive research program; presents an overview of several experiments in support of the effort; and ends with a discussion of perceptual information. One of the simulator experiments involves the use of a non-mimetic task, flying at a zero altitude in the presence of strong gusts, in an effort to maximize adaptation to the low-altitude environment. Implications for simulator use are discussed.

Adaptation, Physiological↗

A new method for the cytological analysis of autoantibody specificities using whole-mount, surface-spread meiotic nuclei.

A new method for the cytological analysis of antinuclear antibody binding offers several advantages over conventional techniques. Nuclei in meiosis, prepared by surface-spreading spermatocytes, provide a detailed examination of the constituents of the nucleus--euchromatin, heterochromatin, sex chromatin, nucleoli, centromeres, and dense patches that seem related to RNA metabolism--and each of these structures can be seen to change in morphology and antibody labeling during the course of meiotic prophase. Results using sera from humans and mice with autoimmune disease, and using several mouse monoclonal antibodies, demonstrate the potential of this method for clinical and research applications, both for more common antibody types and for those that bind epitopes which are unique to germ cells.

Animals↗

Sensitivity of mouse Skh:HR-2 to ultraviolet radiation: melanocyte inactivation.

The hairless mouse, Skh:HR-2, was exposed to doses of ultraviolet (UV) radiation known to induce skin pigmentation. Three parameters associated with perturbations in skin pigmentation were monitored following UV exposure. These include spectroscopy (skin darkness), histology (melanocyte density), and biochemistry (melanin). Within 90 min of UV exposure, the skin became lighter. This was associated with a reduction of quantifiable melanin and the inactivation of epidermal melanocytes.

Animals↗

First-trimester fetal diagnosis for haemoglobinopathies: report on 200 cases.

First-trimester prenatal diagnosis by DNA analysis was found to be possible in 224 (80%) of 281 families at risk of having a child with beta-thalassaemia major. 200 prenatal diagnoses, mainly for beta-thalassaemia or sickle-cell anaemia, were made by means of chorionic villus sampling and fetal DNA analysis. The overall fetal loss rate was 6.7%, the majority being in the first half of the programme. There was one misdiagnosis. Prenatal diagnosis was also carried out successfully for both pairs of twins in two pregnancies. Comparison of these results with 53 prenatal diagnoses made with DNA prepared from amniotic fluid suggests that the first-trimester procedure is more reliable. If further experience confirms that chorionic villus sampling has an acceptably low risk for both mother and fetus it will largely replace other methods for prenatal diagnosis of the haemoglobin disorders and other single-gene conditions.

Amniotic Fluid↗

First-trimester prenatal diagnosis of cystic fibrosis with linked DNA probes.

Linkage analysis with cloned gene probes has shown that the mutation causing cystic fibrosis is located in the middle of the long arm of chromosome 7. First-trimester diagnosis of cystic fibrosis is reported in four informative families and second-trimester diagnosis in one family with fetal DNA prepared from chorionic villi, hybridised with the tightly linked DNA probes, pJ3.11 and met. Risk calculations show that the expected false-negative and false-positive rates are approximately 2% and 6%, respectively, for typical nuclear families with one affected living child. Existing probes are sufficiently informative to allow full diagnosis in about two-thirds of couples presenting with at least one affected child. In half of the remainder, the inheritance of one parental mutant chromosome can be deduced.

Biopsy↗

Adoptive transfer of murine host protection to salmonellosis with T-cell growth factor-dependent, Salmonella-specific T-cell lines.

A spent medium antigen was prepared from the avirulent RIA strain of Salmonella typhimurium. Lymph node cells isolated from female BALB/c mice injected subcutaneously with the spent medium antigen exhibited antigen-specific proliferation. By using these cells and T-cell growth factor, continuous spent medium antigen-specific, Thy 1.2-sensitive lines were generated. These cells exhibited antigen-specific proliferation in vitro and were effective in inducing significant (P less than 0.01) host protection when adoptively transferred to naive syngeneic mice.

Animals↗

Cryptococcal sacroiliitis.

Disseminated cryptococcal disease is known to occur in patients with altered immune status. We have reported an unusual case of cryptococcal disease manifested solely by sacroiliitis, which occurred in a patient on chronic steroid therapy for autoimmune haemolytic anaemia. This case stresses the importance of considering unusual organisms as a cause of sepsis in patients with altered immune status.

Adult↗

Prenatal diagnosis of ornithine carbamoyl transferase deficiency using a gene specific probe.

A gene specific DNA probe has been used to predict the genotype of two fetuses in families at risk for ornithine carbamoyl transferase deficiency. Although the probe does not detect the mutation directly, prediction was possible by examining restriction fragment length polymorphisms of the parents and sibs to identify the X chromosome carrying the mutation. It is suggested that in all pregnancies, regardless of the predicted outcome, the biochemical status of carrier mothers should be monitored because hyperammonaemia and arginine deficiency may have a deleterious effect on the fetus.

Amino Acid Metabolism, Inborn Errors↗