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Biomedical subjects

D Mason

Publications and source records attributed to D Mason.

At least 127 records · Page 7Linked to original sources

Implantable microencapsulated dopamine (DA): prolonged functional release of DA in denervated striatal tissue.

Biodegradable controlled-release microcapsule systems made with the biocompatible biodegradable polyester excipient poly [DL-lactide-co-gly-colide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microcapsules encapsulated within two different polymer excipients into denervated striatal tissue assures a prolonged release of the transmitter in vivo. This technology has a considerable potential for basic and possibly clinical research.

Animals↗

Sources of variability contributing to test-retest differences in threshold-based articulation indices.

This study was conducted to obtain information on test-retest differences in Articulation Indices (AI) when a clinical threshold-based method is used to calculate AI. The AI was calculated using a nine-frequency-band method on 2 separate days for 209 ears. Standard deviations of test-retest differences were calculated. The standard deviations were greatest when the AI was near 50% and least when the AI was near 0% or 100%. The standard deviations for test-retest AI differences were also dependent on the relationship of the hearing thresholds and speech spectrum. Under the assumption that each dB change in threshold would have an affect on the AI, standard deviations of test-retest differences increased significantly. Test-retest standard deviations for nine-band and five-band methods were approximately equal when only five thresholds were actually measured. A small improvement would be expected if the number of threshold measurements increased from five to nine.

Adult↗

Fusion of Rous sarcoma virus with host cells does not require exposure to low pH.

We investigated whether Rous sarcoma virus (RSV) infects cells through a pH-independent or a low-pH-dependent pathway. To do this, the effects of lysosomotropic agents and acid pretreatment on RSV infectivity of, and fusion with, chicken embryo fibroblasts (CEFs) were studied. High concentrations of lysosomotropic agents (ammonium chloride and monensin) did not inhibit virus infectivity: equal titers of RSV were produced in the presence and absence of these agents. Similarly, low-pH pretreatment did not inhibit RSV infectivity. In parallel experiments, lysosomotropic agents and acid pretreatment completely abolished the ability of influenza virus to infect CEFs. To monitor the fusion activity of RSV directly, the viral membrane was labeled with the fluorescent lipid probe octadecyl rhodamine at a self-quenching concentration. Upon fusion with a host cell, the probe is diluted in the cell membrane, resulting in fluorescence dequenching (D. Hoekstra, T. de Boer, K. Klappe, and J. Wilschut, Biochemistry 23:5675-5681, 1984). In this assay, fusion of RSV with CEFs was found to occur in both a time-dependent and a strictly temperature-dependent fashion. No fusion occurred unless cells with prebound virus were warmed to temperatures greater than 20 degrees C. Fusion, but not binding, was abolished if virus was pretreated with low concentrations of glutaraldehyde. High concentrations of ammonium chloride had no effect on fusion of RSV with CEFs but greatly diminished the ability of influenza virus and Semliki Forest virus to fuse with CEFs. Similarly, acid pretreatment of RSV had no effect on fusion with CEFs while markedly inhibiting fusion of both influenza and Semliki Forest viruses. Collectively, our results show that RSV fusion with and hence infection of CEFs does not require exposure of the virus to low pH. In this respect, RSV resembles another retrovirus, human immunodeficiency virus.

Animals↗

Barriers to vaccinating preschool children.

Immunization represents one of the most effective tools in preventive medicine. But despite what should be a universal practice, preschool children, particularly in the inner cities, are not being adequately vaccinated. The responsibility for low immunization levels does not rest solely with the parents. Major obstacles within the health care system provide disincentives to immunization. Local resource problems such as inadequate clinic staff, hours, and locations make immunizations difficult to obtain. When comprehensive care is not easily accessible (e.g., requiring appointments weeks or months in advance), policies which require immunization to take place only within such a setting are further barriers. Many opportunities for vaccination are lost when children interact with the health care system but do not receive all the immunizations they need. Policies must be changed to facilitate immunization and to take advantage of all health care visits to provide vaccines.

Chicago↗

Memory CD4+ T cells in man form two distinct subpopulations, defined by their expression of isoforms of the leucocyte common antigen, CD45.

The leucocyte common antigen, CD45 (T200, Ly-5), exists in a number of isoforms generated by differential usage of three exons that code for an extracellular region close to the NH2 terminus. Use of antibodies to different isoforms of CD45 has lead to the identification of two subsets of CD4+ T cells in rat, man and mouse. Data on the functions of the two rat CD4+ T-cell subsets isolated on the basis of different levels of expression of exon B (and/or C) are largely concordant with those obtained from the two subsets of human CD4+ T cells defined by their levels of expression of exon A. However, results presented in this paper on the CD45 phenotype of rat T cells that produce interferon-gamma (IFN-gamma) are not compatible with the human data, if it is assumed that there are only two functional subsets of CD4+ T cells. The data could, in principle, be reconciled if the expression of exons A and B defined three rather than two subsets, and this possibility has now been examined in man where monoclonal antibodies against both A and B exon products are available. The results show the presence of a third CD4+ T-cell subset and that this extra subset is contained within the population originally shown to provide memory T-cell function.

Animals↗

The role of the neuroendocrine system in determining genetic susceptibility to experimental allergic encephalomyelitis in the rat.

Experimental allergic encephalomyelitis (EAE) can be induced in some strains of rat but not others, by the injection of guinea-pig myelin basic protein in Freund's complete adjuvant. In the susceptible Lewis strain, spontaneous recovery from paralysis occurs and previous studies have shown that this recovery is dependent on the production, during the course of the disease, of high levels of corticosterone from the adrenal glands. Adrenalectomy completely abrogates the recovery phase and the disease becomes uniformly fatal unless steroid replacement therapy is given, which reproduces the serum levels of hormone that develop in intact animals with EAE. The PVG strain is not susceptible to EAE, but here it is shown that PVG rats that had been adrenalectomized developed severe disease from which they do not recover. As in the adrenalectomized Lewis rat, steroid replacement therapy could prevent the fatal outcome and in this case the disease course resembled that seen in intact Lewis animals. By a number of parameters PVG rats appear to make a more vigorous steroid response to stress than do Lewis. A comparison of the ratio of adrenal weight to body weight between these strains indicated that this ratio is larger in PVG, and serum corticosterone levels, in response to stress, were also found to be higher in this strain. Furthermore, basal levels of corticosterone were much more labile in PVG rats and had a higher mean value than those found in the age- and sex-matched Lewis animals with which they were compared. Genetic analysis using congenic rat strains showed that a high adrenal weight to body weight ratio was not linked to the major histocompatibility complex (MHC). It appears that the resistance to EAE of PVG rats depends on an enhanced stress response that mediates its immunosuppressive effect via the adrenal glands. While this stress response plays an essential part in the recovery of Lewis strain rats from EAE, it is sufficiently potent in PVG rats to virtually completely prevent signs of disease. Resistance to the induction of EAE could not be abrogated by adrenalectomy in all strains of rats studied. In particular, congenic PVG.RT1u rats, with the same background genes as PVG but with RT1u rather than the RT1cMHC genes of PVG, did not develop EAE when the adrenal glands were removed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗

The MRC OX-22- CD4+ T cells that help B cells in secondary immune responses derive from naive precursors with the MRC OX-22+ CD4+ phenotype.

CD4+ T cells in the rat can be divided into two nonoverlapping subsets by their reactivity with the mAb MRC OX-22, which binds some of the high molecular weight forms of the CD45 antigen. The lineage relationship between subsets of CD4+ T cells expression different forms of CD45 has been a controversial issue for some time. Experiments described in this paper address this question using in vivo assays of T cell reactivity. Analysis of primary antibody responses in vivo show that it is MRC OX-22+ CD4+ T cells that are active in these assays, whereas antigen-primed T cells that provide helper activity for secondary antibody responses in vivo have the MRC OX-22- CD4+ phenotype. It is demonstrated that these memory T cells derive from MRC OX-22+ CD4+ T cell precursors and not from a putative separate lineage. It is concluded that with respect to the provision of help for B cells, MRC OX-22+ CD4+ T cells are precursors of memory cells with the phenotype MRC OX-22- CD4+.

Animals↗

A human macrophage-associated antigen (CD68) detected by six different monoclonal antibodies.

Antibodies grouped together by the Third Workshop on Leucocyte Differentiation Antigens on the basis of pan-macrophage reactivity on tissue sections were analysed in immunoprecipitation experiments. Antibodies Y2/131, EBM11, Ki-M6 and Ki-M7 all precipitated antigens of Mr 110,000 which were shown to be identical by preclearing experiments. In addition a recently produced antibody, KP1, which identifies macrophages in paraffin-embedded tissue, was shown to recognize the same antigen. The antibodies were tested on murine cells transfected with two clones, which had been isolated by screening a cDNA library with antibodies Y1/82A and EBM11. Cells transfected with the longer cDNA clone, coding for a molecule of Mr 110,000, reacted with antibodies Y2/131, EBM11, Y1/82A and Ki-M6, whilst the shorter clone, encoding a molecule of Mr 70,000 gave the same result except that it did not induce expression of the Ki-M6 epitope. KP1 antibody did not recognize any transfectants, possibly because of differences in glycosylation by the transfected cell line compared with human tissue. Five of the six antibodies appear to recognize different epitopes (the sixth, Ki-M7, not having been evaluated in this way). It was concluded that these six antibodies react with a macrophage-associated antigen for which the gene has been cloned. This group of antibodies has recently been designated CD68 by the Fourth Workshop on Human Leucocyte Differentiation Antigens.

Antibodies, Monoclonal↗

Oral sedation in dentistry.

This review of oral sedation in dentistry will examine the objectives, indications, advantages and disadvantages of oral sedation and will present some of the basic guidelines for its safe use. It will also review the properties, precautions and contraindications (both absolute and relative) of some of the currently popular sedative agents.

Anesthesia, Dental↗

The roles of T cell subpopulations in allograft rejection.

In principle, cell-mediated allograft rejection can be brought about by cytotoxic T cells or by a DTH-like reaction. The first part of this article reviews the relative importance of these two mechanisms in graft rejection and concludes that the bulk of evidence points to cytotoxic T cells as being of major importance. In the discussion an operational definition of DTH is adopted--namely a mechanism that mediates bystander killing and depends on the existence of a radiation-sensitive effector mechanism. The rejection of skin and organ allografts in mammals is T cell dependent and the demonstration that such rejection can occur in heavily-irradiated T cell reconstituted animals and in the absence of demonstrable bystander effects leads to the conclusion drawn. This is not to imply that concomitant DTH reactions may not augment the rejection process nor to deny the possibility that in special circumstances DTH reactions may play an essential part. In the second part of this article, the roles in graft rejection of CD4+ and CD8+ cytotoxic T cells are considered. The classical collaborative interaction between class II-restricted CD4+ cells that play an inductive role, and class I restricted CD8+ cells that differentiate into cytotoxic effector cells, seems to be unnecessary in some allograft responses. Thus, not only can CD4+ T cells differentiate into class II-restricted cytotoxic T cells but CD8+ T cells, at least in some class I MHC-incompatible strain combinations, can develop into mature effector cells without an inductive signal from CD4+ T cells. This autonomy seems to be limited to MHC incompatibilities so that CD8+ cells alone are unable to mediate the rejection of minor-H incompatible grafts. For these latter types of grafts, CD4+ T cells can bring about graft rejection if multiple minor-H determinants are present, but for weak minor-H responses the classical collaborative scheme is necessary.

Antigens, Differentiation, T-Lymphocyte↗