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Biomedical subjects

R N Moore

Publications and source records attributed to R N Moore.

At least 55 records · Page 3Linked to original sources

Dynorphin and related opioid peptides enhance tumoricidal activity mediated by murine peritoneal macrophages.

The influence of dynorphin A (DYN) and related opioid peptides on the tumoricidal function of activated murine peritoneal exudate macrophages (PEM) was investigated. Addition of DYN to macrophage cultures previously activated with mixed alpha + beta-interferon (IFN-alpha/beta) and bacterial lipopolysaccharide (LPS) significantly enhanced their ability to lyse P815 murine mastocytoma cells in a 16 hr chromium-release assay. The effects of DYN were dependent on prior macrophage activation. Peptide subfragments of DYN were effective in a manner similar to that of the 17-amino-acid parent molecule, indicating that peptide interaction with either kappa or delta-opioid receptors on the effector cell is effective in potentiating lytic function. The involvement of opiate receptors was confirmed by inhibition of the effects of DYN and leucine enkephalin by the opioid receptor antagonist naloxone. Finally, in addition to IFN-alpha/beta-primed macrophages, DYN also augmented tumoricidal function in PEM primed for cytotoxicity by either gamma-interferon (IFN-gamma) or the calcium ionophore A23187, indicating that DYN potentiates function in activated macrophages independent of the specific mode of activation.

Animals↗

The regulation of herpes simplex virus-specific CTL induction by suppressor cells.

The incubation of herpes simplex virus (HSV) immune murine splenocytes with HSV antigens induced suppressor cells which inhibited HSV-specific cytotoxic T lymphocyte (CTL) induction. The cell mediating the suppression was identified as a Thy 1+ Lyt 2+ I-J+ cell. The induction of this suppressor cell required the participation of at least three leukocyte populations. That is, depleting the cultures of either Lyt 1+ or Lyt 2+ splenocytes resulted in a failure to induce suppressor cell activity. Likewise the removal of macrophage-like antigen-presenting cells (APC), in particular I-A- I-J+ APC, abolished suppressor-cell induction. Though the Lyt 2+ I-J+ cells had to be provided by HSV-immune mice, both the APC and the Lyt 1+ cells could be provided by HSV-naive mice. Though the induction of the suppressor cell was virus specific, its action was nonspecific as evidenced by the suppression of influenza-specific CTL induction. The implication of our results for the understanding and manipulation of herpesvirus disease is briefly discussed.

Animals↗

A longitudinal study of anteroposterior growth changes in the palatine rugae.

Palatine rugae have been used as internal dental cast reference points for quantification of tooth migration. Some, but not all, investigators have reported the medial rugal region to be stable or to show predictable change. The purpose of this study was to use the longitudinal data base of the Child Research Council of Denver to examine the anteroposterior stability of the medial rugal region. Dental casts of 20 females and 21 males with untreated normal Angle Class I occlusions were selected. Time intervals measured were: T1--primary teeth erupted, T2--earliest cast with permanent first molars erupted, T3--earliest cast with canines and pre-molars erupted, and T4--ages 16 to 22. Distinctive left and right anterior and posterior rugae which appeared on all four casts were identified, the medial ends marked, and the anteroposterior distances measured. The data were evaluated with the paired t test, repeated-measures ANOVA, and Tukey's multiple comparison procedure. From T1--T4, the medial rugal region increased 1.4 +/- 0.6 mm in females and 2.3 +/- 0.8 mm in males. Only two cases showed a trend toward stability. There were no significant differences by side. Significant increases in size occurred between T2 and T3 for females and males and between T3 and T4 for males. Analysis of these data indicates that the medial rugal region increases significantly in anteroposterior length, but not uniformly between the sexes across observation times. Such changes are characteristic of general craniofacial growth and suggest that the rugal region is responding to the differential growth of the underlying bone. Therefore, medial rugal landmarks appear not to be stable reference points for tooth migration research.

Adolescent↗

Implication of defamation for dental educators.

Recent court decisions have indicated that in dealing with their students and colleagues, faculty must balance academic freedom and the individual right of fair consideration. It is also important for faculty and administrators to distinguish between decision-making procedures and criteria. It is quite clear from two recent United States Supreme Court cases that subjective evaluation by professional judgment is permissible as long as standard procedures of procedural due process are followed. In short, courts are more likely to review the application of the criteria than their substance.

Civil Rights↗

Characterization of a two-signal-dependent, Ia+ mononuclear phagocyte progenitor subpopulation that is sensitive to inhibition by ferritin.

Evidence is presented that the ferritin-inhibitable, Ia+ monocyte progenitor in murine marrow requires two signals for stimulation of clonal proliferation. Escherichia coli K235 lipopolysaccharide (LPS) at 0.1 ng/ml enhanced macrophage colony formation by 25 to 70% in murine marrow cultures stimulated with colony-stimulating factor (CSF-1). The progenitors which responded to LPS and CSF-1 represented a distinct subpopulation. Pretreatment of marrow cells with complement plus anti-Ia, anti-H2, anti-asialo GM1, and anti-Mac-1 antibodies specifically depleted the two-signal-requiring progenitors. In addition, the same progenitors were depleted by preincubation with hydroxyurea, indicating that these cells were in cell cycle when removed from the marrow. When compared with the quiescent progenitors, the Ia+, cycling cells were more sensitive to the antiproliferative effects of interferon alpha/beta but were more resistant to inhibition by E prostaglandins. Pretreatment with T cell-specific antibodies and complement specifically enhanced cloning of quiescent progenitors without affecting cloning of the Ia+, cycling subpopulation. Moreover, rat liver ferritin at 10(-8) to 10(-10) M specifically inhibited clonal proliferation of the Ia+ progenitors. Finally, the requirement for LPS as the additional stimulant could be replaced by the addition of haplotype-specific anti-Ia antibody to CSF-stimulated cultures. In contrast to LPS, anti-IA was competitive with inhibitory ferritin in clonal proliferation of the Ia+ progenitors. The significance of these observations in regulation of monocytopoiesis is discussed.

Animals↗

Regulation of herpes simplex virus-specific cell-mediated immunity by a specific suppressor factor.

Our study was designed to investigate the nature of an antigen-specific suppressor factor generated by antigen-stimulated herpes simplex virus (HSV)-immune splenocytes. Factor SF-200, a 90,000- to 100,000-dalton fraction obtained after Sephacryl gel filtration, suppressed the generation of HSV-specific cytotoxic T-lymphocyte and lymphoproliferative responses. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis of SF-200 indicated that it contained an I-J+, anti-idiotypic protein. It was possible to adsorb the suppressor activity of SF-200 to an anti-I-J immunoaffinity column. The suppressor activity could be eluted from the immunoaffinity column with a low-pH buffer. The acid-eluted material was determined to be both I-J+ and reactive with anti-HSV antiserum by Western blot analysis. Both SF-200 and the I-J+ suppressor activity suppressed only HSV-specific cell-mediated immunity responses. However, it was possible to generate nonspecific suppressor activity by incubating the I-J+ suppressor factor with Lyt 1+ splenocytes from HSV-immune mice. The implication of these results with respect to the model for a suppressor cell circuit regulating HSV-specific cell-mediated immunity responses is discussed.

Animals↗

Computer-assisted instruction in mixed dentition analysis.

A computer-assisted instruction (CAI) tutorial in the basics of mixed dentition analysis was developed and evaluated as a substitute for a one-hour lecture segment on the same topic. The instructional effectiveness of the program was evaluated using an experimental CAI-lecture group design. A posttest included in the final examination for the course served to compare learning outcomes of 24 students instructed via the computer with 28 students instructed by the traditional lecture method. The results of this investigation revealed that: the CAI group performed significantly better on the posttest than did the lecture group, there was no significant correlation between posttest scores and the time used to view the program for students in the computer groups, and student attitude toward the use of this CAI program was favorable.

Attitude↗

Interferon produced endogenously in response to CSF-1 augments the functional differentiation of progeny macrophages.

The role of endogenously produced interferon alpha/beta in the functional maturation of newly derived mononuclear phagocytes was investigated. Addition of highly specific anti-interferon alpha + beta antiserum to murine marrow cultures stimulated with colony-stimulating factor-1 (macrophage growth factor) markedly suppressed the capacity of resulting progeny mononuclear phagocytes to ingest opsonized sheep erythrocytes (EAIgG). This impairment was corrected either by direct addition of interferon alpha + beta at a concentration in excess of that neutralized by the antiserum or by the addition of lesser amounts of interferon (33 U/ml) following removal of the anti-interferon from the cultures. Conditioned media from control colony-stimulating factor-stimulated cultures similarly reversed the impairment of maturation resulting from 5 days of growth in the presence of anti-interferon. This enhancement of EAIgG ingestion reflected upon the interferon activity in the conditioned media and was neutralized by anti-interferon. Lastly, the endogenous interferon was found to enhance EAIgG ingestion by a majority of the mononuclear phagocyte progeny and not by a limited subpopulation.

Animals↗

Herpes simplex virus-specific lymphoproliferation: an analysis of the involvement of lymphocyte subsets.

Herpes simplex virus (HSV)-immune murine splenocytes incorporated significant levels of tritiated thymidine when incubated with UV-inactivated, heat-inactivated, and active preparations of HSV. Normal splenocytes incubated with the HSV preparations did not exhibit such proliferation. Maximum incorporation by the immune splenocytes occurred on the fifth day of culture and was mediated by Thy-1+, Lyt-1+, and Lyt-2+ cells. Attempts to correlate lymphoproliferation with other HSV-specific cellular immune responses demonstrated the complexity of this response. While T cells mediating delayed type hypersensitivity responses and cytotoxic T lymphocytes were involved in the lymphoproliferative response, neither could be considered as being exclusively associated with lymphoproliferation. Instead, lymphoproliferation appeared to be indicative of HSV-specific Lyt-1+ helper cells. Evidence was also presented that suppressor cells appeared to be involved in the regulation of the lymphoproliferative response.

Animals↗

Regulation of interleukin 1 production by alpha and beta interferons: evidence for both direct and indirect enhancement.

In this paper, the influence of interferons alpha + beta (IFN alpha + beta) on the levels of interleukin-1 (IL-1) produced by murine peritoneal exudate macrophages following subsequent stimulation with lipopolysaccharide (LPS), colony-stimulating factor-1 (CSF-1), or both was investigated. The results indicate that preincubation with IFN alpha + beta enhances IL-1 production in response to CSF-1 as well as to LPS. Moreover, prior exposure to IFN alpha + beta enhanced the apparently synergistic production of IL-1 in response to the two stimuli combined. Lastly, IFN alpha + beta in dosages exceeding 1,000 u/ml appeared to directly stimulate IL-1 production by exudate macrophages. Direct and augmented stimulation of IL-1 production by IFN alpha + beta could be neutralized by addition of highly specific anti-IFN alpha + beta antiserum. The significance of these findings in terms of the reported inflammatory and pyrogenic effects of IFN is discussed.

Animals↗

Production of soluble suppressor factors by herpes simplex virus-stimulated splenocytes from herpes simplex virus-immune mice.

Indirect evidence indicates that herpes simplex virus (HSV)-specific cytotoxic-T-lymphocyte induction is regulated by suppressor cells. To search for such suppressor effects, supernatant fluids from splenocyte cultures from normal and HSV-immune mice cultured either with or without viral stimulation were tested for their ability to inhibit HSV-specific cytotoxic-T-lymphocyte induction. Only the supernatant fluid from the HSV-stimulated, HSV-immune cultures contained a suppressor activity (HSV-SF). HSV-SF was produced by nylon-wool-purified Thy 1+ cells. HSV-SF was detectable after 3 days of culture and would only suppress cytotoxic-T-lymphocyte induction if HSV-SF was added within 24 h of initiation of the test cultures. HSV-SF was neither dialyzable nor heat stable. Molecular sieve chromatography of HSV-SF yielded multiple peaks of suppressor activity. Although most of these peaks exhibited nonspecific suppressor activity, the suppression mediated by the 90,000 to 150,000-molecular-weight fractions was antigen specific and genetically restricted. These results provide direct evidence for the regulation of HSV-cytotoxic-T-lymphocyte induction by a novel suppressor factor.

Animals↗

Regulation of herpes simplex virus-specific lymphoproliferation by suppressor cells.

We investigated the regulation of the herpes simplex virus (HSV)-specific lymphoproliferative response (LPR) by suppressor cells. The chief cell types in HSV-immune splenocytes proliferating in response to the antigen were Lyt 1+ and Lyt 2+ T cells, which accounted for approximately 60 and 40% of the response, respectively. Because the total responsiveness of splenocytes was enhanced after depletion of Lyt 2+ cells, the LPR was assumed to be subject to regulation by an Lyt 2+ suppressor cell. This was shown to be the case with an experimental design in which suppressor cell activity was induced in one culture, the cells were irradiated, and the effects on LPR were measured in a test antigen-stimulated culture. The cell responsible for suppression was shown to be Lyt 2+ IJ+, and the actual suppressor effect was not antigen specific. Cellular requirements for the generation of suppression were also investigated. The three distinct cell types that appeared to be required were Lyt 2+ and Lyt 1+ T cells and an IJ+ antigen-presenting cell. Of the three cell types, only the Lyt 2+ cell needed to be from HSV-immune animals. The implications of our model system for the better understanding of the role of immunity in herpesvirus pathogenesis are discussed.

Animals↗

Frequency of herpes simplex virus-specific helper T lymphocyte precursors in the lymph node cells of infected mice.

We have established a limited dilution assay to estimate the frequency of herpes simplex virus type 1 (HSV)-specific, interleukin 2 (IL 2)-producing helper T lymphocyte precursors (HTL-P). The estimated frequency of such cells in suspensions of local lymph node (LN) cells 5 days after in vivo virus infection was 1:2470 to 1:5800. Frequencies of HTL-P in cells from uninfected mice were below levels of detection of our system and were judged to be below 1:100,000. Removal of Lyt-2+ cells from responder LN cells before culture increases HTL-P frequency twofold to threefold, indicating the likely operation of some form of suppression in unseparated cultures. The demonstration of HSV-specific HTL-P required that cells from virus-primed mice be reexposed in vitro to viral antigen. In addition, clones expanded during a 9-day culture period failed to generate IL 2 unless reexposed to specific viral antigen or cross-reactivate HSV-2. Thus, HSV-specific HTL-P were strictly antigen dependent. No evidence was obtained for antigen-independent subpopulations of HTL-P as occurs with viral-specific cytotoxic T lymphocyte precursors. The clonal progeny of HTL-P were of the Thy-1+ Lyt+2- phenotype. Priming in vivo for the subsequent in vitro detection of HTL-P required that mice be exposed to infectious virus. Thus neither UV-inactivated nor heat-inactivated nor extracted viral glycoproteins could prime for HTL-P detection. The relevance of these findings for the future use of subunit vaccines against HSV is briefly discussed.

Animals↗

Augmentation of immunity to herpes simplex virus by in vivo administration of interleukin 2.

The immune mechanisms responsible for recovery from herpesvirus infections are multiple and include a principle role for aspects of T cell immunity. Our investigations add further support for this notion. We show that the ability of immune lymphocytes from animals infected i.p. 6 wk previously with herpes simplex virus type one (HSV-1) clear virus more effectively when interleukin 2 (IL 2) is injected into recipients of the adoptive transfers. Mice were treated on two consecutive days with cyclophosphamide and infected in the pinnae with 4 X 10(6) plaque-forming units of HSV-1. Three hours post-infection lymphocyte populations were injected i.v., and after a further 3 days the pinnae were removed, homogenized, and the content of infectious virus assayed. Purified IL 2 obtained from EL-4 cells either was given i.v. 2 hr before and 24 and 48 hr after cell injection or was given subcutaneously 2 hr before and 3, 24, and 48 hr after cell injection. The latter three injections were given i.p. and suspended in 15% gelatin. The immune lymphocyte cell populations were splenocytes and were either injected immediately after preparation of cell suspensions or after 5 days in vitro secondary stimulation with HSV-1. This latter cell population showed greater viral clearance activity, a function shown previously to be a property of Lyt-2+ cells. The clearance activity of cells was markedly enhanced in animals given IL 2 but only with a regimen that included injections in gelatin, a procedure that enhances in vivo circulation time of IL 2. The cell involved in clearance was a T cell and principally the Lyt-2+ subset. Treatment of recipient mice with anti-asialo GM-1 did not affect the clearance efficiency, indicating that NK cells were not responsible for the observed effect. Our experiments indicate that IL 2 may provide an important regulator of immune function in vivo and may warrant its investigation as a therapeutic agent to enhance antiviral immunity in certain circumstances.

Adjuvants, Immunologic↗

Endogenous regulation of macrophage proliferation and differentiation by E prostaglandins and interferon alpha/beta.

Our results indicate that there are at least two levels of interaction involving M-CSF stimulation of committed stem cells and mature mononuclear cells. Mature cells residing in hematopoietic tissues produce both PGE and IFN alpha/beta upon recognition of CSF in their environment. In vitro, both of these mediators act to suppress CSF-induced colony formation in a negative feedback manner. However, additional evidence indicates that the endogenous IFN acts also to enhance functional maturation of the monocyte progeny. Cultures deprived of IFN during clonal expansion displayed severely depressed capacities to produce IL-1, to resist lytic HSV infection, and to phagocytose opsonized erythrocytes via Fc receptors. Thus, it appears that the result of M-CSF stimulation of a mature cell is the production of a differentiation signal (IFN alpha/beta), which in turn affects an immature cell of the same lineage that responds to the CSF-1 growth stimulus. Whether the Ia+ subpopulation of M-CSF responsive progenitor cells represents precursors for a separate cell lineage or a subclass of macrophages remains to be determined. Similarly, the regulation of these cells by PGE and IFN remains to be explored. However, within the parameters of our investigation, neither these cells nor their specific regulator, acidic isoferritin, were of consequence.

Cell Differentiation↗