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Biomedical subjects

R G Miller

Publications and source records attributed to R G Miller.

At least 235 records · Page 13Linked to original sources
PubMed1986

The use of tunicamycin to study the role of cell surface oligosaccharides in lymphocyte recognition.

Cell surface N-linked sugars may play a role in target cell recognition by cytotoxic T lymphocytes (CTL). We have studied this role by treating tumor cell targets with tunicamycin, an effective inhibitor of N-linked glycosylation in mammalian cells. We determined a tunicamycin treatment protocol in which glycosylation was blocked and in which target cell killing by 5-day primary mixed lymphocyte reaction CTL was inhibited, yet in which cell viability was high and expression of major histocompatibility complex molecules was normal. It was found that tunicamycin-treated cells were killed only about one-half as well as untreated targets and that tunicamycin-treated target cells were less effective than untreated target cells as cold target competitors in cold target competition experiments. These observations suggest that for optimal killing, CTL require an interaction with the target cell that involves N-linked glycans on the target cell surface.

Animals↗
PubMed1986

Differentiation from precursors in normal bone marrow of spontaneously cytotoxic cells showing anti-self-MHC specificity.

Colonies containing spontaneously cytotoxic effector cells with specificity for target cells carrying self-MHC can be grown from normal mouse bone marrow (BM). BM was first depleted of nylon wool-adherent cells and was then cultured at low cell number (1 to 300 cells/culture) in multiple replicate microcultures in liquid culture medium containing supernatant from EL4 thymoma cells stimulated with PMA. Frequency of colony growth followed one-hit limiting dilution kinetics. Colonies contained lymphoid, myeloid, or both kinds of cells. About 5% of colonies contained self-specific cytotoxic effector cells. Analysis using the X chromosome-linked isoenzyme PGK-1 confirmed that colonies containing autoreactivity could be clonal. A factor other than IL 2, IL 3, or PMA appears to be required for the growth of autoreactive colonies. Similar colonies, both with and without autoreactive effector cells, could also be grown from the BM of athymic nude mice with frequencies and cytotoxic activities directly comparable to those found for normal BM. C.B-17 scid mice lack both B and T cells, apparently due to a block in the development of lymphoid stem cells. Colonies could be grown with comparable frequency from their BM, but these colonies lacked both lymphoid cells and spontaneous cytotoxic activity. Evidence is presented against the self-reactive effector cells being NK cells, macrophages, or mature T cells. It is speculated that they represent an early stage of the T cell differentiation pathway.

Animals↗
PubMed1986

The use of plasmapheresis, lymphocytapheresis, and staph protein-A immunoadsorption as an immunomodulatory therapy in patients with AIDS and AIDS-related conditions.

Circulating immune complexes, autoantibodies, and suppressor factors to normal lymphoproliferation may play an important role in the induction and maintenance of the cellular immunodeficiency characteristic for the acquired immunodeficiency syndrome (AIDS) and its related conditions. In order to explore the possibility that the removal of circulating humoral factors may have an immunomodulatory effect in patients with AIDS and AIDS-related conditions (ARC), we used apheresis procedures to treat patients with different clinical presentations of AIDS and ARC. Five patients with AIDS and opportunistic infections were treated with plasmapheresis. Four patients with AIDS and Kaposi's sarcoma without opportunistic infections were treated with staph protein-A immunoadsorption and two patients with ARC and peripheral neuropathy were treated with lymphoplasmapheresis. The treatments were tolerated well by all patients. Effective removal of circulating humoral immune factors was observed in all three groups. No significant clinical benefit was seen in the patients with AIDS and opportunistic infections treated with plasmapheresis. Partial tumor responses were observed in three of the four patients with AIDS related Kaposi's sarcoma treated with staph protein-A plasma perfusion, and resolution of neurologic symptoms was seen in both patients with ARC and peripheral neuropathy treated with lymphoplasmapheresis. Our preliminary results suggest that lymphoplasmapheresis may be an effective treatment modality for patients with ARC related peripheral neuropathy, that protein-A immunoadsorption is well tolerated by patients with AIDS-related Kaposi's sarcoma, and that this treatment has antitumor and immunomodulatory effects in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Muscle membrane excitation and impulse propagation velocity are reduced during muscle fatigue.

In order to determine whether or not impulse propagation was impaired during muscle fatigue, evoked muscle compound potentials (MCP) and twitches were recorded, both before and after fatigue, from the first dorsal interosseus (FDI), adductor pollicis (AP), and anterior tibialis (AT) muscles following supramaximal ulnar and peroneal nerve stimulation, respectively. The muscles were fatigued by maintaining maximum voluntary isometric, index finger abduction, thumb adduction, or ankle dorsiflexion for 1-5 minutes. FDI was most markedly altered, with reduced MCP amplitude (mean 32%) and increased MCP duration (mean 47%) after only 1 minute. After fatigue of longer duration (3-5 minutes), there were corresponding reductions in both the MCP amplitudes and the twitch tensions recorded from both the FDI and ankle dorsiflexors. We conclude that (1) a reduction in both the level of excitation and impulse propagation velocity of muscle membranes occurs during muscle fatigue, and (2) the magnitude of this reduced membrane function and its contribution to the mechanisms underlying fatigue depend both on the duration and degree of fatigue, as well as on the intrinsic properties of the particular muscle.

Cell Membrane Permeability↗
PubMed1986

Nerve conduction studies in infants and children.

The electrophysiologic evaluation of peripheral nerves may provide critically important information, both with respect to diagnosis and prognosis, in the child with a suspected neuromuscular disorder. However, special attention to various technical considerations is necessary to avoid misleading results. Utilizing these techniques, both hereditary and acquired neuropathies may be identified and characterized. The latter has become especially important in view of recent advances in the treatment of acquired demyelinating neuropathies.

Child↗
PubMed1986

Prednisone-induced worsening of neuromuscular function in myasthenia gravis.

In patients with myasthenia gravis who received single doses of prednisone orally (40 to 100 mg), we found acute inhibition of neuromuscular function as manifest by increased decremental responses to repetitive nerve stimulation, reduced twitch tension, and lowered maximum voluntary contraction strength. The time course of these changes correlated with plasma methylprednisolone levels, implying direct drug effects on neuromuscular function.

Action Potentials↗
PubMed1986

Results of toxicological testing of Jefferson Parish pilot plant samples.

Five toxicological tests were performed using concentrated drinking water samples collected at a pilot-scale drinking water treatment plant that had streams treated with different disinfectants (no disinfectant, ozone, chlorine dioxide, monochloramine, or chlorine) before treatment with granular activated carbon (GAC). The toxicological tests used in this study were the Ames Salmonella assay, a subchronic in vivo toxicity assay in mice, the SENCAR mouse skin initiation-promotion assay, a rat liver foci assay, and the lung adenoma assay in strain A mice. These tests were conducted to determine the general toxicity and the mutagenic/carcinogenic potential associated with the use of disinfection and/or GAC in the treatment of drinking water. The stability of the mutagenic activity of the samples tested was determined by repeated analysis using the Ames Salmonella assay. Results indicated that the samples remained mutagenic for the duration of the tests. All the drinking water concentrates (4000 X) prepared by the XAD resin adsorption procedure failed to provide statistically significant indication of carcinogenic activity in the SENCAR mouse, rat liver foci, and the lung adenoma assays. However, concentrates of the chlorine, chlorine dioxide, and monochloramine treated waters gave consistent mutagenic responses in the Ames Salmonella assay. GAC was effective for 6 months in removing both the mutagenicity of chlorine-treated water and the potential of water to become mutagenic when treated with chlorine. In the in vivo, subchronic 30-day toxicity test in mice, some statistically significant differences in organ weights and body weights of animals exposed to different concentrates of some of the samples were observed. However, a consistent pattern of these differences indicating overt toxicity was not detected.

Animals↗
PubMed1986

Glycopeptides inhibit allospecific cytotoxic T lymphocyte recognition in an MHC-specific manner.

Attempts to block specific T cell recognition with soluble extracts have been uniformly unsuccessful. However, we found that glycopeptides prepared from three MHC-different tumor cell lines were able to inhibit binding of allospecific cytotoxic T lymphocytes (CTL) to an appropriate tumor cell or Con A blast target cell. Inhibition was only observed when the MHC of the cell providing the glycopeptide was the same as the MHC of the target cell being recognized. This result was obtained by using both fully allogeneic CTL and CTL generated between B10 congenic mice differing only at the MHC. This suggests that the inhibition depends on the MHC expressed by the target cell. Because we extensively pronase digested cell glycoproteins and then enriched for glycopeptides containing small amounts of peptide, we attribute the inhibition to the carbohydrate portion of the glycopeptide. Our observations suggest that CTL may, in part, recognize carbohydrate molecules on the target cell surface whose specific structure(s) is influenced or regulated by genes in or near the MHC. They also suggest that the T cell receptor complex has some lectin-like properties.

Animals↗
PubMed1986

Chronic inflammatory polyradiculoneuropathy with ophthalmoplegia.

We report a case of chronic progressive inflammatory polyradiculoneuropathy with a subacute exacerbation that included ataxia, tendon areflexia, ptosis, and ophthalmoplegia. Spinal fluid protein was elevated and electrophysiological studies revealed a demyelinating neuropathy. This case suggests a continuum between chronic inflammatory polyradiculoneuropathy and the Miller Fisher variant of acute inflammatory polyneuropathy.

Chronic Disease↗
PubMed1986

In vivo activation of lymphocytes in rheumatoid arthritis.

Spontaneous in vivo proliferation of peripheral blood mononuclear cells (PBM) and T and B lymphocytes from 28 patients with rheumatoid arthritis (RA), 20 healthy individuals and 13 patients with psoriatic arthritis was evaluated. PBM, T (E+) and non-T (E-) cells from patients with active RA proliferated significantly more than the same populations from healthy individuals and patients with inactive RA. In contrast, only E+ cells from PSA patients showed a trend to increased proliferation relative to healthy individuals. AET treated sheep red blood cells (SRBC) inhibited 3HTdR incorporation of highly profilerating PBM of active RA patients. The data suggest in vivo activation of both B and T cells in patients with clinically active RA.

Adult↗
PubMed1986

Quantifying human muscle strength, endurance and fatigue.

Physiologic methods have been developed to objectively quantify muscle strength, endurance, and fatigability. Isometric force and rectified/integrated electromyogram were simultaneously recorded during the three phases of a recording session: pre-fatigue, fatigue (1 min duration) and post-fatigue recovery (up to 10 min). Five parameters of muscle performance were computed: Maximum force (MF) exerted during isometric voluntary contraction (muscle strength); Force-time integral--area under force-time plot (endurance); Fatigue index (FI) (% reduction in MF); Neuromuscular efficiency (force/mV of EMG recruited), and Recovery time (RT). Normal values based on data from 20 normal subjects were determined for four muscles: index finger abductor, elbow flexors, knee extensors, and ankle dorsiflexors. Neuromuscular efficiency (NME) decreased significantly (20 to 70%) at the end of the fatigue phase; it generally increased to the pre-fatigue level in 2 to 10 min, during the recovery phase. The period needed to reach pre-fatigue level was referred to as RT. The elbow flexors had the highest mean FI (48%) and the longest RT (greater than 6 min); the ankle dorsiflexors had the lowest mean FI (34%) and the shortest RT (1.5 min). These methods have been used also to evaluate the effects of weight training in two patients with neuromuscular disorders.

Adolescent↗
PubMed1985

Alloreactive cytotoxic T cells. I. Alloreactive and allorestricted cytotoxic T cells.

Nylon wool-nonadherent spleen cells from three inbred mouse strains of H-2k (CBA), H-2d (BALB/c) and H-2b (C57BL/6) haplotype were co-cultured with 2,4,6-trinitrophenyl (TNP)-modified or nonmodified allogeneic stimulator cells in a limiting dilution system. Using a recently described restimulation protocol, a surprisingly large number of splenic cytotoxic lymphocyte precursors (CLP) was clonally expanded in this primary in vitro response to allo-H-2 plus TNP determinants; measured CLP frequencies ranged from 1/30 to 1/300. The lytic specificity patterns of individual microcultures (selected for a high probability of clonality) were defined by split well analysis, and were furthermore followed up in time by sequentially reassaying microcultures at different time points of in vitro incubation. This analysis revealed the following: a large fraction of cytotoxic T lymphocyte clones lysed TNP-modified but not nonmodified allogeneic concanavalin A blast targets, i.e., were allorestricted; this was found in all 6 allogeneic strain combinations set up with b, k and d haplotype mice; allorestricted lytic patterns predominated in microcultures with low numbers of responder cells per well, and at late time points of in vitro culture; allorestricted lytic cultures were specific for the stimulating allogeneic H-2 plus TNP determinant(s); and allorestricted lytic patterns were also found in microcultures stimulated by nonmodified allogeneic cells. To our knowledge, these are the highest CLP frequencies yet reported in limiting dilution systems that used a specific (re)stimulation protocol and measured the lytic responses obtained in a specificity-controlled readout.

Animals↗
PubMed1985

Rapid changes in specificity within single clones of cytolytic effector cells.

We find rapid changes in the specificity of the cytolytic effector cells in a mixed lymphocyte culture. The lysis patterns produced by cytolytic effector cells generated near limiting dilution in murine mixed lymphocyte reactions of three types, F1 anti-parent (F1(A X B) anti-A), allogeneic (C anti-F1(A X B)), and F1 antimodified parent (F1(A X B) anti-A-TNP), were investigated. Cultures were characterized by their ability or inability to lyse a panel of target cells (e.g., A, B, F1). When individual cultures were tested at two different times, changes in lytic pattern were routinely seen, with some patterns reproducibly increasing in frequency and others reproducibly decreasing (e.g., patterns involving lysis of F1 decreased in an F1 anti-A response but increased in a C anti-F1 response). X-linked isoenzyme analysis showed that changes can occur within a single clone of effector cells. These results imply that the T cell specificity repertoire continues to evolve during an ongoing immune response, a conclusion incompatible with clonal selection theory.

Animals↗
PubMed1985

Oral beta-carotene can increase the number of OKT4+ cells in human blood.

Oral doses of beta-carotene (180 mg/day) given for 2 wk to normal human volunteers significantly increased the frequency of OKT4+ (helper/inducer T cells) after 7 days and of OKT3+ (all T cells) after 14 days. The frequency of OKT8+ cells was unaffected, as compared to untreated controls. Plasma levels of beta-carotene were markedly elevated throughout the study. Plasma levels of vitamin A were slightly (but significantly) elevated on days 7 and 14. No toxicity was observed. Oral beta-carotene treatment may be a clinically effective means of enhancing T4+ lymphocytes.

Adult↗