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Biomedical subjects

P A Neighbour

Publications and source records attributed to P A Neighbour.

15 recordsLinked to original sources
PubMed1985

Immunogenic potentials of copolymer I in normal human lymphocytes.

Copolymer I (COP I), a nonencephalitogenic polypeptide analogous to myelin basic protein, is currently being tested for possible effectiveness in treating MS. Peripheral blood mononuclear cells from normal human donors respond blastogenically to the L-form of COP I. This response was greater than that obtained with either bovine or guinea pig myelin basic protein (GPMBP), with no specificity for a particular T-cell subset. Analyses of culture supernatants demonstrated the presence of interleukin-2 and gamma interferon. Mononuclear cells from human fetal cord blood also responded blastogenically to COP I, but the magnitude of the response did not differ from that induced by GPMBP.

Animals↗
PubMed1984

Studies of interferon production and natural killing by lymphocytes from multiple sclerosis patients.

Peripheral blood lymphocytes from patients with multiple sclerosis (MS) have been shown by numerous investigators to function abnormally in a variety of immunological tests in vitro. In this article, data concerning defective natural killer (NK) cell function and interferon production by MS patients' lymphocytes have been reviewed. Production of IFN-alpha and IFN-gamma by appropriately stimulated lymphocytes has been shown to be significantly reduced in many patients with acute remitting or chronic progressive disease. Furthermore, a significant proportion of these patients has been found to exhibit reduced levels of endogenous and augmented NK cell activity. A likely explanation for these phenomena is that altered traffic occurring as a consequence of disease has led to a relative loss of NK and IFN-producing cells from the peripheral circulation. Flow cytometric data obtained using monoclonal antibodies that selectively label these effector populations were presented. Possible explanations for the observed defects and their significance relative to our understanding of the etiopathogenesis of MS were discussed.

B-Lymphocytes↗
PubMed1982

Natural killer cell activity of mononuclear cells from rheumatoid patients measured by a conjugate-binding cytotoxicity assay.

The natural killer cell activity of synovial fluid mononuclear cells and synovial membrane mononuclear cells from patients with rheumatoid arthritis was compared with that of paired peripheral blood mononuclear cells from many of these patients. Natural killer cell activity was measured by the use of a conjugate-binding cytotoxicity assay with an erythroleukemic cell line, K562, as target. There was no significant difference when 15-minute target binding by peripheral blood mononuclear cells was compared with synovial fluid mononuclear cells. Target binding of synovial greater (P less than 0.05) than that of peripheral blood cells. Three-hour target killing, however, was significantly greater when synovial fluid mononuclear cells were compared with the peripheral blood cells, P less than 0.01, and when synovial membrane cells were compared with the peripheral blood cells (P less than 0.05). The products of binding and 3-hour killing, a reflection of the total number of mononuclear cells participating in cytotoxicity, were significantly greater when either synovial fluid or synovial membrane mononuclear cells were compared with peripheral blood mononuclear cells (both P less than 0.01). Electron microscopy confirmed the presence of large granular lymphocytes, representing 20% of the peripheral blood cells and 37% of the synovial fluid mononuclear cells. Interferons were detected in 10/12 rheumatoid and 3/12 nonrheumatoid synovial fluid samples studied. These findings indicate that functional natural killer cells are selectively increased in the rheumatoid joint and may contribute to the overall increase in immunologic activity found in the joints of these patients.

Arthritis, Rheumatoid↗
PubMed1982

Human large granular lymphocytes and natural killing ultrastructural studies of strontium-induced degranulation.

Large granular lymphocytes (LGL) are a subpopulation of human peripheral blood mononuclear cells believed to contain the mediators of spontaneous cytotoxicity or natural killing. In the present study, the mononuclear cells were enriched for LGL by differential density centrifugation on Percoll gradients and examined by transmission electron microscopy. The ultrastructure of LGL and of their binding interaction with natural killer-susceptible target cells (K562) is described in detail. Some morphological similarity between LGL and cells of a myelocytic origin was observed. Studies reported elsewhere have shown that Sr2+, an alkaline earth ion known to degranulate granulocytes, inhibits NK cell function. Comparison of the morphology of control and SR2+-treated LGL showed that Sr2+ caused several characteristic changes in LGL ultrastructure and, indeed, led to their degranulation. The recovery of natural killer function seen following in vitro culture of SR2+-treated effector cells was accompanied by the reappearance of typical intracytoplasmic granules. These data strongly suggest that the granules of LGL are required for and, perhaps, involved in natural killer-mediated cytolysis.

Cell Communication↗
PubMed1982

Sr++-induced inhibition of human natural killer (NK) cell-mediated cytotoxicity.

The cell believed to be responsible for human spontaneous cytotoxicity or natural killing (NK) has been described recently as a large granular lymphocyte (LGL). Because the intracytoplasmic granules of LGL appear to be peculiar to the subpopulation of mononuclear cells containing NK effectors, we have investigated their possible requirement in the cytolytic process. Experiments reported here show that Sr++, a cation known to cause degranulation of granulocytes, caused a dose- and time-dependent inhibition of the NK activity of human peripheral blood mononuclear cells. A single-cell NK assay showed that the number of cytotoxic cells was not significantly reduced, but that Sr++ inhibited NK by preventing individual effector cells from engaging in multiple lethal hits. Moreover, the inhibition of NK appeared to be reversible; culture in vitro of Sr++-treated PBMC resulted in the eventual return of cytolytic activity in these cells. Augmentation of NK by interferon (IFN) was similarly blocked by Sr++. In addition, Sr++ also inhibited the NK activity of IFN-prestimulated effector cells and, as before, NK function returned during subsequent culture. These results indicated that the return of NK function after Sr++ treatment was the result of reactivation of cytotoxic cells rather than recruitment of new effectors. We have shown in other studies that Sr++ degranulates LGL, and the data presented here provide support for the hypothesis that the intracytoplasmic granules of LGL are required for NK-mediated cytotoxicity.

Binding Sites↗
PubMed1982

Endogenous and interferon-augmented natural killer cell activity of human peripheral blood mononuclear cells in vitro. Studies of patients with multiple sclerosis, systemic lupus erythematosus or rheumatoid arthritis.

Peripheral blood mononuclear cells (PBMC) of normal human donors are spontaneously cytotoxic for certain tumour-derived and virus-infected target cells. This so-called natural killing (NK) can be augmented by the action of interferons (IFN) and by IFN-inducers. In this study, we have compared both endogenous and augmented NK activity of normal donors with that of patients suffering from either multiple sclerosis (MS), systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). Endogenous NK was assayed using an NK susceptible target cell (K562), and augmented NK using a target cell (WI-L2) which is lysed only by NK effector cells that have been pre-stimulated by IFN or IFN-inducers. While NK function appeared normal in RA patients, this study confirms previous reports of defective endogenous NK in many MS and SLE patients. In addition, anomalous IFN-augmented NK was also detected in many patients with these two diseases, indicating that defective NK function cannot always be corrected by IFN treatment in vitro. Analysis of IFN production, endogenous NK and IFN-augmented NK by individual patients with MS or SLE showed the defects in their IFN-NK systems to be highly selective, suggesting that individual components of this system may operate independently.

Adult↗
PubMed1981

Immunological studies in senile dementia of the Alzheimer type: evidence for enhanced suppressor cell activity.

To examine immunological variables in senile dementia of the Alzheimer type (SDAT), we compared SDAT patients with elderly and young controls with regard to concanavalin A (Con A)-induced suppression, lymphocyte proliferation, interferon production, and serum immunoglobulin levels. The results showed exaggerated Con A suppression and reduced lymphocyte proliferation in SDAT patients compared to elderly control subjects. Interferon production after stimulation by Con A and immunoglobulin levels did not differ between SDAT and elderly control subjects. The results suggest impaired immunoregulatory mechanisms in patients with SDAT that may be related to the cause or course of SDAT. Alternatively, these immunological changes may be secondary to pathological changes in the central nervous system.

Adult↗
PubMed1981

Interferon responses of leukocytes in multiple sclerosis.

In vitro interferon (IFN) responses of peripheral blood leukocytes to measles virus and to other IFN inducers were determined for multiple sclerosis patients and normal donors. The group mean IFN response to measles virus was significantly lower in patients (15 units) than in normal donors (100 units), and a greater proportion of the patients failed to exhibit a significant IFN response. This defect was not specific for measles virus and was also observed consistently in response to Newcastle disease virus, Poly(I).Poly(C), and concanavalin A. The level of IFN response was not related to the clinical stage of disease.

Adult↗
PubMed1981

Interferon production of vitro by leucocytes from patients with systemic lupus erythematosus and rheumatoid arthritis.

The production of interferons (IFN) by peripheral blood leucocytes from normal donors an patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been investigated in response to several IFN inducers in vitro. Whereas IFN responses of RA donors did not differ significantly from the normal group, those of SLE patients were significantly reduced, and many of these patients failed to respond to all. Patients with active or acute SLE responded significantly less well than those with inactive disease. There was no apparent effect of steroid therapy on the IFN responses of either SLE or RA patients. These data may indicate a basic immunological defect of the circulating leucocytes of SLE patients, which may be responsible for some of the in vitro lymphocyte anomalies reported for this disease.

Adult↗
PubMed1979

Absence of virus-induced lymphocyte suppression and interferon production in multiple sclerosis.

Lymphocytes from normal adult donors exposed in vitro to inactivated measles virus were found to exert significant suppression (33.9%) of the concanavalin A responses of cryopreserved, autochthonous responder cells. In marked contrast, lymphocytes from multiple sclerosis patients exhibited significantly reduced suppression (1.5%), and in 80% of cases failed to suppress at all. The degree of suppression increased slightly with age of the patient but did not vary with the clinical stage of disease. There was no apparent genetic restriction of suppressor activity. Although specificity of this phenomenon for measles virus has not been established, no differences in the responses of lymphocytes from normal or multiple sclerosis patient donors were found with subacute sclerosing panencephalitis, Sendai, canine distemper, mumps, or influenza viruses. Supernates of measles-treated lymphocytes from normal donors possessed both suppressive and antiviral activities. Both activities were resistant to pH 2 treatment and were neutralized by an anti-human leukocyte interferon antiserum, strongly suggesting that interferon (probably type I) was the mediator of suppression. Consistent with their inability to suppress concanavalin A responses, lymphocytes from multiple sclerosis patients failed to produce significant amounts of interferon in response to measles challenge in vitro. These results extend previous observations that multiple sclerosis patients are unable to respond appropriately to measles virus antigen in vitro.

Adult↗
PubMed1978

Murine cytomegalovirus and fertility: potential sexual transmission and the effect of this virus on fertilization in vitro.

Male mice were inoculated with murine cytomegalovirus (MCMV) to produce an acute generalized infection. Infections virus was recovered from both epididymal sperm and seminal vesicles as well as from uterine sperm collected from mated females, suggesting that MCMV might be transmitted sexually. Because the presence of virus in the ejaculate might affect the fertilization process, the effect of MCMV on the fertilization of mouse gametes and on subsequent embryonic development was studied in vitro. Although the fertilization rate was reduced when sperm were preincubated with infectious virus, this was also the case when heat-inactivated virus was used, leading to the conclusion that this effect was not due to a direct infectious interaction between virus and gametes. Subsequent embryonic development was normal, and there was no evidence of productive infection of the preimplantation embryo.

Animals↗
PubMed1978

Susceptibility of mice to acute and persistent measles infection.

Intracerebral inoculation of neonatal mice with the Edmonston strain of measles virus produced an acute, lethal encephalitis and thymic dysplasia in susceptible mice. There was an age-related development of resistance to infection. This resistance was strain-dependent and appeared to be associated with the extent of virus growth in the brain. Studies on the genetic basis for susceptibility, using hybrid and backcross mice, revealed that the principal determinant of host resistance to acute infection was a dominant gene or genes which segregated independently of the H-2 complex. A small number of survivors of the acute infection showed persistence of measles virus antigens in the cerebellum and spleen for up to 2 months after inoculation. However, the low frequency of this persistence indicated that, at this time, intracerebral inoculation of neonatal mice with the Edmonston strain of measles virus constitutes a difficult model for the study of persistant measles infection.

Acute Disease↗
PubMed1978

Studies on the susceptibility of the mouse preimplantation embryo to infection with cytomegalovirus.

Intact and zona-free mouse preimplantation embryos were exposed to murine cytomegalovirus in vitro at various stages of development. The embryos developed normally to the blastocyst stage, and there was no evidence of embryonic infection. Intraperitoneal inoculation of female mice with this virus produced an acute generalized infection, and embryonic development was retarded in vivo. The embryos themselves were not productively infected, and they developed into apparently normal fetuses when transferred to uninfected mice.

Animals↗
PubMed1976

The effect of maternal cytomegalovirus infection on preimplantation development in the mouse.

Mice were inoculated with murine cytomegalovirus at 14 and 7 days before and 1 and 4 days after mating. The effects of maternal infection on early pregnancy were investigated. Inoculation 7 days before and 1 day after mating, i.e. around ovulation and implantation, significantly reduced pregnancy rate. Embryos in these females were developmentally retarded, perhaps because of the inflammatory effect of the infection on the genital tract. Retarded embryos developed normally when cultured.

Animals↗