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Research paper thumbnail of The Interferon—Natural Killer Cell System in Multiple Sclerosis

Clinics in Immunology and Allergy

Research paper thumbnail of Susceptibility of mice to acute and persistent measles infection

Infection and Immunity, 1978

Intracerebral inoculation of neonatal mice with the Edmonston strain of measles virus produced an... more 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.

Research paper thumbnail of 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

Clinical and experimental immunology, 1982

Peripheral blood mononuclear cells (PBMC) of normal human donors are spontaneously cytotoxic for ... more 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 co...

Research paper thumbnail of Interferon production of vitro by leucocytes from patients with systemic lupus erythematosus and rheumatoid arthritis

Clinical and experimental immunology, 1981

The production of interferons (IFN) by peripheral blood leucocytes from normal donors an patients... more 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.

Research paper thumbnail of Studies on the susceptibility of the mouse preimplantation embryo to infection with cytomegalovirus

Reproduction, 1978

Intact and zona-free mouse preimplantation embryos were exposed to murine cytomegalovirus in vitr... more 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.

Research paper thumbnail of 27 Chronic Experimental Allergic Neuritis in the Lewis Rat

Journal of Neuropathology and Experimental Neurology, 1984

Research paper thumbnail of Sr++-induced inhibition of human natural killer (NK) cell-mediated cytotoxicity

The Journal of Immunology

The cell believed to be responsible for human spontaneous cytotoxicity or natural killing (NK) ha... more 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 b...

Research paper thumbnail of Working Group on Conflicts of Interest. The Working Group members are

The Council on Governmental Relations (COGR) is an association that includes among its membership... more The Council on Governmental Relations (COGR) is an association that includes among its membership 150 research-intensive universities. This document is the result of the efforts of the COGR

Research paper thumbnail of Immunogenic potentials of copolymer I in normal human lymphocytes

Neurology, 1985

Copolymer I (COP I), a nonencephalitogenic polypeptide analogous to myelin basic protein, is curr... more 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.

Research paper thumbnail of Tulane University

Comment letter on Department of Commerce recommendations on deemed export controls

Research paper thumbnail of The Role of H-2 in Resistance and Susceptibility to Measles Virus Infection

Genetic Control of Natural Resistance to Infection and Malignancy, 1980

Research paper thumbnail of The Council on Governmental Relations (COGR) is an association that includes among its membership 150 research-intensive universities. This document is the result of the efforts of the COGR Working Group on Conflicts of Interest. The Working Group members are

Research paper thumbnail of Interferon and NK Cells in Resistance to Persistently Virus-Infected Cells and Tumors

Natural Cell-mediated Immunity Against Tumors, 1980

Research paper thumbnail of Interactions Between Interferon and Cells of the Immune System

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

Fertility and sterility, 1978

Male mice were inoculated with murine cytomegalovirus (MCMV) to produce an acute generalized infe... more 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.

Research paper thumbnail of The Council on Governmental Relations (COGR) is an association that includes among its membership 150 research-intensive universities. This document is the result of the efforts of the COGR Working Group on Conflicts of Interest. The Working Group members are

Research paper thumbnail of Studies of Human NK Cell Function in Chronic Diseases

NK Cells and Other Natural Effector Cells, 1982

Research paper thumbnail of The effect of maternal cytomegalovirus infection on preimplantation development in the mouse

Reproduction, 1976

Mice were inoculated with murine cytomegalovirus at 14 and 7 days before and 1 and 4 days after m... more 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.

Research paper thumbnail of Absence of virus-induced lymphocyte suppression and interferon production in multiple sclerosis

Proceedings of the National Academy of Sciences, 1979

Research paper thumbnail of Interferon responses of leukocytes in multiple sclerosis

Neurology, 1981

I agree with Dr. Pincus that prison studies are a reasonable way of investigating any association... more I agree with Dr. Pincus that prison studies are a reasonable way of investigating any association between fits and violent behavior because it is possible to match epileptics and nonepileptics in terms of many other important social and psychological variables. Therefore, I am surprised that he did not emphasize that when this was done in my small study the epileptics did not prove to have more violence in their histories. Dr. Berger and co-workers" allude to the possible political overtones of giving men medication to control their violence. Here, I also agree with Dr. Pincus that they misrepresent his case, because he is only talking about ordinary voluntary medication, not compulsory treatment. However, it does seem to me that Dr. Pincus is again guilty of loose thinking. Benefits gained from taking anticonvulsants do not prove that the patient suffers from epilepsy. Most anticonvulsants are also sedatives; maybe the patients benefit from sedation. Double-blind control studies are required.

Research paper thumbnail of The Interferon—Natural Killer Cell System in Multiple Sclerosis

Clinics in Immunology and Allergy

Research paper thumbnail of Susceptibility of mice to acute and persistent measles infection

Infection and Immunity, 1978

Intracerebral inoculation of neonatal mice with the Edmonston strain of measles virus produced an... more 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.

Research paper thumbnail of 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

Clinical and experimental immunology, 1982

Peripheral blood mononuclear cells (PBMC) of normal human donors are spontaneously cytotoxic for ... more 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 co...

Research paper thumbnail of Interferon production of vitro by leucocytes from patients with systemic lupus erythematosus and rheumatoid arthritis

Clinical and experimental immunology, 1981

The production of interferons (IFN) by peripheral blood leucocytes from normal donors an patients... more 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.

Research paper thumbnail of Studies on the susceptibility of the mouse preimplantation embryo to infection with cytomegalovirus

Reproduction, 1978

Intact and zona-free mouse preimplantation embryos were exposed to murine cytomegalovirus in vitr... more 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.

Research paper thumbnail of 27 Chronic Experimental Allergic Neuritis in the Lewis Rat

Journal of Neuropathology and Experimental Neurology, 1984

Research paper thumbnail of Sr++-induced inhibition of human natural killer (NK) cell-mediated cytotoxicity

The Journal of Immunology

The cell believed to be responsible for human spontaneous cytotoxicity or natural killing (NK) ha... more 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 b...

Research paper thumbnail of Working Group on Conflicts of Interest. The Working Group members are

The Council on Governmental Relations (COGR) is an association that includes among its membership... more The Council on Governmental Relations (COGR) is an association that includes among its membership 150 research-intensive universities. This document is the result of the efforts of the COGR

Research paper thumbnail of Immunogenic potentials of copolymer I in normal human lymphocytes

Neurology, 1985

Copolymer I (COP I), a nonencephalitogenic polypeptide analogous to myelin basic protein, is curr... more 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.

Research paper thumbnail of Tulane University

Comment letter on Department of Commerce recommendations on deemed export controls

Research paper thumbnail of The Role of H-2 in Resistance and Susceptibility to Measles Virus Infection

Genetic Control of Natural Resistance to Infection and Malignancy, 1980

Research paper thumbnail of The Council on Governmental Relations (COGR) is an association that includes among its membership 150 research-intensive universities. This document is the result of the efforts of the COGR Working Group on Conflicts of Interest. The Working Group members are

Research paper thumbnail of Interferon and NK Cells in Resistance to Persistently Virus-Infected Cells and Tumors

Natural Cell-mediated Immunity Against Tumors, 1980

Research paper thumbnail of Interactions Between Interferon and Cells of the Immune System

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

Fertility and sterility, 1978

Male mice were inoculated with murine cytomegalovirus (MCMV) to produce an acute generalized infe... more 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.

Research paper thumbnail of The Council on Governmental Relations (COGR) is an association that includes among its membership 150 research-intensive universities. This document is the result of the efforts of the COGR Working Group on Conflicts of Interest. The Working Group members are

Research paper thumbnail of Studies of Human NK Cell Function in Chronic Diseases

NK Cells and Other Natural Effector Cells, 1982

Research paper thumbnail of The effect of maternal cytomegalovirus infection on preimplantation development in the mouse

Reproduction, 1976

Mice were inoculated with murine cytomegalovirus at 14 and 7 days before and 1 and 4 days after m... more 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.

Research paper thumbnail of Absence of virus-induced lymphocyte suppression and interferon production in multiple sclerosis

Proceedings of the National Academy of Sciences, 1979

Research paper thumbnail of Interferon responses of leukocytes in multiple sclerosis

Neurology, 1981

I agree with Dr. Pincus that prison studies are a reasonable way of investigating any association... more I agree with Dr. Pincus that prison studies are a reasonable way of investigating any association between fits and violent behavior because it is possible to match epileptics and nonepileptics in terms of many other important social and psychological variables. Therefore, I am surprised that he did not emphasize that when this was done in my small study the epileptics did not prove to have more violence in their histories. Dr. Berger and co-workers" allude to the possible political overtones of giving men medication to control their violence. Here, I also agree with Dr. Pincus that they misrepresent his case, because he is only talking about ordinary voluntary medication, not compulsory treatment. However, it does seem to me that Dr. Pincus is again guilty of loose thinking. Benefits gained from taking anticonvulsants do not prove that the patient suffers from epilepsy. Most anticonvulsants are also sedatives; maybe the patients benefit from sedation. Double-blind control studies are required.