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Biomedical subjects

J I Greenstein

Publications and source records attributed to J I Greenstein.

17 recordsLinked to original sources
PubMed1995

Cholecystokinin potentiates morphine anticonvulsant action through both CCK-A and CCK-B receptors.

Recent studies have suggested that cholecystokinin may have a role in modulating the effects of the endogenous opioid system in physiological functions such as thermoregulation and pain control. However, the possible interaction of cholecystokinin and morphine in epileptogenesis is unknown. We studied the effect of subcutaneous morphine and intracerebroventricularly administered cholecystokinin octapeptide sulphate ester and receptor antagonists CCK-A (MK 329) and CCK-B (L 365,260) on seizures provoked by maximal electroshock in male Sprague-Dawley rats. Seizures were induced through electrode-gel-coated ear clip electrodes by a high voltage, high internal resistance constant current generator, 30 minutes after morphine administration and 10 minutes after cholecystokinin-8-SE, CCK-A and CCK-B infusion. Morphine decreased the length of the tonic component of the seizure and cholecystokinin potentiated this decrease. Cholecystokinin antagonists blocked the effects of both cholecystokinin and morphine. The results suggest that cholecystokinin acts as an endogenous agonist with opioids in the regulation of seizure susceptibility through both CCK-A and B receptors and may be responsible for part of the anticonvulsant action of morphine.

Animals↗
PubMed1993

Identification and characterization of [125I]arginine vasopressin binding sites on human peripheral blood mononuclear cells.

Arginine vasopressin (AVP) is a nonapeptide that has been shown to be released from the posterior pituitary during stress. Although noted primarily for its hemodynamic and homeostatic properties, AVP also appears to have an effect on the immune system. It may modulate cellular immunity via its enhancement of the autologous mixed lymphocyte response (AMLR), an effect which we have demonstrated to occur over a wide dose range with a maximum at 10(-7) M. In this study, we examined the binding of [125I]AVP, and AVP analogues to human peripheral blood mononuclear cells (PBMC). AVP inhibited [125I]AVP (0.2 nM) binding on PBMC in a dose-dependent manner with maximal inhibition being reached at 10(-8) M. Specific [125I]AVP binding, as defined as that which could be displaced by 1 x 10(-6) M AVP, was saturable, time-dependent, and linear to cell concentration. Specific binding reached saturation at approximately 1000 pM in 45 minutes. From Scatchard analysis of saturation experiments it appeared to be a homogeneous population of binding sites with KD of approximately 0.5 nM and Bmax of approximately 7.6 fmole/8 x 10(6) cells, corresponding to approximately 527 binding sites/cell. There was a good correlation between AVP binding and cell number. AVP failed to dissociate completely from its binding sites in 60 minutes, perhaps because of the formation of a high-affinity ligand-binding site complex. From competitive binding studies with various AVP antagonists and analogues, it was found that the AVP binding site appeared to be V1-like. AVP binding occurred predominantly on B-cells and macrophages. Having provided evidence for the existence of specific, high affinity, and saturable V1-like AVP binding sites, we suggest a potential modulatory role for AVP in the communication between the neuroendocrine and immune systems.

Amino Acid Sequence↗
PubMed1993

Systemic recombinant human interferon-beta treatment of relapsing-remitting multiple sclerosis: pilot study analysis and six-year follow-up.

A pilot study was undertaken to test the safety and establish the side effect profile of recombinant human interferon-beta 1b (Betaseron, Berlex Laboratories, Richmond, CA), in patients with relapsing-remitting multiple sclerosis (RRMS). During the initial dose finding period (24 weeks), five groups of 6 patients each were treated by subcutaneous injection three times each week with either 0.8, 4, 8, or 16 million units (mU) of Betaseron or placebo (WHO Standard). Although some side effects were noted in all groups, a dose-related trend in reduction of exacerbation frequency and side-effect profile was noted. Patients given 16 mU had no exacerbations during the initial dosing period, but associated side effects led to dose reduction or dropout. An 8 mU dose was selected for further study after 24 weeks, and continuous dosing at 8 mU in 15 patients has now exceeded 6 years. Side effects abated over time. Neutralizing antibody developed in most patients, but titers were variable, fluctuated independently of clinical course, and tended to fall with prolonged treatment. A dose-dependent rise in neopterin levels was observed during the initial dosing period. This pilot study has demonstrated responsiveness to Betaseron, shown a stable safety profile over time, and established guidelines for a dosing regimen to evaluate and optimize further the efficacy of Betaseron in RRMS.

Adolescent↗
PubMed1992

The effect of arginine vasopressin on the autologous mixed lymphocyte reaction.

Arginine vasopressin (AVP) is a nonapeptide that has been shown to be released from the supraoptic and paraventricular nuclei of the hypothalamus during stress. Although noted primarily for its hemodynamic as well as homeostatic properties, AVP also appears to have an effect on the immune system. It may modulate cellular immunity via its enhancement of the autologous mixed lymphocyte response (AMLR), an effect which we have demonstrated to occur over a wide dose range with a maximum at 10(-7) M. The increase in proliferation following a single addition of AVP in a 6-day culture appears to be augmented when the peptide is added daily throughout the same culture period. Enhanced proliferation appears to be a specific response that is influenced by arginine residues in position 8 of this nonapeptide. Having provided evidence for the existence of receptors with moderate affinity for AVP, we suggest a potential modulatory role for AVP in support of the concept of a communication between the neuroendocrine and immune systems. Since various autoimmune conditions may be aggravated by stress, stress-induced release of neuropeptides such as AVP may play an important role in modulating immune regulation of these disease states.

Amino Acid Sequence↗
PubMed1989

Studies on protein methyltransferase in human cerebrospinal fluid.

Protein methyltransferases, rich in most mammalian brains, were studied in human cerebrospinal fluid (CSF). Among several well-characterized groups of methyltransferases, protein methylase I (S-adenosylmethionine:protein-arginine N-methyltransferase, EC 2.1.1.23) was found in significant amounts in human CSF samples. Both myelin basic protein (MBP) -specific and histone-specific protein methylase I activities were observed, the latter being generally higher in most CSF. S-Adenosyl-L-homocysteine, a potent product inhibitor for the methyltransferase, inhibited approximately 90% of MBP-specific protein methylase I activity at a concentration of 1 mM. The optimum pH of the MBP-specific protein methylase I was found to be around 7.2. Identity of exogenously added MBP as the methylated substrate for CSF enzyme was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. An amino acid analysis of the [methyl-3H]protein hydrolysate showed two major radioactive peaks cochromatographing with monomethyl- and dimethyl (symmetric)-arginine. Human CSF contained relatively high endogenous protein methylase I activity (activity measured without added substrate protein): The endogenous substrate can be immunoprecipitated by antibody raised against calf brain MBP. Finally, CSF from several neurological patients were analyzed for protein methylase I, and the results are presented.

Humans↗
PubMed1986

Characterization of antigen-specific T cells in multiple sclerosis twins with elevated proliferative responses to measles virus.

The proliferative response to measles virus in normal individuals is low compared with the response to mumps virus. This is probably due to a low precursor frequency of OKT4+, IL 2-secreting helper cells. The presence of a measles high-responder state has previously been identified in some twin individuals with multiple sclerosis. Further characterization of the measles response in these high-responder individuals has demonstrated that the enhanced measles responses are due to a greater response by OKT4+ cells, which secrete higher levels of IL 2; this contrasting with the low levels of IL 2 secretion and OKT4+ cell proliferation seen in the unaffected twins. No evidence for suppression by either accessory or T cells, which would account for the quantitative differences between the high responders with multiple sclerosis and their unaffected low-responder twin siblings, was detected. The results indicate that a clonally expanded population of measles-specific responder cells is responsible for the high-responder state in these twins with multiple sclerosis. The mechanism producing this state may have relevance to possible immunoregulatory abnormalities producing autoimmunity in multiple sclerosis.

Antigen-Presenting Cells↗
PubMed1986

Systemic recombinant alpha-2 interferon therapy in relapsing multiple sclerosis.

This report describes the first use of recombinant-DNA-produced human interferon in patients with multiple sclerosis (MS). Ninety-eight patients who were clinically definite for MS with two or more documented exacerbations during the preceding two years were admitted to this placebo-controlled double-blind randomized trial. Although both groups were similar, placebo patients had later MS onset. Patients injected themselves with 2 X 10(6) IU of alpha-2 interferon or placebo three times each week for up to 52 weeks. This dose of interferon was well tolerated in that side effects were minimal. During the trial, the exacerbation rate was sharply reduced in both groups. In the three-month follow-up period after stopping treatment, more patients who were receiving interferon than placebo became worse neurologically. More patients who were receiving interferon than placebo changed from exacerbating MS to progressive MS during the trial. Thus, no clear therapeutic benefit of alpha-2 interferon for MS was detected.

Adult↗
PubMed1984

The lymphoproliferative response to measles virus in twins with multiple sclerosis.

The cellular immune response to measles virus, as measured by lymphocyte proliferation in normal individuals, is considerably lower than that to mumps or vaccinia viruses, and stable multiple sclerosis patients do not differ significantly from the norm. The response to these viruses was studied in 28 twin sets both concordant and discordant for multiple sclerosis. Normal responses to mumps and vaccinia viruses occurred throughout. Seven affected twins manifested a persistently elevated response to measles virus, whereas the unaffected twins had a (normal) low response. The differences were unrelated to differences in T cell subsets, unusual kinetics of the response, or differential susceptibility of lymphocytes to the effects of measles virus infection in vitro. The specificity of the response resides in an E+ subpopulation, and the addition of low-responder E+ cells to high-responder E+ cells failed to identify an active low-responder suppressor population. These findings suggest the presence of clonally expanded measles-specific T cell populations in the high responders with multiple sclerosis.

Adult↗
PubMed1983

Expansion of antigen-specific T cells from cerebrospinal fluid of patients with multiple sclerosis.

We have expanded cerebrospinal fluid (CSF) T lymphocytes obtained from four patients with multiple sclerosis (MS). Fresh CSF cells were placed into culture with medium, interleukin-2, irradiated autologous peripheral blood mononuclear cells, and either myelin basic protein (BP) or measles virus antigen. Two CSF cell lines demonstrated a mild degree of antigen-specific proliferation to BP, a third reacted with measles virus, and the fourth demonstrated no known antigenic specificity. The percentage of HLA-DR + cells was increased in all four cell lines. The culture procedure has thus selected for a population of activated T cells, some of which demonstrate reactivity with antigens of potential relevance to the pathogenesis of MS.

Cerebrospinal Fluid↗
PubMed1983

Response of human lymphocytes to measles virus after natural infection.

The lymphoproliferative response to measles, mumps, and vaccinia virus-infected monolayers measured in seropositive adults by thymidine incorporation demonstrated that only 5% of individuals responded well to measles virus (stimulation index, greater than 5). Possible explanations for this occurrence include a lack of sensitization, active suppression, or failure in long-term stimulation. To distinguish among these possibilities, we studied the responses to measles virus in 22 immunocompetent individuals during early convalescence from natural measles infection. Substantial responses occurred (stimulation index, 7.03), particularly in a smaller group which included those individuals with milder cases of the disease. The level of responsiveness declined over a period of weeks. Responder and nonresponder cell mixing showed no active cellular suppression. These studies indicate that the low responses to measles virus found in late convalescence represent a lack of prolonged stimulation of the cell population measured in this assay.

Adolescent↗
PubMed1981

Infection of the central nervous system produced by R1 vesicular stomatitis virus.

Previous studies of vesicular stomatitis virus infection of the central nervous system in mice have demonstrated that both temperature-sensitive mutants and defective interfering particles produce alterations from wild type disease. To examine further the role of the biologic properties of the virus, we studied the disease produced by R1-vesicular stomatitis virus, a temperature-insensitive revertant derived from the temperature-sensitive T1026 mutant. Whereas wild type produced acute encephalitis and death in 2 to 3 days in BALB/c mice, R1 produced, in contrast, a paralytic disease 5 to 6 days postinoculation and death on days 6 to 7. R1 infection is productive, although with altered kinetics of growth. No alterations of the biologic properties of the virus following intracerebral passage could be detected. The morphologic features showed a striking localization of viral replication and damage to the anterior horns of the spinal cord with sparing of the ependymal cells, unlike the situation in wild type infection. At the time of clinical onset of R1 disease, the morphologic appearances were degenerative in nature. These features correlate with the clinical localization and development of disease. In addition, morphologic evidence for trans-synaptic spread of R1 and wild type has been found. Although the delayed and altered central nervous system disease resembles aspects of delayed disease produced in other situations, it seems clear that the mechanisms operative here are unlike those previously described and may be related to a unique genomic defect in R1 or its interaction with host cell factors.

Animals↗
PubMed1979

Ataxia-telangiectasia. Report of a case with Lewy bodies and vascular abnormalities within cerebral tissue.

The neuropathologic findings in a 31 year old patient with ataxia-telangiectasia are presented. There was an unusually severe and widespread distribution of the recognized abnormalities within the nervous system. In addition, there were Lewy bodies in the substantia nigra and widely distributed vascular changes in cerebral tissue. The nature of the vascular changes is discussed. These findings underline and expand the known spectrum of nervous system involvement in this condition.

Adult↗