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Biomedical subjects

R M Ransohoff

Publications and source records attributed to R M Ransohoff.

126 records · Page 7Linked to original sources
PubMed1989

Organization and expression of 5S rRNA genes in the parasitic nematode, Brugia malayi.

DNA sequence analysis of genes encoding 5S rRNA in the human parasitic nematode Brugia malayi (B. malayi) indicates a surprising degree of heterogeneity. This variation in coding sequence is not accompanied by corresponding heterogeneity in flanking regions which are highly conserved. Six out of eight potential 5S coding regions differed; of these sequence variants, two were abundant in the B. malayi genome. Direct RNA sequence analysis indicated that one of these abundant variants accounts for most if not all of expressed 5S RNA at two stages of development.

Animals↗
PubMed1989

Interferon-beta impairs induction of HLA-DR antigen expression in cultured adult human astrocytes.

We studied the effect of interferons on the expression of class II histocompatibility (HLA-DR) antigens by cultured adult human astrocytes. Cultures were derived from brain tissue resected for surgical treatment of intractable epilepsy. Cultured astrocytes did not spontaneously display HLA-DR antigen as determined by immunocytochemistry and flow cytometry with antibody to HLA-DR. Astrocytes cultured for 72 h with recombinant or natural interferon-gamma (IFN gamma) demonstrated a dose-dependent increase in HLA-DR expression with optimal stimulation by 100 U/ml IFN gamma. HLA-DR expression was not detectable in astrocytes cultured with IFN gamma for less then 48 h, and peak HLA-DR expression (over 80% of cells) was seen at 120 h of culture. Optimal HLA-DR expression required continuous presence of IFN gamma. Exposure of astrocytes to recombinant or natural interferon-beta (IFN beta) did not induce HLA-DR and pretreatment of astrocytes with IFN beta or interferon-alpha (IFN alpha) significantly inhibited subsequent induction of HLA-DR expression by IFN gamma. These observations suggest that interferons may function in regulating human astrocyte HLA-DR expression within the central nervous system.

Adult↗
PubMed1989

High-signal periventricular lesions in patients with sarcoidosis: neurosarcoidosis or multiple sclerosis?

The vast majority of periventricular abnormalities visualized with MR imaging in patients less than 50 years old represents multiple sclerosis (MS) lesions. There are many other causes of periventricular lesions, most of which can be differentiated from MS on the basis of history and physical or MR findings. Five cases of biopsy- or Kveim test-proved sarcoidosis with MR findings consistent with MS are reported. Each of these patients, diagnosed as having sarcoidosis, had symptoms identical to those seen in MS. Although these patients have not had histologic characterization of the intraparenchymal lesions seen on MR, they illustrate the difficulty of differentiating sarcoidosis with CNS involvement from MS in some patients on the basis of clinical, radiographic, electrodiagnostic, or CSF testing. This series contributes to a growing body of evidence that neurosarcoidosis probably should be included in the differential diagnosis of isolated periventricular lesions in patients less than 50 years old.

Adult↗
PubMed1987

Priming of influenza mRNA transcription is inhibited in CHO cells treated with the methylation inhibitor, neplanocin A.

Chinese hamster ovary cells were pretreated with Neplanocin A, a potent inhibitor of RNA methylation. Analysis of polyadenylated RNA from treated cells by high-pressure liquid chromatography revealed marked decreases of 2'-O-methylation within mRNA cap structures and of internal N6-methyladenosine residues. In these Neplanocin A-treated cells, influenza viral mRNA accumulation was virtually abolished. Cellular RNA from Neplanocin A-treated cells was substantially less efficient than RNA from control cells in priming cell-free influenza transcription reactions. These results suggest that the observed inhibition of influenza virus replication is due at least in part to impaired recognition of undermethylated cellular mRNA cap structures by the influenza polymerase complex.

Adenosine↗
PubMed1985

Enhanced DNA synthesis of human glial cells exposed to human leukocyte products.

DNA synthesis was studied in primary glial cell cultures derived from adult human non-neoplastic and neoplastic brain tissues. Enhanced DNA synthesis occurred in 5/5 non-neoplastic astrocyte, one oligodendroglioma, and 2/5 astrocytoma cultures after exposure to medium containing 1.25-12.5% supernatant fluid (SF) from insoluble concanavalin A (Con A) stimulated unseparated or T lymphocyte-enriched human mononuclear leukocytes (MNL). Analyses of SF indicated that the presence of platelet-derived growth factor (PDGF) could not account for glial cell stimulation, and exposure to semi-purified interleukin-2 (IL-2) in amounts comparable to those in SF from Con A-stimulated MNL had no effect on glial cells. These data indicate that non-neoplastic astrocytes and other human glial cells are stimulated by products of human MNL.

Astrocytoma↗
PubMed1985

Effect of human alpha A interferon on influenza virus replication in MDBK cells.

To determine the molecular mechanism whereby interferon induces resistance to influenza virus, we began an investigation of influenza virus replication in MDBK cells treated with recombinant human alpha A interferon. Negative- and positive-strand virus-specific RNA accumulation was monitored by blot hybridization with cloned probes. Primary transcription (transcription of infecting viral negative strands by the virion-associated polymerase) was inhibited by interferon treatment of MDBK cells. At moderate levels of interferon treatment (10 U/ml), this inhibition was restricted to transcripts of polymerase genes, whereas at higher levels of interferon treatment (50 U/ml), accumulation of all primary transcripts was markedly inhibited. Secondary transcripts and viral negative strands did not accumulate to any significant extent in interferon-treated MDBK cells. These results suggest that interferon-induced mechanisms which inhibit influenza virus replication in MDBK cells act at the level of primary transcription.

Animals↗
PubMed1983

Impaired autologous mixed lymphocyte reaction with normal concanavalin A-induced suppression in adult polymyositis/dermatomyositis.

Polymyositis/dermatomyositis (PM/DM) is an autoimmune disorder of unknown aetiology. In order to study whether immunoregulatory abnormalities might be involved in this autoimmune state, we investigated the autologous mixed lymphocyte reaction (AMLR) and concanavalin A-induced suppressor cell function (Con A-induced suppression) in adult patients with primary PM/DM. We found the AMLR to be significantly depressed in patients; responsiveness could not be enhanced by increasing the numbers of non-T stimulator cells in culture, nor by varying the day on which cultures were harvested. Con A-induced suppression of T cell proliferative responses to mitogenic stimuli was normal. These findings implicate abnormal immunoregulation in the pathophysiology of PM/DM. Further, the dissociation of AMLR reactivity from Con A-inducible suppression suggests that events important for immunoregulatory competence may occur in the AMLR culture, despite the absence of an observed proliferative response.

Adult↗
PubMedDate not supplied

Regulation and function of central nervous system chemokines.

In this paper, we discuss the potential involvement of a new family of cytokines, termed chemokines, in CNS inflammatory pathology. Chemokines are a family of proinflammatory cytokines which are able to stimulate target-cell-specific directional migration of leukocytes. Because of this feature, chemokines may be potent mediators of inflammatory processes. We have previously reported observations indicating that chemokines may be involved in the process of lesion formation during autoimmune inflammation within CNS, and, in particular, are likely participants in the process of influx of inflammatory cells into the CNS parenchyma. We observed also that mechanical injury of brain and subsequent post-traumatic inflammation may in part be mediated by chemokines. Chemokines undoubtedly co-operate with cell-associated adhesion molecules during recruitment of leukocytes from blood to CNS. The sequential expression of soluble and membrane-bound signals for leukocyte migration is an intricate process that can be interrupted by a variety of strategies. Our data suggest that chemokines may represent a promising target for future therapy of inflammatory conditions, including CNS inflammation resulting from varied insults.

Animals↗
PubMedDate not supplied

Unusual long-standing Gd-DTPA enhancement in a chronic progressive myelopathy.

Chronic spinal syndromes without evidence of cord compression often represent a real diagnostic challenge. We report a case of chronic progressive myelopathy with an unusual long-standing gadolinium-diethylenetriamine pentaacetic acid (Magnevist, Berlex Laboratories) enhanced spinal cord lesion demonstrated on MRI, through a 14 month follow-up period. In the context of continuous neurological decline the patient underwent two biopsies at 1 year intervals. The final diagnosis was obtained only after the second biopsy, which demonstrated a demyelinating plaque with reactive astrocytosis. The clinical condition of our patient has been stable for 5 years. A repeated workup including MRI of the cervical and thoracic spine demonstrated a mildly atrophic cord in the upper thoracic region, with no evidence of pathological signal or enhancement at this time. Brain MRI and visual evoked potentials were normal. This case provides interesting clinical, pathological, and MRI correlations in a longitudinal follow-up of a spinal demyelinating lesion.

Adult↗
PubMedDate not supplied

Expression of chemokines RANTES, MIP-1alpha and GRO-alpha correlates with inflammation in acute experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an investigator-initiated disorder that serves as an animal model for the common human demyelinating disease multiple sclerosis. Both diseases are typified by disseminated perivascular and submeningeal cuffs in the central nervous system (CNS). It was shown recently that chemokines are integral to the pathogenesis of EAE. In the present study we analyzed the gene expression of three chemokines, RANTES, MIP-1alpha and GRO-alpha, at the onset of acute EAE, and correlated that expression with the intensity of inflammatory changes in the CNS. We showed that all three chemokines are upregulated simultaneously with symptom onset of acute EAE, and that chemokine expression correlates with the intensity of inflammation in the CNS. This consistent relationship supports the hypothesis that chemokines are relevant to leukocyte accumulation in CNS parenchyma.

Acute Disease↗
PubMedDate not supplied

Anterior uveitis and multiple sclerosis.

Three patients with clinically definite multiple sclerosis and uveitis were studied. The uveitis presented as inflammation of the anterior segment of the eye (iridocyclitis) and was characterized by large keratic precipitates and posterior synechiae, consistent with a granulomatous iridocyclitis. Clinical and laboratory evidence militated against other central nervous system diseases often associated with uveitis including neurosarcoidosis, Behçet's syndrome, Vogt-Koyanagi-Harada disease, neurosyphilis, and tuberculosis. Further attention should be directed to the possibility of granulomatous anterior uveitis in patients with multiple sclerosis.

Adolescent↗
PubMedDate not supplied

Experimental therapies for multiple sclerosis: current status.

Multiple sclerosis is the most common cause of nontraumatic disability affecting young adults in the United States. Its etiology remains unclear, but evidence points to alteration of normal immune system function in the pathogenesis of this illness. This article reviews the results of clinical trials of experimental therapeutic agents in multiple sclerosis. The background and action of each treatment are described, and the clinical experience with each agent is reviewed. Obstacles to evaluating the effectiveness of treatment methods in MS and challenges to the design of future clinical trials and the interpretation of trial outcomes are discussed.

Azathioprine↗
PubMedDate not supplied

Pharmacotherapy of multiple sclerosis: current status.

Pharmacotherapy plays an important part in the overall management of patients with multiple sclerosis. Most therapies directed at altering the natural history of the underlying disease process are only partially effective or are controversial or experimental. However, many effective symptomatic therapies are available to the clinician. The action and uses of corticosteroids in multiple sclerosis are discussed, and approaches to the treatment of spasticity, paroxysmal disorders, bladder dysfunction, cerebellar ataxia, neurobehavioral manifestations, fatigue, and acute and chronic pain in patients with multiple sclerosis are examined.

Acute Disease↗