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Biomedical subjects

R S Murray

Publications and source records attributed to R S Murray.

At least 19 recordsLinked to original sources

Detection of coronavirus RNA and antigen in multiple sclerosis brain.

Epidemiological studies of patients with multiple sclerosis (MS) and animal model data support the hypothesis that viruses initiate the immunopathogenic events leading to demyelination in MS. There have been no reports, however, of consistent detection of viruses in MS central nervous system tissue. We probed MS and control brain with cDNA probes specific for human, murine, porcine, and bovine coronaviruses. We report the in situ hybridization detection of coronavirus RNA in 12 of 22 MS brain samples using cloned coronavirus cDNA probes. In addition, tissue was screened for coronavirus antigen by immunohistochemical methods; antigen was detected in two patients with rapidly progressive MS. Significant amounts of coronavirus antigen and RNA were observed in active demyelinating plaques from these two patients. These findings show that coronaviruses can infect the human central nervous system and raise the possibility that these viruses may contribute to the pathogenesis of MS in some patients.

Antigens, Viral

Absence of measles, mumps, and rubella viral genomic sequences from multiple sclerosis brain tissue by polymerase chain reaction.

We tested for measles, mumps, and rubella viruses in multiple sclerosis by polymerase chain reaction (PCR). Using RNA extracted from 19 multiple sclerosis and 8 control brain specimens, nested PCR was performed after reverse transcription (RT) of the RNA to cDNA using primer pairs directed against two regions in the genomes of measles and mumps viruses and one region in the rubella virus genome. Despite enhanced sensitivity of nested RT PCR, measles, mumps, and rubella viral genomic sequences were not found in any brain specimen.

Adult

Coronavirus infects and causes demyelination in primate central nervous system.

Two species of primates, Owl and African green monkeys, were inoculated intracerebrally with either the neurotropic mouse hepatitis virus JHM or the putative multiple sclerosis brain coronavirus isolate SD. These viruses caused an acute to subacute panencephalitis and/or demyelination in the infected animals. The course of pathogenesis and sites of detected viral RNA and antigen was dependent both on animal species and virus strain but the results clearly showed that these viruses replicated and disseminated in the central nervous system (CNS) of these primates. This study suggests that human CNS may be susceptible to coronavirus infection.

Animals

The effect of high-dose steroids on MRI gadolinium enhancement in acute demyelinating lesions.

Gadolinium (Gd) enhancement of brain lesions by MRI is a marker of active blood-brain barrier damage secondary to an inflammatory process. We studied the effects of high-dose (1,000 mg/d) intravenous (IV) methylprednisolone (Mp) for 4 to 8 days on Gd-enhancing lesions in seven patients with acute demyelinating diseases and compared pretreatment brain MRIs with studies obtained 1 to 4 days after treatment. Five patients had complete suppression, and two had significant suppression of Gd enhancement following treatment. In addition, six of seven patients had Gd-enhancing lesions that explained their clinical signs; in five of six of these patients, suppression of the Gd-enhanced lesions temporally correlated with clinical improvement. Thus, short courses of high-dose IV Mp suppress Gd enhancement in acute demyelinating lesions, and this correlates with clinical improvement.

Adult

Relevance to prenatal diagnosis of the identification of a human Y/autosome translocation by Y-chromosome-specific in situ hybridisation.

Routine cytogenetic analysis of an amniotic fluid sample revealed a large brightly fluorescent region in the short arm of chromosome 14 in an otherwise normal male karyotype (46,XY,14p+ + +). This site was also present in the paternal karyotype. In situ hybridisation to a Y-chromosome-specific DNA probe confirmed that the father had a Y/14 translocation. The incidence of two hybridisation bodies (large hybridisation sites), detecting both the translocated Y chromatin and the normal Y chromosome, was lower in interphase nuclei (44.3%) than in metaphase spreads (95.2%). The relevance of these observations to the potential use of in situ hybridisation to interphase nuclei for prenatal diagnosis is discussed.

Adult

Effects of oral caffeine on postdural puncture headache. A double-blind, placebo-controlled trial.

Forty postpartum patients with postdural puncture headache (PDPH) were randomly assigned to receive oral caffeine (300 mg) or a placebo. Intensity of headache, quantitated using a visual analogue pain scale (VAS), was assessed immediately before drug administration and 4 and 24 h later. Relief of PDPH measured as delta VAS (initial VAS - VAS at 4 h) was significantly better in the caffeine than in the placebo group (P = 0.014). Six patients (30%) whose PDPH was relieved by caffeine at 4 h had recurrence of symptoms the following day. Our study demonstrates that caffeine administered orally provides relief, albeit if sometimes transient, from PDPH with minimal side effects.

Administration, Oral

Intracellular detection of sense and antisense enteroviral RNA by in situ hybridization.

We prepared sense (S) and anti-sense (AS) 3H-labelled single-stranded RNA probes by polymerase-directed in vitro transcription of a coxsackievirus B3-derived cDNA fragment cloned in the PGEM2 plasmid vector. The probes detected, by in situ hybridization, both S and AS forms of viral RNA in the cytoplasm of coxsackievirus-infected tissue culture cells. More S (genomic and messenger) RNA was present than AS (negative and replicative intermediate) RNA. We confirmed and quantitated this observation with slot-blot hybridization of lysates of infected cells in which the ratio of detectable S to AS RNA was 40:1. The selective detection and localization of both forms of RNA in infected cells with sensitive and specific bi-directional probes advances the applicability of in situ hybridization to the study of viral pathogenesis.

Cell Line

Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia.

Lysates of radiolabeled explants from four human trigeminal ganglia were immunoprecipitated with antibodies to varicella-zoster virus (VZV) and to herpes simplex virus. Both herpes simplex virus- and VZV-specific proteins were detected in lysates of all four ganglia. Absence of reactivity in ganglion explants with monoclonal antibodies suggested that herpes simplex virus and VZV were not reactivated during the culture period. In situ hybridization studies demonstrated the presence of RNA transcripts from the VZV immediate early gene 63. This approach to the detection of herpes simplex virus and VZV expression in human ganglia should facilitate analysis of viral RNA and proteins in human sensory ganglia.

Adult

Chronic progressive varicella-zoster virus encephalitis in an AIDS patient.

A patient with AIDS developed chronic, progressive encephalitis. Pathologic changes indicated that the encephalitis was produced primarily by a human herpesvirus. Hybridization of radiolabeled RNA probes transcribed from cloned DNA fragments of varicella-zoster virus (VZV), herpes simplex virus, cytomegalovirus, and the human immunodeficiency virus to DNA extracted from the patient's brain identified VZV as the causative agent. The results suggest that VZV should be considered in the differential diagnosis of chronic encephalitis of unknown etiology, particularly in immunosuppressed patients.

Acquired Immunodeficiency Syndrome

Supplemental oxygen after ambulatory surgical procedures.

The aim of this study was to determine the need for supplemental oxygen during recovery from general anesthesia for ambulatory surgery in healthy women without obesity or respiratory disease. Arterial oxygen saturation by pulse oximetry (SpO2) was monitored throughout the first postoperative hour in 164 patients. The patients breathed room air during recovery. Supplemental oxygen was given only to those who became hypoxemic (SpO2 less than or equal to 92%). It was discontinued at the end of 15 minutes and reinstituted for another 15 minutes if hypoxemia recurred. Twelve patients (7%) became hypoxemic and required supplemental oxygen for various periods of time up to 105 minutes. The need for supplemental oxygen increased with increasing age (P less than 0.05) but was not associated with a history of cigarette smoking, tracheal intubation, amount of opioids or sedatives given intraoperatively, anesthetic duration, or level of consciousness during recovery. Hypoxemia was neither predictable nor clinically apparent. We recommend that, unless arterial oxygenation is monitored, ambulatory patients should routinely receive supplemental oxygen during recovery from general anesthesia.

Adult

Interferon treatment of experimental Ross River virus polymyositis.

Ross River virus (RRV), an alpha togavirus, causes an inflammatory myopathy in mice, which probably results from direct lytic effects of virus or viral products on myofibers. Administration of recombinant hybrid human leukocyte interferon-alpha A/D (rIFN-alpha A/D) ameliorates clinical illness and reduces mortality from 86 to 42%. Peak concentrations of virus are reduced by 1,000-fold in serum and by 30-fold in muscle, but anti-RRV antibody production is not altered. Treatment with rIFN-alpha A/D dramatically reduces inflammation and necrosis in muscle. Beneficial effects of rIFN-alpha A/D on experimental, RRV-induced polymyositis result in part from inhibition of viral replication and spread, though immunomodulation might also play an important role.

Animals

Bilateral trochlear nerve palsies. A clinicoanatomic correlate.

A patient with bilateral trochlear nerve palsies is presented. Computed tomographic (CT) brain scan localized an anterior cerebellar vermis lesion compressing the area caudal to the inferior colliculi where the fourth nerves decussate and exit the dorsal brain stem. This lesion was probably responsible for the bilateral trochlear nerve dysfunction. Pertinent anatomy and pathologic involvement are discussed.

Adenocarcinoma

Elemental analysis in murine central nervous system: elevation of rubidium subsequent to Newcastle disease virus encephalopathy.

The Cg strain of Newcastle disease virus (NDV) produces neurologic signs and death in mice. This illness is unusual because of the lack of typical features of a viral encephalitis. Specifically, there is a paucity of infectious virus, detectable cellular inflammatory reaction, cytopathic effect, and viral antigen by immunofluorescence. We previously showed an elevation of alpha-aminoisobutyric acid in the CNS of moribund NDV-infected mice, indicating cellular membrane dysfunction. In an attempt to further our understanding of the pathogenesis of the illness, we evaluated CNS concentrations of sodium, potassium, iron, copper, zinc, magnesium, selenium, and rubidium. Elemental analysis revealed no difference between infected and control mice for all elements except for rubidium, which was significantly elevated in infected mice. Elevation in rubidium was detected in infected mice by X-ray fluorescence and atomic absorption spectrophotometry, whereas rubidium concentrations for control mice were similar by both methods. Neurologic symptoms correlated directly with rising rubidium concentrations. Our data suggest that abnormal trace element levels during viral infection may be one mechanism responsible for the clinical symptoms.

Animals