ABSTRACT
OBJECTIVES: To compare the expression of endogenous retroviruses in MS patients and controls. MATERIAL AND METHODS: Peripheral blood mononuclear cells were obtained from 22 MS patients, a corresponding number of matched healthy donors and five patients with other central nervous system disease. Also brain specimens from MS patients and controls were obtained. Transcripts of various endogenous retroviruses in these samples were detected by RNA-PCR. RESULTS: Several endogenous retroviral sequences were transcribed in peripheral blood mononuclear cells and brain tissue from MS patients as well as controls. A composite transcript of an endogenous retrovirus and a zinc finger sequence was more frequently found in healthy donors than in MS patients. CONCLUSION: Some endogenous retroviruses are normally transcribed in white blood cells and brain tissue. The significance of those findings, which concerned the composite transcripts of the zinc finger sequence and its associated endogenous retrovirus is uncertain.
Subject(s)
Multiple Sclerosis/virology , Retroviridae/genetics , Adult , Brain/virology , Female , Gene Expression Regulation, Viral/physiology , Humans , Male , Middle Aged , Monocytes/virology , Polymerase Chain Reaction , Retroviridae Infections/virology , Transcription, Genetic/genetics , Zinc Fingers/geneticsABSTRACT
Neurotensin receptor autoradiography reveals dense binding in normal human substantia nigra. In nigra from patients with Parkinson's disease, nigral receptor binding is only about one-third of control values. 'Saturation' analysis suggests that these changes result from receptor loss. These results support a neurotensin-dopamine interaction in human nigro-striatal circuits.
Subject(s)
Neurotensin/metabolism , Parkinson Disease/metabolism , Receptors, Neurotransmitter/metabolism , Substantia Nigra/metabolism , Adult , Age Factors , Aged , Autoradiography , Humans , Kinetics , Middle Aged , Receptors, Neurotensin , Reference Values , TritiumABSTRACT
The regional distribution and chromatographic characteristics of somatostatin-like immunoreactivity (SLI) were studied in autopsy specimens of 8 human brains. SLI concentrations in 8 different regions of these brains ranged from (mean +/- S.E.) 756.3 +/- 363.4 pmol/g tissue in anterior hypothalamus to 1.6 +/- pmol/g in cerebellum. Chromatography of the extracts of human brain cortex, anterior hypothalamus, thalamus and amygdala on Sephadex G-50 disclosed one major peak which corresponded to the elution peak of synthetic somatostatin. Since the human brains were obtained at autopsy 11-36 h after death, the effects of temperature and time lapse between death and tissue extraction on SLI concentration and chromatographic pattern in rat brain were examined. After storage at 4 degrees C or 23 degrees C for 2 h and 8 h, a significant increase in SLI concentration was noted, although by 24 h in increase was no longer observed. A gradual loss in the eluting forms of SLI on gel chromatography was observed with storage at 4 degrees C or 23 degrees C.
Subject(s)
Brain/metabolism , Somatostatin/metabolism , Adult , Aged , Brain Mapping , Chromatography, Gel , Female , Humans , Male , Middle Aged , RadioimmunoassayABSTRACT
An assessment was made of a bioassay for a multiple sclerosis (MS)-associated agent claimed to cause a depression in the proportion of circulating polymorphonuclear neutrophils (PMN) in mice. Serum (1 sample), supernate from brain homogenates (four samples) and cerebrospinal fluid (four samples), and corresponding control materials, were tested under code by intraperitoneal injection into BALB/c mice. Results were plotted of proportions and absolute numbers of PMN over observation periods up to 2 weeks. Handling, injection and bleeding of mice did not significantly influence "baseline" counts of PMN. However, all samples from MS patients and controls caused an initial increase in PMN over 1--4 days, and then a later fall towards baseline. The claimed effect of MS materials in depressing counts of PMN in mice was not observed in these experiments, and variations in counts of PMN did not discriminate between samples from MS patients and controls.
Subject(s)
Brain/microbiology , Multiple Sclerosis/microbiology , Neutrophils/physiology , Tissue Extracts/pharmacology , Animals , Biological Assay , Humans , Kinetics , Leukocyte Count , Mice , Mice, Inbred BALB C , Multiple Sclerosis/blood , Multiple Sclerosis/cerebrospinal fluid , Neutrophils/drug effectsABSTRACT
Fourteen patients with AIDS were treated for 23 neurologic complications: four episodes of acute meningoencephalitis; eight episodes of subacute encephalopathy; two cases of progressive multifocal leukoencephalopathy; and nine cases of polyneuropathy. Nine patients were treated with 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), one with 3'-azido-3'-deoxythymidine (AZT), and four initially with DHPG directed against cytomegalovirus (CMV) retinitis or encephalitis and subsequently with AZT against human immunodeficiency virus (HIV) encephalopathy. CMV retinitis was a helpful clinical observation indicating neurologic involvement. DHPG produced improvement in two of three cases of acute meningoencephalitis but was ineffective in cases of subacute encephalopathy or neuropathy. AZT therapy resulted in resolution in both of the two treated cases of acute confusional state and in two of the four treated cases of polyradiculoneuropathy with paraparesis but was ineffective in the late stage of subacute encephalopathy. These results suggest that CMV is important in some cases of acute meningoencephalitis, whereas HIV is a dominant pathogen in subacute dementia and polyneuropathy in patients with AIDS. DHPG may be beneficial in the former, whereas AZT appears to be effective in the latter complications.
Subject(s)
Acquired Immunodeficiency Syndrome/complications , Acyclovir/analogs & derivatives , Antiviral Agents/therapeutic use , Central Nervous System Diseases/drug therapy , Ganciclovir/analogs & derivatives , Thymidine/analogs & derivatives , Acute Disease , Acyclovir/therapeutic use , Adult , Central Nervous System Diseases/etiology , Eye Diseases/drug therapy , Eye Diseases/etiology , Humans , Magnetic Resonance Imaging , Male , Meningoencephalitis/drug therapy , Meningoencephalitis/etiology , Thymidine/therapeutic use , ZidovudineABSTRACT
The aim of the present study was to examine whether there is an abnormal expression of certain endogenous retroviruses in MS patients. For this purpose samples of peripheral blood mononuclear cells were obtained from 22 MS patients, a corresponding number of age and sex-matched healthy donors and five patients with other diseases affecting the central nervous system. In addition, brain specimens of macroscopic normal white and gray matter from four MS patients and a similar number of controls were included in the study. Using an enzymatic amplification technique, we found expression of the endogenous retroviral sequences, HRES-1, HERV-K10 and ERV3 in most samples of peripheral blood mononuclear cells from MS patients and controls without obvious differences between these two groups. In contrast, composite transcripts of ERV3 and a zinc finger sequence were more frequently detected in healthy donors than in MS patients. At present, the possible significance of this is uncertain. The retroviral element 4-1 was not transcribed or only transcribed at a very low level in peripheral blood cells of controls and MS patients. Transcripts of various endogenous retroviruses were also detected in the brain samples, but a different pattern was not apparent in the MS group as compared with controls. Aspects concerning a possible association between endogenous retroviruses and autoimmunity are considered.