Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelin basic protein (MBP) was serially measured in 177 CSF samples of 33 patients with leptomeningeal metastases and in 34 cancer controls. The mean level in cancer controls (free of neural involvement) was 5.7 +/- 0.33 ng/ml (normal less than 5 ng/ml) with abnormal elevation of MBP detected in 17%. The activity of the leptomeningeal disease was classified as either acute-progressive, stable or in remission on the basis of clinical and CSF cytological findings. CSF MBP levels were analysed in each stage. Abnormal elevation of MBP was detected in 74% of the 68 samples obtained in the acute-progressive stage (mean +/- SEM: 18.25 +/- 1.4 ng/ml, P less than 0.0001), in 24% of the 79 samples in the stable phase (mean: 7.99 +/- 0.8 ng/ml, NS) and in 20% of the 30 samples in remission (mean 5.7 +/- 0.3 ng/ml, NS). Similar changes in levels of CSF MBP were also observed in longitudinal studies of patients responding to treatment or relapsing to the acute stage. Eight patients developed treatment induced necrotizing leukoencephalopathy with typical CT-scan findings; elevated levels of CSF MBP were detected in 7 of them (mean: 21 +/- 3 ng/ml) when measured within 2 weeks of diagnosis but not when measured 2 months earlier. Our study suggests that in leptomeningeal metastases, CSF MBP levels are indicators of the disease activity, particularly if longitudinal determinations are used.
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PMID:CSF myelin basic protein levels in leptomeningeal metastases. Relationship to disease activity. 243 54

Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) was quantified from 28 patients with acute facial palsy. The mean value of MBP in CSF in the study group was 3.4 +/- 0.22 micrograms/l (mean +/- SEM), which was significantly higher than the found in 37 healthy subjects (2.4 +/- 0.13 micrograms/l). Using a 95% confidence interval, 10 patients demonstrated significantly increased CSF concentrations of MBP (greater than 3.95 micrograms/l). Auditory brainstem response (ABR) test showed that 5 patients had abnormal brainstem responses. No significant correlation was observed between elevated MBP in CSF and either pathologic auditory brainstem responses or the clinical degree of the palsy. These results suggest that a brainstem involvement may occur in patients with Bell's palsy. Furthermore, our data accord with previous reports suggesting Bell's palsy to be part of a polyneuropathy.
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PMID:Elevated levels of myelin basic protein in CSF in relation to auditory brainstem responses in Bell's palsy. 243 60

Injections of Copolymer 1 (Cop-1), a synthetic cathodic polymer, have been reported to prevent and treat successfully acute and recurrent EAE and has been employed in patients with multiple sclerosis (MS). It has been suggested that the therapeutic effect is due to cell-mediated immune (CMI) cross-reactivity between Cop-1 and myelin basic protein (MBP), the antigen that induces EAE. We found that Cop-1 treatment of guinea pigs (GP) sensitized with MBP in adjuvant (20 micrograms/animal): (a) lowers the incidence of clinical disease (8/20 vs 14/15); (b) decreases severity of disease in affected GP; (c) has little effect on pathologic lesions (mean pathology index +/- SEM: 1.2 +/- 0.2 vs 1.6 +/- 0.3; P greater than 0.1). Lymphocytes of MBP-sensitized GP treated with Cop-1 exhibited in vitro proliferative responses to MBP equivalent to lymphocytes of untreated EAE-GP (14,134 +/- 6,532 vs 11,821 +/- 3,874; mean cpm +/- SEM). GP sensitized to MBP or Cop-1 (100 micrograms/animal) showed reactivity to the sensitizing antigen but little in vitro reactivity to the other antigen. There was no correlation between the in vitro lymphocytes response to MBP and Cop-1 in individual GP. Treatment of MBP sensitized GP with calf-thymus histone (CTH) also resulted in a lower incidence of clinical EAE with less severe disease in affected GP. There was little effect on the pathologic index and no evidence of either inhibition of MBP-induced lymphocyte proliferative responses or cross-reactivity between MBP and CTH. Thus, treatment with Cop-1 or CTH inhibits clinical manifestations of acute EAE without suppressing inflammatory cell infiltrates or sensitization to MBP.
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PMID:Effect of treatment with Copolymer 1 (Cop-1) on the in vivo and in vitro manifestations of experimental allergic encephalomyelitis (EAE). 619 66

Our group recently demonstrated that autoimmune T cells directed against central nervous system-associated myelin antigens protect neurons from secondary degeneration. We further showed that the synthetic peptide copolymer 1 (Cop-1), known to suppress experimental autoimmune encephalomyelitis, can be safely substituted for the natural myelin antigen in both passive and active immunization for neuroprotection of the injured optic nerve. Here we attempted to determine whether similar immunizations are protective from retinal ganglion cell loss resulting from a direct biochemical insult caused, for example, by glutamate (a major mediator of degeneration in acute and chronic optic nerve insults) and in a rat model of ocular hypertension. Passive immunization with T cells reactive to myelin basic protein or active immunization with myelin oligodendrocyte glycoprotein-derived peptide, although neuroprotective after optic nerve injury, was ineffective against glutamate toxicity in mice and rats. In contrast, the number of surviving retinal ganglion cells per square millimeter in glutamate-injected retinas was significantly larger in mice immunized 10 days previously with Cop-1 emulsified in complete Freund's adjuvant than in mice injected with PBS in the same adjuvant (2,133 +/- 270 and 1,329 +/- 121, respectively, mean +/- SEM; P < 0.02). A similar pattern was observed when mice were immunized on the day of glutamate injection (1,777 +/- 101 compared with 1,414 +/- 36; P < 0.05), but not when they were immunized 48 h later. These findings suggest that protection from glutamate toxicity requires reinforcement of the immune system by antigens that are different from those associated with myelin. The use of Cop-1 apparently circumvents this antigen specificity barrier. In the rat ocular hypertension model, which simulates glaucoma, immunization with Cop-1 significantly reduced the retinal ganglion cell loss from 27.8% +/- 6.8% to 4.3% +/- 1.6%, without affecting the intraocular pressure. This study may point the way to a therapy for glaucoma, a neurodegenerative disease of the optic nerve often associated with increased intraocular pressure, as well as for acute and chronic degenerative disorders in which glutamate is a prominent participant.
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PMID:Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: implications for glaucoma. 1124 90

Experimental allergic encephalitis, (EAE) a Th1-cell-dependent autoimmune disease of the central nervous system (CNS) used to study immune responses relevant to multiple sclerosis (MS) displays gender susceptibility. The underlying basis of the sexual dimorphism may reflect multiple factors including gender-specific hormones. To study the relationship between ovarian hormones and CNS inflammation, we induced EAE in susceptible female Lewis rats ovariectomized (OVX) 7 days earlier and implanted with blank capsules or capsules containing estradiol (E), progesterone (P), or both (EP). Rats were immunized with complete Freunds' adjuvant alone or combined with guinea pig myelin basic protein. Motor function was scored 0-5 on standard criteria (days 7-11 postimmunization). On day 11, the rats were euthanized and the lumbar spinal cord was analyzed for Nissl, neuron nuclear antigen, and DNA fragmentation with a TUNEL assay. Inflammation was judged qualitatively on a scale of 0-4. Our immunization protocol induced limited sensorimotor deficits in OVX rats (2.3 +/- 0.6, mean +/- SEM) with moderate inflammation (2.5 +/- 0.4). E limited both behavioral impairments (1.0 +/- 0.4) and inflammation (0.5 +/- 0.2). P-treated rats had more severe sensorimotor deficits (3.1 +/- 0.5) with increased inflammatory infiltrates (3.6 +/- 0.4) and markedly increased numbers of TUNEL(+) neurons. Neuron counts of the outer two Rexed lamina (L3-L5) showed a 20% neuron loss (P < 0.02) in P-treated rats with EAE in comparison to other groups. Coadministration of E with P prevented the consequences of P, including neuronal apoptosis (behavioral score, 0.6 +/- 0.6; inflammation, 1.4 +/- 0.5). Our results suggest a potential and novel function of P that increases the vulnerability of neurons to apoptotic injury in EAE and may have pathophysiologic implications in the progression of disability in women with MS.
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PMID:Divergent effects of ovarian steroids on neuronal survival during experimental allergic encephalitis in Lewis rats. 1157 79

The effects of cerebral ischemia on white matter changes in ovine fetuses were examined after exposure to bilateral carotid artery occlusion. Fetal sheep were exposed to 30 min of ischemia followed by 48 (I/R-48, n = 8) or 72 (I/R-72, n = 10) h of reperfusion or control sham treatment (control, n = 4). Serial coronal sections stained with Luxol fast blue/hematoxylin and eosin were scored for white matter, cerebral cortical, and hippocampal lesions. All areas received graded pathologic scores of 0 to 5, reflecting the degree of injury where 0 = 0%, 1 = 1% to 25%, 2 = 26% to 50%, 3 = 51% to 75%, 4 = 76% to 95%, and 5 = 96% to 100% of the area damaged. Dual-label immunofluorescence using antibodies against glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) were used to characterize white matter lesions. Basic fibroblast growth factor (FGF-2) was measured in the frontal cortex by ELISA. Results of the pathologic scores showed that the white matter of the I/R-72 (2.74 +/- 0.53, mean +/- SEM) was more (p < 0.05) damaged when compared with the control (0.80 +/- 0.33) group. Cortical lesions were greater (p < 0.05) in the I/R-48 (2.12 +/- 0.35) than the control (0.93 +/- 0.09) group. White matter lesions were characterized by reactive GFAP-positive astrocytes and a loss of MBP in oligodendrocytes. The ratio of MBP to GFAP decreased (p < 0.05) as a function of ischemia, indicative of a proportionally greater loss of MBP than GFAP. FGF-2 concentrations were higher (p < 0.05) in the I/R-72 than the control group and there was a direct correlation between the pathologic scores (PS) and FGF-2 concentrations (FGF-2 = e((1.6 PS-0.90)) + 743, n = 17, r = 0.73, p < 0.001). We conclude that carotid artery occlusion results in quantifiable white matter lesions that are associated with a loss of MBP from myelin, and that FGF-2, a purported mediator of recovery from brain injury in adult subjects, increases in concentration in proportion to the severity of brain damage in the fetus.
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PMID:White matter injury after cerebral ischemia in ovine fetuses. 1203 76

Activated myelin-specific T cells are thought to mediate inflammatory tissue damage in multiple sclerosis (MS). Applying a large panel of myelin antigens, we demonstrate the direct ex vivo detection of viable IFN-gamma/TNF-alpha producing CD4+/CD69+ T cells 6 hours after antigenic challenge, by intracellular flow cytometry in 3/33 MS patients and 2/26 healthy controls with calculated frequencies of (mean +/- SEM): 0.031% +/- 0.002% versus 0.037% +/- 0.029%. By comparison, the recently developed IL-7 modified proliferation assay revealed i) a higher number of individuals showing myelin reactivity (17/37 MS patients and 12/24 healthy individuals) and ii) a significant difference in the response to myelin basic protein (MBP) between the two groups in a longitudinal analysis, indicating a higher activity of myelin-specific T cells in MS patients. Our data provide new perspectives in detecting pathogenetically relevant T cells, but clearly demonstrate the different conclusions which must be drawn from various approaches concerning the quantification of autoreactive T cells.
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PMID:Cross-sectional and longitudinal analysis of myelin-reactive T cells in patients with multiple sclerosis. 1537 55

Transgenic and disease model mice have been used to investigate the molecular mechanisms of demyelinating diseases. However, less attention has been given to elucidating changes in nerve conduction in these mice. We established an experimental system to measure the response latency of cortical neurons and examined changes in nerve conduction in cuprizone-induced demyelinating mice and in myelin basic protein-deficient shiverer mice. Stimulating and recording electrodes were placed in the right and left sensori-motor cortices, respectively. Electrical stimulation of the right cortex evoked antidromic responses in left cortical neurons with a latency of 9.38 +/- 0.31 ms (n = 107; mean +/- SEM). While response latency was longer in mice at 7 days and 4 weeks of cuprizone treatment (12.35 +/- 0.35 ms, n = 102; 11.72 +/- 0.29 ms, n = 103, respectively), response latency at 7 days and 4 weeks after removal of cuprizone was partially restored (10.72 +/- 0.45 ms, n = 106; 10.27 +/- 0.34 ms, n = 107, respectively). Likewise, electron microscopy showed cuprizone-induced demyelination in the corpus callosum and nearly complete remyelination after cuprizone removal. We also examined whether the myelin abnormalities in shiverer mice affected their response latencies. But there were no significant differences in response latencies in shiverer (9.83 +/- 0.24 ms, n = 103) and wild-type (9.33 +/- 0.22 ms, n = 112) mice. The results of these electrophysiological assessments imply that different demyelinating mechanisms, differentially affecting axon conduction, are present in the cuprizone-treated and shiverer mice, and may provide new insights to understanding the pathophysiology of demyelination in animal models in the CNS.
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PMID:Differential changes in axonal conduction following CNS demyelination in two mouse models. 1897 89