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)

Interferons are biological molecules with antiviral, antiproliferative, and immunomodulatory actions. Interferon alpha (IFN-alpha) and -beta are potentially useful in the treatment of multiple sclerosis (MS). IFN-gamma, in contrast, increases the frequency of exacerbations of MS. In this study, we compared the effect of recombinant human IFN-alpha, -beta, and -gamma on suppressor function in patients with MS. Nonspecific suppressor cell function, measured in a concanavalin A suppressor assay, was significantly decreased in 16 patients with progressive MS (mean percent suppression +/- SEM, 14.4 +/- 5.5 in patients with MS, 33.5 +/- 4.8 in 16 normal subjects; p less than 0.001). Recombinant human IFN-beta augmented suppressor function in MS to 45.4 +/- 5.1% (p less than 0.001) and in control subjects to 56.8 +/- 3.8% (p less than 0.001). Similarly, recombinant human IFN-alpha improved suppression in MS to 43.0 +/- 5.6% (p less than 0.001) and in control subjects to 51.1 +/- 5.9% (p less than 0.001). In contrast, recombinant human IFN-gamma had no effect on suppressor function in patients with MS and in control subjects. This study shows that IFN-alpha and -beta augment deficient suppressor function in MS, whereas IFN-gamma has no effect on suppressor function in the progressive phase of the disease.
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PMID:Contrasting effects of alpha, beta, and gamma interferons on nonspecific suppressor function in multiple sclerosis. 137 8

To assess whether an virus-specific immune defect may be associated with multiple sclerosis (MS), we have examined the ability to generate measles virus-and influenza virus-specific cytotoxic T cells (CTL) in patients with MS, normal individuals, and other disease controls (ODC). The mean (+/- SEM) measles virus-specific CTL response for normal individuals and ODC was 26.9 +/- 2.9% (N = 17) and 26.7 +/- 2.8% (N = 13) specific lysis, respectively. In contrast, the capacity of MS patients to generate measles virus-specific CTL was markedly diminished. Peripheral blood lymphocytes from MS patients stimulated with measles virus lysed their measles virus-infected autologous B cell line at a group mean level of 6.0 +/- 1.4% (N = 16) specific lysis. MS patients had significantly lower measles virus-specific CTL responses than normal individuals (p less than 0.00001) or ODC (p less than 0.0001). Importantly, this lowered response did not reflect a generalized depressed cytolytic activity of MS patients, since influenza virus-specific CTL and NK activity from these patients were comparable to normals and ODC. Thus, in MS there is a significant depression of measles virus-specific CTL which suggests that this virus-specific immune dysfunction may play a role in the pathogenesis of this disorder.
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PMID:Impaired measles virus-specific cytotoxic T cell responses in multiple sclerosis. 241 41

The aim of this study was to determine the effect of two years of treatment with cyclosporine A on blood pressure and the rates of secretion into the circulation of the vasoconstrictor thromboxane A2 and the vasodilator prostacyclin. Seven patient suffering from multiple sclerosis took part. Their blood pressures and urinary concentrations of 2,3-dinor-thromboxane A2 (a major urinary metabolite of thromboxane A2) and of 2,3-dinor-6-keto-prostaglandin F1 alpha (the major urinary metabolite of prostacyclin) were determined at the end of two years of treatment with cyclosporine A, and once again three months after cessation of this treatment. No other drugs were given during or after cyclosporine A. Mean arterial blood pressure was 113 +/- 5 mmHg (mean +/- SEM) during the cyclosporine A treatment, but fell to 94 +/- 4 mmHg after the three-month's wash-out period. Urinary excretion of the thromboxane metabolite decreased slightly from 674 +/- 150 pg.mg-1 creatinine during cyclosporine A therapy to 503 +/- 90 pg.mg-1-creatinine after the end of therapy. At the same time the prostacyclin metabolite increased significantly from 82 +/- 17 pg.mg-1 creatinine to 113 +/- 23 pg.mg-1 creatinine (P less than 0.05). The ratio of 2,3-dinor-thromboxane B2 to 2,3-dinor-6-keto-prostaglandin F1 alpha (taken as a measure of vasoconstrictor prostanoid activity) fell significantly from 8.4 +/- 0.8 4.7 +/- 0.6 (P less than 0.005). The shift in prostanoid production observed during cyclosporine A treatment could be one causal factor for the hypertensive and thromboembolic events associated with the use of this drug.
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PMID:An increase in the ratio of thromboxane A2 to prostacyclin in association with increased blood pressure in patients on cyclosporine A. 266 62

We compared trace element status in multiple sclerosis (MS) patients (n = 27) with and without treatment with corticosteroids and groups of healthy subjects. Concentrations of plasma ceruloplasmin, selenium, and zinc and erythrocyte (RBC) glutathione peroxidase, Se, and Zn were similar in all groups. RBC copper concentrations were significantly lower in MS patients than in control subjects (mean +/- SEM: 0.048 +/- 0.005 vs 0.060 +/- 0.002 mumol/g Hb) because of decreased RBC Cu with steroid therapy. RBC Zn-Cu ratios were significantly higher (14.9 +/- 1.0 vs 10.1 +/- 0.3) in MS patients than in control subjects, differing in both groups of MS patients. In MS and control subjects, RBC Cu correlated significantly with RBC Zn (r = 0.56, 0.49). Disease acuity and disability had no effect on trace-mineral status. These data suggest that in MS there is altered Cu and Zn homeostasis that may cause or result from the disease and is influenced by corticosteroid therapy. Systemic trace element alterations might provide clinically useful markers of MS.
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PMID:Trace element status in multiple sclerosis. 275 Jun 86

Pulmonary functions at rest and cardiorespiratory responses to low speed treadmill walking were investigated in 24 patients (P), (mean age, 38 years; range, 20 to 56 yr) with multiple sclerosis and compared with a control group (C). The following parameters were significantly (p less than 0.01) different in P from those in C. At rest in P, the residual volume to TLC ratio was 21% greater, respiratory muscle strength index was 28% lower, and heart rate (HR) was 11 beats/min-1 higher. During treadmill walking at a given speed, HR, minute ventilation (VE), and O2 consumption (VO2) were all elevated (37 to 119%). In addition, the energy cost of walking, per unit distance, above resting, was 2 to 3 times greater, with mean +/- SEM values for P of 0.299 +/- 0.019 and C of 0.147 +/- 0.006 at 2 km/h and 0.275 +/- 0.042 and 0.110 +/- 0.005 (for P and C, respectively) ml O2 kg-1 m-1 at 4 km/h; the HR and VE/VO2, also when referred to a given VO2, were higher. We conclude that a high energy cost of walking may be an important contributing factor to breathlessness and leg fatigue in patients with multiple sclerosis. Poor conditioning, altered cardiovascular control, and respiratory muscle weakness may play additional roles.
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PMID:Energy cost of walking and exertional dyspnea in multiple sclerosis. 377 62

Periphlebitis retinae in multiple sclerosis appears as transitory cellular infiltrations around veins in an otherwise normal retina. Similar cellular infiltrations have been found around veins in the central nervous system. In the present study the blood-retinal barrier has been investigated by vitreous fluorophotometry. Eight multiple sclerosis patients with actual periphlebitis retinae and 9 patients with previous but not active periphlebitis retinae were included in this study. Abnormal leakage of fluorescein was manifest in the group of multiple sclerosis patients with periphlebitis retinae. Permeability (1.8 +/- 0.2 X 10(-7) cm/sec; mean +/- SEM) but not in the control group as a whole permeability (1.3 +/- 0.1 X 10(-7) cm/sec; mean +/- SEM) compared to 17 normals (permeability 1.1 +/- 0.005). It is thus concluded that breakdown of the blood-retinal barrier may be transitory when connected with periphlebitis retinae in multiple sclerosis.
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PMID:Breakdown of the blood-retinal barrier in multiple sclerosis measured by vitreous fluorophotometry. 381 71

Soluble glial fibrillary acidic protein (GFAP) was quantified in human cerebrospinal fluid (CSF) and amniotic fluid. A normal value in lumbar CSF of 4.3 +/- 0.7 ng GFAP/ml (mean +/- SEM) was obtained from 18 non-neurological patients. Increased GFAP concentrations in CSF were found in patients with intracranial tumours or with normal pressure hydrocephalus, while normal values were found in multiple sclerosis patients and in patients with degenerative dementia. In addition, a concentration gradient between ventricular and lumbar CSF was demonstrated, the GFAP content being significantly higher in ventricular than in lumbar samples. Amniotic fluids from normal pregnancies contained 13 +/- 5.5 ng GFAP/ml (N = 117). Increased GFAP concentrations were observed in amniotic fluid from some but not all pregnancies with fetal anencephaly or encephalocele, but not from pregnancies with fetal spina bifida or any of the other fetal malformations investigated. The quantification method was an enzyme-linked immunosorbent assay employing a monoclonal antibody specific for GFAP.
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PMID:Quantification of glial fibrillary acidic protein (GFAP) in human body fluids by means of ELISA employing a monoclonal antibody. 400 33

In 27 patients with multiple sclerosis (MS), and in 10 control subjects of comparable age, percent ideal body weight and sex ratio, the cerebrospinal fluid (CSF) content of somatostatin was measured by radioimmunoassay. The results showed that the group of patients in relapse (n = 16) had significantly lower somatostatin content in CSF (95 +/- 4.1 (SEM) pg/ml) than both the control group (142 +/- 8.4 pg/ml) and the group of MS patients (n = 11), who had been in a clinical stable phase for more than 6 months (131 +/- 3.2 pg/ml). Duration of the disease and degree of neurological impairment were apparently without relation to the reduction of somatostatin content in the CSF. There was no relationship between CSF content of somatostatin and the content of total protein or IgG, neither of which showed any relationship to the activity of the disease.
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PMID:Low somatostatin content in cerebrospinal fluid in multiple sclerosis. An indicator of disease activity? 610 86

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

Using in vitro lymphocyte proliferation induced by the phytomitogen concanavalin A (Con A), we investigated immune function and regulation in patients with myasthenia gravis (MG) and multiple sclerosis (MS). Unfractionated peripheral blood mononuclear cells of normal individuals responded to a wide range of ConA concentrations; the T cell fraction responded to a lesser degree and only to high concentrations. These findings suggest the presence of two receptors for ConA, one of high affinity present on a non-T cell accessory cell and the other of low affinity present on T cells. Contrasting defects in the level of response of unfractionated lymphocytes and T cells were found in patients with MG and MS. The peak response of T cells in the MG patients was 22.6 +/- 9.6 X 10(3) cpm (mean +/- SEM) compared with 54.6 +/- 6.5 X 10(3) for controls (p less than 0.05), while the response of unfractionated lymphocytes did not differ from that in controls. For MS patients, the unfractionated lymphocyte response was diminished: 56.3 +/-2.8 X 10(3) cpm versus 70.5 +/- 4.5 X 10(3) for controls (p less than 0.05), while the T cell response was normal. These results indicate a defect in the direct T cell response in MG; in contract, in MS the response requiring T cell-accessory cell interaction is abnormal.
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PMID:Defective mitogenic responses in myasthenia gravis and multiple sclerosis. 698 Jun 19


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