[When HbA1c is unreliable : a case report of hereditary spherocytosis]. / Cas clinique. Quand le dosage de l'HbA1c n'est pas fiable : à propos d'un cas de sphérocytose héréditaire.

Glycated haemoglobin (HbA1c) is a biological parameter used in the management of diabetic patients. Independent of the daytime glycaemic variations, but complementary to the measurement of blood glucose or subcutaneous glucose concentrations, it allows both the clinician and the patient to have an appreciation of the glycaemic balance of the last weeks. In this way, anti-diabetic treatment can be adjusted if necessary to achieve the desired goal and hopefully delay or prevent diabetes-related micro- and macroangiopathic complications. Some conditions can alter the glycation of haemoglobin. In this case, the HbA1c level becomes difficult to interpret. Hereditary spherocytosis may be revealed by a dissociation between low HbA1c level and high blood glucose levels. A family history, Coombs-negative haemolytic anaemia, or a finding of spherocytes in the blood smear is suggestive of hereditary spherocytosis. Fructosamine testing may be an alternative. This article will present a patient with hereditary spherocytosis in whom the HbA1c level was not interpretable when compared to the elevated blood glucose measurements.

: L'hémoglobine glyquée (HbA1c) est une valeur biologique utilisée dans le suivi des patients diabétiques. Indépendante de la variation glycémique nycthémérale, mais complémentaire à la mesure de la glycémie ou de la concentration sous-cutanée de glucose, elle permet tant au clinicien qu'au patient d'avoir une appréciation de l'équilibre glycémique des dernières semaines. De cette manière, le traitement anti-diabétique peut être éventuellement adapté pour atteindre l'objectif escompté et espérer retarder, voire prévenir, les complications micro- et macroangiopathiques liées au diabète. Certaines affections peuvent altérer la glycation de l'hémoglobine. Dans ce cas, le taux d'HbA1C devient difficile à interpréter. La sphérocytose héréditaire peut se révéler par un tableau de dissociation entre un taux bas d'HbA1C et des valeurs élevées de glycémie. Des antécédents familiaux, une anémie hémolytique à Coombs négatif, ou une observation de sphérocytes dans le frottis sanguin sont en faveur d'un diagnostic de sphérocytose héréditaire. Le dosage de la fructosamine peut être une alternative. Le présent article abordera le cas d'un patient atteint d'une sphérocytose héréditaire chez qui le taux d'HbA1c n'était pas interprétable en regard des contrôles glycémiques.

[Granulicatella adiacens: an underestimated cause of endocarditis]. / Granulicatella adiacens: une cause sous-estimée d'endocardite.

We report the case of an old man who was affected by an endocarditis related to Granulicatella adiacens, an uncommon bacteria, difficult to isolate and responsible for an important morbidity and mortality. Thus, it is mandatory to seek for endocarditis when this germ is demonstrated in order to start quickly an effective antibiotic treatment. Inversely, in the presence of unexplained endocarditis, further bacteriological investigations are needed to seek for this life nutrition deficient bacteria.

[Hoffmann syndrome presenting to the emergency department]. / Syndrome de Hoffmann aux urgences.

We report a case of hypothyroid myopathy, or Hoffmann syndrome, in a 31-year-old man who presented to the emergency department with asthenia, muscular pain, cramps, and joint pain. Tests revealed increased creatine phosphokinase level (8102 U/L) and severe hypothyroidism (content of T4=3.8 pg/ml, T3=1.3 pg/ml, and thyrotropin stimulating hormone>150 microU/ml). Other causes of myopathy were excluded by anamnestic investigation and paraclinical exam. Treatment was begun with thyroid hormones (from 75 to 175 microg) and good clinical evolution was rapid. The pathophysiology of hypothyroid myopathy, clinical aspects and pathologic anatomic elements are described. The exact etiology of hypothyroidism must be known because some pathologic features are benign and treatment can have good results, whereas others, such as cancer, have worse prognosis.

[Spontaneous coronary artery dissection on the 10th post-partum day: a case report]. / Dissection spontanée d'une artère coronaire au 10e jour post-partum: observation clinique.

Spontaneous coronary artery dissection is a rare cause of myocardial infarction. It most commonly occurs in young women in the peri-partum period. The aetiology remains obscure. The authors describe the case of a 38 year old woman who suffered an inferior wall myocardial infarction on the 10th post-partum day. After failure of thrombolysis, coronary angiography showed dissection of the right coronary artery. An attempted angioplasty was unsuccessful and the patient was treated medically with a favourable clinical outcome. Spontaneous coronary artery dissection should be considered in all young patients without coronary risk factors presenting with acute myocardial ischaemia, especially young women in the peri-partum period. Emergency coronary angiography should be undertaken to establish the diagnosis and orientate appropriate treatment which may be medical, interventional or surgical.

The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature.

C-erbB-2 prognostic value for survival in patients with lung cancer remains controversial. We performed a systematic review of the literature to clarify its impact. Studies were identified by an electronic search in order to aggregate the survival results, after a methodological assessment using the scale of the European Lung Cancer Working Party. To be eligible, a study had to deal with c-erbB-2 assessment in lung cancer patients and to analyse survival according to c-erbB-2 expression. In total, 30 studies were eligible: 24 studies dealt with non-small-cell lung carcinoma (NSCLC), five with adenocarcinoma and one study dealt with small-cell carcinoma. In all, 31% of the patients were positive for c-erbB-2. According to c-erbB-2 expression, 13 studies were 'negative' (significant detrimental effect on survival), one 'positive' (significant survival improvement) and 16 not significant. Significant studies had a better subscore relative to analysis and results report than nonsignificant studies. In total, 86% of the significant studies and only 56% of the nonsignificant studies were evaluable for the meta-analysis. This suggests a possible bias in our aggregated results. For NSCLC, the hazard ratio was 1.55 (95% CI: 1.29-1.86) in favour of tumours that do not express c-erbB-2. In conclusion, the overexpression of c-erbB-2 might be a factor of poor prognosis for survival in NSCLC, but there is a potential bias in favour of the significant studies with an overestimation risk of the magnitude of the true effect of c-erbB-2 overexpression.

[VEGF and survival of patients with lung cancer: a systematic literature review and meta-analysis]. / VEGF et survie des patients atteints d'un cancer pulmonaire. Revue systématique avec méta-analyse.

The process of angiogenesis is an important factor in tumour development. One of the principal factors implicated in this process is vascular endothelial growth factor (VEGF) which induces, among other things, an increase in vascular permeability. We have undertaken a systematic review of the English and French literature in order to clarify its effect on the survival of patients with small cell (SCLC) and non-small cell (NSCLC) lung cancer. To be eligible studies had to deal with the the evaluation of VEGF or its receptors in lung cancer and describe the relationship of their expression to survival. The survival figures were subject to meta-analysis after a methodological evaluation by means of a specific numerical scale evaluating the design of the study, the methodology (including laboratory techniques), and the analysis of results. Among the 20 studies selected 15 identified VEGF expression, using univariate analysis, as a statistically significant indicator of poor prognosis. 17 reported sufficient data to allow aggregation of the survival figures, of which 15 were devoted to NSCLC (1,549 patients). The median overall methodological score was 48.3% (range 21.8-72.4%), without significant difference (p=0.63) between studies eligible or non-eligible for meta-analysis. The meta-analysis, using the authors' threshold of positivity for VEGF, showed that VEGF is an unfavourable prognostic factor in NSCLC (HR=1.48; 95% confidence interval 1.27-1.72). The data were insufficient to determine the prognostic value of VEGF in SCLC and that of its two receptors Flt-1 and KDR, with 1, 2 and 1 published studies respectively. In conclusion the expression of VEGF in MSCLC is a factor indicating a poor prognosis.

The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis.

The prognostic value of epidermal growth factor receptor (EGF-R) for survival of patients with lung cancer remains controversial. The authors performed a systematic review of the literature in order to clarify its impact. Published studies were identified using an electronic search in order to aggregate the available survival results, after a methodological assessment using a scale specifically designed by the European Lung Cancer Working Party (ELCWP). To be eligible, a study had to have dealt with EGF-R assessment in lung cancer patients on the primary site and to have analysed survival according to EGF-R expression. Among the 16 eligible studies, 14 assessed any nonsmall-cell lung cancer (NSCLC) subtype, one adenocarcinoma only and one squamous-cell carcinoma only. The overall median quality score was 56.3%, with no significant difference either between studies assessable or not assessable for meta-analysis or between studies with significant and nonsignificant results. One individual trial reported a survival benefit for patients with EGF-R expression, three a survival disadvantage and 12 no statistically significant difference. Eleven studies (2,185 patients) provided sufficient data to allow a meta-analysis of the survival results. EGF-R expression positivity was determined according to the cut-off as determined by the authors. The meta-analysis showed that EGF-R expression was not a statistically significant prognostic factor for survival in NSCLC. In the subgroup of studies using immunohistochemistry, statistical tests reached a significant level against EGF-R. Epidermal growth factor receptor might be a poor prognostic factor for survival in nonsmall-cell lung cancer. The amplitude of the impact is small, however, and may be subject to publication bias.

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis.

In order to determine whether angiogenesis is a prognostic marker in lung cancer, we performed a systematic review of the literature to assess the prognostic value on survival of microvessel count in patients with lung cancer. Published studies were identified by an electronic search in order to aggregate survival results, after a methodological assessment using a quality scale designed by the European Lung Cancer Working Party. To be eligible, a study had to deal with microvessel count assessment in lung cancer patients on the primary site and to provide survival analysis according to microvessel count expression. Microvessel count has been assessed on surgical samples by immunohistochemistry using factor VIII in 14 studies, CD34 in 10 and CD31 in eight. Respectively 1866, 1440 and 1093 non-small cell lung cancer patients were considered. The overall median quality scores were respectively 52, 59 and 59% for studies assessing microvessel count via factor VIII, CD34 and CD31, without significant difference between studies evaluable or not for meta-analysis nor between studies with significant or non significant results. Seven 'factor VIII' studies, nine 'CD34' and seven 'CD31' provided sufficient data allowing a meta-analysis on survival and were evaluable for results aggregation. This showed that a high microvessel count in the primitive lung tumour was a statistically significant poor prognostic factor for survival in non small cell lung cancer whatever it was assessed by factor VIII (HR: 1.81; 95% CI: 1.16-2.84), CD34 (HR: 1.99; 95% CI: 1.53-2.58) or CD31 (HR: 1.80; 95% CI: 1.10-2.96). Variations in survival among the individual studies can be explained in addition to patients selection criteria by the heterogeneous methodologies used to stain and count microvessels: different antibody clones, identification of 'hotspots', Weidner or Chalkey counting method, cut-off selection. Microvessel count, reflecting the angiogenesis, appears to be a poor prognostic factor for survival in surgically treated non small cell lung cancer but standardisation of angiogenesis assessment by the microvessel count is necessary.

Influence of culture conditions on the alpha 1,2-fucosyltransferase and MUC gene expression of a transformed cell line MM-39 derived from human tracheal gland cells.

Human tracheal glands cells (HTGC) in culture are able to respond to adrenergic, cholinergic and purinergic agonists by increasing their serous and mucin secretions. These secretagogues are also able to maintain an optimal responsiveness of serous cells to stimulation when they are regularly and briefly delivered to the cells, making the HTGC a suitable model to study the serous secretion (Merten, in press). Our interest has been focused on the effects of cholinergic and purinergic secretagogues associated to histamine, on the mucous function of the transformed human tracheal gland cell line MM-39, which has a mixed, both serous and mucous, phenotype. When the cells were exposed to short stimulation every 2 days for 3 weeks with 10 or 100 microM carbachol, UTP and histamine, modifications of their mucous phenotype were observed. The expression of MUC genes appeared dependent on the culture conditions. Transcripts of MUC1, MUC4, and MUC5B genes were observed when the cells were regularly exposed to the mixture of secretagogues at a concentration of 10 microM, in contrast to the unstimulated expression of MUC1 and MUC4 in control cells. MUC1, MUC4, MUC7, MUC6 and MUC11 transcripts were observed when the cells were regularly exposed to the mixture of secretagogues at a concentration of 100 microM. These culture conditions were also able to induce an alpha 1,2-fucosyltransferase activity absent in the MM-39 cells cultivated with standard conditions. There was no marked effect on the alpha 2,3-sialyltransferase activity although the expression pattern of the sialyltransferase genes was reduced to the unique presence of ST3Gal III. In conclusion, MM-39 cells exposed to repeated stimulation by secretagogues at different concentrations express different sero-mucous phenotypes.

Recognition of Lewis x derivatives present on mucins by flagellar components of Pseudomonas aeruginosa.

Pseudomonas aeruginosa binds to human respiratory mucins by mechanisms involving flagellar component-receptor interactions. The adhesion of P. aeruginosa strain PAK is mediated by the flagellar cap protein, FliD, without the involvement of flagellin. Two distinct types of FliD proteins have been identified in P. aeruginosa: A type, found in strain PAK, and B type, found in strain PAO1. In the present work, studies performed with the P. aeruginosa B-type strain PAO1 indicate that both the FliD protein and the flagellin of this strain are involved in the binding to respiratory mucins. Using polyacrylamide-based fluorescent glycoconjugates in a flow cytometry assay, it was previously demonstrated that P. aeruginosa recognizes Le(x) (or Lewis x) derivatives found at the periphery of human respiratory mucins. The aim of the present work was therefore to determine whether these carbohydrate epitopes (or glycotopes) are receptors for FliD proteins and flagellin. The results obtained by both flow cytometry and a microplate adhesion assay indicate that the FliD protein of strain PAO1 is involved in the binding of glycoconjugates bearing Le(x) or sialyl-Le(x) determinants, while the binding of flagellin is restricted to the glycoconjugate bearing Le(x) glycotope. In contrast, the type A cap protein of P. aeruginosa strain PAK is not involved in the binding to glycoconjugates bearing Le(x), sialyl-Le(x), or sulfosialyl-Le(x) glycotopes. This study demonstrates a clear association between a specific Pseudomonas adhesin and a specific mucin glycotope and demonstrates that fine specificities exist in mucin recognition by P. aeruginosa.

Differential effect of GalNAcalpha-O-bn on intracellular trafficking in enterocytic HT-29 and Caco-2 cells: correlation with the glycosyltransferase expression pattern.

Our previous work has shown that long-term treatment of mucus-secreting HT-29 cells with 1-benzyl-2-acetamido-2-deoxy-alpha-D-galactopyranoside (GalNAcalpha-O-bn), a competitive inhibitor of O-glycosylation, induced several phenotypic changes, in particular a blockade in the secretion of mucins, which are extensively O-glycosylated glycoproteins. Here, we have analyzed the effects of GalNAcalpha-O-bn upon the intracellular trafficking of basolateral and apical membrane glycoproteins at the cellular and biochemical levels in two types of cells, HT-29 G(-) and Caco-2, differentiated into an enterocyte-like phenotype. In HT-29 G(-) cells, but not in Caco-2 cells, DPP-IV and CD44 failed to be targeted to the apical or basolateral membrane, respectively, and accumulated inside intracytoplasmic vesicles together with GalNAcalpha-O-bn metabolites. We observed a strong inhibition of alpha2,3-sialylation of glycoproteins in HT-29 G(-) cells correlated to the high expression of alpha2,3-sialyltransferases ST3Gal I and ST3Gal IV. In these cells, DPP-IV and CD44 lost the sialic acid residue substituting the O-linked core 1 structure Galbeta1-3GalNAc (T-antigen). In contrast, sialylation was not modified in Caco-2 cells, but a decrease of alpha1,2-fucosylation was observed, in correlation with the high expression of alpha1,2-fucosyltransferases Fuc-TI and Fuc-TII. In conclusion, in HT-29 G(-) cells, GalNAcalpha-O-bn induces a specific cellular phenotype, which is morphologically characterized by the formation of numerous intracellular vesicles, in which are accumulated defectively sialylated O-glycosylproteins originally targeted to basolateral or apical membranes, and GalNAcalpha-O-bn metabolites.

[Is it reasonable to prescribe growth hormones in the elderly?]. / Est-il raisonnable de prescrire de l'hormone de croissance aux personnes âgées?

During normal aging, there is a +/- 60% decrease of the endogenous GH secretion ("somatopause"). However it is safe to prescribe GH therapy only to those people who show a clear cut decrease of GH release as evidenced by low integrated 24 hr secretion and/or low plasma IGF-1. In our view, a complete clinical check up must also show, on the one hand, an abnormal decrease of the optimal quality of life and, on the other hand a willing to maintain a reasonable intellectual and physical activity in the absence of major clinical and biological abnormalities. The benefits are likely to be an increase of muscular strength and of exercise tolerance, a decrease of trabecular osteopenia, a decrease of abdominal obesity, an increase of immunocompetence and a general improvement of the "quality of life". A "pharmacological" prescription is contra-indicated whereas very low dose regimen could induce, through feed back mechanism, a putative decrease of endogenous GH-RH (and GHRPs?) function whose deleterious psychoneuroendocrine effects remain to be demonstrated.

Human airway mucin glycosylation: a combinatory of carbohydrate determinants which vary in cystic fibrosis.

Human airway mucins represent a very broad family of polydisperse high molecular mass glycoproteins, which are part of the airway innate immunity. Apomucins, which correspond to their peptide part, are encoded by at least 6 different mucin genes (MUC1, MUC2, MUC4, MUC5B, MUC5AC and MUC7). The expression of some of these genes (at least MUC2 and MUC5AC) is induced by bacterial products, tobacco smoke and different cytokines. Human airway mucins are highly glycosylated (70-80% per weight). They contain from one single to several hundred carbohydrate chains. The carbohydrate chains that cover the apomucins are extremely diverse, adding to the complexity of these molecules. Structural information is available for more than 150 different O-glycan chains corresponding to the shortest chains (less than 12 sugars). The biosynthesis of these carbohydrate chains is a stepwise process involving many glycosyl- or sulfo-transferases. The only structural element shared by all mucin O-glycan chains is a GalNAc residue linked to a serine or threonine residue of the apomucin. There is growing evidence that the apomucin sequences influence the first glycosylation reactions. The elongation of the chains leads to various linear or branched extensions. Their non-reducing end, which corresponds to the termination of the chains, may bear different carbohydrate structures, such as histo-blood groups A or B determinants, H and sulfated H determinants, Lewis a, Lewis b, Lewis x or Lewis y epitopes, as well as sialyl- or sulfo- (sometimes sialyl- and sulfo-) Lewis a or Lewis x determinants. The synthesis of these different terminal determinants involves three different pathways with a whole set of glycosyl- and sulfo-transferases. Due to their wide structural diversity forming a combinatory of carbohydrate determinants as well as their location at the surface of the airways, mucins are involved in multiple interactions with microorganisms and are very important in the protection of the underlying airway mucosa. Airway mucins are oversulfated in cystic fibrosis and this feature has been considered as being linked to a primary defect of the disease. However, a similar pattern is observed in mucins from patients suffering from chronic bronchitis when they are severely infected. Airway mucins from severely infected patients suffering either from cystic fibrosis or from chronic bronchitis are also highly sialylated, and highly express sialylated and sulfated Lewis x determinants, a feature which may reflect severe mucosal inflammation or infection. These determinants are potential sites of attachment for Pseudomonas aeruginosa, the pathogen responsible for most of the morbidity and mortality in cystic fibrosis, and the expression of the sulfo- and glycosyl-transferases involved in their biosynthesis is increased by TNFalpha. In summary, airway inflammation may simultaneously induce the expression of mucin genes (MUC2 and MUC5AC) and the expression of several glycosyl- and sulfo-transferases, therefore modifying the combinatory glycosylation of these molecules.

Influence of TNFalpha on the sialylation of mucins produced by a transformed cell line MM-39 derived from human tracheal gland cells.

In order to investigate the influence of inflammation on the peripheral glycosylation of airway mucins, a human respiratory glandular cell line (MM-39) was treated by TNFalpha. The expression and the activity of sialyl- and fucosyl-transferases, involved in the biosynthesis of peripheral carbohydrate determinants like sialyl-Lewis x, were investigated by RT-PCR and by HPAEC respectively. The mRNA steady-state level of sialyl- (ST3Gal III) and of fucosyl- (FUT3) transferases was moderately up-regulated by TNFalpha; a 52% increase of alpha2,3-sialyltransferase activity was also observed in TNFalpha-stimulated MM-39 cells. After metabolic radio-labelling with [(3)H]glucosamine and [(3)H]fucose, the mucins released in the culture supernatant were purified by Sepharose CL-4B, density-gradient centrifugation and treatment with glycosaminoglycans-degrading enzymes. The mucins, released in the culture supernatant from control MM-39 cells, were constituted by two populations of molecules having the same 1.39-1.44 mg/ml density but carrying either high or low amounts of sialic acid residues at their periphery. TNFalpha was able to increase the sialylation of the weakly sialylated mucins. This effect and the enhancement of the alpha2,3-sialyltransferase activity by TNFalpha argue in favour of a regulation of the mucin sialylation by this pro-inflammatory cytokine. Despite the moderate overexpression of FUT3, no fucosylation of mucins produced by MM-39 cells was induced by TNFalpha. In conclusion, the influence of TNFalpha on the sialylation of mucins could explain why the mucins from infected patients suffering either from cystic fibrosis or from chronic bronchitis are more sialylated.

Sialyl-Le(x) and sulfo-sialyl-Le(x) determinants are receptors for P. aeruginosa.

Pseudomonas aeruginosa, the main pathogen in the airways of patients suffering from cystic fibrosis (CF), binds to carbohydrate chains of respiratory mucins. Using flow cytometry and polyacrylamide based fluorescent glycoconjugates, it was previously demonstrated that several strains of P. aeruginosa recognize a set of neutral and acidic carbohydrate epitopes found at the periphery of respiratory mucins, especially sialyl-Le(x). This structure, overexpressed in mucins from CF patients, could be responsible in part for the persistence of lung infection in CF patients. The aim of the present work was to determine whether a glycoconjugate bearing the 6-sulfo-sialyl-Le(x) epitope, also found in abundance in CF airway mucins, is also preferentially recognised by different strains of P. aeruginosa. The study was conducted with a nonpiliated strain 1244-NP and four mucoid strains isolated from CF patients. For four strains out of five, the affinity for 6-sulfo-sialyl-Le(x) was as high as for sialyl-Le(x) derivative. These results were confirmed for strain 1244-NP by a microtiter plate assay.

Measles antibodies, anti-proteinase and plasminogen distribution in serum and plasma from patients affected with multiple sclerosis and patients affected with non-neurological diseases.

Total protein content, alpha 1-antitrypsin, alpha 2-macroglobulin and plasminogen levels and measles antibody titers were determined in serum and plasma from patients affected with multiple sclerosis and patients affected with non-neurological diseases. The results were compared with those from a control group of healthy donors. Both multiple sclerosis patients and patients affected with non-neurological diseases differed from controls for the following parameters: total protein, plasminogen and measles antibody activity. However, when studied longitudinally the different parameters were not altered to the same degree in multiple sclerosis and non-neurological diseases, a fact which is translated in the difference of significance levels. Individual plasminogen values were very often higher in non-neurological diseases than in multiple sclerosis, whereas for increased measles antibody titers it was the reverse. Also, there were no notable changes in alpha 1-antitrypsin and alpha 2-macroglobulin values in multiple sclerosis, whereas in some non-neurological disease patients particularly high alpha 1-antitrypsin and alpha 2-macroglobulin values were observed. In the multiple sclerosis patients, no correlations existed between the duration of the disease and disturbed biochemical parameters, or between the disturbed parameters themselves.

Clinical parameters and intrathecal IgG synthesis as prognostic features in multiple sclerosis. Part I.

In a search for early prognostic features in multiple sclerosis, the progression rate was calculated in 200 consecutive multiple sclerosis patients who had had a lumbar puncture, and correlated with age at onset, type of disease course, the patient's sex, as well as with indices of blood-brain barrier breakdown and intrathecal IgG synthesis. The present study demonstrates that age at onset plays a role in determining whether the disease will be remitting-relapsing or chronic progressive. Age at onset is also a factor determining the rate of progression of the remitting-relapsing form, but is without influence on the progression of the chronic progressive form. A chronic progressive disease course per se (independent of age at onset) is also associated with a more rapid deterioration. The patient's sex does not appear to be a differentiating factor. Only inconsistent correlations were found between IgG index or number of oligoclonal bands in the CSF and disease progression.

Cell-mediated immunity in multiple sclerosis as determined by sensitivity of different lymphocyte populations to various brain tissue antigens.

Peripheral blood lymphocytes from patients with multiple sclerosis (MS) or other neurological diseases and from healthy individuals were separated by density gradient sedimentation into several subfractions. Individual cell populations were cultured in the presence of several human brain tissue antigens. In comparison to controls, mononuclear cells with a density of less than 1.077 gm/cm3 from MS patients displayed a significantly increased sensitivity after incubation with purified human myelin basic protein (MBP) but not with other brain tissue antigens. In particular, the lymphocytes of patients suffering from MS for more than four years reacted positively with MBP, suggesting that the reaction dependent. No difference between MS patients and controls in sensitivity to any brain tissue antigen could be detected with cells of lower density (i.e., 1.073 to 1.069 gm/cm3 or less than 1.069 gm/cm3). Comparable lymphocyte activity was found to antigens isolated from both MS and control brain tissue. These results suggest that patients with chromic progressive MS have a secondary immune activity to MBP.