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Biomedical subjects

D Bernard

Publications and source records attributed to D Bernard.

At least 19 recordsLinked to original sources
PubMed2007

Protection from oxidative stress by enhanced glycolysis; a possible mechanism of cellular immortalization.

Reactive oxygen species (ROS) play a crucial role not only in the physiological signal transduction but also in the pathogenesis of several human diseases such as atherosclerosis, neuro-degenerative diseases, metabolic disorders, aging or cancer amongst others. Oxidative stress is also responsible for cellular and organism senescence, in accordance with what Harman initially proposed in the free radical theory of aging. Recent findings support the notion that protection from oxidative stress can increase life span significantly. We reported that enhanced glycolysis could modulate cellular life span with reduction of oxidative stress. Moreover, the tumor suppressor gene p53 controls post-transcriptionally the level of the glycolytic enzyme, phosphoglycerate mutase (PGM). As enhanced glycolysis is a distinctive and prominent feature of cancer cells (termed the Warburg effect), our findings disclosed a novel aspect of the Warburg effect: the connection between senescence and oxidative stress.

Animals↗
PubMed2006

[Pronostic value of C-reactive protein measure in elderly patient with acquired pneumonia: correlation with Fine's score].

UNLABELLED: The Fine's score, a predictive score of infectious pneumonia gravity, does not integrate inflammatory parameters, which are routinely used in the management of infectious pneumonia. The aim of our study was to establish a correlation between the Fine's score and C reactive protein. PATIENTS AND METHODS: One hundred patients hospitalized for infectious pneumonia, 57 men and 43 female, with an average age of 85 years were retrospectively recorded. RESULTS: The median level of C reactive protein was 157 mg/L. Global mortality rate was 26% and respectively 5, 16 and 45% in the grades III, IV, V of the Fine's score. Beyond 75,5 mg/L C reactive protein concentration, the mortality rate was contained between 28 and 32%. The comparison of the ROC curves of the Fine's score and C reactive protein did not showed any difference. CONCLUSION: C-Reactive protein is less precise than the Fine's score to assess infectious pneumonia gravity but seems to be an indicator of the potential gravity of the pneumonia.

Aged, 80 and over↗
PubMed2006

The methyl-CpG-binding protein MECP2 is required for prostate cancer cell growth.

The incidence of prostate cancer is increasing in western countries because of population aging. Prostate cancer begins as an androgen-dependent disease, but it can become androgen independent at a later stage or in tumors recurring after an antihormonal treatment. Although many genetic events have been described to be involved in androgen-dependent and/or -independent prostate cancer growth, little is known about the contribution of epigenetic events. Here we have examined the possibility that the methyl-CpG-binding protein MECP2 might play a role in controlling the growth of prostate cancer cells. Inhibition of MECP2 expression by stable short hairpin RNA stopped the growth of both normal and cancer human prostate cells. In addition, ectopic expression of the MECP2 conferred a growth advantage to human prostate cancer cells. More importantly, this expression allowed androgen-dependent cells to grow independently of androgen stimulation and to retain tumorigenic properties in androgen-depleted conditions. Analysis of signaling pathways showed that this effect is independent of androgen receptor signaling. Instead, MECP2 appears to act by maintaining a constant c-myc level during antihormonal treatment. We further show that MECP2-expressing cells possess a functional p53 pathway and are still responsive to chemotherapeutic drugs.

Androgens↗
PubMed2005

[Isolated increase of the serum aspartate aminotransferase level in a young asymptomatic patient: macro-AST].

A 23-year-old asymptomatic patient wanted to become pregnant and had a blood analysis done at her general practitioner's office. The serum aspartate aminotransferase (AST) level was unexpectedly elevated: 139 U/l (reference value: < 32). The values for the other liver enzymes were normal. Extensive biochemical and imaging studies revealed no other abnormalities. The presence of so-called macro-AST was suspected. In this condition, AST forms complexes with other proteins, primarily IgG, which leads to an increased serum level. This has no clinical consequences. The presence of such complexes was confirmed by means ofa polyethylene glycol precipitation assay. This is a simple test for the detection of macro-AST, which saves the asymptomatic patient further invasive diagnostic procedures.

Adult↗
PubMed2005

Coronary risk factors and inflammation in patients with coronary artery disease and internal cardioverter defibrillator implants.

BACKGROUND: The internal cardioverter defibrillator (ICD) is increasingly used to treat ventricular tachyarrhythmias in patients with coronary artery disease (CAD). The burden of coronary risk factors and inflammation is however not well studied in these high risk patients. STUDY AIMS: The aim of the present study was to describe the prevalence of coronary risk factors (including lipid values) and inflammation (including high sensitive-C-reactive protein, hs-CRP) in patients with CAD and ICD implants. METHODS: Baseline clinical characteristics and laboratory results of all eligible patients for the Cholesterol Lowering and Arrhythmias Recurrences after Internal Defibrillator Implantation trial (CLARIDI trial) were used. All patients had documented CAD, an ICD implant and were not yet treated with statins. Coronary risk factors, lipid values, glycated haemoglobin (HbA(1c)) and hs-CRP levels were determined. RESULTS: In the 110 included patients (mean age 68+/-9 years, LVEF 40+/-17%, NYHA class II-III in 47%), a high prevalence of coronary risk factors was documented: current smoking in 18%, body mass index > or =30 kg/m(2) in 16%, blood pressure > or =140/90 mm Hg in 40%, history of diabetes in 12%, and HbA(1c) > or =6% in 16% of patients not known with diabetes. A total cholesterol >175 mg/dl was found in 76% of patients and an LDL cholesterol >100 mg/dl in 83%. Finally, median hs-CRP was 4.8 mg/l (interquartile range 2.5-13.9 mg/l). Hs-CRP values > or =2 mg/l were noted in 83% of all patients and in 68% of patients who had an ICD implant more than 6 months before inclusion. CONCLUSION: In CAD patients with ICD implants, the burden of coronary risk factors is high, often unrecognized and/or under-treated. Persistent inflammation is found in the majority of these patients.

Adult↗
PubMed2005

Identification and characterization of a novel retroviral-like aspartic protease specifically expressed in human epidermis.

Proteases play a pivotal role in epidermal differentiation and desquamation. Separation of a total protein extract from human reconstructed epidermis by two-dimensional gel electrophoresis and subsequent peptide analysis of a specific protein spot identified a new protein exhibiting similarities with the retroviral aspartic protease family. Cloning of the corresponding full-length cDNA revealed an open reading frame encoding for a new protease of 343 amino acids, containing a putative aspartic protease catalytic domain. We named this protein Skin ASpartic Protease (SASPase). RT-PCR and northern blot analysis of various human tissues revealed that SASPase was specifically expressed within the epidermis. Immunohistochemical analysis showed a particularly intense expression restricted to the granular layers, whereas in diseased skin, its expression was changed. Western blot analysis, using a monoclonal antibody, revealed the expression of two forms of the enzyme: a 28 kDa putative proform and the active 14 kDa form. Recombinant truncated SASPase (SASP28) was generated from a prokaryotic expression system in Escherichia coli as a fusion protein with GST. SASP28 degraded insulin and to a lesser extent casein with a pH optimum of 5. As seen for retroviral proteases, an auto-activation processing was evidenced, generating a 14 kDa protein (SASP14). Site-directed mutagenesis inhibited auto-activation of the enzyme. Indinavir, a potent HIV protease inhibitor used in AIDS therapy, had a significant inhibitory effect on rSASPase auto-activation, which could explain its side effects on skin.

Amino Acid Sequence↗
PubMed2004

Gene expression profiles of three different models of reconstructed human epidermis and classical cultures of keratinocytes using cDNA arrays.

The gene expression profiles of three different models of reconstructed human epidermis were analyzed in a comparative study using cDNA array technology. The study also included normal human subconfluent keratinocytes cultured on plastic. Arrays were custom-made and comprised 504 known genes related to cutaneous biology. The gene expression profiles of the three reconstructed epidermis models shared 86% similarity; only 22 of the 504 examined genes showed a different expression level. A comparison of the 3D models with keratinocyte cultures on plastic dishes revealed a set of six genes with a considerably higher expression in the 3D models. These genes were keratin 1, corneodesmosin, filaggrin, loricrin, calmodulin-like skin protein and caspase 14, all related to keratinocyte terminal differentiation. The reported data may contribute to a better understanding and characterization of reconstructed epidermal models and may also serve as established references for investigations related to epidermal differentiation and proliferation.

Adult↗
PubMed2003

Health and access issues among Australian adolescents: a rural-urban comparison.

INTRODUCTION: Previous research has reported rural-urban differences in health concerns and access issues. However, very little of this has concerned young people, and what has been published has been mainly from countries other than Australia and may not generalise to Australian youth. The study described in this paper is a subset of a larger study on health concerns and access to healthcare for younger people (12-17 years) living in New South Wales (NSW), Australia. This paper reports findings on rural-urban similarities and differences. The specific study objective was to identify and describe rural-urban differences, especially those associated with structural disadvantage. METHOD: The reported findings form part of a larger state-wide cross-sectional study of access to healthcare among NSW adolescents. Adolescents were drawn from high schools in ten of the 17 Area Health Services in NSW. These Area Health Services were selected because they represent most aspects of rural-urban NSW with respect to population characteristics and health services. Eighty-one focus groups were conducted with adolescents (35 with boys and 46 with girls), of which 56 were conducted in urban, 22 in rural and 3 in regional areas. The focus groups were tape-recorded, transcribed and analysed using the computer software package NUD*IST 4. RESULTS: The analysis revealed certain health concerns that were common to both rural and urban adolescents: use of alcohol and illicit drugs, bullying, street safety, diet and body image, sexual health, stress and depression. However, certain concerns were mentioned more frequently in rural areas (eg depression), and two concerns were raised almost exclusively by rural youth (youth suicide and teenage pregnancy). There were also structural differences in service provision: adolescents in rural areas reported disadvantage in obtaining access to healthcare (limited number of providers and lengthy waiting times); having only a limited choice of providers (eg only one female doctor available), and cost (virtually no bulk billing--ie direct charge to Medicare with no patient co-payment). A lack of confidentiality as a barrier to seeking service access was raised by both rural and urban youth, but was a major concern in rural areas. No issues specific to urban areas were raised by urban youth. Male and female rural adolescents were more likely than urban adolescents to express concerns over limited educational, employment and recreational opportunities, which they believed contributed to their risk-taking behaviour. Gender differences were evident for mental health issues, with boys less able to talk with their peers or service providers about stress and depression than girls. These gender differences were evident among adolescents in both rural and urban areas, but the ethos of a self-reliant male who does not ask for help was more evident among rural boys. CONCLUSIONS: While Australian rural and urban youth shared many health concerns, rural-urban differences were striking in the almost exclusive reporting of youth suicide and teenage pregnancy by rural adolescents. The findings suggest that structural disadvantage in rural areas (limited educational, employment opportunities, and recreational facilities) impact adversely on health outcomes, particularly mental health outcomes, and contribute to risk-taking behaviour. Such disadvantages should be considered by health-service policy makers and providers to redress the imbalance. Gender differences were also evident and efforts to target the specific needs of Australian adolescent boys are warranted.

Journal Article↗
PubMed2003

Analysis of proteins with caseinolytic activity in a human stratum corneum extract revealed a yet unidentified cysteine protease and identified the so-called "stratum corneum thiol protease" as cathepsin l2.

Desquamation is described as a protease-dependent phenomenon where serine proteases with a basic pH optimum play a key role. Recently proteases with an acidic pH optimum were identified in the stratumcorneum and associated with desquamation, e.g., cathepsin D and the stratum corneum thiol protease. The purpose of this study was to investigate if human stratum corneum contains proteases different from the above, exhibiting similar properties. After gel filtration, we identified four distinct proteolytic activities in a human stratum corneum extract, a cathepsin-E-like activity (80 kDa), a cathepsin-D activity (40 kDa), a yet unknown cathepsin-L-like form (28 kDa) exhibiting the highest caseinolytic activity, and a chymotrypsin-like protein (24 kDa) containing the acidic activity of the well described stratum corneum chymotryptic enzyme. We named the new 28 kDa protease stratum corneum cathepsin-L-like enzyme. Characterization of stratum corneum cathepsin-L-like enzyme provided clear evidence that this new protease, despite its membership to the cathepsin-L-like family, is distinct from cathepsin L and from the recently described stratum corneum thiol protease. Its ability to hydrolyze corneodesmosin, a marker of corneocyte cohesion, was in favor of a role of stratum corneum cathepsin-L-like enzyme in the desquamation process. A more detailed analysis did not allow us to identify stratum corneum cathepsin-L-like enzyme at the molecular level but revealed that stratum corneum thiol protease is identical with the recently described cathepsin L2 protease. Reverse transcription polymerase chain reaction studies and the use of a specific antibody revealed that, in contrast to earlier reports, expression of stratum corneum thiol protease in human epidermis is not related to keratinocyte differentiation. Our results indicate that the stratum corneum thiol protease is probably expressed as a pro-enzyme in the lower layers of the epidermis and in part activated by a yet unidentified mechanism in the upper layers during keratinocyte differentiation.

Amino Acid Sequence↗
PubMed2002

Non-transferrin-bound iron in untreated and ribavirin-treated chronic hepatitis C patients.

BACKGROUND: In patients with chronic hepatitis C, elevations in serum iron levels, hepatic iron content and oxidative stress-related molecules have been reported. Treatment with ribavirin induces an increase in hepatic iron concentration. In situations of iron overload, non-transferrin-bound iron can appear. Therefore, we determined non-transferrin-bound iron levels in untreated chronic hepatitis C patients and in patients during interferon-ribavirin treatment. MATERIALS AND METHODS: In 10 untreated and 19 interferon-ribavirin-treated chronic hepatitis C patients, we examined non-transferrin-bound iron levels by a colorimetric method using nitrilotriacetic acid as a ligand and sodium triscarbonatecobalt (III) to block free iron binding sites on transferrin. RESULTS: Despite the presence of high serum iron saturation and ferritin levels, non-transferrin-bound iron was absent in the majority of hepatitis C virus patients (25/29, 86%). There was no difference in non-transferrin-bound iron levels between untreated and treated patients. Four patients with high non-transferrin-bound iron levels were distinguished by higher serum iron levels. In two of these patients, hepatocytic iron was present on liver biopsy. CONCLUSIONS: In the majority of chronic hepatitis C patients, non-transferrin-bound iron levels are normal. Treatment with ribavirin does not induce high non-transferrin-bound iron levels. Non-transferrin-bound iron levels are only higher than normal in hepatitis C patients with higher serum iron levels.

Adult↗
PubMed2001

Selective blockade of T lymphocyte K(+) channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis.

Adoptive transfer experimental autoimmune encephalomyelitis (AT-EAE), a disease resembling multiple sclerosis, is induced in rats by myelin basic protein (MBP)-activated CD4(+) T lymphocytes. By patch-clamp analysis, encephalitogenic rat T cells stimulated repeatedly in vitro expressed a unique channel phenotype ("chronically activated") with large numbers of Kv1.3 voltage-gated channels (approximately 1500 per cell) and small numbers of IKCa1 Ca(2+)-activated K(+) channels (approximately 50-120 per cell). In contrast, resting T cells displayed 0-10 Kv1.3 and 10-20 IKCa1 channels per cell ("quiescent" phenotype), whereas T cells stimulated once or twice expressed approximately 200 Kv1.3 and approximately 350 IKCa1 channels per cell ("acutely activated" phenotype). Consistent with their channel phenotype, [(3)H]thymidine incorporation by MBP-stimulated chronically activated T cells was suppressed by the peptide ShK, a blocker of Kv1.3 and IKCa1, and by an analog (ShK-Dap(22)) engineered to be highly specific for Kv1.3, but not by a selective IKCa1 blocker (TRAM-34). The combination of ShK-Dap(22) and TRAM-34 enhanced the suppression of MBP-stimulated T cell proliferation. Based on these in vitro results, we assessed the efficacy of K(+) channel blockers in AT-EAE. Specific and simultaneous blockade of the T cell channels by ShK or by a combination of ShK-Dap(22) plus TRAM-34 prevented lethal AT-EAE. Blockade of Kv1.3 alone with ShK-Dap(22), but not of IKCa1 with TRAM-34, was also effective. When administered after the onset of symptoms, ShK or the combination of ShK-Dap(22) plus TRAM-34 greatly ameliorated the clinical course of both moderate and severe AT-EAE. We conclude that selective targeting of Kv1.3, alone or with IKCa1, may provide an effective new mode of therapy for multiple sclerosis.

Animals↗
PubMed2001

cRel induces mitochondrial alterations in correlation with proliferation arrest.

We have previously shown that overexpressing cRel, a transcription factor of the Rel/NF-kappa B family, concomitantly inhibits proliferation of HeLa cells and makes them resistant against TNF alpha-induced apoptosis. Both effects rely on the upregulation of the manganese superoxide dismutase (MnSOD), a mitochondrial enzyme that converts O(2)(*-) in H(2)O(2). Here we describe additional alterations induced by cRel, namely mitochondrial clustering and accumulation of dense dark granules near the nucleus. These changes preferentially occur in cells that display a sustained cRel expression in the nucleus and that are cell-cycle arrested. As the cell-cycle arrest, these changes are reproduced by directly overexpressing MnSOD or by treating cells with H(2)O(2), suggesting they are due to MnSOD induction and ensuing H(2)O(2) accumulation. We propose that mitochondria cluster because they are damaged by the H(2)O(2) they overproduce. They would then be autophagocytosed and degraded in secondary lysosomes. In support of this scenario, we documented the occurrence of oxidative damage and the presence of lysosomes in the area of mitochondrial clustering. In addition, we identified the dense dark granules as lipofuscin, based on their autofluorescence. Lipofuscin could directly originate from the mitochondrial degradation products that would aggregate and become indigestible because of the presence of H(2)O(2) in the secondary lysosomes. Altogether, our findings show that cRel overexpression in HeLa cells creates, via the induction of MnSOD, an oxidative injury that culminates in mitochondrial degeneration, proliferation blockage, and resistance against TNF alpha-induced apoptosis.

Cell Cycle↗
PubMed2001

Rel/NF-kappaB transcription factors protect against tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by up-regulating the TRAIL decoy receptor DcR1.

Rel/nuclear factor (NF)-kappaB transcription factors play a major role in the regulation of programmed cell death. A few anti-apoptotic Rel/NF-kappaB target genes have been characterized; they act either downstream in the apoptotic pathway or upstream, for example at the tumor necrosis factor (TNF) receptor level. We found using DNA arrays, reverse transcription-polymerase chain reaction, and immunofluorescence that Rel/NF-kappaB factors up-regulate DcR1, a receptor for TNF-related apoptosis-inducing ligand (TRAIL), a cytokine of the TNF family that induces apoptosis in tumor cells. Four related receptors bind TRAIL, two death receptors (DR4 and DR5) that signal apoptosis and two decoy receptors (DcR1 and DcR2) that act as dominant negative inhibitors of TRAIL-mediated apoptosis. DcR1 is devoid of an intracellular domain and is anchored at the cell surface membrane by a glycophospholipid. Our results indicate that overexpression of cRel or activation of endogenous Rel/NF-kappaB factors by TNFalpha in HeLa cells up-regulates DcR1 without changing the expression of DcR2, DR4, and DR5 and makes cells resistant against TRAIL-induced apoptosis. This resistance is a consequence of DcR1 up-regulation, because it was abolished when DcR1 was removed from the cell surface by a phosphatidylinositol phospholipase C. Therefore, Rel/NF-kappaB transcription factors could regulate the sensitivity of cells to TRAIL, by controlling the ratio of TRAIL-decoy to -death receptors.

Apoptosis↗
PubMed2001

Antiproliferative and antiapoptotic effects of crel may occur within the same cells via the up-regulation of manganese superoxide dismutase.

Rel/nuclear factor kappaB transcription factors were shown to have either pro- or antiapoptotic as well as pro- or antiproliferative functions, and it is often assumed that the outcome of their activation depends on the cell type or cellular context. Inconsistent with this assumption, we show here that cRel is able in one cell type to inhibit proliferation, protect against apoptosis induced by tumor necrosis factor alpha (TNF-alpha) + cycloheximide (CHX), and increase the basal rate of apoptosis. Both the effects of proliferation inhibition and protection against TNF-alpha + CHX-induced apoptosis are massive and occur in the same cells. Using reverse transcription-PCR, Western blot and immunofluorescence, and transactivation assays, we found that the manganese superoxide dismutase (MnSOD), an enzyme that converts O2*- in H2O2, is up-regulated by cRel through a kappaB site in intron 2. Inhibition of MnSOD induction by antisense oligonucleotides and overexpression of MnSOD respectively reverts and mimics both the antiproliferative and antiapoptotic effects of cRel, suggesting that they both occur via the induction of this gene. On one hand, MnSOD could improve the efficiency of cRel-overexpressing cells in eliminating toxic O2*- produced on TNF-alpha treatment, explaining why they escape TNF-alpha-induced apoptosis. On the other hand, cRel-overexpressing cells should accumulate H2O2. We present evidence linking this H2O2 accumulation to the proliferation arrest induced by cRel. Therefore, different effects on proliferation and apoptosis could arise from the induction of MnSOD and thus coexist in cRel-overexpressing cells.

Apoptosis↗
PubMed2001

Relationships between depression and psychotic symptoms of schizophrenia during an acute episode and stable period.

The aim of the present study is to explore the relationship between depression and psychotic symptoms of schizophrenia over the course of illness. Sixty-eight patients meeting DSM-IV criteria for schizophrenia were enrolled, 27 in an acute episode, 41 when stable. Assessments were performed using the Calgary Depression Scale for Schizophrenia (CDSS) for depression and the Positive and Negative Syndrome Scale (PANSS) for psychotic symptoms. When considering patients in an acute episode (52% depressed), the CDSS score was correlated only with the PANSS positive sub-scale score. For patients in the stable period (38% depressed), the CDSS score was correlated with positive as well as negative and general psychopathology sub-scale scores. Hence, the relationship between depression and other symptoms of schizophrenia appear to differ during different stages of illness.

Acute Disease↗
PubMed2001

Refined characterization of corneodesmosin proteolysis during terminal differentiation of human epidermis and its relationship to desquamation.

Corneodesmosin is a putative adhesion glycoprotein located in the extracellular part of the desmosomes in the upper layers of the epidermis. Synthesized by granular keratinocytes as a 52-56-kDa protein, corneodesmosin is progressively proteolysed during corneocyte maturation. This processing is a prerequisite for desquamation. Two glycine- and serine-rich domains of the protein might take on the conformation of adhesive secondary structures similar to glycine loops. Corneodesmosin proteolysis was further characterized. Deglycosylation experiments and reactivity with lectins demonstrated that the corneodesmosin carbohydrate moiety does not prevent the proteolysis. Immunoblotting, immunohistochemistry, and immunoelectron microscopy experiments using affinity-purified anti-peptide antibodies raised to four of the five structural domains of corneodesmosin and a monoclonal antibody against its fifth central domain showed that the first step in corneodesmosin processing is the cleavage of its extremities and probably occurs before its incorporation into desmosomes. Then the glycine loop-related domains are cleaved, first the N-terminal and then part of the C-terminal domain. At the epidermis surface, the multistep proteolytic cleavage leaves intact only the central domain, which was detected on exfoliated corneocytes and probably lacks adhesive properties. Importantly, corneodesmosin was demonstrated to be a preferred substrate of two serine proteases involved in desquamation, the stratum corneum tryptic and chymotryptic enzymes.

Amino Acid Sequence↗
PubMed2001

Selective blocking of voltage-gated K+ channels improves experimental autoimmune encephalomyelitis and inhibits T cell activation.

Kaliotoxin (KTX), a blocker of voltage-gated potassium channels (Kv), is highly selective for Kv1.1 and Kv1.3. First, Kv1.3 is expressed by T lymphocytes. Blockers of Kv1.3 inhibit T lymphocyte activation. Second, Kv1.1 is found in paranodal regions of axons in the central nervous system. Kv blockers improve the impaired neuronal conduction of demyelinated axons in vitro and potentiate the synaptic transmission. Therefore, we investigated the therapeutic properties of KTX via its immunosuppressive and symptomatic neurological effects, using experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. The T line cells used to induce adoptive EAE were myelin basic protein (MBP)-specific, constitutively contained mRNA for Kv1.3. and expressed Kv1.3. These channels were shown to be blocked by KTX. Activation is a crucial step for MBP T cells to become encephalitogenic. The addition of KTX during Ag-T cell activation led to a great reduction in the MBP T cell proliferative response, in the production of IL-2 and TNF, and in Ca(2+) influx. Furthermore, the addition of KTX during T cell activation in vitro led a decreased encephalitogenicity of MBP T cells. Moreover, KTX injected into Lewis rats impaired T cell function such as the delayed-type hypersensitivity. Lastly, the administration of this blocker of neuronal and lymphocyte channels to Lewis rats improved the symptoms of EAE. We conclude that KTX is a potent immunosuppressive agent with beneficial effects on the neurological symptoms of EAE.

Adoptive Transfer↗