MS Abstracts 04c-2g1

  1. Genetic susceptibility to Multiple Sclerosis: detection of polymorphic nucleotides and an intron in the 3' untranslated region of the Major Histocompatibility Complex Class II transactivator gene
    Hum Immunol 2001 Apr;62(4):371-377

  2. Induction of RANTES Chemokine expression in human Astrocytic cells is dependent upon activation of NF-kappaB transcription factor
    Int J Mol Med 2001 May;7(5):527-533

  3. Efficacy of an energy conservation course for persons with Multiple Sclerosis
    Arch Phys Med Rehabil 2001 Apr;82(4):449-456

  4. Multiple Sclerosis: clinical and laboratorial correlation
    Arq Neuropsiquiatr 2001 Mar;59(1):89-91

  5. Determination of soluble ICAM-1 and TNFalphaR in the CerebroSpinal Fluid and Serum levels in a population of Brazilian patients with Relapsing/Remitting Multiple Sclerosis
    Arq Neuropsiquiatr 2001 Mar;59(1):18-22

  6. Regional Brain atrophy is associated with physical disability in Multiple Sclerosis: semiquantitative magnetic resonance imaging and relationship to clinical findings
    J NeuroImaging 2001 Apr;11(2):129-36

  7. Clinical features of Myelitis in patients with atopic symptoms
    No To Shinkei 2001 Mar;53(3):241-5

  8. Acquired pendular Nystagmus associated with the lesion of Tegmentum Mesencephali in a patient with probable Multiple Sclerosis
    Rinsho Shinkeigaku 2000 Oct;40(10):1012-7

  9. Two subsets of Dendritic Cells are present in human CerebroSpinal Fluid
    Brain 2001 Mar;124(Pt 3):480-92


Genetic Susceptibility To Multiple Sclerosis: Detection Of Polymorphic Nucleotides And An Intron In The 3' Untranslated Region Of The Major Histocompatibility Complex Class II Transactivator Gene

Rasmussen HB, Kelly MA, Clausen J
Hum Immunol 2001 Apr;62(4):371-377
Roskilde University, Dept of Life Sciences and Chemistry (H.B.R., J.C.), Roskilde, Denmark
PMID# 11295470

The master player in the transcriptional regulation of Major Histocompatibility (MHC) Class II Genes is a factor known as the MHC Class II transactivator (CIITA).

In this study we searched for polymorphisms in the 5' and 3' ends of the human CIITA Gene to assess whether or not there is an association between alleles of this Gene and Multiple Sclerosis (MS).

Polymorphism screening based upon detection of single strand conformational changes (SSCP analysis) followed by sequencing revealed six single nucleotide variations.

Namely one in the promoter utilized by B-Cells and five in the 3' untranslated region (UTR) of the gene.

Determination of alleles at these polymorphic sites was facilitated by treatment of amplified DNA fragments with a panel of appropriate restriction enzymes.

The distributions of CIITA alleles did not differ between MS patients and control subjects (p > 0.05).

After subgrouping of the patients into Relapsing/Remitting MS and Primary/Progressive MS, we found that the distribution of promoter alleles in the latter of these two patient groups differed from that of healthy control subjects (p = 0.04).

There was no evidence of linkage disequilibrium between the polymorphic site in the B-Cell specific promoter and those in the 3' UTR.

Based upon the polymorphic sites in the 3' UTR we identified two common CIITA haplotypes which were present at similar frequencies in patients and control subjects.

Assuming that susceptibility to MS depends upon type of MHC Class II molecule, as well as the amounts of expressed Class II molecules, we tested for interaction between DR15 status and CIITA alleles.

No such interaction was detected. Unexpectedly, we identified an Intron in the 3' UTR of the human as well as the mouse CIITA gene.

Due to the proximity of these Introns to the termination Codon in both the human and mouse CIITA gene, the mechanism for regulation of transcript stability known as nonsense-mediated decay is probably not involved in the PostTranscriptional control of the expression of these Genes.

So far, the function and significance of the Intron in the human and mouse CIITA Genes are unknown.


Induction Of RANTES Chemokine Expression In Human Astrocytic Cells Is Dependent Upon Activation Of NF-kappaB Transcription Factor

Li QQ, Bever CT, Burt DR, Judge SI, Trisler GD
Int J Mol Med 2001 May;7(5):527-533
Univ of Maryland, School of Medicine, Depts of Neurology and Pharmacology and Experimental Therapeutics, Baltimore, MD 21201, USA
PMID# 11295116

RANTES is a C-C (beta)-family Chemokine that is implicated in the migration of peripheral blood Leucocytes to Brain lesions in Multiple Sclerosis (MS), an Inflammatory DeMyelinating Disease of the Central Nervous System (CNS).

Glial Cells are active participants in the inflammatory response in the CNS, and they have been shown to respond to and produce a number of Cytokines and Chemokines in vivo and in vitro.

Recently, we have shown inducibility of RANTES Gene expression by TNF-alpha in human Astrocytic Cells. Therefore, the goal of the current study was to investigate the transcription activating factor involved in the process.

We found that the induction of RANTES mRNA and protein by TNF-alpha in human Astrocytic Cells is associated with increased NF-kappaB DNA-binding activity.

p65 and p50 were determined to be the components of the activated NF-kappaB transcription factor complex by supershift assay.

In addition, the blockade of NF-kappaB activation by three known NF-kappaB inhibitors markedly reduced the TNF-alpha-induced RANTES expression at the mRNA and protein levels.

Furthermore, the reduction in NF-kappaB binding activity to the promoter of the human RANTES Gene caused by the NF-kappaB inhibitors parallels a decrease in RANTES expression in these cells.

Our data suggest that NF-kappaB may mediate the induction of RANTES Gene expression, in human Glial Cells, through its cognate cis-acting element.


Efficacy Of An Energy Conservation Course For Persons With Multiple Sclerosis

Mathiowetz V, Matuska KM, Murphy ME
Arch Phys Med Rehabil 2001 Apr;82(4):449-456
Univ of Minnesota, Dept of Physical Medicine & Rehabilitation, Minneapolis;
College of St. Catherine, Dept of Occupational Therapy; and
Services to Persons with Mobility Impairment, Accessible Spaces, St. Paul, MN
PMID# 11295003

To evaluate the efficacy of an energy conservation course on fatigue impact, self-efficacy, and quality of life (QOL) for persons with Multiple Sclerosis (MS).

Design & Setting
Repeated measures with control and experimental interventions conducted during a 19-week study, in a community based treatment center.

Participants & Intervention
A convenience sample of 54 individuals from 79 community dwelling volunteers with fatigue secondary to MS, during a 6-session, 2-hr/wk energy conservation course, taught by occupational therapists for groups of 8 to 10 participants.

Main Outcome Measures
Fatigue Impact Scale (self-report measure of fatigue impact on cognitive, physical, social functions), Self-Efficacy Gauge (self-report measure of confidence in ability to perform specific behaviors), and Medical Outcomes Study Short-Form Health Survey (QOL measure).

Participants reported, as predicted, significantly less fatigue impact, increased self-efficacy, and improved QOL (ie, 3 of 4 subscales expected to improve).

There were no significant differences, as predicted, in any of the dependent variables after the control (ie, support group) and no intervention periods.

Results provide strong evidence for the efficacy of this energy conservation course for persons with MS.

Copyright 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation


Multiple Sclerosis: Clinical And Laboratorial Correlation

Puccioni-Sohler M, Lavrado FP, Bastos RR, Brandao CO, Papaiz-Alvarenga R
Arq Neuropsiquiatr 2001 Mar;59(1):89-91
Projeto Atlantico-Sul, Laboratorio Especializado de LCR (Neurolife), Rio de Janeiro, Brasil
PMID# 11299438

The clinical and demographic characteristics of 86 Brazilian patients with Clinically Definite Multiple Sclerosis (MS) were compared to the CerebroSpinal Fluid (CSF) findings.

The disease course was Relapsing/Remitting in 71% and Chronic/Progressive in 29% of the cases.

The IgG index was increased in 76% in the Chronic/Progressive status and 46% and 49% during the bout and remission, respectively (p < 0.005).

Only 36% of the MS patients using CorticoSteroids had increased IgG index, in comparison to the 64% of the patients without ImmunoSupressive treatment.

OligoClonal IgG Bands were detected in the CSF of 77% and 88% of the MS CorticoSteroids users and non-users, respectively.

The quantitative study of Intrathecal synthesis of IgG contributes to demonstrate the Immunological differences between the two forms of MS, the Relapsing/Remitting and the Chronic/Progressive.

The treatment with CorticoSteroids decreases quantitatively the Intrathecal synthesis of IgG but not the presence of OligoClonal Bands.


Determination Of Soluble ICAM-1 And TNF-alphaR In The CerebroSpinal Fluid And Serum Levels In A Population Of Brazilian Patients With Relapsing/Remitting Multiple Sclerosis

Alves-Leon SV, Batista E, Papais-Alvarenga R, Quirico-Santos T
Arq Neuropsiquiatr 2001 Mar;59(1):18-22
Rio de Janeiro University, Dept of Specialized Medicine, Rio de Janeiro, Brazil
PMID# 11299425

Cytokines and Adhesion Molecules have been implicated in the PathoGenesis of Multiple Sclerosis (MS), a chronic inflammatory disease of the Central Nervous System.

In this study we analyzed Intrathecal (CSF) and Serum levels of Soluble InterCellular Adhesion Molecule (ICAM-1) and TNF-alphaR (60kD) from 20 patients with Clinically Definite MS during acute relapse or stable disease.

Comparing to control groups of healthy individuals and patients with InterVertebral herniated disc, MS patients showed increased levels (p< 0.001) of sICAM-1 and TNF-alphaR in both Serum and CSF samples.

Regardless stage of disease there was no significant difference in the levels of sICAM-1 during acute relapse (657+/-124.9 ng/ml) or remission (627+/-36.2 ng/ml).

A steady increase of TNF-alphaR (60kD) in both Serum and CSF, indicate the existence of a continuous inflammatory process within the Brain tissue of MS patients despite absence of clinical signs of disease activity.


Regional Brain Atrophy Is Associated With Physical Disability In Multiple Sclerosis: Semiquantitative Magnetic Resonance Imaging And Relationship To Clinical Findings

Bakshi R, Benedict RH, Bermel RA, Jacobs L
J NeuroImaging 2001 Apr;11(2):129-36
State Univ of New York at Buffalo, Imaging Services, Kaleida Health, Buffalo, NY, USA
PMID# 11296581; UI# 21191295

Brain Atrophy may occur early in the course of Multiple Sclerosis (MS) and may be associated with disability.

Brain Magnetic Resonance Imaging (MRI) of 114 MS patients (group A) were analyzed for Regional Atrophy (vs age-/gender-matched controls) and T1 and T2 lesions using 4-point rating systems.

Thirty-five separate patients (group B) were analyzed for Cortical Atrophy (ordinal scale), Third Ventricular width, and total T2 HyperIntense Lesion Volume (computer assisted).

In group A, regression modeling indicated that Inferior Frontal Atrophy (P = .0003) and T2 lesions in the Pons (P = .02) predicted physical disability (Expanded Disability Status Scale [EDSS] score).

Secondary/Progressive (S/P) versus Relapsing patients were predicted by Inferior Parietal (P = .002), Superior Parietal (P = .006), Temporal (P = .008), Inferior Frontal (P = .01), Superior Frontal (P = .01), Cerebellum (P = .01), Occipital (P = .01), and MidBrain (P = .02) Atrophy.

S/P patients were also predicted by total Atrophy (P = .01) and Third Ventricular enlargement (P = .03) but not T1 or T2 lesions.

Mean kappa coefficients of ordinal ratings were 0.9 (intraobserver) and 0.8 (interobserver). Ordinal ratings correlated well with quantitative assessments.

The authors conclude that Brain Atrophy is closely associated with physical disability and clinical course in MS patients and can be appreciated using a semiquantitative MRI regional rating system.


Clinical Features Of Myelitis In Patients With Atopic Symptoms

Furuya T, Miwa H, Hatano T, Miyashita N, Tanaka S, Mizuno Y
No To Shinkei 2001 Mar;53(3):241-5
Juntendo UnivUrayasu Hospital, Dept of Neurology, 2-1-1 Tomioka, Urayasu-City, Chiba 279-0021, Japan
PMID# 11296397; UI# 21191110

It is rare to see Atopic symptoms in patients with Multiple Sclerosis (MS). However, it has been reported that in Atopic patients, particularly in patients with Atopic Dermatitis, a Benign Myelitis occasionally occurs.

In the present report, three atopic patients with Myelitis were studied clinically and NeuroraDiologically.

All the patients were adult men (Case 1, 2, and 3 were 41-year-old, 31-year-old, and 34-year-old, respectively), and all of them had Bronchial Asthma without histories of Atopic Dermatitis.

Their manifestations were not severe and were only Numbness of upper and/or lower extremities.

There was no Motor Weakness, Ataxia, or Urinary Incontinence.

MRI studies revealed a T2-high intensity lesion in the high Cervical Spinal Cord in the two patients (Case 2 and 3) and a T2-high intensity lesion in the Lumber Spinal Cord in the remaining patient(Case 1).

Their clinical courses were essentially all Benign and well responsive to Steroid therapy. Although Myelitis of these patients may be a first attack of MS, their findings appear to support a recently emerging concept of the Atopic Myelitis.


Acquired Pendular Nystagmus Associated With The Lesion Of Tegmentum Mesencephali In A Patient With Probable Multiple Sclerosis

Inobe J, Arakawa T, Mori T, Kumamoto T, Tsuda T
Rinsho Shinkeigaku 2000 Oct;40(10):1012-7
Oita Medical University, Third Dept of Internal Medicine, Oita, Japan
PMID# 11296365; UI# 21191082

A 42-year old woman was admitted to our hospital because of sudden onset of dizziness and Oscillopsia.

Neurologic Examination revealed horizontal, binocular Pendular Nystagmus, which increase their amplitude on left lateral gaze.

She also showed that mild Right Blephaloptosis, right facial spasms, increased tendon reflexes and positive pathological reflexes of four limbs and mild Chorea-like movement of both feet.

MRI showed an abnormal high intensity area on a T2weighted and Proton Density images located at the right Tegmentum Mesencephali.

She was diagnosed as Clinically Probable Multiple Sclerosis according to the Poser's Criteria.

The Nystagmus was suppressed by Clonazepam and Diazepam.

To our knowledge, it is a first report of acquired Pendular Nystagmus associated with the lesion of Tegmentum Mesencephali.

We speculate that the involvement of the tract of paramedian Pontine Reticular Formation causes the Nystagmus and the dysfunction of GABAnergic Neurons might play an important role of the Nystagmus.


Two Subsets Of Dendritic Cells Are Present In Human CerebroSpinal Fluid

Pashenkov M, Huang YM, Kostulas V, Haglund M, Soderstrom M, Link H
Brain 2001 Mar;124(Pt 3):480-92
Karolinska Institutet, Huddinge Univ Hospital, Division of Neurology, R54, SE-14186 Huddinge, Sweden
PMID# 11222448; UI# 21124581

Little is known about the presence of Dendritic Cells in the human CNS. To investigate the occurrence of Dendritic Cells in the CSF.

Paired blood/CSF samples from patients with Multiple Sclerosis, acute Optic Neuritis, Lyme NeuroBorreliosis, other Inflammatory Neurological Diseases and Non-Inflammatory Neurological Diseases were examined using flow cytometry.

Almost all CSF samples contained Myeloid (lin-CD11c+HLA-DR++CD123(dim)) and plasmacytoid (lin-CD11c-HLA-DR+CD123(high)) Dendritic Cells.

In Non-Inflammatory Neurological Diseases, Dendritic Cells of either subset only constituted up to 1% of CSF MonoNuclear Cells. Myeloid CSF Dendritic Cells were elevated in Optic Neuritis, NeuroBorreliosis and other Inflammatory Neurological Disorders.

While plasmacytoid Dendritic Cells were elevated in all NeuroInflammatory conditions studied, with especially high numbers in NeuroBorreliosis. Numbers of CSF Dendritic Cells correlated with the common parameters of CNS inflammation.

The myeloid Dendritic Cells in CSF expressed higher levels of HLA-DR, CD86, CD80 and CD40 than those in blood, whereas expression of these molecules by plasmacytoid Dendritic Cells was equal in blood and CSF.

Both CSF and blood Dendritic Cells expressed the Chemokine receptor CCR5. This is the first demonstration that Dendritic Cells are present in human CSF and that plasmacytoid Dendritic Cells are present in a Non-Lymphoid compartment.

Myeloid and plasmacytoid Dendritic Cells in CSF may contribute to orchestration of the local Immune Responses.

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