Beta7 Integrins Contribute To DeMyelinating Disease Of The Central Nervous System
Kanwar JR, Harrison JE, Wang D, Leung E, Mueller W, Wagner N, Krissansen GW
J NeuroImmunol 2000 Mar 1;103(2):146-52
Univ of Auckland, School of Medicine and Health Science, Dept of Molecular Medicine, Auckland, New Zealand
PMID# 10696909; UI# 20159982
A role for 4 Integrins in different forms of the Multiple Sclerosis-like disease Experimental AutoImmune EncephaloMyelitis (EAE) has been demonstrated.
But the individual contributions of 4ß1, 4ß7, and the related Eß7 Integrin have not been determined.
The P7 Integrins 4ß7 and Eß7 play a central role in Chronic Inflammation.
Mediating the trafficking, entry, and/or adhesion of Lymphocytes in the inflamed Pancreas and Gut, and their Ligands MAdCAM-1, VCAM-1 and E-Cadherin are expressed on Brain Endothelial Cells and/or on MicroVessels in the inflamed Central Nervous System.
Here, we show that an AntiBody directed against the beta7 subunit greatly attenuates a Non-Remitting form of EAE, induced by adoptive transfer of Myelin Oligodendrocyte Peptide (MOG35-55)-stimulated T-Cells.
Combinational treatment with both Anti-ß7 and A4 Integrin subunit AntiBodies led to more rapid and complete remission than that obtained with anti-A4 AntiBody alone, potentially implicating a role for Eß7 in disease progression.
Remission correlated with the down-regulation of the Vascular Addressins VCAM-1. MAdCAM-1, and ICAM-1 on Cerebral blood vessels.
Attenuated forms of disease were induced by adoptive transfer of either wild-type EncephalitoGenic T-Cells to beta7-deficient Gene knockout mice, or of beta7-/-EncephalitoGenic T-Cells to wild-type recipients.
The former finding indicates that beta7 + ve recruited cells contribute to disease progression.
Thus 4ß1, 4ß7, and Eß7 Integrins may all play a contributory role in the progression of Chronic forms of DeMyelinating Disease, and together with their Ligands could represent potential targets for improved treatment of some forms of Multiple Sclerosis.
Drop In Relapse Rate Of MS By Combination Therapy Of Three Different PhosphoDiesterase Inhibitors
Suzumura A, Nakamuro T, Tamaru T, Takayanagi T
Mult Scler 2000 Feb;6(1):56-8
Nara Medical University, Dept of Neurology, 840 Shijo-cho, Kashihara, Nara 634-0813, Japan
PMID# 10694847; UI# 20161030
PhosphoDiEsterase Inhibitors (PDEIs), when used in combination, synergistically suppress TNF- production by various cells and also suppress experimental DeMyelination at very low concentrations.
We conducted a pilot study to determine whether the combination of three PDEIs suppresses the relapse of MS at the usual therapeutic doses.
Of the 12 Relapsing/Remitting MS, the mean relapse rate/year dropped remarkably (from 3.08+/-3.32 to 0.92+/-1.86) after PDEI treatment. Seven out of 12 (58.3%) were relapse-free in the follow up period (499+/-142 days).
The combination of three PDEIs can be safe and useful strategy for the future treatment of MS.
Multiple Sclerosis (2000) 6 56 - 58
Cortical Deficits In Multiple Sclerosis On The Basis Of SubCortical Lesions
Jeffery DR, Absher J, Pfeiffer FE, Jackson H
Mult Scler 2000 Feb;6(1):50-5
Wake Forest Univ, School of Medicine, Dept of Neurology, The Sticht Center, Medical Center Boulevard, Winston-Salem, North Carolina, NC 27157, USA
PMID# 10694846; UI# 20161029
Patients suffering from Multiple Sclerosis have a high frequency of Cognitive Deficits usually attributable to DeMyelination and Axonal loss in the SubCortical White Matter.
Neurologic abnormalities referable to Cortical function are uncommon but have been described.
The present study describes three patients with Clinically Definite MS with deficits in Cognitive function referable to Cortical location.
Two of the patients underwent Positron Emission Tomography and showed profound Cortical hypometabolism adjacent to SubCortical White Matter lesions seen on MRI.
This paper points out that Neurologic deficits referable to Cortical sites may be caused by SubCortical White Matter lesions and that Cognitive Dysfunction in patients with MS may progress rapidly in the absence of motoria deficits or other evidence of clinical deterioration.
Multiple Sclerosis (2000) 6 50 - 55
Contrast-Enhanced MR activity In Relapsing/Remitting Multiple Sclerosis
A short term natural history study
Bagnato F, Tancredi A, Richert N, Gasperini C, Bastianello S, Bash C, McFarland H, Pozzilli C, Frank JA
Mult Scler 2000 Feb;6(1):43-9
Univ of Rome La Sapienza, Dept of Neurological Science, Italy
PMID# 10694845; UI# 20161028
Magnetic Resonance Imaging (MRI) has been used to study the history of Multiple Sclerosis (MS).
We analyze the relationship between MRI activity in the first scan compared to the subsequent five scans, and we evaluate whether a shorter observation period of 3 months may predict the subsequent 3 months.
Monthly enhanced MRI was performed in 103 Relapsing/Remitting (RR) MS patients for 6 months.
Thirty-five per cent of patients had an inactive scan on the initial examination. More than 80% of them developed MRI activity during the following 5 months.
Eighteen per cent of patients had three consecutive inactive scans; 65% of them had at least one active scan on the subsequent 3 monthly MRI's. The relationship between the first scan and all subsequent scans demonstrates a clear weakening over time.
Eighty-two per cent of patients had at least one active scan during the initial 3 consecutive months, the chance of becoming inactive decreased from 23% to 0% over the subsequent 3 months, according with the mean number of enhancing lesions during the first 3 months.
These results suggest that neither a single scan nor a short baseline of 3 months may adequately describe the natural history of disease in an individual R/R-MS patient.
Multiple Sclerosis (2000) 6 43 - 49