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Biomedical subjects

K G Warren

Publications and source records attributed to K G Warren.

At least 37 records · Page 2Linked to original sources
PubMed1992

Purification of primary antibodies of the myelin basic protein antibody cascade from multiple sclerosis patients. Immunoreactivity studies with homologous and heterologous antigens.

Previous research has demonstrated a myelin basic protein (MBP) antibody cascade in cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. The purpose of this study was to determine whether primary antibodies to MBP (anti-MBP) reacted similarly with homologous (human) and heterologous (bovine and porcine) MBP. Myelin basic protein was prepared from central nervous system white matter of humans as well as bovine and porcine species. Immunoglobulin G (IgG) was purified by protein A-Sepharose affinity chromatography from concentrated CSF of MS patients with active or inactive disease or from non-MS controls. Antibodies to MBP were isolated from purified CSF IgG of MS patients with acute relapses by two-step antigen specific (MBP-Sepharose) affinity chromatography. Anti-MBP in the context of whole CSF, in purified CSF-IgG or as purified antibody, reacted identically with homologous and heterologous MBP. Kinetic studies of anti-MBP titers demonstrated that when anti-MBP was reacted in vitro with increasing amounts of homologous or heterologous MBP, the antibody was equally neutralized by either antigen. Neutralization of anti-MBP by homologous and heterologous MBP or their synthetic peptides may also be possible in vivo as a potential therapeutic tool.

Animals↗
PubMed1992

Prevalence of multiple sclerosis in Barrhead County, Alberta, Canada.

A prevalence study of multiple sclerosis (MS) was carried out in the town of Barrhead and surrounding county of Barrhead, in Alberta, Canada. The prevalence rate for clinically probable/definite multiple sclerosis on January 1, 1990 was 196/100,000. The average annual incidence rates for patients living in the area at onset were 1.31/100,000 for 1950-59, 4.97/100,000 for 1960-69, 3.77/100,000 for 1970-79, and 4.22/100,000 for 1980-89. Fifty percent of the patients were relapsing-remitting. Sixty percent were still walking without assistance. The female-to-male ratio was 1:1. Mean current age, age at onset and duration of illness were 49, 27 and 22 years respectively. The majority of patients (40%) experienced multiple symptom onset. Fifty percent were of single ethnic origin (either British or German); the rest were predominantly North European combinations. Forty percent of patients reported another MS relative. MS had affected the work status of 60% of the patients, 15% of whom were confined to an extended care centre.

Adult↗
PubMed1991

Emotional stress and coping in multiple sclerosis (MS) exacerbations.

Ninety-five pairs of MS patients in exacerbation and remission were compared on emotional stress in the previous three months. Patients in exacerbation scored higher on emotional disturbance and intensity of stressful events than patients in remission, but lower on frequency of compensating uplifts. There was also a tendency for more patients in exacerbation than remission to favour emotion-focused coping techniques over problem-solving or social support. Whether patients building to an exacerbation over-react to various events or unresolved emotional stress precipitates exacerbations, MS patients might benefit from counselling in stress reduction techniques.

Adaptation, Psychological↗
PubMed1991

Purification of autoantibodies to myelin basic protein by antigen specific affinity chromatography from cerebrospinal fluid IgG of multiple sclerosis patients. Immunoreactivity studies with human myelin basic protein.

Immunoglobulin G (IgG) was purified by single-step protein A-Sepharose (Pharmacia) affinity chromatography from the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients and controls. Autoantibodies to myelin basic protein (anti-MBP) were isolated from the purified IgG fraction by two-step antigen specific affinity chromatography. Anti-MBP in the context of whole CSF or in purified form reacts equally to MBP prepared from non-MS or MS brain tissue. Kinetic studies of anti-MBP titers demonstrate that when anti-MBP is reacted with increasing amounts of non-MS or MS MBP, the autoantibody is immunoabsorbed by either antigen in vitro. Immunoabsorption of anti-MBP by MBP or its synthetic peptides may also be possible in vivo as a potential therapeutic tool.

Autoantibodies↗
PubMed1991

Risk factors by onset age in multiple sclerosis.

Some investigators have suggested that there are different forms of multiple sclerosis (MS) based on onset age, and that each has a different etiology. 173 Canadian MS patients were matched to controls on age, gender, race and risk zone prior to age 15. Data were collected on: age at onset, gender, initial symptom, disability level, residence history and family background. Three onset age subgroups (early, intermediate and late) were derived. Matched-pair logistic regression analysis indicated that rural residence, use of well water and an MS family history distinguished between patients and controls overall, but showed no significant interaction with onset age. A family history of diabetes distinguished between patients and controls with evidence of age interaction, in that this risk factor decreased in importance as onset age increased.

Adolescent↗
PubMed1990

A myelin basic protein antibody cascade in purified IgG from cerebrospinal fluid of multiple sclerosis patients.

Immunoglobulin G (IgG) was purified by affinity chromatography from the CSF of multiple sclerosis (MS) patients and controls. In MS patients, the IgG fraction contains anti-myelin basic protein (anti-MBP), anti-MBP neutralizing antibody and an antibody which inhibits neutralization of anti-MBP. Anti-MBP was detected in patients with acute relapses, anti-MBP neutralizing antibody was present in patients in clinical remission and the inhibiting antibody was detected in patients with chronically progressing MS. A myelin basic protein antibody cascade could be involved in the mechanism of MS.

Autoantibodies↗
PubMed1989

Cerebrospinal fluid autoantibodies to myelin basic protein in multiple sclerosis patients. Detection during first exacerbations and kinetics of acute relapses and subsequent convalescent phases.

In order to determine if free (F) and bound (B) levels of autoantibodies to myelin basic protein (anti-MBP) are present from the onset of multiple sclerosis (MS), 201 patients referred to our clinic were clinically divided into a group diagnosed as having an initial MS relapse and a group of non-MS controls. Ninety-four of 106 patients thought to have an initial MS relapse had increased CSF anti-MBP, while only 14 of 95 controls had elevated antibody levels; 9 of these 14 positive controls were subsequently shown to have MS by magnetic resonance imaging and/or clinical follow-up. CSF anti-MBP was more frequently abnormal than 3 estimates of intrathecal IgG synthesis in the group with suspected MS. Kinetics of F and B CSF anti-MBP were determined in a group of 29 patients with clinically definite MS during an acute relapse and 97.4 +/- 54 days later in the subsequent convalescent phase when in clinical remission. F and B anti-MBP levels were highly dependent on the timing of the CSF sampling; generally, as patients entered into clinical remission F anti-MBP declined, B antibody levels rose and F/B anti-MBP ratios initially above unity gradually declined towards zero. These data suggest that anti-MBP may be involved in the mechanism of MS.

Acute Disease↗
PubMed1988

Cerebrospinal fluid antibodies to myelin basic protein in acute idiopathic optic neuritis.

Free and bound levels of anti-myelin basic protein (anti-MBP) antibodies were measured by radioimmunoassay in the cerebrospinal fluid of 20 patients with acute idiopathic optic neuritis, 133 patients with multiple sclerosis (MS) divided into three clinical subgroups, and 76 normal control subjects. Patients with idiopathic optic neuritis had elevated levels of anti-MBP predominantly in free form, resulting in an elevated (above unity) free/bound anti-MBP ratio similar to that of MS patients with acute relapses. These data suggest that acute idiopathic optic neuritis, like active MS, is associated with anti-MBP.

Autoantibodies↗
PubMed1988

Neutralization of anti-myelin basic protein by cerebrospinal fluid of multiple sclerosis patients in clinical remission.

Autoantibodies to myelin basic protein (anti-MBP) can be detected in the cerebrospinal fluid (CSF) of MS patients using a solid phase radioimmunoassay. Acute relapses of MS are characterized by an elevated, above unity, free (F) to bound (B) anti-MBP ratio; while in contrast, patients with chronic progressing disease have a low, below unity, free to bound ratio of anti-MBP. As patients with acute relapses enter into remission, the F/B anti-MBP ratio gradually decreases and eventually the level of these autoantibodies becomes undetectable. Neutralization of free anti-MBP was observed in intra- and interpatient experiments in which CSF from MS patients in remission was reacted with CSF of patients with acute relapses. Inhibition of anti-MBP neutralization was produced by CSF from MS patients with chronic progressing disease.

Autoantibodies↗
PubMed1987

A correlation between cerebrospinal fluid myelin basic protein and anti-myelin basic protein in multiple sclerosis patients.

Free and bound levels of myelin basic protein (MBP) and anti-myelin basic protein (anti-MBP) antibodies were measured by radioimmunoassay in the cerebrospinal fluid of patients with multiple sclerosis who were experiencing acute exacerbations or progressing disease. In a cross-sectional study, free levels of MBP correlated with those of free anti-MBP, and bound MBP levels correlated with those of bound anti-MBP in both groups of patients with active disease. However, acute exacerbations of multiple sclerosis were characterized by higher free MBP and anti-MBP levels with lower levels of bound fractions. Conversely, patients with progressing disease had higher titers of bound than free fractions. Longitudinal studies of individual patients confirmed the association of higher titers of free anti-MBP with acute exacerbations and higher levels of bound anti-MBP with chronic progressing disease.

Adult↗
PubMed1986

Diagnostic value of cerebrospinal fluid anti-myelin basic protein in patients with multiple sclerosis.

Prevalence and titer of total, free, and bound cerebrospinal fluid anti-myelin basic protein (MBP) antibodies as well as free/bound ratios were determined in four groups of patients with multiple sclerosis (MS) and three groups of controls. All patients with clinically active MS have elevated levels of total anti-MBP, which may be present in either free or bound form. Patients whose disease is in remission have undetectable anti-MBP levels, and some patients with clinically stable disease with residual disability may have detectable antibody titers. Chronically progressive MS is usually associated with high levels of antibody in the bound rather than the free form, resulting in a low or normal free/bound ratio. In contrast, MS exacerbations are characterized by relatively high levels of free anti-MBP in the cerebrospinal fluid, resulting in a high free/bound antibody ratio. Bound anti-MBP was also detected in elevated levels in 1 patient with subacute sclerosing panencephalitis and 2 of 8 patients with postinfectious encephalomyelitis. Although elevated levels of cerebrospinal fluid anti-MBP are not specific for MS, they are strongly associated with disease activity and may be involved in the pathogenesis of demyelination in patients with MS.

Autoantibodies↗
PubMed1986

Intrathecal synthesis of autoantibodies to myelin basic protein in multiple sclerosis.

A solid phase radioimmunoassay was used to detect anti-myelin basic protein (MBP) antibodies in the CSF and serum of multiple sclerosis (MS) patients and controls. CSF and serum samples were assayed prior to acid hydrolysis in order to detect free anti-MBP as well as after acid hydrolysis to measure the total (free and bound) amount of antibody. An anti-MBP index controlling for serum levels as well as the degree of breakdown of the blood brain barrier was used to estimate intrathecal synthesis of anti-MBP. MS patients with acute exacerbations or chronically progressive disease have significantly elevated levels of both free and total CSF anti-MBP. The anti-MBP index is also significantly increased in MS patients with both forms of active disease. Anti-MBP antibodies are intrathecally produced in MS patients with active disease.

Autoantibodies↗
PubMed1986

Effect of methylprednisolone on CSF IgG parameters, myelin basic protein and anti-myelin basic protein in multiple sclerosis exacerbations.

Clinical exacerbations of multiple sclerosis (MS) are characterized by elevated levels of cerebrospinal fluid (CSF) myelin basic protein (MBP). The purposes of this study were to determine whether anti-MBP antibodies are present in increased titer in CSF of MS patients with exacerbations, and whether they can be suppressed by the administration of immunosuppressive dosages of methylprednisolone (MP). A solid phase radio-immunoassay (RIA) was used to detect free and total anti-MBP antibodies before and after acid hydrolysis of CSF. In MS exacerbations, the majority of elevated anti-MBP is in the free form. With the exception of subacute sclerosing panencephalitis (SSPE) and some cases of post infectious encephalomyelitis, anti-MBP antibodies are not present in either MS patients in remission or in non-MS controls. Anti-MBP levels remained elevated over a 10 day period when patients are managed by bed rest only or when treated with intravenous (IV) ACTH. IV administration of MP in "high" (160 mg/day) or "mega" (2 g/day) dosages produces a highly significant reduction of both MBP (p less than 0.01) and anti-MBP (p less than 0.001) levels. Total intrathecal IgG synthesis is also significantly suppressed by IV-MP but not by ACTH.

Adrenocorticotropic Hormone↗
PubMed1986

Cerebral evoked potentials in multiple sclerosis.

Multimodal evoked potentials were analyzed from 58 possible, 62 probable and 100 definite (total 220) multiple sclerosis (MS) patients. Visual evoked potentials (VEP) were most frequently abnormal yielding 39%, 69%, 84% in the three diagnostic groups respectively. Median nerve sensory evoked potentials (SEP) yielded abnormalities in 26%, 65%, 79% respectively. Brainstem auditory evoked responses (BAER) were abnormal in 17%, 39%, 66% respectively. We measured the combined amplitude (CA) of waves III, IV, V in the BAER of these patients as an objective measure of amplitude asymmetry. The CA was considered abnormal if it was 1SD below the lowest CA value in the control group. The CA was abnormal in 9.2% of BAER with normal central conduction time. The BAER diagnostic yield in MS patients increased 11% by using CA analysis.

Adult↗
PubMed1986

The role of myo-inositol in multiple sclerosis.

Myo-inositol was given orally to nine multiple sclerosis patients and nine healthy control subjects. Pattern reversal evoked potential testing was used to assess its effect. The principal positive wave increased in amplitude, duration and area in a dose-dependent manner in the multiple sclerosis group compared with controls. Cerebrospinal fluid concentrations of myo-inositol in multiple sclerosis and controls were similar. The significance of these observations is discussed in relation to recent discoveries in inositol phospholipid function.

Adult↗
PubMed1985

The relationship between levels of cerebrospinal fluid myelin basic protein and IgG measurements in patients with multiple sclerosis.

Cerebrospinal fluid (CSF) myelin basic protein (MBP) levels, CSF/serum albumin ratio (CSF/S alb), and 4 CSF IgG measurements--absolute CSF IgG level (CSF IgG), CSF IgG/albumin ratio, the Tibbling-Link IgG index, and the daily rate of intrathecal IgG synthesis--were measured in patients with multiple sclerosis and control subjects. In four clinical subgroups of patients, including 22 with polysymptomatic exacerbations, 22 with monosymptomatic exacerbations, 41 with chronic progressive disease, and 21 in remission, there was no correlation between CSF MBP and either CSF/S alb or the CSF IgG measurements. This finding was also observed in longitudinal studies of patients. CSF MBP levels, as determined in a cross-sectional study of 325 patients with multiple sclerosis, are an excellent indicator of disease activity.

Cross-Sectional Studies↗
PubMed1985

A double-blind controlled pilot study of plasma exchange versus sham apheresis in chronic progressive multiple sclerosis.

Twenty patients with chronically progressive multiple sclerosis (MS) were randomised in a double-blind controlled study to assess the efficacy of plasma exchange therapy. All patients were immunosuppressed with prednisone and azathioprine and underwent either plasma exchange or sham apheresis. The 10 patients in each group were similar in age, sex, duration of disease and degree of disability. Clinical and laboratory responses were assessed immediately following the course of exchange or sham therapy, and 3 to 6 months later, by individuals blinded to the type of therapy administered. Although modest improvement was suggested on clinical examination in 7 of 10 patients exchanged and 3 of the 10 sham treated group, this was transient and was not accompanied by any change in disability status scores. No differences in abnormal laboratory investigations were demonstrable between the two patient groups following therapy. We conclude that plasma exchange therapy using this protocol is unlikely to be of clinical benefit as an adjunct in the management of chronically progressive M.S.

Adult↗