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Biomedical subjects

D H Mattson

Publications and source records attributed to D H Mattson.

29 records · Page 2Linked to original sources
PubMed1982

Oligoclonal IgG in rabbits with experimental allergic encephalomyelitis: non-reactivity of the bands with sensitizing neural antigens.

Oligoclonal IgG bands have recently been reported to occur in cerebrospinal fluid (CSF) and serum of rabbits with experimental allergic encephalomyelitis (EAE). To examine the specificity of these bands, a) individual bands eluted from rabbit CSF and sera were tested by radioimmunoassay (RIA) for anti-MBP activity and b) rabbit sera were absorbed with the neuroantigens used for sensitization. RIA of eluates from sequential agar gel slices of the entire IgG region of serum or CSF from MBP sensitized rabbits showed that anti-MBP activity occurred throughout the IgG region and did not localize to specific band-containing fractions. Furthermore, there was no change in banding patterns following absorption of EAE rabbit sera with washed brain homogenates, soluble MBP or MBP conjugated to Sepharose beads. Therefore, our results indicate that the oligoclonal IgG response in EAE is not preferentially directed against the sensitizing neuroantigen, and we raise the possibility of nonspecific B cell activation.

Animals↗
PubMed1982

Light chain composition of CSF oligoclonal IgG bands in multiple sclerosis and subacute sclerosing panencephalitis.

The light chain composition of MS and SSPE CSF oligoclonal IgG bands was examined using isoelectric focusing and a sensitive peroxidase-antiperoxidase (PAP) staining technique specific for gamma heavy chains (gamma), kappa light chains (k), or lambda light chains (lambda) and a radioimmunoassay (RIA) for gamma, k or lambda. Many bands in the 7 MS and 4SSPE CSF examined were monoclonal, staining for either IgG-k or IgG-lambda. By staining, all MS CSF were k predominant; SSPE CSF were variously k or lambda predominant. RIA confirmed the k predominance of MS CSF. Three MS and 2 SSPE CSF contained bands staining for lambda alone, i.e. free light chains. Analysis of RIA data confirmed these findings in 2 MS cases. The difference in light chain predominance of MS and SSPE CSF may reflect differences in the antigenic target, or the age of patient at the time when band-synthesizing clones are triggered. Six of 7 MS and all 4 SSPE CSF contained oligoclonal bands staining for gamma and for both kappa and lambda, probably representing artifacts of IEF. No predominant immunochemical differences between bands in MS and SSPE were detected.

Humans↗
PubMed1982

Oligoclonal IgG in multiple sclerosis and subacute sclerosing panencephalitis brains.

IgG was obtained from multiple sclerosis (MS) and subacute sclerosing panencephalitis (SSPE) brain materials by elution at neutral and acid pH, and by freezing and thawing. Serum, cerebrospinal fluid (CSF), and brain eluates were compared by isoelectric focussing (IEF) with sensitive peroxidase-anti-IgG staining. In 3 MS cases, different plaques or regions of the same brain had IgG patterns with some common and some different bands. Pooled white matter eluates contained the summation of bands seen in individual plaques or regions. Comparison of serum, CSF, and neutral and acid brain eluate IgG patterns showed many common bands but also unique bands. In two SSPE cases, eluates from different regions of the same brain showed virtually identical IgG patterns. Comparisons of serum, CSF, and neutral and acid eluates of the same brain also showed a common pattern of bands. Similarities in IgG patterns of sera, CSF, and regional brain eluates, from single cases of SSPE, suggest a common response to the same antigen in all regions or compartments. Differences in IgG patterns of sera, CSF, pooled brain eluates, and plaques or regional eluates from single cases of MS, suggest: either that (a) all MS oligoclonal IgG is "nonsense' antibody in terms of disease pathogenesis, or (b) much of the MS oligoclonal IgG is "nonsense' antibody, present as part of a specific oligoclonal immune reaction.

Brain↗
PubMed1981

Comparison of agar gel electrophoresis and isoelectric focusing in multiple sclerosis and subacute sclerosing panencephalitis.

Isoelectric focusing (IEF) and agar gel electrophoresis (AGE) were used to examine cerebrospinal fluid (CSF) and sera from patients with multiple sclerosis (MS) and subacute sclerosing panencephalitis (SSPE). All 15 SSPE samples and 29 of the 33 MS CSF samples showed oligoclonal IgG bands by AGE and IEF. Serum bands were more frequent in SSPE than in MS and were more commonly detected by IEF than by AGE. In MS CSF the number of bands on IEF correlated with: (1) disease duration, (2) CSF IgG, (3) CSF IgG/albumin ratio, and (4) central nervous system IgG synthesis. Serial studies revealed increases in IEF band number in 4 of 10 MS and 3 of 5 SSPE CSF specimens; fluctuations in band intensity were also noted. Densitometric scans of CSF IEF gels showed high, sharply angled IgG band peaks in SSPE; the CSF band peaks in MS were flatter and had higher background IgG. The SSPE pattern could be made to resemble the MS pattern through addition of normal polyclonal IgG to SSPE CSF. These findings suggest that in addition to oligoclonal IgG, polyclonal IgG is synthesized locally within the central nervous system in MS.

Adolescent↗
PubMed1981

Cerebrospinal fluid and serum oligoclonal IgG bands in rabbits with experiment allergic encephalomyelitis.

Rabbits sensitized with whole nervous tissue or myelin basic protein (MBP) plus adjuvant and developing experimental allergic encephalomyelitis (EAE) were studied for the presence of oligoclonal immunoglobulin (Ig) bands in spinal fluid and serum. Samples obtained prior to sensitization and at the time of sacrifice were concentrated and subjected to agar gel electrophoresis. Of 11 rabbits receiving whole nervous tissue and developing severe clinical signs of EAE, 7 showed new oligoclonal Ig bands in spinal fluid and in serum obtained 19 days or more after sensitization. With MBP sensitization, 2 of 6 rabbits exhibited new spinal fluid bands, while all 6 rabbits studied demonstrated serum banding. The bands were identified as IgG by immunochemical studies using peroxidase-labeled antisera and by Staph. protein A absorption. The majority of animals showed no banding in presensitization samples. The finding of oligoclonal IgG in EAE reveals yet another immunologic correlation between EAE and the human demyelinating disease, multiple sclerosis.

Animals↗
PubMed1980

Isoelectric focusing of IgG eluted from multiple sclerosis and subacute sclerosing panencephalitis brains.

Elevated IgG distributed in oligoclonal bands is characteristically observed in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) or subacute sclerosing panencephalitis (SSPE). Similarly, IgG in bands has been detected in neutral saline (NS) and acid eluates of brain material from these two diseases. We have now used isoelectric focusing (IEF) to compare IgG eluted from control brain, three plaques and a white matter pool of an MS brain, and three regions of an SSPE brain. A direct peroxidase-conjugated anti-human IgG staining technique was used to stain IgG exclusively and to visualize the minute amounts of IgG obtained from individual MS plaques. Eluates from individual MS plaques have distinct IgG patterns; in contrast, those from separate SSPE brain areas have essentially identical IgG patterns. The identical IgG patterns in three areas of SSPE brain suggest a common response to the same antigen. The different IgG patterns among MS plaques suggest: (1) variable response to the same 'MS antigen' in each plaque, (2) response to different MS antigens in different plaques, (3) synthesis of 'nonsense' antibodies irrelevant to the pathogenesis of MS in each plaque, or (4) some combination of the above.

Antibody Specificity↗
PubMed1980

Immunoperoxidase staining of cerebrospinal fluid IgG in isoelectric focusing gels: a sensitive new technique.

An isoelectric focusing (IEF) technique using direct peroxidase or peroxidase-antiperoxidase (PAP) overlay staining for detection of cerebrospinal fluid (CSF) oligoclonal IgG is described. The method involves chemical fixation of all proteins in the gel followed by application of peroxidase coupled antiserum as a specific stain. The direct peroxidase system is 4 times and the PAP system 8 times as sensitive as Coomassie blue staining after standard IEF or Coomassie blue staining of immunofixed gels. As little as 0.5 microgram (direct peroxidase) or 0.3 microgram (PAP) of IgG can be detected. Direct peroxidase staining of IgG in IEF gels can be used to examine unconcentrated CSF, with banding patterns similar to those obtained by Coomassie blue staining after standard IEF of concentrated CSF.

Humans↗
PubMed1977

Quantitative analysis of methadone in biological fluids using deuterium-labeled methadone and GLC-chemical-ionization mass spectrometry.

The (+)-,(-)-, and (+/-)-2H5-methadones, which contained five deuterium atoms in one aromatic ring, were synthesized for use in clinical pharmacological studies and as internal standards. GLC-chemical-ionization mass spectrometry was used to determine plasma and urinary methadone levels by an inverse isotope dilution assay. Plasma drug levels could be determined to 10 pmoles/ml, and urine levels could be measured to 5 pmoles/ml. Plasma methadone levels were examined in several patients undergoing methadone maintenance therapy. These levels generally ranged between 100 and 400 ng/ml (320-1300 pmoles/ml) after an average oral dose of 1 mg/kg/day. The methadone half-life was 28.8 +/- 4.8 hr.

Adult↗