Biomedical subjects

U Traugott

Publications and source records attributed to U Traugott.

At least 19 recordsLinked to original sources

PubMed1992

A prospective study of depression and immune dysregulation in multiple sclerosis.

This study examined psychologic distress and immune function in patients with chronic-progressive multiple sclerosis participating in a placebo-control trial of cyclosporine. Immune measures included percentages and absolute numbers of CD2+, CD4+, CD8+, Leu-11-b+, HLA-DR (IA+), and transferrin-receptor-positive cells, which were evaluated by immunofluorescence using monoclonal antibodies. Distress was measured with self-report scales. The Expanded Disability Status Scale assessed neurologic disability. Subjects were followed up for 2 years, and their high-depressed and low-depressed times were compared. Times of greater depression were associated with lower CD8+ cell numbers and CD8+%, and a higher CD4/CD8 ratio. CD4+ cell numbers and percent were also higher when subjects were depressed, but only in the placebo group. There were no differences in Expanded Disability Status Scale when subjects were more depressed. Evaluation of a single subject revealed that Ia+ and transferrin-receptor-positive lymphocytes increased 3 months before distress increased. It was concluded that distress is associated with immune dysregulation in multiple sclerosis, although the mechanisms of this association have yet to be delineated.

Adult↗

PubMed1992

On the immunopathology of multiple sclerosis lesions.

Active chronic multiple sclerosis (MS) lesions contain numerous T-200 and leukocyte function associated antigen (LFA)-1-positive infiltrating cells. Macrophages at the lesion edge are stained for immunoglobulins (Ig), Class I and Class II major histocompatibility complex (MHC) antigens, for interferon (IFN)-alpha and for the beta-2 integrin adhesion molecule gp 150/95. In the periplaque area, numerous CD2, CD4, and CD8 positive T cells and cells reactive for the CD45RO phenotype of memory cells and for gamma/delta T cell receptors are located between MHC-positive glial cells. White matter at the edge is diffusely stained for intercellular adhesion molecule (ICAM)-1 and LFA-3. Remote from lesions, labeling for Class II MHC, ICAM-1 and LFA-3 was enhanced on some endothelial and glial cells. These findings indicate that adhesion molecules are involved in the formation and possibly also in the reactivation of MS lesions.

Antigens, CD↗

PubMed1991

Phase I and pharmacokinetic study of D-verapamil and doxorubicin.

The calcium antagonist verapamil (a mixture of D- and L-racemers) is a potent modulator of the multi-drug resistance phenotype in vitro at a concentration of 6 microM. Clinical studies have shown dose-limiting toxicity of hypotension and heart block when plasma levels approach the concentrations active in vitro. Previous data indicate that the D-isomer is less cardioactive than the L-isomer but they appear to be equipotent in reversing drug resistance in vitro. In an attempt to increase plasma verapamil concentrations, we have treated ten patients (total of 27 courses) with oral D-verapamil (DVPM), 150-300 mg 6 h, and doxorubicin i.v. 70 mg m2 q 3 weeks. Hypotension (supine systolic BP less than 100 mmHg or a fall in systolic BP of greater than 30 mmHg) occurred in 5/6 patients at 1200 mg day DVPM, in 1/5 at 800 mg day, and in 1/5 at 600 mg day. PQ prolongation (greater than 0.23 s) was demonstrated in 2/5 patients at 800 mg day DVPM. Plasma levels of DVPM and its active metabolite norverapamil were measured and, combining these, levels of 3-4 microM were achieved at 1200 mg day DVPM; however this dose is likely to lead to unacceptable toxicity in the outpatient setting. Using an oral outpatient schedule of administration, an appropriate dose of DVPM is 800 mg day. This provides a combined plasma level (for VPM and DVPM) of 2-3 microM. If DVPM is to prove useful as a resistance modulator, it may require to be administered intravenously with careful inpatient monitoring and support.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1991

[Reversal of multidrug resistance with (R)-verapamil in vitro and in vivo].

The clinical use of racemic (R/S)-verapamil (CAS 52-53-9) as resistance modifier is limited because of the cardiovascular activity of the substance. The stereoisomer (R)-verapamil shows significant less cardiovascular activity. Therefore we tested the resistance modifying abilities of (R)-verapamil and (R/S)-verapamil in murine multidrug-resistant L 1210 ascites-tumor-cells in vitro and in vivo. The present results demonstrate, that the (R)-isomer has the same resistance modifying effects as racemic verapamil. Both modifying substances have no effects in the parental (sensitive) and cytosine-arabinoside resistant L 1210 ascites-tumor-cells. Thus, (R/S)-verapamil and (R)-verapamil show their resistance modifying abilities only in multidrug-resistant tumor-cells.

Animals↗

PubMed1990

Increase in anti-astrocyte antibodies in the serum of guinea pigs during active stages of experimental autoimmune encephalomyelitis.

From previous studies on the induction and treatment of experimental autoimmune encephalomyelitis (EAE) in guinea pigs and mice, antibodies have been implicated during both demyelination and remyelination. In the present study, sera from guinea pigs with acute, chronic and myelin basic protein/galactocerebroside (MBP/GC)-treated chronic EAE were evaluated for the presence of anti-glial cell antibodies by immunocytochemical techniques. Antigen specificity was confirmed by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The majority of sera from acute and chronic active EAE animals displayed intense labelling of astrocytes and only weak staining of oligodendrocytes when tested on sections of normal guinea pig brain tissue. In contrast, sera from animals with chronic EAE treated with MBP/GC gave strong labelling of oligodendrocytes and only minor staining of astrocytes. By immunoblotting, astrocyte staining was shown to be due to the presence of antiglial fibrillary acidic protein (GFAP) antibodies. The intense oligodendrocyte staining observed in sections reacted with sera from MBP/GC-treated guinea pigs corresponded well with high titers of serum anti-GC and anti-MBP antibodies measured by an ELISA. It was concluded that the presence of antibodies against astrocytes was possibly related to astrocytic antigens within the disease-inducing emulsion, at least during the initial phases of EAE, and not to their release from the central nervous system of affected animals.

Animals↗

PubMed1979

Oligodendrocyte staining by multiple sclerosis serum is nonspecific.

The immunofluorescent staining properties of 65 serum samples from 54 patients with multiple sclerosis (MS), 63 samples from 55 patients with other neurological diseases (OND), and sera from 14 healthy normal individuals were examined on frozen sections of bovine and human brain. When tested on bovine brain sections, positive oligodendrocyte staining was present in 63% of MS sera, 43% of OND sera, and 29% of normal sera. The percentages were lower with human brain tissue. Astrocyte and myelin staining was common. F(ab')2 fragments purified from selected positive and negative MS and control sera gave no staining, though IgG fractions from the same sera prior to pepsin digestion gave positive staining. When tested against antihuman IgM and IgA conjugates, the same positive sera and their IgG-depleted globulin fractions gave minimal or no staining. These results indicate that oligodendrocyte staining is not specific for MS, is not due to specific antibody, and is probably the result of nonspecific binding to Fc receptors.

Animals↗

PubMed1979

Multiple sclerosis: circulating antigen-reactive lymphocytes.

Circulating lymphocyte populations were examined in 85 patients with multiple sclerosis (MS), 26 of whom showed exacerbations; 48 patients with other neurological diseases (OND); 14 patients suffering from psychiatric disorders; and 2 normal subjects. The study involved the assay of early (active, high-affinity rosetting) T-cells, myelin basic protein (MBP)-reactive early T-cells, late (total, 24-hour rosetting) T-cell levels were significantly lower in MS (p less than 0.01) than in OND subjects. Exacerbations in MS were usually accompanied by further decreases in early T-cells. The lower levels of early T-cells in MS and their fluctuations are believed to reflect disease activity. MBP-reactive early T-cells were more frequently increased in MS (75% of cases) than OND (50%), and while this might be indicative of increased sensitization against myelin antigens, it was found not to be an MS-specific phenomenon.

Adult↗

PubMed1979

Experimental allergic encephalomyelitis. Frequent sampling of blood alters disease course.

Previous studies have shown that Strain 13 guinea pigs sensitised for experimental allergic encephalomyelitis (EAE) as adults usually develop an acute, fatal form of disease while animals inoculated as juveniles usually display a chronic relapsing form. The present study reports that following repeated short-interval blood sampling by cardiac puncture for the estimation of lymphocyte populations, some adult Strain 13 guinea pigs sensitised for acute EAE unexpectedly survived and developed chronic EAE, while a group of juveniles sensitised for chronic EAE and bled under the same conditions, developed a more severe, acute form of EAE. It is suggested that this reversal of disease course was related to the depletion of circulating factors.

Age Factors↗

PubMed1979

Chronic relapsing experimental allergic encephalomyelitis. Correlation of circulating lymphocyte fluctuations with disease activity in suppressed and unsuppressed animals.

Groups of juvenile Strain 13 guinea pigs sensitized for chronic relapsing experimental allergic encephalomyelitis (EAE) with isogeneic central nervous system (CNS) tissue in complete Freund's adjuvant (CFA) were either left to develop late-onset chronic EAE (unsuppressed), or given a series of injections of bovine myelin basic protein (MBP) in incomplete Freund's adjuvant (IFA) to suppress the disease. All unsuppressed animals developed disease and all suppressed animals remained healthy over a 27-month period of study. some unsuppressed and suppressed animals were rechallenged with CNS tissue in CFA 12 or 26 months post-inoculation (PI). Unsuppressed animals all became sick 2-4 weeks after rechallenge, while rechallenged, suppressed animals were protected, indicating that the suppression was permanent. Pathologic findings in the CNS complemented the clinical changes. Circulating lymphocyte studies were performed on animals from all groups. Early (active, high-affinity rosetting) T cell levels in unsuppressed animals showed significant decreases during exacerbations (P less than 0.01) and normal values during remissions. After rechallenge, circulating early T cells decreased in unsuppressed animals with the development of signs. In suppressed animals, early T cells showed significant elevations during, and for a short time after, the period of suppressive injections, and normal values afterwards. These levels did not change significantly after rechallenge. Late (total, 24 hour rosetting) T cell and B cell values showed minor fluctuations only which did not correlate with disease activity. These results indicate that chronic relapsing EAE can be successfully suppressed with MBP in IFA, that this suppression is permanent and that the immunologic findings presented correlate well with the clinical and pathologic facets of the disease. the findings are presented in terms of their relevance to multiple sclerosis.

Animals↗

PubMed1979

Acute experimental allergic encephalomyelitis. Myelin basic protein-reactive T cells in the circulation and in meningeal infiltrates.

MBP-reactive early T cells were determined simultaneously in the circulation and in inflammatory cells from the meninges of guinea pigs with acute EAE. In addition, early and late T cells as well as B cells were estimated in both compartments. Within the circulation, early T cells were found to decrease at the onset of clinical signs, and MBP-reactive early T cells were significantly higher than in normals. Different changes were found in inflammatory cells from the meninges. In this cell population, early T cells were increased but did not show significant, further elevation after incubation with MBP. This may indicate that the majority of early T cells in meningeal infiltrates had been previously activated by MBP in vivo.

Acute Disease↗

PubMed1978

T and B lymphocytes in the cerebrospinal fluid of various neurological diseases.

Cerebrospinal fluids (CSF) from 66 patients with a variety of neurological disorders were studied for total protein content, absolute amount of albumin, IgA, IgG and IgM, as well as their quotients (fraction to total protein ratio), cell numbers and B cell and T cell levels. In addition, the percentage of B cells and T cells in the blood was determined in 34 patients and serum immunoglobulin levels were estimated in 51 patients. In noninflammatory diseases of the CNS, the percentage of B cells was slightly higher and T cell levels were lower in the CSF in comparison to corresponding blood values. The B cell to T cell ratio in viral meningitis was altered in the CSF. An apparent increase in the T cell level led to a decrease of B cell values. Similar changes were also found in optic neuritis. The percentage of T cells was higher in relapsing multiple sclerosis than in the chronic progressive form. There were less striking changes in the B cell to T cell ratios in the CSF of other inflammatory diseases of the CNS.

Adolescent↗

PubMed1978

Chronic relapsing experimental allergic encephalomyelitis: CNS plaque development in unsuppressed and suppressed animals.

Central nervous system (CNS) lesion morphology has been studied in inbred Strain 13 guinea pigs sensitized for chronic relapsing EAE in which the disease was either left to develop (unsuppressed) or was suppressed with injections containing myelin basic protein (MBP). Pathologic changes correlated well with clinical activity. In unsuppressed chronic EAE animals, active clinical disease was invariably matched by acute inflammation in the CNS. In more chronic states, the CNS displayed fibrosis and remyelination while relapses showed the CNS to contain recent changes superimposed upon old lesions. In animals in which the disease was suppressed by injections of MBP, clinical signs did not develop. However, some early subclinical changes were seen morphologically. These lesions were able to remyelinate early on and there was no progression in lesion formation. Apparently, therefore, MBP had a beneficial effect upon the course of the disease and had promoted structural repair. It thus appears that MBP therapy might be one effective approach for the prevention of chronic relapsing EAE. The findings should prove relevant to future MBP trials in multiple sclerosis.

Animals↗

PubMed1978

Suppression of chronic allergic encephalomyelitis: relevance to multiple sclerosis.

The expression of chronic relapsing experimental allergic encephalomyelitis in strain 13 guinea pigs was suppressed with a single series of injections of myelin basic protein in incomplete Freund's adjuvant. The suppression appeared permanent, and subsequent rechallenge with central nervous system antigen failed to elicit exacerbations.

Animals↗

PubMed1978

[Tetanus antitoxin in serum and cerebral spinal fluid in viral meningitis in children (author's transl)].

Tetanus antitoxins were measured in serum and cerebro spinal fluid from 58 children--35 boys and 23 girls--with viral meningitis. The concentrations of IgG, IgA and IgM were also determined. The appearance of tetanus antitoxins in cerebral spinal fluid depends on absolute antitoxin levels in serum as well as on the antitoxin/IgG ratio. Antitoxin/IgG ratios in serum and cerebro spinal fluid were in the same order of magnitude. Detection of tetanus antitoxins in the cerebral spinal fluid of children with viral meningitis shows clearly that antibody found in cerebral spinal fluid is not an absolute proof of a certain disease. The results further indicate that local production of IgG antibody cannot be postulated by detecting certain antibodies in the CSF. It is also necessary to prove that antibody/globulin ratios are of significantly different magnitude in serum and CFS.

Adolescent↗

PubMed1978

Encephalitogenic properties of purified preparations of bovine oligodendrocytes tested in guinea pigs.

The present study has investigated central nervous system disease in guinea pigs inoculated with emulsions containing purified preparations of bovine oligodendroglia and their fractions isolated with or without trypsinization, whole bovine white matter or myelin basic protein (MBP). The MBP content of the oligodendroglial fractions was determined by radioimmunoassay. It was found that oligodendroglia prepared from trypsinized fresh brain contained minute amounts of MBP and did not induce disease. The corresponding cell fraction from non-trypsinized frozen brain was rich in MBP and induced disease. Bovine white matter and MBP induced typical experimental allergic encephalomyelitis (EAE). The structural preservation of the non-encephalitogenic trypsinized MBP-poor cells was very good and that of the encephalitogenic MBP-rich non-trypsinized cells very poor. It has been concluded that the encephalitogenicity observed was due to MBP, rather than to a specific oligodendroglial antigen.

Animals↗

PubMed1978

Characterization of antioligodendrocyte serum.

An antioligodendrocyte serum (AOS) has been raised in rabbits against preparations of isolated bovine oligodendrocytes. The antibody was assayed by two techniques. By complement fixation with isolated oligodendrocytes, the titer of the antibody was 1:64 to 1:128. By indirect immunofluorescence testing of oligodendrocyte suspensions and frozen brain sections, the titer of the AOS was 1:256 to 1:512. When unabsorbed AOS was used, immunofluorescent staining proved it specific for bovine oligodendrocytes in suspension and in sections, and for human oligodendrocytes in sections. In cell suspensions, the staining was membrane related and in sections, cytoplasmic. The oligodendrocyte staining could be totally removed by absorption of AOS against oligodendrocyte suspensions, whereas absorption against bovine myelin, bovine myelin basic protein, and bovine neurons did not affect the staining reaction. AOS also stsined Schwann cells, a property possible related to antigens shared with oligodendrocytes. It is concluded that AOS is specific for oligodendrocytes and can now be applied to fundamental and disease-rel

Animals↗

PubMed1978

Glial bridges and Schwann cell migration during chronic demyelination in the C.N.S.

The formation of fibrotic bridges from subpial astrocytes into the subarachnoid space of the spinal cord and the migration of Schwann cells to the central nervous system (C.N.S.) is appraised in chronically demyelinated C.N.S. lesions. Spinal cord tissue was studied from inbred, Strain 13 guinea pigs with chronic experimental allergic encephalomyelitis (EAE). It has been found that uncommitted Schwann cells are present around remyelinated fibres in nerve root entry zones, between meningeal cells at a distance from the roots and along blood vessels within the spinal cord parenchyma. It is speculated that these cells migrate via the above route to the C.N.S. In the present model, this invasion might be aided by glial fibrosis, a process which leads to surface irregularities in the spinal cord, an extensive extracellular space and possible breaches in the glia limitans through which Schwann cells might penetrate.

Animals↗

PubMed1978

Experimental allergic encephalomyelitis--migration of early T cells from the circulation into the central nervous system.

Study of lymphocytes from the blood of guinea pigs with acute EAE induced by isologous spinal cord in adjuvant reconfirmed that in comparison to normals, the percentage of early (active or high affinity rosetting) T cells decreases dramatically and that these changes can be correlated with clinical signs. In addition, we have investigated matching samples of CNS infiltrating cells recovered by ultrasonication and have found that coinciding with the decrease in early T cells in the circulation, significantly higher levels (P less than 0.001) of these cells appear within the CNS compartment; It is concluded that the decrease of early T cells in the circulation is caused by their migration to the target organ, the CNS.

Animals↗