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Biomedical subjects

G Konat

Publications and source records attributed to G Konat.

At least 37 records · Page 2Linked to original sources
PubMed1984

Blood-brain and blood-spinal cord barrier permeability during the course of experimental allergic encephalomyelitis in the rat.

Experimental allergic encephalomyelitis (EAE) was induced in young male Lewis rats. Blood-brain barrier permeability to radiotracers of different molecular sizes was studied at intervals after induction using a tissue sampling technique. The results were correlated to the clinical picture and to the histological appearance of the central nervous system. Significant increase in blood-brain barrier permeability to small molecules was found to precede clinical symptoms by one day in the lumbar spinal cord and to coincide with the onset of clinical disease in other regions. In all regions, increased blood-brain barrier permeability preceded the occurrence of histological lesions (perivascular cellular infiltrates). No permeability increase to large molecules could be demonstrated.

Animals↗
PubMed1984

Immunological expression of gangliosides in multiple sclerosis and in a demyelinating model disease in rabbits.

Accumulating evidence suggests that the process of demyelination in MS might involve an autoimmune response to one or more myelin components. A combination of myelin basic protein and myelin haptens was considered as possibly enhancing a cellular or humoral autoimmune reaction in MS. In line with this motion we have used an in-vitro E-rosette assay that correlates with in-vivo delayed hypersensitivity to demonstrate specific immunologic sensitivity of lymphocytes from MS patients to polysialogangliosides. A recent report that only lymphocytes from patients in relapse, but not in remission, are primed by gangliosides, underscores the relevance of the antigenic expression of gangliosides during the active pathological phase of the disease. The antigenic capacity of gangliosides to induce upon immunization a neurological disorder featured by demyelination in the CNS was demonstrated in rabbits. This and previous reports on the induction of peripheral demyelination in rabbits immunized with gangliosides will be further analyzed to gain insight on the possible role of these myelin lipid components as targets for an autoimmune mechanism in MS.

Adult↗
PubMed1984

Triethyllead and cerebral development: an overview.

The immature brain is unduly vulnerable to the toxic effects of triethyllead (Et3Pb). Both brain growth and main developmental events in the tissue are appreciably restrained by this neurotoxin. Generally, the susceptibility of brain cells to Et3Pb appears to diminish with age. The major cellular alterations in the affected tissue include the destruction of cell processes, and swelling and vacuolization in the pericaryon. The effect of Et3Pb-induced poisoning is one of hypomyelination as seen from the prominent reduction in the content of cerebral myelin. Myelin-producing cells (oligodendrocytes) seem to be particularly vulnerable to Et3Pb relative to other components of the tissue. Furthermore, the toxin specifically hampers the process of myelin membrane assembly. The inhibitory effects of Et3Pb can be attributed to the interaction of this amphiphilic compound with cellular membranes and with the process of their biogenesis.

Animals↗
PubMed1982

Elevated ganglioside concentration in serum and peripheral blood lymphocytes from multiple sclerosis patients in remission.

The ganglioside concentration in pooled serum from 20 patients with clinically definite multiple sclerosis (MS) was determined and compared with that in pooled serum from a similar number of healthy blood donors. There as a significant increase in the concentration of ganglioside-bound sialic acid from 691 +/- 57 micrograms/100 ml in the control sera to 926 +/-m 83 micrograms 100 ml in MS patients' sera. The profile of individual gangliosides in the two groups was identical, the four main structures being GM3, GD3, and GD1a and GT1b. The ganglioside pattern and concentration in peripheral blood lymphocytes derived from MS patients and controls was identical with the predominant GM3, and small proportions of Gd3. MS lymphocytes also showed a 39% increase in ganglioside content over control lymphocytes. The implication of such pronounced ganglioside increases is discussed with regard to the impaired immunocompetence of lymphocytes reported in MS.

Adult↗
PubMed1982

Abnofmalities in brain myelin or rabbits with experimental autoimmune multiple sclerosis-like disease induced by immunization to gangliosides.

An experimental autoimmune multiple sclerosis-like disease (EAMSD) was induced in rabbits by immunizing them with bovine brain gangliosides. Forebrain myelin was isolated and fractionated on a discontinuous sucrose gradient into light myelin (LM, buoyant density less than or equal to 0.625 M), and heavy myelin (HM, buoyant density greater than 0.625 M). No abnormalities in either protein or lipid composition of EAMSD myelin fractions were observed. However, the EAMSD tissue yielded 31% less light and 39% more heavy myelin compared to the control brains. Thus, the HL/LM ratio was two-fold greater in experimental than in control myelin. This pathological pattern is similar to that which has been observed in myelin obtained from the brains of multiple sclerosis patients and from the optic nerves of rabbits with experimentally-induced demyelination.

Animals↗
PubMed1981

Lymphocyte stimulation by gangliosides, cerebrosides and basic protein in juvenile rheumatoid arthritis.

Peripheral blood lymphocytes from patients with juvenile rheumatoid arthritis (JRA), patients with neurological diseases (ND) and healthy children were tested for reactivity to gangliosides, cerebrosides and basic protein (BP) by the active E-rosette test (AER). None of the lymphocytes from ND patients, healthy children or two children with psoriatic arthritis responded by increased rosette formation to gangliosides, cerebrosides and BP. Lymphocytes from all 16 children with JRA were sensitized to at least one antigen as shown by the AER test. The percentage of active T-cells was significantly lower (p less than or equal to 0.05)( in children with JRA as compared to others. The significance of the results in relation to immunopathogenesis of JRA is discussed.

Adolescent↗
PubMed1980

Stimulation of active E-rosette forming lymphocytes from multiple sclerosis patients by gangliosides and cerebrosides.

An active subpopulation of blood T-lymphocytes, characterized by rapid (4 min) rosette formation with sheep erythrocytes was measured in multiple sclerosis (MS) patients, other neurological diseases (OND) and healthy subjects after 15 min incubation with low doses (0.1-5 pg) of brain cerebrosides and gangliosides. A 15% rise in the active E-rosettes after incubation with antigens was indicative of a response to given antigen. Peripheral blood lymphocytes from all 35 patients with MS responded to brain cerebrosides in the active E-rosette test (AER). Lymphocytes from 33 MS patients also responded to brain gangliosides. Three out of 26 other neurological patients were stimulated by cerebrosides and gangliosides. Fifteen healthy subjects did not respond to any antigen in the AER test. The significance of the results in relation to the process of demyelination is discussed.

Adult↗
PubMed1980

Suppressive effect of triethyllead on entry of proteins into the CNS myelin sheath in vitro.

Incorporation of [14C]leucine into the myelin sheath was studied in brain stem slices prepared from 22-day-old rats. Individual major myelin proteins were separated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. There was a time lag before incorporation of the label into proteolipid protein (PLP) and intermediate protein (IP) reached maximal rates. Labelling of basic proteins (BP) and Wolfgram proteins (WP) revealed a much shorter lag in entry. Appearance of radioactive proteins in the myelin sheath was significantly hampered by triethyllead (PbEt3) added to the incubation medium at micromolar concentrations. Inhibition values were highest in the case of PLP and were closely followed by the values for IP. BP and WP were less inhibited, although incorporation of these proteins into myelin was still suppressed more than was synthesis of total homogenate protein. Thus, myelin -forming cells seem to be unduly vulnerable to the toxin relative to the rest of the tissue. Furthermore, the results indicate an interference of PbEt3 with certain posttranslational process involved in furnishing of integral myelin proteins.

Animals↗
PubMed1979

Stimulation of active E-rosette forming lymphocytes by myelin basic protein and specific antigens from multiple sclerosis brains.

Peripheral blood lymphocytes from 30 patients with multiple sclerosis (MS) responded to low doses (i.e. 0.1--5 pg total protein) of crude MS myelin basic protein (BP) as assayed by the active E-rosette test (AER). Of the MS patients studied 20 (65%) responded to control BP. The optimum response of MS lymphocytes to MS BP was obtained at a lower concentration than their response to control BP. Thirty percent of other neurological patients (OND) were stimulated by both MS and control BP. Lymphocytes of all MS patients but none of the OND responded to partially purified protein fraction of MS brain ("peak 2"). Crossed immunoelectrophoresis revealed the presence of one common specific antigen in crude MS BP and MS "peak 2" antigens. The nature of these antigens is discussed.

Adult↗
PubMed1979

The enhancing effect of multiple sclerosis brain homogenates on the active E-rosette forming lymphocytes in neurological disorders.

Peripheral blood lymphocytes from 23 out of 27 (85%) patients with multiple sclerosis responded to MS brain homogenates by increased formation of active E-rosettes. Lymphocytes from only six out of 78 (8%) patients with other neurological diseases responded to MS brain homogenates. The possible value of the test in the diagnosis of MS is discussed.

Adolescent↗
PubMed1979

Partial purification of MS specific brain antigens.

The present study was devoted to an immunochemical elucidation of antigenic similarities and differences between cytoplasmic and microsomal fractions of six multiple sclerosis (MS) and seven non-MS brain autopsy specimens. The antigenic composition of the samples studied was traced by crossed immunoelectrophoresis using antibodies made by immunization of rabbits with the corresponding fraction. The following data were obtained: 1. A measles antigen (defined as an antigen formed in vero cells during measles infection) and two specific antigens have been purified more than 3000-fold from MS brains by means of molecular filtration and DEAE cellulose chromatography. 2. All three antigens have a molecular weight between 10(5)-10(6) daltons and isoelectric points between 3.5-6.0. 3. Measles antigen has also been found in three out of seven non-MS brains, however, it did not stimulate antibody formation in rabbits in contrast to measles antigen of MS brain. The significance of the above-mentioned data is discussed in view of the immunological abnormalities previously found in MS patients. It cannot be excluded that the antigens found represents one or more viral antigens.

Adult↗