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Biomedical subjects

J Clausen

Publications and source records attributed to J Clausen.

At least 145 records · Page 8Linked to original sources

Leucocyte glutathione peroxidase activity and selenium level in multiple sclerosis.

In continuation of our previous studies, which demonstrated a decreased glutathione peroxidase (GSH-Px) activity of erythrocytes from multiple sclerosis (MS) patients the activity of some enzymes regulating the peroxide level (GSH-PX and glutathione reductase (GSSG-Rd)) in leucocytes and erythrocytes respectively, the selenium level of whole blood and the beta-glucuronidase activity of serum (marker of lysosomal membrane damage) were assayed in this group of patients. GSH-Px activity in lymphocytes and granulocytes from MS patients was significantly (2 alpha smaller than or equal to 0.01) decreased by 35-50%. Erythrocyte glutathione reductase activity was only insignificantly decreased in MS patients. Erythrocyte GSH-Px : GSSG-Rd ratio was 11.0 for the control group, but 8.0 for the MS group. The selenium content of whole blood and serum from Danish MS patients was normal. The selenium level in erythrocytes from Danish MS patients was however higher than the selenium level in erythrocytes from controls.

Erythrocytes↗

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↗

Abnormal serum alpha 2-macroglobulin in Dyggve-Melchior-Clausen syndrome.

The high levels of alpha 2-macroglobulin found in the serum of three patients suffering from Dyggve-Melchior-Clausen syndrome, an autosomal recessive metabolic disorder, resembling mucopolysaccharidoses, have been further characterised by crossed immunoelectrophoresis. The immunoprecipitate of patients' alpha 2-macroglobulin forms a double arc, this may be helpful in the diagnosis of the syndrome.

Humans↗

Loss of lysosomal neutral proteinase from leucocytes induced by the action of multiple sclerosis-specific brain antigens.

Lysosomal neutral proteinase levels were assayed in leukocytes of patients with other neurological diseases before and after the reaction with MS-specific brain antigens (MSG2). The lysosomal neutral proteinase activity of MS leucocytes was found to be higher than in the two other groups under investigation. To assay the effect of MSG2, 1 x 10(6) leucocytes were incubated with 500 ng of protein MSG2 and with 500 ng of protein of a corresponding fraction from control brain (KG2). Intracellular levels of lysosomal neutral proteinase in leucocytes of all the subjects studied were found to be lowered by the action of both MSG2 and KG2. However, loss of intracellular neutral proteinase induced by the action of MSG2 on all leucocytes was significantly higher than that by KG2 (P less than 0 . 0025). It is suggested that macrophages (monocytes) were stimulated to increased lysosomal enzyme activity, initiated by stimulation of T lymphocytes caused by MS-specific brain antigens.

Adult↗

Different tissue responses of mixed function oxidases and detoxifying enzymes to aflatoxin B1 administration in the rat.

The carcinogenic effects of aflatoxin B1 have been related to the formation of an active intermediate metabolite, an epoxide produced via the cytochrome P-450-mediated mixed function oxidase. The toxicity of this intermediate is dependent on metabolic transformations by enzymes such as aryl hydrocarbon hydroxylase, glutathione S-transferase and glutathione peroxidase. Like the mixed function oxygenase, these enzymes are inducible, and dependent on the action of specific drugs and inducers. The present study describes the effect of a single sublethal i.p. dose (6 mg/kg body wt) of aflatoxin B1 on the specific activities of microsomal demethylases, aryl hydrocarbon hydroxylase (AHH), glutathione S-transferase and glutathione peroxidase in rat liver, kidney, lung, brain and adrenals. The enzymes were assayed 24 h after the toxin treatment. Among the different tissues, only liver AHH showed an induction on toxin treatment whereas those of kidney and brain declined. Microsomal demethylase was also high in liver and low in kidney. However, no significant alteration was induced by aflatoxin B1 on glutathione S-transferase and glutathione peroxidase activities in the various tissues examined except the adrenals, which showed a significant increase. The present study revealed that the reaction sequence for metabolic transformation of aflatoxin B1 is more complex than foreseen from the activities of these inducible metabolite-transforming enzymes.

Aflatoxins↗

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↗

Organochlorine compounds in adipose tissue of Greenlanders and southern Danes.

Abdominal fat tissue samples from the general population of Greenland and from southern Denmark were analyzed for o,p'-DDE and p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], p,p,-DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane], o,p'-DDT and p,p'-DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], lindane (1,2,3,4,5,6-hexachlorocyclohexane), aldrin (1,2,3,4,10,10-hexachloro-1,4,4a,5,8,8a-hexahydro-endo-exo-1,4:5,8-dimethanonaphthalene), dieldrin (1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-endo-exo-1,4:5,8-dimethanonaphthalene), heptachlor (1,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-methanoindene), heptachlor epoxide, and polychlorinated biphenyls (PCBs). Fat tissue from Greenlanders contained significantly higher amounts of p,p'-DDE (p less than or equal to 0.05), p,p'-DDT (p less than or equal to 0.01), and total DDT (SIGMA DDT, the sum of DDT and its metabolites) (p less than or equal to 0.01) than southern Danes. Lindane, aldrin-like residue, dieldrin heptachlor-like residue, heptachlor epoxide, and PCBs were present in adipose tissue of both groups and there were no significant differences between the groups. The p,p'-DDE level in Greenland was lower than that in the United States, eastern Europe, and India. Among Greenlanders of different ages the highest sigma DDT was found in the age group of 22-45 yr; the content of PCBs increased with age. Among southern Danes the highest sigma DDT was found in a higher age group than in Greenlanders. Among Greenlanders the content of aldrin-like residue decreased with age and that of dieldrin increased with age. A significant correlation was found (on the basis of wet weight) between p,p'-DDE and PCB content in southern Danes (p less than or equal to 0.02). The correlation between sigma DDT and PCB content was also significant in this population (p less than or equal to 0.01). These two relationships were not significantly correlated for the Greenlanders. The DDE/PCB and sigma DDT/PCB ratios were higher in Greenlanders than in southern Danes. These ratios are age-dependent and are highest in the age group 22-45 yr among the Greenlanders. A low DDE/PCB ratio and a low sigma DDT/PCB ratio have been proposed as markers for industrialization. In Greenlanders p,p'-DDE represented about 70% of sigma DDT. For southern Danes this level was about 90%. The data obtained are presented and discussed on the basis of both lipid and wet weight levels.

Adipose Tissue↗

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↗

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↗

Relationships between abnormal IgG index, oligoclonal bands, acute phase reactants and some clinical data in multiple sclerosis.

The IgG-index and acute phase reactants were measured and oligoclonal bands were looked for in 30 patients with clinically definite multiple sclerosis (MS) and were compared with the clinical data. IgG-index was found elevated in 77% against 22% in a comparable material of patients with other neurological diseases. Oligoclonal bands were found in 74 and 17%, respectively. No correlation was found between these parameters and age, duration of illness, disability, coefficient of progression or age of onset. A statistical evaluation defines the specificity, sensitivity and validity of the methods used. CRP could no be demonstrated in 28, the rest had normal values. C3A was normal in all cases, but appeared to be elevated a little with increasing age, and to be positively correlated to the albumin-index, indicative of a defective blood-brain barrier. No correlation was found between CRP, C3A and the clinical data.

Acute Disease↗

Serum fatty acids and peroxidase abnormalities in Batten's disease.

The linoleic acid content of serum lipids was measured in 10 paitents with Batten's disease and 11 healthy control subjects by gas liquid chromatography. The fatty acid patterns of serum lipids in this disease may reflect a primary or secondary deficiency in essential fatty acid (linoleic acid) probably related to a glutathione peroxidase abnormality.

Adolescent↗

Biochemical abnormalities in Dyggve-Melchior-Clausen syndrome.

In continuation of previous studies, which showed a catabolic defect in proteoglycan metabolism, enzymes which degrade the proteoglycan macromolecules, e.g. proteinases (cathepsin D, elastase, and cathepsin G) and glycoisidases (arabinosidase and xylosidase) have been assayed in leucocytes of DMC patients. The regulator of lysosomal proteinases, cyclic AMP and serum antiproteinases, e.g. alpha1-AT and alpha2-M, have also been assayed. The proteinases assayed were normal in DMC patients. Arabinosidase activity in leucocytes of the patients was found to be decreased three fold, while xylosidase activity was increased three fold. A four-fold increased concentration of cyclic AMP in leucocytes of the patients and an increased serum concentration of alpha2-M associated with its abnormal pattern in crossed immunoelectrophoresis have been found. The abnormality in serum alpha2-M of DMC patients may be explained by a complex formation of alpha2-M with collagenase released from the lysosomes. Finally, an abnormal peptidoglycan has been demonstrated in DMC urine.

Adolescent↗

Toxicology of triethyllead, methylmercury and cadmium, determined in chick embryo brain cell cultures.

The toxicology of water soluble chemical compounds may be investigated in tissue culture systems. The toxicology of triethyllead chloride, methylmercury chloride and cadmium acetate was studied in chick embryo brain cell cutlures. Tetraethyllead is added to petrol as an anti-knock agent. When tetraethyllead is absorbed by the organism, it is converted to triethyllead which cause the symptoms of tetraethyllead poisoning. Chick embryo brain cell cultures derived from cerebrum of 11-day-old chick embryos developed both neurons and glial cells. The neurons formed nerve processes and synapsis in the cultures. The effect of triethyllead chloride was investigated by addition of triethyllead chloride to the nutrient medium. The median tissue culture lethal dose, TCLD50 = 1.9 mg/l, was determined as the concentration of triethyllead chloride at which the confluent layer of glial cells was destroyed in 50% of the cultures. The neurons lost their processes at even lower concentration, TCED50 = 0.57 mg/l. Electron microscopy revealed cells with swollen Golgi apparatus and dilated endoplasmic reticulum in chick embryo brain cell cultures which were treated with triethyllead chloride, 1.0 mg/l. Studies with radioactive labelled precursors revealed that triethyllead chloride inhibited the synthesis of DNA, sulfatides and cerebrosides without hydroxyfatty acids.

Animals↗