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Biomedical subjects

J Clausen

Publications and source records attributed to J Clausen.

At least 109 records · Page 6Linked to original sources

Demential syndromes and the lipid metabolism.

The present communication surveys the present knowledge about the extent to which formation of free radicals in the central nervous system may give rise to cross-linking reactions finally ending in the deposition of lipofuscin pigments. Free radicals may be formed by autoperoxidation of polyunsaturated fatty acids. These fatty acids, e.g., C22:6 omega 3, are enriched in rods and cones of the eye and in phosphatidyl ethanolamine of synaptosomes. By peroxidation, malondialdehyde is formed. This aldehyde may cross-link through amino groups of proteins and certain phospholipids. Hereby, lipofuscin is deposited. The peroxidation process is counteracted by certain enzymic systems and by antioxidants. Thus, glutathionperoxidase (GSH-Px), catalase and superoxid dismutase may eliminate peroxides. GSH-Px is a selenium-containing enzyme. Peroxides are also formed by metabolic transformation of dopamine. 3 demential syndromes, i.e. Alzheimer's, Parkinson's and Batten's diseases, are discussed with regard to whether the "free radical theory" may explain the pathogenesis. Finally, it is discussed whether an antioxidative treatment including vitamins E and C as well as a supplement of selenium, e.g. sodiumselenite, may be a therapeutic alternative to other types of treatment of demential syndromes or a direct supplement to the L-DOPA treatment of Parkinson's disease.

Alzheimer Disease↗

State-dependent variations in brainstem auditory evoked responses in human subjects.

BAERs from 16 subjects during 3 sessions varied in the latency or amplitude of some components depending upon level of arousal as indicated by EEG patterns. There was a general tendency for activation to produce the fastest responses with the largest amplitudes and for drowsiness to produce the slowest responses with the smallest amplitudes. The latency of P2 was significantly prolonged during drowsiness, relative to those during relaxation or activation. For right-ear stimulation, P5 latency was longest during drowsiness, and shortest during activation while for left-ear stimulation the shortest latency occurred during relaxation. The amplitudes of Wave II and Wave VII were significantly smaller during drowsiness than during activation. Although the differences were below the level of clinical significance, the data indicate a modification in the characteristics of brainstem transmission as a function of concurrent activity in other brain areas.

Adult↗

Estimation of levels of IgG to multiple sclerosis specific brain antigens in the cerebrospinal fluid of MS patients.

The binding of partially purified multiple sclerosis (MS) specific brain antigens (MSG2) and of the corresponding antigens of non-MS brains (KG2) to cerebrospinal fluid IgG of patients with MS and other neurological diseases was assayed employing sandwich enzyme linked immunosorbent assay (ELISA). Assay of the antigen-antibody binding revealed that the concentration of MSG2 required for the optimum binding to IgG in the undiluted MS CSFs was lower than that of KG2 in all cases. The index for IgG binding capacity of an antigen (IgBC) was expressed as a ratio of the optical density of the enzymic products in ELISA at the optimal antigen-antibody binding to the lowest concentration of the antigen required for the optimal binding. The IgBC of MSG2 was found to be linearly correlated with the IgG concentration in the CSF of MS patients. These results indicate that IgG with specificity to MSG2 may be present in the CSF of MS patients.

Adult↗

Electron microscopical study of rat mast cell maturation.

The development of peritoneal mast cells in rats in the early post-natal period was found to take 7-8 weeks. A slightly shorter time was needed for the reappearance of mature peritoneal mast cells following their total destruction in adult rats. In both groups of animals mast cell ultrastructure was studied in successive phases of development. The maturation process was gradual, but no well-defined morphological stages could be demonstrated. The morphology of young peritoneal mast cells seems to indicate that they arise in the peritoneal fluid from macrophage-like cells.

Animals↗

Serum antibodies against cytosol antigens in multiple sclerosis.

Immunologically pure IgG was isolated from serum of multiple sclerosis (MS) patients and normal controls. The F(ab)2 moiety of IgG was then isolated by salting out between 12.5 and 19.0% Na2SO4 of the pepsin digest of IgG. The ability of the 131I-labelled F(ab)2 to bind to subcellular brain fractions (nuclei, synaptosomes, mitochondria, myelin, microsomes and cytosol) of MS and control brains was assayed and expressed as radioactivity/mg protein of respective fractions. No significant difference could be traced with regard to F(ab)2 binding to the particulate fractions from MS patients and normal controls. MS F(ab)2 did, however, bind about two times more to MS cytosol than to non-MS cytosol antigens and up to 50% more MS than the control F(ab)2 did bind to the MS cytosol. MS F(ab)2 and control F(ab)2 did bind equally to control cytosol. The immunoprecipitate of MS F(ab)2-MS-cytosol was isolated and used for immunization of rabbits. The antiserum formed could be demonstrated by means of crossed immunoelectrophoresis to contain antibodies to one to three MS antigens. Thus it must be concluded that MS serum contains antibodies to one to three MS antigens occurring in MS brain cytosol.

Antibody Specificity↗

Ultrastructure of the tympanic membrane in the Rhesus monkey.

The tympanic membranes of 8 Rhesus monkeys (macaca mulatta) were investigated by transmission electron microscopy. The interface of the epidermis and the fibrous framework appeared rather smooth and the contact between the basal cell layer and the lamina propria was secured by a dermo-epidermal junction. Cross-sectioned fibrils varied in shape and thickness, the thin fibrils being quadrangular. The findings of this study indicate a great similarity between the tympanic membrane of man and that of the Rhesus monkey. A corresponding similarity has been documented concerning the function of the Eustachian tube--middle-ear system, and it is concluded that the Rhesus monkey is highly suitable for studies of the tympanic membrane.

Animals↗

Thymidine uptake by lymphocytes in the presence of supernatants of polymorphonuclear leucocytes incubated with multiple sclerosis brain antigens.

The effects of factors secreted by polymorphonuclear leucocytes (PMNL) incubated with multiple sclerosis (MS) and control brain antigens (MSG2 and KG2 respectively) were evaluated by assay of thymidine uptake by lymphocytes from normal individuals and MS patients. It was found that the cellular uptake of thymidine of both MS and normals was significantly lower in the presence of MSG2-PMNL supernatants compared to that in the presence of KG2-PMNL or without antigen-PMNL supernatant. The findings indicate that an inhibitor of lymphocyte proliferation either may be released from PMNL by the action of MSG2 or may be synthesized in response to challenge by MSG2.

Adult↗

Fetal arterial involvement in Behcet's disease: an electron microscope study.

A fetus, 16 weeks old, was removed by hysterotomy from a patient suffering from Behcet's disease. The patient received systemic steroids during pregnancy. Electron microscopy of the fetal thoracic aorta revealed edema of the sub-endothelial space and of the luminal part of the tunica media, as well as a pronounced rarefaction and disarrangement of the smooth-muscle cells. Results obtained from two human fetal aortae used as controls suggest that the fetal aortic lesions were caused by the maternal disease and not by the exposure to steroids.

Adult↗

Multiple sclerosis-specific central nervous system antigens (MSG2): a blind study.

A blinded study was designed to determine if a glycoprotein fraction, G2, shown in previous studies to be specific for multiple sclerosis (MS), could be isolated from cryopreserved autopsy central nervous system (CNS) tissue. Coded tissue sections were obtained from the Human Neurospecimen Bank, Los Angeles, Calif.; and the code was broken after all data were analyzed. Multiple sections of the CNS from 23 MS patients, 12 patients with other neurologic diseases (OND), and 10 individuals who died as a sudden death were utilized. Crossed immunoisoelectrophoresis (CIE) of G2 against anti-MS cytosol antibodies to MS-specific CNS antigens (MSG2) and tandem CIE of the G2 fraction with a known MSG2 preparation were carried out. MSG2 was found in one or more CNS sections from 78% of MS patients, all sections from MS spinal cord, and no sections from OND or control individuals. We propose that the MSG2 found in the MS CNS may contain a glycoprotein of a persistent virus, such as measles and/or myelin.

Adult↗

Unusual immunofluorescence findings in pemphigus vegetans.

An 84-year-old man with massive verrucous lesions in the intertriginous areas is reported. The clinical, histological and electron microscopical findings indicated pemphigus vegetans. However, in addition to the intraepidermal findings direct immunofluorescence showed a linear deposit of IgG and C3 at the basement membrane.

Aged↗

Leucocyte glutathione peroxidase activity and selenium level in Batten's disease.

The glutathione peroxidase (GSHPx) activity was found significantly reduced in whole lymphocytes from patients suffering from Batten's disease. By means of two different procedures for isolation of subcellular fractions of lymphocytes it was possible to demonstrate an increased GSHPx activity of the particulate fractions (20.000 g-av and 105.000 g-av precipitates). However, the GSHPx activity of the supernatants was decreased. The GSHPx activity of the 20.000 g-av supernatant correlated significantly with the serum selenium content both in normal controls and in Batten's disease. A similar correlation was traced with GSHPx activity of erythrocyte haemolysate and serum selenium level in Batten's disease but not in normal controls. The GSHPx activity was also found decreased in the 20.000 g-av and 105.000 g-av supernatants of granulocytes. The abnormal subcellular distribution of GSHPx activities was related to the distribution of enzymes which were used as markers for different subcellular components. The data presented are discussed in relationship to the theory that Batten's disease is due to an increased peroxidation damaging the cellular membranes.

Adenosine Monophosphate↗

Effects of phenobarbital and sodium salicylate on cytochrome P-450 mixed function oxygenase and glutathione S-transferase activities in rat brain.

The effects of acute and therapeutic doses of phenobarbital and sodium salicylate on cytochrome P-450 mixed function oxygenase (EC 1.14.14.1) and glutathione S-transferase (EC 2.5.1.18) activities have been studied in rat brain and compared with those of rat liver. P-450 enzymic activity was assayed by N-demethylation of p-chloro-N-methylaniline and 1-chloro-2,4-dinitrobenzene was used as substrate for glutathione S-transferase activity. The acute effects of a single daily dose of phenobarbital (75 mg/kg/day; i.p.) and sodium salicylate (500 mg/kg/day; i.p.) for 3 days increased cytochrome P-450 as well as glutathione S-transferase in rat liver. But the same doses of both drugs decreased glutathione S-transferase levels in rat brain and increased cytochrome P-450 dependent N-demethylation of p-chloro-N-methylaniline. The therapeutic doses of sodium salicylate (50 mg/kg/day; i.p.) and phenobarbital (10 mg/kg/day; i.p.) daily for 21 days increased cytochrome P-450 in rat liver as well as in brain. The increase in brain glutathione S-transferase by prolonged treatment of phenobarbital was significant compared to the control values.

Animals↗

Electron microscopic study of the regeneration in vivo of rat peritoneal mast cells after histamine secretion.

Peritoneal mast cells regenerate their histamine granules in 5-6 weeks after intraperitoneal injection of the degranulating agent compound 48/80. In the beginning of the regeneration the small exocytic cavities containing the non-secreted granule remnants coalesce to a single large cavity. Later on this cavity decreases in size and becomes a small vacuole containing a very condensed material. After two weeks of regeneration mast cells are already capable of another secretory event.

Animals↗