Kidney and skin biopsy in amyotrophic lateral sclerosis.
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Biomedical subjects
Publications and source records attributed to J Palo.
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Increased urinary excretion of indican was detected in earlier studies of patients with the form of progressive myoclonus epilepsy (PME) where no Lafora bodies are present in the brain and other tissues. Since then, all PME patients have been given sodium valproate and/or clonazepam. In a series of 10 patients now examined the mean excretion was on the same level as that of other epileptic and non-epileptic neurological patients (53 +/- 27 mg/g creatinine). Alternate reduction of the two drugs in one patient over a period of 24 days increased the excretion up to the high level measured earlier (96 mg/g creatinine) and caused marked worsening of the clinical condition while no remarkable changes were observed in another PME patient who received her normal medication. The highest values ever measured were found in one PME patient just before his death. In two patients who had no medication the excretion was also high but returned to the normal level during medication with sodium valproate. It is unknown at the moment whether this change is due to the improved clinical condition of the patients or to the compound itself.
A pair of identical female twins were discordant for amyotrophic lateral sclerosis. The affected twin was not breast-fed; was bitten by a poisonous snake, and was operated on for struma. She had more infections than her sister but no fractures. Her plasma insulin response to glucose loading was also higher. The twins lived separated in their early childhood.
Fibronectin is a glycoprotein found in plasma (cold-insoluble globulin), connective tissues, and cultures of fibroblasts and astroglial cells. This paper describes the identification of fibronectin in human CSF. Fibronectin in CSF was immunologically indistinguishable from the plasma form, as shown by double-diffusion analysis and by radioimmunoassay specific for fibronectin. Fibronectin was isolated from human CSF by affinity chromatography on Sepharose-coupled gelatin and was further analyzed by SDS-polyacrylamide gel electrophoresis. It showed a polypeptide band similar to that of plasma fibronectin. The fibronectin concentration in CSF of 17 neurological outpatients without demonstrable organic lesion in the CNS was 3.0 +/- 1.6 microgram/ml (mean +/- S.D.) which is about 0.6% of total CSF protein. In CSF of 11 MS patients, the concentration was significantly (p less than 0.005) lower (1.6 +/- 0.2 microgram/ml). Of patients with brain tumors, seven had very low levels, three were normal, and two had very high levels. The cause for the low levels in MS and tumor patients is not known.
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The frequency of malignant diseases among 1866 living and 340 deceased multiple sclerosis (MS) patients was investigated in Finland. The study revealed a low prevalence (0.64%) and mortality (0.07%) rate of cancer among MS patients. The difference between MS patients and general population was significant. The highest rate was found in the group from 40 to 49 years while in the general population the rate of cancer among MS patients tended to fall after the age of 50. The possible role of selenium, one of the antioxidants in the pathogenesis of MS and cancer, is discussed because recent data have shown a very high negative correlation between selenium and cancer death rates.
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Neuropathological evidence of demyelination was found in the brain and sciatic nerve of diabetic patients at autopsy. The activity of acid proteinase was somewhat increased in the white matter but decreased in the gray matter of diabetic patients. No increase was observed in the activity of neutral proteinase in diabetic white and gray matter. The activities of beta-glucuronidase and 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP) were of the same level as those of the controls. The activities of all 4 enzymes appeared to be increased in the diabetic nerve, with the possible exception of CNP which was measured from only 1 nerve. Furthermore, the amount of total protein was markedly decreased in diabetic peripheral myelin. The encephalitogenic basic protein of diabetic brain myelin was normal in the disc gel electrophoretic patterns of brain myelin proteins. However, the basic proteins of peripheral myelin were reduced in a number of diabetic patients. The present biochemical findings for diabetic white and gray matter were largely normal. Instead, the increased activities of at least the proteinases and beta-glucuronidase in diabetic peripheral nerve, together with the loss of basic proteins, indicate extensive biochemical damage of the peripheral nervous system in diabetes. They suggest that demyelination and other phenomena observed in diabetic peripheral nerve are not caused only by angiopathy and impaired circulation.
The activities of three lysosomal enzymes were measured from the lymphocytes and granulocytes of patients with multiple sclerosis and of controls. The activity of acid phosphatase was increased in the granulocytes and that of beta-glucuronidase in the lymphocytes of MS patients in remission, as compared to those in relapse. No marked increases were observed in the activity of acid proteinase. These findings suggest that a number of lysosomal enzymes in both lymphocytes and granulocytes can be activated during demyelinating processes for reasons unknown at the moment.
Seven polyols, erythritol, arabinitol, anhydroflucitol, mannitol, sorbitol, myoinositol and possibly ribitol were identified in human cerebrospinal fluid by means of gas-liquid chromatography and mass spectrometry. Quantitative data were obtained for five polyols, arabinitol, anhydroglucitol, mannitol, sorbitol and myoinositol, by screening of 205 CSF samples. These five polyols represented 90-95 per cent of the polyol-concentration which was 340 +/- 105 mumol/1 in the total series. The concentration of polyols in the CSF was two times higher than that in the plasma (148 +/- 30 mumol/1), where only anhydroglucitol and myoinositol could be quantitated. The variations noted were not associated with age, sex or the plasma concentrations of polyols. The polyols of the CSF most likely originate from brain tissue and/or spinal cord since penetration from the plasma against a gradient seems unlikely.
Five polyols, arabinitol, anhydroglucitol, mannitol, sorbitol and myoinositol, normally present in the cerebrospinal fluid (CSF), were studied. Quantitative gas-liquid chromatographic analysis of 211 CSF and 112 plasma samples indicated significantly altered concentrations in several clinical conditions. All five polyols were decreased in the CSF of patients suffering from meningitis, cerebral atrophy, sepsis, and in patients receiving intrathecal cytostate therapy. Equilibration between plasma and CSF may explain the changes in sepsis and meningitis, while decreased total number of functioning cells may cause the decrease in cerebral atrophy. Intrathecal cytostates seem to have a destroying effect on the cell metabolism of the central nervous system. Renal failure causes accumulation of polyols in the plasma. Alterations in the metabolism of sorbitol, myoinositol and anhydroglucitol seem to be present in diabetes. The plasma concentration of anhydroglucitol is decreased in renal failure.
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