Yasunobu Antoku

Clinical improvement of adrenoleukodystrophy following intravenous gammaglobulin therapy

A patient with adrenoleukodystrophy was successfully treated by means of intravenous gammaglobulin injections. The clinical symptoms, especially visual loss, were apparently relieved and no neurological deterioration was observed during a 18-month period following the start of the gammaglobulin treatment.

Adrenoleukodystrophy Abnormality of very long‐chain fatty acids in erythrocyte membrane phospholipids

Long-chain fatty acids in erythrocyte membrane phospholipids were analyzed in three patients with adrenoleukodystrophy (ALD) and four diseased controls with other neurologic diseases by high performance liquid chromatography (HPLC). HPLC chromatograms showed the increase of a very long-chain fatty acid C26:0 in glycerophospholipids of ALD erythrocyte membranes, which was not so prominent in sphingomyelin. The ratio of C26:0 to C22:0 increased in glycerophospholipids as well as sphingomyelin in ALD. These results suggest that ALD has a generalized abnormal metabolism of very long-chain saturated fatty acids.

Correlations of elevated levels of hexacosanoate in erythrocyte membranes with risk factors for atherosclerosis

We analyzed erythrocyte membrane C26:0 from 504 volunteers by high-performance liquid chromatography. The associations between the elevated levels of erythrocyte membrane C26:0 (0.20 or greater than 0.20%) and sex, obesity (body mass index> or =26.4), smoking (> or =20 cigarettes per day), present illnesses and past diseases were examined with the chi(2) test. The correlations among age and the levels of erythrocyte membrane C26:0, plasma total cholesterol, triglycerides, LDL cholesterol and HDL cholesterol were analyzed using Spearmans correlation coefficient. Moreover, the frequencies of high levels of erythrocyte membrane C26:0 were examined in male and female subjects divided into seven age groups. The elevated levels of erythrocyte membrane C26:0 were significantly more frequent in male subjects than in females, and were closely associated with obesity, smoking, and atherosclerosis-related diseases of present illnesses. The levels of erythrocyte membrane C26:0 were highly correlated with age and the levels of plasma total cholesterol, triglycerides and LDL cholesterol, and inversely with those of HDL cholesterol. The frequency of high levels of erythrocyte membrane C26:0 in male subjects was greater than that in female subjects in all of the seven age groups. Elevated levels of erythrocyte membrane C26:0 may be closely related with atherosclerosis.

Erythrocyte membrane cation-stimulated ATPase activities in myotonic muscular dystrophy

The cation-stimulated ATPase activities of erythrocyte membranes from patients with myotonic muscular dystrophy (MyD) were compared with the activities in age- and sex-matched controls. The enzymes included ouabain-sensitive ATPase, Mg2+-ATPase and Ca2+ + Mg2+-ATPase. Sampling and processing of the materials from patients with MyD and controls were simultaneously done in each experiment. The enzyme activities were varied with or without EGTA in the reaction medium, or with different temperatures for membrane storage, but no significant differences between MyD and control were observed in any conditions. The present study indicates no specific abnormality of the cation-stimulated ATPase activities of erythrocyte membranes in MyD.

Adrenoleukodystrophy: fatty acid analysis of total glycerophospholipids in erythrocyte membranes

ABSTRACT – The saturated fatty acids released from the erythrocyte membranes of four patients with adrenoleukodystrophy (ALD) and 14 diseased controls were analyzed by high performance liquid chromatography. The ratios of C26:0 to other saturated fatty acids in ALD were higher than those of diseased controls, and neither false‐positive nor false‐negative samples were observed. These results suggest that a study of fatty acids of total glycerophospholipids in erythrocyte membranes by high performance liquid chromatography is a useful diagnostic method of ALD.

Very long-chain fatty acids in neutral lipids and glycerophospholipids of adrenoleukodystrophy-cultured skin fibroblasts

Three major lipid fractions, i.e., cholesterol ester, triacylglycerol and glycerophospholipids, were investigated cultured fibroblasts to clarify whether very long-chain fatty acids were accumulated or not. Abnormally accumulated very long-chain fatty acids were confirmed in all three lipid fractions. Our results support our previous report that there may be a generalized abnormal metabolism of very long-chain fatty acids in adrenoleukodystrophy.

Adrenoleukodystrophy and variants. Clinical, neurophysiological and biochemical studies in patients and family members.

Clinical, neurophysiological and biochemical studies were performed in patients with various forms of adrenoleukodystrophy (ALD) and their family members. The patients showed an abnormality in saturated very long chain fatty acids and in the somatosensory and brain stem auditory or visual evoked potentials. Female presumptive carriers without abnormal neurological manifestations also showed abnormality in the somatosensory or brain stem auditory evoked potentials and in saturated very long chain fatty acids. One ALD patient and his mother, a female carrier, had the decreased beta-galactosidase activity. The increase in saturated very long chain fatty acids was found, not only in sphingomyelin, but also in phosphatidylcholine and phosphatidylserine. Our results suggest that a generalized abnormal metabolism of VLFA and an abnormality in the central nervous system exist in our patients and female carriers.

A Study on Erythrocyte Membrane Plasmalogen in Myotonic Dystrophy

Phospholipid classes that included plasmalogens of erythrocyte membranes in seven myotonic dystrophy (MyD) patients and seven normal controls were analyzed by HPLC. No significant difference in phospholipid classes was found between patients with MyD and normal controls, but there was a visible difference in peak profiles of compounds of the phosphatidylethanolamine class. In the study of plasmalogens, we used two preparation methods: exposure to HCl and deacylation with mild alkaline. The area ratio of the plasmalogen form to the diacyl form in the phosphatidylethanolamine class of MyD erythrocyte membranes was significantly lower than that of normal controls. Fatty acid analyses showed that fatty acids of both phosphatidylethanolamine subclasses have less unsaturation in MyD.

Erythrocyte membrane in myotonic dystrophy. A study with acetylcholinesterase.

Erythrocyte membrane in myotonic dystrophy (MyD) was studied with respect to acetylcholinesterase (AchE), an enzyme localized on the external surface of the membrane. The activity was determined over the temperature range of 7-41 degrees C (in hemolysates) and 25-41 degrees C (in ghosts). The activity, the transition temperature in the Arrhenius plots, and the activation energy either above or below the transition temperature did not differ between MyD and controls. The Hill coefficient for the inhibition by fluoride was approximately 1 in MyD and in controls at 13, 25 and 37 degrees C. The dose of fluoride for 50% inhibition of the enzyme activity differed between different temperatures but not between MyD and controls. There seems to be no gross abnormality in AchE or its environment in erythrocyte membrane in MyD.

A comparison of erythrocytes, lymphocytes and blood plasma as samples in fatty acid analysis for the diagnosis of adrenoleukodystrophy

We studied the very-long-chain fatty acids of blood plasma, erythrocyte membranes and lymphocytes in 4 adrenoleukodystrophy patients, 5 adrenoleukodystrophy obligate carriers, 12 normal controls and 81 patients with various neurological disorders by high-performance liquid chromatography and compared the reliabilities in the diagnosis of adrenoleukodystrophy of these 3 components of peripheral blood. Of 81 patients with various neurological disorders, 2 myotonic dystrophy and 2 spinocerebellar degeneration patients showed increased ratios of C26:0 to C22:0 in erythrocyte membranes, but not in blood plasma and lymphocytes. None of the 12 normal controls showed increased ratios of C26:0 to C22:0 in erythrocyte membranes, blood plasma and lymphocytes. These results suggest that fatty acid analysis for the diagnosis of adrenoleukodystrophy is more reliable when blood plasma and lymphocytes are used than when erythrocyte membranes are used.