Soichi Kodama

Effects of ketogenic diet on electroconvulsive threshold and brain contents of adenosine nucleotides.

The anticonvulsive effect of a ketogenic diet was investigated using mice fed on a ketogenic milk powder which contained medium-chain triglycerides (MCT). Electroconvulsive shocking and determination of adenosine nucleotides in mice brain were performed on three mice groups, (1) a control group; free access to a commercially available diet, (2) a fasted group; fasted for two days, and (3) a ketotic group; fasted for two days and then fed on the ketogenic milk powder for two weeks. The maximal electroconvulsive threshold of the ketotic group was significantly higher than that of the fasted group (p less than 0.001). The maximal electroconvulsive threshold of the fasted group was significantly higher than that of the control group (p less than 0.05). The contents of adenosine triphosphate (ATP) in the brain of the ketotic group was significantly higher than that of the control group (p less than 0.01). These results suggest that chronic ketosis with the ketogenic diet increases the contents of ATP in the brain and this increase in ATP probably accounts for the neuronal stability.

The 3260 mutation in mitochondrial DNA can cause mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS).

Laboratory Medicine, National Center Hospital for Mental, Nervous and Muscular Disorders, NCNP, Tokyo, Japan (Dr. Nonaka); Himeji Red Cross Hospital, Hyogo, Japan (Drs. Komatsu and Kodama); and Department of Human Genetics, National Institute of Genetics, Mishima, Japan (Dr. Horai). Acknowledgment: The authors thank Dr. S. M. Sumi, University of Washing- ton, for his helpful comments on the manuscript. Address reprint requests to lchizo Nishino, MD, Department of Ultrastruc- tural Research, National Institute of Neuroscience, National Center of Neu- rology and Psychiatry (NCNP), Kodaira, Tokyo, Japan. Accepted for publication April 22, 1996

Cockayne syndrome: Magnetic resonance images of the brain in a severe form with early onset

SummaryA 2-year-old boy with an early onset and severe form of Cockaynes syndrome (CS) showed differences from the common CS form, which made the clinical diagnosis difficult. However, the cellular characteristics of CS, that the patients skin fibroblasts exhibited the hypersensitivity to the lethal effect of 254 nm ultraviolet light (UV) and a defective recovery of post-UV DNA synthesis, but normal level of UV-induced unscheduled DNA synthesis, were observed. The magnetic resonance imaging (MRI) by the inversion-recovery method of the brain at age of 26 months showed atrophy or poor development of high signal images of the white matter. The MRI spin-echo image showed a low signal image of the lenticular nucleus. The T1 and T2 values of the cerebrum (grey matter, white matter, lenticular nucleus and thalamus) were greater than those of the age-matched controls, but similar to infant brains with much free water. Such MRI findings may suggest hypomyelination leading to the severe atrophy of the brain in this CS patient. His severe symptoms progressed rapidly until his death at 35 months due to systemic sepsis and renal dysfunction. Autopsy revealed severe microcephaly, severe atrophy of cerebrum, cerebellum and brain stem, and calcification throughout the brain, especially in the basal ganglia. Myelin staining showed numerous patchy losses of myelination in the cortical white matter.

Thyroid Function in Children with Long-Term Anticonvulsant Treatment

Thyroid functions were studied in 287 children given long-term treatment with anticonvulsants. Of these 287 patients, 26 were treated with carbamazepine (CBZ) alone, 63 with phenobarbital (PB) alone, 66 with sodium valproate (VPA) alone and 132 with combination therapy. Serum triiodothyronine (T3) and thyroxine (T4) concentrations were decreased after more than 3 years of treatment with CBZ. The regression line of serum T4 concentrations against serum CBZ concentrations indicated a negative correlation. Serum T3 and T4 concentrations were decreased after more than 6 years of treatment with PB, although there was no statistical significance in the relationship between serum T4 and PB concentrations. There was no significant decrease in serum T3 or T4 concentration in patients treated with VPA. Serum-free T4 and thyroxine-binding globulin were decreased and serum thyrotropic hormone concentration was increased in patients with low serum T4 concentrations. We conclude that thyroid functions should be examined in children given long-term treatment with anticonvulsants.

Childhood bullous pemphigoid: Immunohistochemical, immunoelectron microscopic, and Western blot analysis

The most reliable diagnostic criteria of childhood bullous pemphigoid (BP) have been the linear deposition of IgG and C3 at the basement membrane zone (BMZ) and the frequent presence of circulating IgG BMZ antibodies. To characterize further the immunologic features of childhood BP, we performed direct and indirect immunoelectron microscopy (IEM) and Western immunoblotting on specimens from a 3-month-old boy with BP who had immunofluorescence evidence of linear BMZ IgG and C3 deposition and circulating IgG BMZ antibody. By direct IEM, autoantibody deposits were seen in the upper portion of the lamina lucida and on the undersurface of basal keratinocytes. Indirect IEM showed that the binding sites of BP antibody were closely related to the intracellular attachment plaques of hemidesmosomes. By Western blotting, the patients serum recognized 180 kd epidermal protein.

Congenital generalized lipodystrophy with insulin-resistant diabetes

Hyperglycemia, glucose intolerance, hyperinsulinemia and resistance to exogenous insulin were found in a 10-year-old Japanese boy diagnosed as having congenital generalized lipodystrophy.Studies on insulin receptors of circulating mononuclear leucocytes indicated that insulin-resistant diabetes combined with congenital generalized lipodystrophy may be due to disturbance of insulin binding to membrane receptors. No insulin-binding antibody or antibody that impairs insulin-receptor binding was found.Plasma glucagon showed an exaggerated response to L-arginine before treatment. After treatment with a controlled diet and an oral sulfonylurea (500 mg/day) for 4 weeks, there was improvement in the plasma glucagon response to L-arginine. Improvement in the hyperglycemia, hyperinsulinemia and acanthosis nigricans was also observed.On the other hand, on completion of a 7-day high-fat diet, a marked increase in serum free fatty acids, triglycerides and β-lipoproteins was observed. The total plasma post-heparin lipolytic activity during the high fat diet was within the normal range. However, the level of protamine-inactivated activity was 3 times that of the control.

Platelet glucose-6-phosphatase activity in patients with von Gierke's disease and their parents

The present report describes the results of an assay of platelet glucose-6-phosphatase (G-6-Pase) in patients with von Gierkes disease and their parents. The G-6-Pase activity of the patients was found to be about 10–25% of that of controls, while that of the parents showed an intermediate value between that of the patients and that of the controls, which led to the conclusion that the parents were the heterozygotes of the disease. These results suggest a possible method for the diagnosis of G-6-Pase deficiency as well as for detection of the heterozygotes of the disease by a platelet G-6-Pase assay without making a G-6-Pase assay of liver biopsy materials. As for the separation of platelets, a differential centrifugation was undertaken using Na2 -EDTA as an anticoagulant. In the G-6-Pase assay, universally 14C-labelled glucose 6-phosphate ([U-14C]-G-6-P) was used as a substrate and the enzyme activity was measured by the amount of glucose liberated by the platelet suspension after the reaction. The effect of non-specific phosphatase was estimated by using universally 14C-labelled glucose 1-phosphate ([U-14C] -G -6-P) as substrate. In the diagnosis of von Gierkes disease, as well as the detection of the heterozygotes of the disease by the G-6-Pase assay using platelets as material, the effect of non-specific phosphatase was considered to be negligible.

A simple method to diagnose adrenoleukodystrophy using a dried blood spot on filter paper

A new, simple method for the diagnosis of adrenoleukodystrophy (ALD) using a dried blood spot sample, is described. Fatty acid from the dried blood spot was extracted and methylated simultaneously with HCl-methanol. Fatty acid methyl esters were analyzed by gas chromatography-mass spectrometry. Fatty acid compositions of the blood spot from four patients with ALD and five healthy controls were determined from the mass chromatograms of the m/z 143 ion, [(CH2)6 COOCH3]+. The ratios of tetracosanoic acid to docosanoic acid (C24:0/C22:0) and hexacosanoic acid to docosanoic acid (C26:0/C22:0) were significantly greater in ALD patients than in the controls. The fatty acid composition of the dried blood spot did not change at room temperature within a week. Since the specimens can be sent by mail, this method could be applied to the screening of ALD.

Dysgenesis of the deep venous system as a diagnostic criterion for holoprosencephaly

SummaryThe angiographic features of three cases with holoprosencephaly are reported. In all of them, the galenic venous system seemed to be deficient and the basal ganglia were drained by peculiar veins which coursed laterally and drained directly into the lateral sinus. These peculiar veins are considered to be remnants of the embryonic diencephalic viens, suggesting that these patients retain their early embryonic pattern of venous drainage. The diagnosis of alobar holoprosencephaly is established by the demonstration of the azygos anterior cerebral artery coursing along the frontal bone with excessive undulations. But with lobar holoprosencephaly, this characteristic feature is not present, and dysgenesis of the deep venous system is important for the diagnosis of holoprosencephaly.

Glycogen phosphorylase kinase deficiency: A survey of enzymes in phosphorylase activating system

Abstract A four year-old Japanese boy with hepatomegaly and hypoglycemia has low activity of hepatic phosphorylase. A survey of enzymes involved in the phosphorylase activating system has revealed that liver phosphorylase kinase is deficient although adenosine 3′,5′-monophosphate (cyclic AMP)-dependent protein kinase and total phosphorylase measured in a mixture supplemented by rabbit muscle phosphorylase kinase show normal activities. The hormone receptor as well as adenyl cyclase system appears to be normal since cyclic AMP increases immediately after intravenous injection of glucagon. His muscle phosphorylase activating system is normal.