Non-ketotic hyperglycinemia (NKH) is a well-recognized metabolic cause of life-threatening illness in the neonate. The fundamental defect is in the glycine cleavage enzyme (GCE), which consists of four protein components. Our study revealed that the majority of NKH patients had a specific defect in P-protein (glycine decarboxylase). The primary lesion of NKH in gene level was investigated, using cDNA encoding human glycine decarboxylase. A three-base deletion; resulting in deletion of Phe756 was found in a Japanese patient with NKH. In the majority of NKH patients in Finland, where there is a high incidence of NKH, it was found to be due to a common mutation--a point mutation resulting in amino acid alternation from Ser564 to Ile564. Prenatal diagnosis is possible by determining the activity of GCE and also by DNA analysis. Recent findings suggest that the high concentrations of glycine in the brain may contribute to the pathophysiology of NKH by overactivating NMDA receptors via an action at the associated glycine modulatory site. These provide a possibility that early treatment with NMDA receptor antagonist may prevent brain damage in NKH.

Amino Acid Oxidoreductases↗

PubMedDate not supplied

Cerebral glucose metabolism in five patients with Lennox-Gastaut syndrome.

Regional cerebral glucose metabolic rates were estimated by positron emission tomography, in parallel with electroencephalography and cranial computed tomography in 5 patients with Lennox-Gastaut syndrome. The 5 patients, 3 boys and 2 girls, ranged in age from 10-15 years. Computed tomography revealed no gross abnormalities. Each patient received 2-5 mCi of 2-(18F)-fluoro-2-deoxy-D-glucose (18F-FDG) intravenously. Averaged cerebral glucose metabolic rates were reduced in each cerebral region as compared with controls. Unilateral hypometabolism was present in 4 patients: one in the inferior frontal gyrus as well as the posterior portion of the superior temporal gyrus; one in the inferior frontal gyrus; one in the posterior portion of the superior temporal gyrus; and one demonstrated diffuse hemispheric hypometabolism including the inferior frontal and posterior portion of the superior temporal gyrus. The side of hypometabolism was the same as the epileptogenic focus on the electroencephalogram. No focal changes were demonstrated on the electroencephalogram of a patient whose positron emission tomography revealed hemispheric hypometabolism. Hypometabolism of the inferior frontal and posterior portion of the superior temporal gyrus may relate to the possible pathogenesis of Lennox-Gastaut syndrome. Positron emission tomography has the potential to reveal a latent focal or lateralized abnormality in some patients with non-localized electroencephalographic changes.

Blood Glucose↗

PubMedDate not supplied

Cytochrome C oxidase-deficient mitochondria in mitochondrial myopathy.

Electron microscopic cytochemistry was used to evaluate the behavior of cytochrome c oxidase (COX) in cultured skin fibroblasts from 4 patients with decreased COX activity (Leigh encephalopathy, fatal infantile COX deficiency). In patients with Leigh encephalopathy, all mitochondria reacted to COX staining either equivocally or negatively, indicating that all mitochondria were abnormal in these patients. In 1 patient with fatal infantile COX deficiency, intercellular heterogeneity of mitochondria was observed by COX staining. In another patient with fatal infantile COX deficiency, intracellular heterogeneity of mitochondria was observed. Patients with Leigh encephalopathy appeared to have a different type of mitochondrial COX deficiency than those with fatal infantile COX deficiency. Our result suggest that these 2 diseases may result from different genetic mechanisms.

Acidosis, Lactic↗

PubMedDate not supplied

Presence of dopamine DA-1 receptors in human decidua.

To evaluate the role of dopamine in human parturition, we studied the presence of dopamine receptors in human decidua obtained immediately after delivery, using a radiolabelled receptor assay. [3H]SCH23390, a dopamine DA-1 receptor ligand was used to identify and characterize the DA-1 receptor. Scatchard analysis of our saturation experiments revealed one class of high-affinity binding sites. The equilibrium dissociation constant (Kd) for binding of [3H]SCH23390 to decidual DA-1 receptors was 1.87 +/- 0.16 nM (mean +/- s.d. n = 3) at 30 degrees C. The maximum binding capacity (Bmax) was 79.0 +/- 15.4 fmol/mg protein at 30 degrees C. The specificity of DA-1 receptor binding was inhibited by SCH23390 (a DA-1 antagonist), SKF38393 (a DA-1 agonist) and dopamine with the inhibitory constants (Ki) of 5.82 +/- 2.27 nM (mean +/- s.d., n = 3), 45.6 +/- 30.5 nM (mean +/- s.d. n = 3) and 2.86 +/- 1.02 microM (mean +/- s.d., n = 3) respectively. However, (+/-)-sulpiride (a DA-2 antagonist) and (-)-propranolol (a beta-adrenergic antagonist) were without effect. The specific binding of [3H]spiperone (a DA-2 receptor ligand) was not detected. We previously reported that in vitro the human decidual tissues produce significant amounts of prostaglandins in the presence of dopamine. We postulate that dopamine regulates the production of prostaglandin in human decidua via DA-1 receptors.

Benzazepines↗

PubMedDate not supplied

Voluntary dislocation of the radial head.

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Adult↗

PubMedDate not supplied

Epstein-Barr virus transforms precursor B cells even before immunoglobulin gene rearrangements.

The very early stages of the human B-cell differentiation pathway are poorly understood, primarily because of the lack of appropriate permanent cell lines. Epstein-Barr virus (EBV) is a putative human oncogenic virus which transforms human B cells in vitro into continuously proliferating cells. It has been believed that EBV transforms mature B cells, but recently, transformation of immature pre-B-cell lines has been reported, suggesting that EBV might also transform cells much earlier in the B-cell lineage. We report here the establishment of cell lines transformed by EBV at various stages of the B-cell differentiation pathway. Interestingly, two lines showed the complete absence of immunoglobulin synthesis and the lack of immunoglobulin gene rearrangement despite containing EBV genome and surface markers of B cells. Our results indicate that EBV can infect and transform cells of the B lymphocyte lineage even before immunoglobulin gene rearrangement.

Animals↗