A point mutation at ATP-binding region of the ALD gene in a family with X-linked adrenoleukodystrophy.

A prenatal diagnosis was performed in a family with X-linked adrenoleukodystrophy (ALD). A fetus was at high risk of suffering the disease by segregation analysis and by very long chain fatty acid-CoA synthetase activity assay. A transition (G to A) at codon 617 of the candidate ALD gene was detected by reverse transcription PCR (RT-PCR) based sequencing of the fetal liver RNA. The mutation was located in highly conserved ATP-binding site in this gene and deduced amino acid transversion R617H was thought to be the cause of ALD in this family.

Effect of myasthenic IgG on degradation of junctional acetylcholine receptor.

We investigated the effect of the IgG from patients with myasthenia gravis (MG) on the degradation of normal rat junctional acetylcholine receptor (AChR) labeled with 125I-alpha-bungarotoxin (BuTx) and calculated the degradation rate (DR). The DR for the IgG from these patients was significantly higher than that from healthy volunteers and patients with other autoimmune diseases. For MG, DR was significantly correlated with the severity of the disease but not with anti-AChR antibody titer. DR was accelerated by IgG from patients with generalized MG whose antibody titers were in the normal range and by IgG from patients with ocular MG. These results indicate that measurement of the DR of junctional AChR in normal rats is more closely correlated with the severity of the disease than is measurement of anti-AChR antibody and that the former is a sensitive and confirmatory method for evaluating MG.

Treatment of myasthenia gravis: a comparison of the natural course and current therapies.

Ninety-five patients with generalized myasthenia gravis were followed for 10 years to evaluate the long term effects of prednisolone, thymectomy, or both, and they were compared with a group only with anticholinesterase treatment. Only 15.0% of the patients with anticholinesterase alone had showed improvement 10 years after the onset, but more than 60% of those treated with prednisolone, thymectomy, or both showed improvement. Especially thymectomy induced complete remissions at 10 years after surgery in more than 20% of the patients. There was no difference between the histology of the thymi and clinical severity, or anti-acetylcholine receptor (AChR) antibody titer. In patients who showed improvement classified "good" of higher 10 years after thymectomy with or without prednisolone, anti-AChR antibody titers swiftly decreased to 37.8% of the value before surgery, and remained low thereafter. This result suggests that the marked decrease in anti-AChR antibody titers within 1 month after thymectomy is a favorable prognostic sign in myasthenia gravis patients who have undergone thymectomy.

[A case of foreign-body granuloma treated with steroid hormone].

A 68-year-old woman was admitted to Nagasaki University Hospital complaining of gait disturbance. She had suffered from hemifacial spasm since the age of 56 and had undergone neurovascular decompression for the spasm in another hospital five years before admission. At surgery, the vertebral and posterior inferior cerebellar arteries had been separated from the facial nerve with cotton string and attached to the clivus with alpha-cyanoacrylate monomer. Although the hemifacial spasm had improved postoperatively, the patient had suffered from gait disturbance and headache for two months after surgery, and hearing disturbance and hemifacial palsy on the same side as the hemifacial spasm for seven months after surgery. At the time of the present admission, contrast-enhanced CT scan revealed a mass at the left cerebello-pontine angle. In the T1-weighted inversion recovery sequence of MRI, the mass showed a slightly lower intensity than that of surrounding tissues. In the T2-weighted spin echo sequence of MRI, it showed a heterogenously low intensity with some high intensity spots. We diagnosed this mass as a foreign-body granuloma and treated it with dexamethasone injected intramuscularly. Edema decreased around the granuloma, and her gait disturbance improved markedly. But the hearing disturbance and hemifacial palsy did not improve at all, indicating that these two symptoms might not be caused only by brain edema but also by direct damage due to granuloma or inflammation. We thought that the steroid hormone elicited good results in the treatment of inoperable foreign-body granuloma.

Myasthenogenicity of a human acetylcholine receptor alpha-subunit peptide: morphology and immunology.

Each of 10 rats inoculated with a synthetic peptide comprising residues 125-147 (without a disulfide bond) of human acetylcholine receptor (AChR) alpha-subunit (H alpha) had deposits of IgG and C3 (immune complexes) and showed morphological changes in the fine structure at the motor end-plates 5 weeks after a single immunization. Antibody to the H alpha peptides was elevated 1 week after immunization, but, antibody levels to solubilized human or rat AChR were very low in 8 of the 10 rats. These results suggest that the immune response to peptide H alpha is the myasthenogenic site, which induces morphological change at the end-plates.

[Study of 123I-IMP SPECT on diabetic patients].

The involvement of peripheral nerves and nerve roots often leads to neurological manifestations which have frequently been described in association with diabetes mellitus. Whether there is any specific involvement of the central nervous system in this process has yet to be determined. Recently, many reports have suggested that significant neurophysiologic abnormalities in the central nervous system can sometimes be found in diabetic patients. In order to accurately examine the existence of central nervous system involvement in patients with diabetes mellitus, comparisons of 123I-IMP (IMP) washout rates were made between normal adults (n = 19, average age 43.3 years) and diabetic patients (n = 23, average age 43.3 years), and these results were graphically demonstrated by color images. Early images were obtained 30 minutes after intravenous injection, while delayed images were made 4 hours after injection. The IMP washout rate was obtained by subtracting the values of the delayed image with the early image. The standard deviation (SD) of the IMP washout rate for each patient was compared to the averaged SD obtained from healthy adults. After calculating the deviation from SD levels of healthy adults, we made an image of the patient's IMP washout rates. These images were divided into seven degrees (I, II: normal, III, IV: borderline, V-VII: abnormal) and the ratio of each degree was expressed by a histogram in each cerebral hemisphere as the washout rate index. In 23 diabetic subjects, seven patients were found to be borderline while sixteen patients were abnormal. These impairments were not related either to the presence of diabetic neuropathies or the duration of disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Hippocampus and frontal cortex are the potential mediatory sites for convulsions induced by new quinolones and non-steroidal anti-inflammatory drugs.

The combined administration of enoxacin, a new quinolone, and fenbufen, a non-steroidal anti-inflammatory drug induced convulsions in mice, but convulsion did not occur when a single administration of each drug was given. Inhibition by enoxacin of [3H]muscimol binding to mouse and human brain membranes was remarkably facilitated by fenbufen. These inhibitions were much more prominent in the hippocampus and frontal cortex than in the cerebellum of human and mouse brain. Enoxacin and fenbufen each at a high concentration produced a moderate and slight inhibition of the [3H]muscimol binding, respectively, in the hippocampus and frontal cortex but not in the cerebellum. It would thus appear that the drug interaction between enoxacin and fenbufen on the gamma-aminobutyric acidA receptor in hippocampus and frontal cortex plays a role in inducing convulsions.

Magnetic resonance imaging in diagnosis and follow-up of minimal thyroid ophthalmopathy.

We report a case of minimal thyroid ophthalmopathy treated with intravenous methylprednisolone, in which precise identification of the involved muscle was possible with the use of surface coil magnetic resonance (MR) imaging. Intravenous methylprednisolone was more effective than the oral prednisolone as judged by orbital MR imaging. MR imaging is one of the useful tools in the diagnosis and assessment of treatment in this field.

CT demonstration of spinal epidural emphysema after strenuous exercise.

We report a case of spinal epidural emphysema after strenuous exercise. The emphysema was without clinical signs and disappeared after 2 weeks.