A nationwide survey on transient hyperammonemia in newborn infants in Japan: prognosis of life and neurological outcome.

A nationwide survey of transient hyperammonemia in newborns was carried out in Japan. A total of 18 patients, consisting of 12 male and 6 female infants, were reported from 11 facilities. These neonates exhibited hyperammonemia with plasma ammonia levels in the range from 124 to 6256 micrograms/dl. Four newborn infants of the 18 died in the neonatal period, and an additional one died in the early infancy. Among the 13 infants who were alive at the time of this survey, 6 had neurological sequelae, including mental retardation, spastic quadriplegia and epilepsy. The multivariate analysis revealed that the Apgar score at 1 minute, peak plasma ammonia concentration, birth weight and sex were significant factors affecting the prognosis of life.     

Assembly, disassembly, and exchange of glial fibrillary acidic protein

The kinetics and dynamics of glial fibrillary acidic protein (GFAP) assembly was explored by a fluorescence energy transfer assay method. Purified GFAP was stoichiometrically labeled at a single cysteine residue with fluorescein-maleimide. Soluble labeled GFAP in a low ionic strength buffer was assembled into 10 nm filaments by rapidly increasing the ionic strength, and the kinetics of GFAP assembly was monitored by the reduction in fluorescence due to self-quenching of fluorescein. The extent of fluorescence quench correlated with both the formation of 10 nm filament morphology and the amount of protein pelleted at 12,000g. The assembly of GFAP is critically dependent upon both protein and magnesium ion concentration, and at the critical concentration for GFAP assembly is approximately 40 micrograms/ml. Disassembly of GFAP filaments was also observed as a relief of fluorescence quenching after dilution of labeled GFAP filaments. When labeled GFAP filaments were mixed with an excess of unlabeled filaments, a rapid increase of fluorescence was observed, which is due to an exchange of subunits between labeled and unlabeled GFAP filaments. These results indicate that GFAP filaments are dynamic structures and that a small pool of kinetically active unassembled GFAP subunits are in a dynamic equilibrium with assembled GFAP filaments. The ability of GFAP to assemble, disassemble, and undergo subunit exchange has important implications for the organization and dynamics of astroglia cell cytoskeleton during development and in response to injury.     

Ultrastructural characterization of the tau-immunoreactive tubules in the oligodendroglial perikarya and their inner loop processes in progressive supranuclear palsy

Coiled bodies and interfascicular threads are conspicuous white matter abnormalities of brains of patients with progressive supranuclear palsy (PSP). Both structures are argyrophilic and immunoreactive for the microtubule-binding protein tau. This report concerns the ultrastructural localization of interfascicular threads and their relationship to coiled bodies in five PSP patients. We showed for the first time that abnormal tubules with a 13- to 15-nm diameter and fuzzy outer contours were the common structures of coiled bodies in the oligodendroglial perikarya and of interfascicular threads. Moreover, the tubules were immunolabeled by anti-tau antibodies. The abnormal tau-positive tubules of interfascicular threads were located in the inner loop of the myelin sheath. Our study further indicated that the thread-like structures in the white matter comprised, at least in part, oligodendroglial processes, and that they were also present in gray matter. We consider that the formation of coiled bodies in the perikarya and of interfascicular threads represents a common cytoskeletal abnormality of the oligodendroglia of PSP patients. Moreover, even though the white matter alterations of PSP resemble those of corticobasal degeneration, there are certain ultrastructural differences in the abnormal oligodendroglial tubules of the two diseases. Received: 4 October 1996 / Accepted: 6 December 1996     

Non-ketotic hyperglycinaemia due to a deficiency of T-protein in the glycine cleavage system in liver and brain

Non-ketotic hyperglycinaemia was diagnosed in a girl at 3 weeks of age because of the typical clinical presentation, the elevated glycine concentration in urine, plasma and especially in cerebrospinal fluid and the normal profile of organic acids in urine. An EEG showed the typical burst suppression pattern. Therapeutic approaches with either pyridoxine (50 mg d-1) alone or in combination with N5-formyltetrahydrofolate (3 X 3 mg d-1) or with strychnine (0.3 mg per kg body weight) did not result in improvement. In postmortem liver and brain of the patient the overall activity of the glycine cleavage system was deficient; examination of the activity of the individual components of the glycine cleavage system in the tissues revealed that the activity of the T-protein was undetectable, whereas that of the other components and of lipoamide dehydrogenase was normal.     

Dissecting aneurysm of the vertebral artery as a cause of Wallenberg's syndrome

Although it is well known that Wallenberg's syndrome is caused by occlusion of the vertebral artery (VA) or the posterior inferior cerebellar artery (PICA), the etiology of the occlusion is rarely documented. During the course of Wallenberg's syndrome, patients often complain of headache. We thought that these headaches might be caused by dissecting aneurysm (DA) of the vertebral artery, and so we studied the incidence of DA in our cases with Wallenberg's syndrome. Although many variants exist, Wallenberg's syndrome encompasses several neurological symptoms due to a disorder of the nucleus and nerve tracts located in the lateral part of the medulla. We diagnosed our patients as having Wallenberg's syndrome on the basis of symptoms such as loss of pain and temperature sensation in the unilateral face and contralateral body, cerebellar ataxia, and dysphasia. We investigated 22 cases of Wallenberg's syndrome over a five-year period, and excluded patients who developed subarachnoid hemorrhage upon onset of the syndrome. Our cases can be divided into two groups; one with severe stenosis or occlusion of VA (n = 15) and the other with occlusion of PICA (n = 5). The angiograms of the two remaining patients showed no abnormal findings. The mean age of the VA group (42.5 yrs.) was younger than that of the PICA group (64.2 yrs.). The age distribution of the PICA group is similar to that of other occlusive cerebrovascular diseases. Seven cases of the VA group demonstrated aneurysmal dilatation and luminal stenosis, and so they were diagnosed as having dissecting aneurysm of VA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunological Detection and Quantitation of DNA Adducts Formed by 4-Aminoazobenzene Species in vivo

Antibodies to 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and 2-methoxy-4-aminoazobenzene (2-MeO-AAB) DNA adducts were raised in rabbits against in vitro-adducted DNA samples. The enzyme-linked immunosorbent assay (ELISA) was used to determine the sensitivity and specificity of these antibodies. They proved highly specific for the modified DNA used as the immunogen, but cross-reacted with each other. Moreover, they showed cross reactivity with DNA modified by 4-( o -tolylazo)- o -toluidine, but not by other carcinogens, such as 4-aminobiphenyl or 4-nitroquinoline 1-oxide. The 50% inhibition level of antibody binding in the competitive ELISA was at 10–20 fmol of modified base per assay (equivalent to 1–2 adducts per 10⁶ bases). Immunohistochemical staining indicated that these antibodies bind specifically to nuclear components of the liver in rats given either 3-MeO-AAB or 2-MeO-AAB at the dose of 50 mg/kg body weight.     

Malignant pilomatricoma. An immunohistochemical study with antihair keratin antibody.

A case is reported of malignant pilomatricoma confirmed by immunohistochemistry using anti-human hair keratin (anti-HHK) antibody prepared by the authors. The tumor occurred in the soft tissue of the inguinal region of an 88-year-old woman, with later invasion of the epidermis. No other possible primary lesion was found at autopsy. Histologically, the tumor was squamous cell carcinoma with nests of tumor cells and shadow cell-like necrotic cells showing central keratinization and focal calcification. Immunohistochemically, the hair keratin was positive in this tumor and in benign pilomatricomas exclusively. All other skin lesions and various squamous cell carcinomas examined were negative for this antigen. The staining patterns of commercial antiepidermal keratin and antiinvolucrin antibodies were significantly different from that of anti-HHK in normal skin and in these lesions. To the authors' knowledge, this is the first case of malignant pilomatricoma tested with anti-HHK staining. Malignant pilomatricoma is generally a low-grade malignant tumor, but it can metastasize and be fatal as it was in this case.