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.     

The spectral signature method for the analysis of PET brain images

We introduce the concept of the metabolic centroid spectrum as the feature space to characterize the distribution of metabolic activity in three-dimensional brains. The method computes the metabolic centroid of a brain subvolume for each increment of metabolic activity occurring in the whole brain. The result is the metabolic spectral signature, a continuous three-dimensional curve whose shape reflects the distribution of metabolic rates in the brain. The method's sensitivity to metabolic distribution asymmetries is greatly increased over that of the metabolic centroid method, while retaining its advantages; it is almost invariant to head size, head positioning, photon scatter, and the positron emission tomography (PET) camera's full width at half-maximum. It does not require magnetic resonance, computed tomography, or x-ray images. To test the method we analyzed the metabolic PET images of 40 normal subjects and 20 schizophrenics. The results show a unification of several metabolic characteristics of schizophrenic brains, such as laterality, hypofrontality, cortical/subcortical abnormalities, and overall brain hypometabolism, which were identified by different laboratories in separate studies using differing methodologies. Here they are presented by a single automatic objective method.     

Ganglioside or sialic acid attenuates ethanol-induced decrements in locomotion, nose-poke exploration, and anxiety, but not body temperature.

1. This laboratory has previously reported that pretreatment with ganglioside, or even with its constituent, sialic acid (SA), can attenuate certain intoxicating effects of ethanol. It was important to see if these findings could be replicated, particularly by using other measures of ethanol effects. Herein we report that pretreatment with either gangliosides or SA attenuated ethanol-induced decrements in locomotion, nose-poke exploration, and anxiety, but not body temperature. 2. An ethanol dose of 4 gm/kg caused a temperature drop of about 3 degrees C, which was unaffected by any pretreatment. The onset to sleep, however, was delayed an average of 18 or 36 secs in mice pretreated with ganglioside or SA, respectively. Ethanol-only (4 gm/kg) depressed mean cumulative locomotor activity to 31% of normal, whereas the depression was 83% of normal with beef brain ganglioside pretreatment. At 2 gm/kg ethanol alone decreased nose poking in a hole-board test to 29% of normal, but the depression was only 55-63% of normal with SA or ganglioside pretreatment. In a staircase climbing anxiety test, this dose of ethanol had no effect by itself, but both ganglioside and SA pre-treatment increased climbing by 22%. Ethanol did depress rearing to only 11% of normal, whereas rearing was 51 and 99% of normal with SA and ganglioside pretreatment, respectively. In a dark-preference test, ethanol-only caused mice to spend 64% of the time in the light, compared to 31% for controls. Time in the light was only 39 and 46% with ganglioside and SA pretreatment, respectively. 3. Blood levels of ethanol were not significantly affected by pretreatment. 4. When given alone, gangliosides significantly stimulated locomotion and staircase climbing. SA significantly decreased rearing in the staircase test. Both gangliosides and SA tended to increase nose poking, number of crossings in the dark-preference test, and time in a lighted compartment. Thus, it is possible that some of the attenuation of intoxication is attributable to non-specific stimulant properties of gangliosides and SA.     

Widespread serum amyloid P immunoreactivity in cortical amyloid deposits and the neurofibrillary pathology of Alzheimer's disease and other degenerative disorders

Amyloid P (AP) component is present in all types of systemic amyloid deposits. Recently, it has been shown to be also present in cerebral amyloid lesions of Alzheimer's disease (AD). In this study, we used immunocytochemical methods to extend these findings at the electron microscope level and characterize the spectrum of AP immunoreactivity in neurofibrillary pathology (NFP) of AD and other neurodegenerative disorders including Down's syndrome (DS), Creutzfeldt-Jakob, Parkinson's, Pick's and diffuse Lewy body diseases and progressive supranuclear palsy. In AD and DS, AP immunoreaction product was evident in all the classical amyloid lesions and NFP in a large sample of all cortical areas examined. The distribution and relative intensity of immunostaining was similar to that of thioflavin S staining in serial sections. In many cases, however, plaques and vessels stained by anti-AP serum were not apparent with thioflavin S. Serial sections immunostained with antiserum to amyloid A, C-reactive protein or to other proteins involved in systemic amyloidoses and the acute phase response showed no evidence of staining in any of the cerebral lesions. Electron microscopy confirmed that AP immunoreactivity was associated with the abnormal filaments characteristic of NFP as well as amyloid fibrils found in plaques and vessels showing congophilic amyloid angiopathy. Plaques of Creutzfeldt-Jakob disease, Pick bodies of Pick's disease, tangles and Lewy bodies in Parkinson's disease and a subpopulation of Lewy bodies in the diffuse Lewy body disease coexistent with AD were also stained. With the exception of vessels in two of the five cases, AP was not detected in age-matched controls. Our observations indicate AP to be a consistent feature of cerebral NFP and amyloid deposits.     

A role for GABAB receptors in excitation and inhibition of thalamocortical cells.

Gamma-aminobutyric acid (GABA) in the thalamus has mainly been associated with the inhibitory modulation of the sensory and cortical flow of information via a 'classical', chloride-dependent, GABAA receptor-mediated action. However, the discovery of a late, long-lasting potassium-dependent inhibitory postsynaptic potential (IPSP) mediated by GABAB receptors present on thalamocortical cells, has allowed new insights into our understanding of the physiological role of this neurotransmitter. In particular, work on the dorsal lateral geniculate nucleus indicates that together with a relatively weak inhibition, GABAB receptor-mediated IPSPs 'prepare' thalamocortical cells for burst firing by activating low-threshold calcium potentials. Thus, GABA in the thalamus can no longer be viewed only as a 'classical' inhibitory transmitter but also as a neuromodulator with a 'priming' role for burst firing excitation. This dual role of GABAB receptors in inhibition and excitation of thalamocortical cells might allow different interpretations of earlier findings in animals and humans, both in healthy and pathological conditions. It will also help to identify new functions for postsynaptic GABAB receptors in other parts of the central nervous system.     

Temporomandibular joint eminence augmentation by down-fracture and inter-positional cartilage graft. A new surgical technique.

A new surgical technique for the treatment of recurrent temporomandibular joint subluxation or dislocation is described. Following a horizontal osteotomy and down-fracture of the articular eminence an inter-positional bovine cartilage xenograft is inserted in order to augment the vertical height of the eminence. The procedure combines simplicity with minimal post-operative morbidity. The increase in eminence height is both predictable and stable.     

Cochlear ablation in deafness mutant mice: 2-deoxyglucose analysis suggests no spontaneous activity of cochlear origin

Deafness mutant mice show no stimulus-related cochlear potentials as well as abnormal electrically-evoked responses recorded from the inferior colliculus. Abnormal spontaneous activity in the auditory periphery could result in abnormal development and/or maintenance of the central auditory pathways. We therefore assessed spontaneous activity of cochlear origin in the central nuclei of the mutants by ablating one cochlea and subsequently using the 2-deoxyglucose (2DG) technique to study metabolic activity. Any asymmetries in labeling in a given nucleus should be due to spontaneous activity in the cochlear nerve on the unoperated side. In control animals (+/dn mice undergoing unilateral cochlea ablation), statistically significant decreased 2DG labeling was observed in the ipsilateral PVCN and AVCN, and contralateral MNTB and IC; all receive primary excitatory input from the ablated ear. No significant differences in labeling between right and left sides were observed in any of the nuclei studied in the mutant animals. These findings suggest that there is no spontaneous activity of cochlear origin in these mutants, even though many cochlear nerve fibers and spiral ganglion cells survive.