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.     

Skip mediastinal nodal metastases in non-small cell lung cancer

Objective: To reveal the incidence and clinical significance of mediastinal nodal metastases without N1-station nodal metastases (‘skip-N2 metastases’) in non-small cell lung cancer (NSCLC). Methods: A total of 450 NSCLC patients who underwent tumor resection with a systemic mediastinal nodal dissection were retrospectively reviewed. p53 status and proliferative activity represented as proliferative index (PI) were also examined immunohistochemically. Results: Skip-N2 metastases were documented in 49 (13%) patients of all 450 patients; among 334 patients without N1-nodal involvement, 18% patients had skip-N2 metastases. The postoperative survival of skip-N2 patients was almost same as that for patients with metastases to both N1 and N2 nodes. Skip-N2 metastases were significantly more frequent in male patients and squamous cell carcinoma patients. In addition, the mean PI for tumor with skip-N2 metastases was significantly higher than that for any other pathologic nodal (pN)-status diseases. Combined with histologic type and PI, the incidences of skip-N2 metastases for adenocarcinoma showing lower PI were only 5% (7/137) of all patients and 7% (7/94) of patients without N1-nodal involvement. Conclusions: N1 nodal status is not a useful predictor of N2 nodal status in NSCLC, because skip-N2 metastases were documented in 18% patients showing no N1-nodal involvement. However, N1 node-guided dissection might be performed in patients with adenocarcinoma showing lower PI, because the incidence of skip-N2 metastases was extremely low.     

Clarke's column in sporadic amyotrophic lateral sclerosis

Summary Histological, ultrastructural and morphometrical observations on Clarke's column were carried out in 18 patients with sporadic amyotrophic lateral sclerosis (ALS) and 15 age-matched control subjects. Of the 18 ALS patients 6 had been on a respirator before death. Bunina bodies were found in the neuronal cytoplasm in 7 of the 12 non-respirator-supported ALS patients and in 3 of the 6 respirator-supported patients. The number of spheroids was significantly higher in the non-respirator-supported patients (P<0.01) than in the control subjects; however, the number in the respirator-supported patients was about equal to that in the controls. The number of neurons in Clarke's column in the non-respirator-supported ALS patients was not reduced, but in the respirator-supported patients they tended to disappear with time after respiratory support. These findings suggest that Clarke's column neurons are also involved primarily in the disease process in sporadic ALS. However, they may begin to disappear only after the patients require respiratory support.Supported in part by a research grant for CNS degenerative diseases from the Ministry of Health and Welfare, Japan     

Cytotoxicities of sodium benzoate in primary culture of hepatocytes from adult rat liver

The cytotoxicities of sodium benzoate was studied using primary culture of hepatocytes established from adult rat liver by a collagenase perfusion technique and maintained as a monolayer in serum-free culture medium. The activities of ornithine transcarbamylase (as a marker of mitochondria) and tyrosine aminotransferase (as a marker of cytosol) were clearly suppressed by sodium benzoate at concentration in excess of 500 micrograms/ml. Intracellular protein synthesis and DNA synthesis were also suppressed, and the suppression of DNA synthesis was observed even with a lower concentration of benzoate (100 micrograms/ml).     

Plasma carnitine concentrations in patients undergoing open heart surgery.

Carnitine is an essential cofactor for fatty acid (FA) metabolism, the predominant source of ATP in the normal aerobic heart. During myocardial ischemia, FA metabolism is impaired and tissue carnitine levels are depleted. Since the heart cannot synthesize carnitine, plasma carnitine could play an important role in maintaining myocardial carnitine levels during reperfusion. The purpose of this study was to determine the incidence of abnormal plasma carnitine concentrations in open heart surgery. Blood samples were obtained from eleven patients before, immediately after, and two hours after cardiopulmonary bypass (CPB). Total and free carnitine levels were significantly reduced immediately after CPB (p<0.01) and remained depressed until two hours after CPB (p<0.01 vs. pre CPB), while acyl carnitine levels were unchanged over the course of this study. These depressed free carnitine levels might affect cardiac metabolism in the heart after open heart surgery. Carnitine supplement might be a useful adjunct in the therapy after open heart surgery.     

Extracellular or ghost Pick bodies and their lack of tau immunoreactivity: a histological,immunohistochemical and electron microscopic study

Histological, immunohistochemical, and electron microscopic evidence of an extracellular, or ghost Pick body has been found in the granular cell layer and, rarely, in the pyramidal cell layer of the hippocampus of an autopsy case of Pick's disease. The ghost Pick body appeared as a blurred, weak argyrophilic mass in the neuropil, and it was composed of accumulated fibrillary structures, 13 nm in diameter, intermingled with glial filament bundles. These ghost Pick bodies did not react with anti-tau and antiubiquitin antibodies, but did react weakly with antiglial fibrillary acidic protein antibody, whereas intracytoplasmic Pick bodies were strongly immunolabeled with anti-tau but only weakly with anti-ubiquitin anti-bodies. These results suggest that the Pick body is discharged into the neuropil after destruction of the mother neuron, loses its immunoreactivity to certain tau and ubiquitin antibodies during this process (thereby inducing a glial reaction) and remains in the neuropil as a ghost Pick body.     

Retrospective survey of urea cycle disorders: Part 1. Clinical and laboratory observations of thirty-two Japanese male patients with ornithine transcarbamylase deficiency

In a retrospective survey done from 1978-1988 in Japan, 32 male patients with ornithine transcarbamylase (OTC) deficiency were identified. We classified a neonatal and 2 late-onset groups, depending on clinical manifestations and the age at onset; group 1 (0-28 days; N = 10), group 2 (29 days-5 years; N = 13), and group 3 (greater than 5 years; N = 9). Compared to findings in the group 2 patients, there was a higher rate of mortality and a higher incidence of mental retardation in association with a great decrease in enzyme activity in group 1. In group 3, the mortality rate and enzyme activities were similar to those in group 1. However, patients in this group were asymptomatic prior to the first episode. Enzyme activities were measured mostly in autopsy samples. The serum citrulline levels (enzyme product) were highest in this group. Thus, the mutant enzymes were apparently labile with greater activities in vivo than in vitro. Treatments, including a protein-restricted diet, arginine supplementation, and sodium benzoate administration, resulted in a favorable prognosis for survivors with partial enzyme deficiency. We wish to emphasize that the incidence of late onset of this disease is higher than heretofore considered.     

Sensory inputs from the oral region to the cerebral cortex in behaving rats: an analysis of unit responses in cortical somatosensory and taste areas during ingestive behavior

1. The responses of 90 cortical neurons in the somatosensory and gustatory areas were recorded with chronically implanted fine wires in freely moving Wistar rats. The responses were analyzed mainly while the animals were freely licking solutions and eating dry pellets. Cortical neurons were classified into several groups according to their response properties. 2. "Mechanosensitive" neurons (n = 20) showed rhythmic phasic activity in different phases of the licking cycle, depending on the location of their receptive field in the peripheral orofacial region. 3. "Movement-related" neurons (n = 27) changed their activities tonically during licking, chewing, or grooming behavior. The responses were either excitatory or inhibitory. Receptive fields and adequate stimuli could not be identified. These neurons might receive somatosensory (except light tactile) inputs from wide or deep areas of intra- or perioral regions, or might be related to orofacial active movement. 4. "Taste" neurons (n = 35) increased or decreased their discharge rates during licking of particular taste solutions. Some taste neurons received convergence from somatosensory inputs. 5. "Temperature" neurons (n = 2) responded exclusively to water of temperatures lower or higher than room temperature. The responses were opposite in direction between cold and warm stimuli. 6. "Anticipation" neurons (n = 4) increased their impulse discharges before the start of licking in the situation in which the animal expected access to the drinking tube. 7. "Attention" neurons (n = 2) responded to arousal stimulation such as sound, a flash of light, and body touch. These neurons showed only a slightly increasing response during ingestive behavior. 8. The locations of 56 of 90 units were histologically identified. Mechanosensitive neurons were located in the appropriate parts of the somatotopic pattern within the primary somatic sensory area in the granular cortex. Taste neurons were found evenly in the dysgranular cortex and the agranular insular cortex. Other types of neurons were located mainly in the dysgranular cortex between the granular cortex and agranular insular cortex, and some were intermingled with taste neurons in the agranular insular cortex. 9. The present study has shown that cortical neurons in the orolingual somatosensory and taste areas have different response characteristics related to each aspect of ingestive behavior.(ABSTRACT TRUNCATED AT 400 WORDS)