Heme oxygenase-1 inhibits cigarette smoke-induced increase in the tracheal mucosal permeability in guinea pigs in vivo.

OBJECTIVE: To examine whether heme oxygenase (HO)-1 inhibits cigarette smoke (CS)-induced increase in the airway mucosal permeability. METHODS: Mucosal permeability was quantified by monitoring the rate of appearance in the circulation of horseradish peroxidase that had been instilled into the isolated tracheal segment in guinea pigs in vivo, after exposure to CS or room air. RESULTS: Exposure to 10 puffs of CS did not increase the tracheal mucosal permeability but did increase the permeability after pretreatment with zinc protoporphyrin, a competitive inhibitor of HO-1. Moreover, pretreatment with hemin, a potent inducer of HO-1, inhibited the increase in the permeability of the tracheal mucosa induced by 20 puffs of CS exposure. CONCLUSION: It is concluded that HO-1 has an important role in suppressing the increase in the mucosal permeability induced by CS in guinea pig trachea.

Electroencephalogram is activated by addition of pentobarbital in the isolated perfused head of the rat.

To evaluate the direct effects of a barbiturate on cerebral functions without its influence on brain perfusion pressure, circulatory hormones and metabolites, the electroencephalogram (EEG) was studied in the isolated rat head. Male Wistar rats were anesthetized, and EEG electrodes were inserted into the cranium. A Krebs-Ringer bicarbonate buffer solution containing heparinized rat whole blood, 20 mmol/l glucose, 200 mmol/l mannitol and 0.1 mg/ml dexamethasone was used for the perfusate. The bilateral common carotid arteries were cannulated, pumped at a rate of 6 ml/min and the head was isolated. The venous effluent was reoxygenated and recirculated into the brain. Twenty-five min after isolation of the heads pentobarbital was added to the perfusate at concentrations of 0.1, 0.5 and 2.5 mg/ml. EEG was recorded before and during perfusion. EEG activity could be recorded for more than 25 min after the beginning of perfusion. EEG activity gradually declined from 42+/-5 microV before perfusion (in vivo) to 4+/-1 microV at 25 min after the beginning of perfusion. Then, 3 min after the addition of pentobarbital, the EEG activity became significantly higher in the high dose groups; 12+/-3 microV in the 0.5 mg/ml group (p<0.05) and 12+/-1 microV in 2.5 mg/ml group (p<0.05) compared with the group without pentobarbital (2+/-2 microV). The present study suggests that a barbiturate has mitigating effects on the brain damage induced by the in vitro brain perfusion.

A new neurological entity manifesting as involuntary movements and dysarthria with possible abnormal copper metabolism.

A few patients with an affected CNS involving abnormalities in copper metabolism have been described that do not fit any known nosological entities such as Wilson's disease or Menkes' disease. Three sporadic patients (two men and one woman) were examined with involuntary movements and dysarthria associated with abnormal concentrations of serum copper, serum ceruloplasmin, and urinary copper excretion. The onset of neurological symptoms occurred at the age of 15 to 17 years. The common clinical symptoms were involuntary movements and dysarthria. The involuntary movements included dystonia in the neck, myoclonus in the shoulder, athetosis in the neck, and rapid orobuccal movements. The dysarthria consisted of unclear, slow, and stuttering speech. Two of the three patients did not have dementia. A cousin of the female patient had been diagnosed as having Wilson's disease and had died of liver cirrhosis. Laboratory findings showed a mild reduction in serum copper and ceruloplasmin concentrations, whereas urinary copper excretion was significantly reduced in all three patients. Two of the three patients showed a high signal intensity in the basal ganglia on T2 weighted brain MRI. In conclusion, the unique findings of involuntary movements, dysarthria, and abnormal serum copper and urinary copper concentrations suggest that the three patients may constitute a new clinical entity that is distinct from either Wilson's or Menkes disease.

Pod-2, along with pod-1, defines a new class of genes required for polarity in the early Caenorhabditis elegans embryo.

The asymmetric division of the one-cell Caenorhabditis elegans zygote gives rise to two cells of different size and fate, thereby establishing the animal's anterior--posterior (a-p) axis. Through genetics, a number of genes required for this polarity have been characterized, but many components remain unidentified. Recently, our laboratory discovered a mutation in the pod-1 gene (for polarity and osmotic defective) that uniquely perturbed polarity and osmotic protection. Here, we describe a new C. elegans polarity gene identified during screens for conditional embryonic lethals. Embryos in which this gene has been mutated show a loss of physical and developmental asymmetries in the one-cell embryo, including the mislocalization of PAR and POD-1 proteins required for early polarity. Furthermore, mutant embryos are osmotically sensitive, allowing us to designate this gene pod-2. Thus, pod-2, along with pod-1, defines a new class of C. elegans polarity genes. Genetic analyses indicate that pod-2 functions in the same pathway as pod-1. Temperature-shift studies indicate that pod-2 is required during oogenesis, indicating that aspects of embryonic polarization may precede fertilization. pod-2 mutant embryos also exhibit a unique germline inheritance defect in which germline identity localizes to the wrong spot in the one-cell embryo and is therefore inherited by the wrong cell at the four-cell stage. Our data suggest that pod-2 may be required to properly position an a-p polarity cue.

A new familial adult-onset leukodystrophy manifesting as cerebellar ataxia and dementia.

BACKGROUND: Among hereditary leukodystrophies, a considerable number remain unclassified. PATIENTS AND RESULTS: We investigated the clinical course and histopathology of one patient in a family of adult-onset leukodystrophy with possible dominant inheritance. A 44-year-old man presented with cerebellar ataxia as the initial symptom, and later, dementia and hyperreflexia with ankle clonus developed. T2-weighted brain MRI showed brain atrophy and diffuse high signal intensity of the cerebral white matter and the brain stem. The patient's mother and older brother also had cerebellar ataxia and dementia, and his older brother had been diagnosed as having spinocerebellar degeneration. An older sister of our patient possibly had similar neurological symptoms of adult-onset. Our patient died of pneumonia 5 years after the onset of disease. The histopathological findings consisted mainly of patchily observed vacuolar changes in the cerebral and cerebellar white matter and the brain stem. The subcortical regions and the cortex were unaffected. It is suggested that the pathological changes began in the cerebellum, and later spread to the frontal lobe and the brain stem. In the occipital regions, the vacuolations were associated with accumulation of macrophages and astrocytosis, which implied that the vacuolations were of recent origin. CONCLUSIONS: The diagnosis in this patient is adult-onset leukodystrophy with possibly autosomal dominant inheritance. The clinicopathological features are different from those, of previously reported adult-onset leukodystrophies.

Streptozotocin-induced diabetic hyperglycaemia produces more EEG activity than normoglycaemia and hypoglycaemia during and after anoxia loading in rats.

The brain requires oxygen and glucose for energy metabolism. Electroencephalogram (EEG) was recorded to determine the effect of glucose concentration on the cerebral function in hypoxic episode. Rats were divided into 3 groups: a streptozotocin-induced diabetic hyperglycaemic group, a normoglycaemic group, and an insulin-induced hypoglycaemic group. Hypoxia was induced by ventilating with 100% N2 for 3 min. EEG amplitude both 5 and 10 min after anoxia loading was higher in the diabetic hyperglycaemic than in the normoglycaemic group, though not significantly. Time for decreasing the EEG amplitude during anoxia loading was significantly longer in the hyperglycaemic than in the normoglycaemic group. Time for recovering the EEG amplitude after anoxia loading was significantly shorter in the hyperglycaemic group and was longer, though not significantly, in the hypoglycaemic group than in the normoglycaemic one. These results suggest the brain is more tolerant to hypoxia during diabetic hyperglycaemia than during normoglycaemia.

Increased serum hyaluronic acid in amyotrophic lateral sclerosis: relation to its skin content.

BACKGROUND: Abnormalities of hyaluronic acid (HA) of skin have been reported in patients with amyotrophic lateral sclerosis (ALS). However, little is known concerning the changes of serum HA in ALS. The purpose of this study was to investigate skin HA content and serum HA levels in ALS patients. METHODS: We measured skin HA content and serum HA levels in patients with ALS, and compared the results with those of control subjects. RESULTS: Skin HA content in ALS patients was significantly higher than in diseased control subjects and control subjects without neurological disorders, and increased significantly, the longer the duration of illness. Serum HA concentrations in patients with ALS were significantly higher than in diseased control subjects and in healthy control subjects, and were positively and significantly associated with duration of illness. There was an appreciable positive correlation between serum HA concentrations and skin HA content in ALS patients. CONCLUSION: These data suggest that a metabolic alteration of HA may take place in ALS and increased levels of serum HA may reflect an increased content of skin HA in ALS.

The Noh mask test for analysis of recognition of facial expression.

A preliminary study on the Noh mask test for analysis of recognition of facial expression was performed. The present study was conducted on 15 normal subjects (mean age: 32 years, SD 9.7 years) as the first step to test for the differences between psychiatric patients and normal subjects. Stimuli were created by photographs of 15 Noh masks at different vertical angles. Subjects were given 12 tasks (12 emotion items), and each task consisted of 15 trials (15 Noh mask images). In each trial, the subject viewed a colour monitor, and was shown an emotion item, followed by a Noh mask image. The subject pressed either the yes or no key to indicate whether the Noh mask image expressed the emotion item. The subject's response and reaction time to each Noh mask image showed no deviation, although the subject's response and reaction time to each emotion item showed some deviation. As the vertical angle of the Noh mask changed, normal subjects recognized all emotion items except the 'uncanny' expression. Factor analysis of the 15 Noh mask images produced three factors, and the analysis of 12 emotion items produced five factors. Thus, the Noh mask test was simplified to nine images and nine items. Further developments of the Noh mask test may include the evaluation of the dysfunction of perception on delicate facial expression in psychiatric patients.