Identification of vimentin in rat peritoneal mast cells and its phosphorylation in association with histamine release.

Stimulation of rat peritoneal mast cells with histamine releasers, such as compound 48/80 and substance P, caused a similar pattern of protein phosphorylations: the molecular weights of the two major phosphorylated proteins were 45 kDa and 59 kDa. When rat mast cells permeabilized with beta-escin were exposed to Ca2+ at concentrations higher than 0.6 microM, phosphorylated proteins of identical molecular weight were also detected. By a radioimmunoprecipitation assay using anti-vimentin mouse monoclonal antibody, the 59 kDa protein was identified as vimentin, one of the intermediate cytoskeletal proteins. Moreover, it became apparent that the phosphoamino acid in phosphorylated vimentin was a serine residue. Sequential changes in vimentin phosphorylation were similar to that of histamine release elicited by histamine releasers: phosphorylation took place within 5 s of stimulation and reached a maximum within 10 s. When permeabilized mast cells were treated with calphostin C, a specific protein kinase C inhibitor, phosphorylation was markedly inhibited. Fluorescence images of mast cells stained with FITC-labelled anti-vimentin antibody showed filamentous structures surrounding the granules in the cytoplasm. However, after exposure to compound 48/80, the filamentous structures promptly disappeared and a dim fluorescence was observed homogeneously in the cell indicating that a rapid depolymerization of vimentin had taken place. From the present study, it became clear that when rat peritoneal mast cells were stimulated, vimentin was rapidly phosphorylated by protein kinase C and this phosphorylation process seems to be related to histamine release.     

Effect of hypertension on asymmetrical septal hypertrophy: an echocardiographic study

The effect of hypertension on asymmetrical septal hypertrophy was studied by echocardiography to differentiate idiopathic asymmetrical septal hypertrophy (ASH) from ASH with hypertension. One hundred eight patients with ASH proven by echocardiography were categorized in two groups; 53 patients with hypertension (greater than 160 systolic, greater than 95 diastolic) (hypertensive group: HT) and 55 patients with normal blood pressure (normotensive group: NT). Septal hypertrophy was classified as mid-portion (M-type), diffuse (D-type), and basal (B-type) hypertrophy by the long-axis view, and also diffuse (I-type), anterolateral (II-type), anteroseptal (III-type), and anterior septal (IV-type) by the short-axis view, respectively. Endomyocardial biopsy and left ventriculography were performed in 50 patients (18 hypertensives and 32 normotensives). In the hypertensive group, 45%, 30%, and 25% of cases had diffuse, basal and mid-portion hypertrophy, respectively. There was no case in the basal hypertrophy whose biopsy findings were compatible with hypertrophic cardiomyopathy. In the normotensive group, 78% and 22% of patients had midportion and diffuse hypertrophy, respectively, but none of them had the basal hypertrophy. Type IV was seen in only six patients in the normotensive group.     

A case-control study of breast cancer among Japanese women: with special reference to family history and reproductive and dietary factors

Summary To study the effects of family history and reproductive, anthropometric, and dietary factors on the risk of breast cancer among low risk populations, we conducted a hospital-based case-control study involving 908 patients with breast cancer and their matched controls, in Japan. A positive family history of breast cancer significantly increased the risk of breast cancer (odds ratio = 1.52, 95% confidence interval: 1.14–2.03). The risk further increased with increasing number of family members affected. Obesity, single marital status, fewer births, a late childbirth, and less consumption of green-yellow vegetables and dairy products were also associated with an increased risk of breast cancer. These associations were independent in multivariate analyses. There was no increase in risk associated with consumption of high fat foods. When analyzed by menopausal status, the association with family history of breast cancer, especially in the first degree of relatives, was more evident for premenopausal breast cancer. The associations with obesity and lower consumption of dairy products were more pronounced for postmenopausal breast cancer, while those with lower parity and single marital status were stronger for premenopausal breast cancer.     

Effect of lipopolysaccharide on transport and metabolism of arginine in mouse peritoneal macrophages.

The transport activity of arginine in mouse peritoneal macrophages was strongly induced when they were cultured with 1 ng/ml bacterial lipopolysaccharide (LPS) for 12 h. Arginine in the medium decreased whereas ornithine in the medium increased during the culture. This time-dependent change of arginine to ornithine was accelerated by LPS. However, the activity of arginase in the macrophages did not change during the culture with or without LPS and release of arginase from the cells to the medium was not detected. It is suggested that the transport of arginine and ornithine was a rate-limiting step in arginine-to-ornithine conversion in the macrophage culture medium. A possible role of the induction of arginine transport activity in the macrophage cytocidal activity due to arginine depletion and nitric oxide production is discussed.     

Effect of nebracetam on the disruption of spatial cognition in rats.

Central cholinergic hypofunction causes the disruption of spatial cognition, while cholinomimetics improve this disruption in rats. Scopolamine (0.5 mg/kg, i.p.) has also been reported to disrupt radial maze performance in rats. Nebracetam (WEB 1881 FU), a new nootropic candidate, was able to correct this scopolamine-induced disruption of spatial cognition at the dose of 10 mg/kg, p.o. Furthermore, nebracetam enhanced oxotremorine-induced tremors in mice. These results indicate that nebracetam has a cholinergic enhancing effect. The scopolamine-induced disruption of spatial cognition has been previously reported to improve not only by cholinomimetics but also by brain noradrenergic drugs such as L-threo-DOPS and amantadine. Nebracetam reversed the change of brain noradrenaline contents in the frontal cortex and hippocampus in which the noradrenaline content decreased by treatment with scopolamine. Nebracetam also decreased the delta 9-tetrahydrocannabinol (6 mg/kg, i.p.)-induced disruption of spatial cognition, which was reported to be related to the lymbic noradrenergic function. These results suggest that the cognitive enhancing effect of nebracetam involves not only cholinergic mechanisms but also involves lymbic and hippocampal noradrenergic mechanisms.     

Serotonin reduction in the mouse neostriatum during hyperthermia-induced convulsions studied by immunohistochemistry

Summary Changes occurring in serotonin neurons during hyperthermia-induced convulsions were examined by means of a modified immunohistochemical method. All mice (8–12 weeks of age) exposed to the temperature of 50°C had convulsions, showing a generalized tonic and/or clonic pattern. Immediately after the convulsions, the animals were perfused transcardially with a fixative. A significant reduction in serotonin immunoreactivity was observed in the neostratum (caudate-putamen complex) of the mice which had hyperthermia-induced seizures, while the serotonin immunoreactivity remained unchanged in the neocortex and paleostriatum. These results suggest that serotonin may be an important mediator in the mechanism of hyperthermia-induced convulsions or that the susceptibility of serotonin neurons to a convulsive state is greatest in the neostriatum.Supported in part by Grant No. 86-05 from the National Center for Nervous, Mental and Muscular Disorders (NCNMMD) of the Ministry of Health and Welfare and Grant No. 62770677 from the Ministry of Education, Science and Culture, Japan     

Gadolinium-based balloon angioplasty for pulmonary artery stenosis in an infant with a right isomerism.

We report here the first described case of utilizing gadolinium-based contrast material as the contrast agent during a catheter intervention treatment for pulmonary artery stenosis. The patient, a male infant with complex heart disease associated with a right isomerism, had a history of severe allergic reaction to iodine-containing contrast agents. A combination of digital subtraction angiography and a gadolinium contrast agent, however, provided us with good-quality images both before and after balloon angioplasty without any associated complications. This method should therefore be considered as an alternative angiographic procedure in children with a high risk of iodine-related allergic complications.     

Bilateral symmetric tonic posturing suggesting propagation to the supplementary motor area in a patient with precuneate cortical dysplasia.

We report a patient manifesting seizures with bilateral symmetric tonic posturing, which were markedly reduced after resection of the left precuneus. A 16-year-old man had sudden onset, complex partial seizures with bilateral symmetric tonic posturing since the age of eight years. Magnetic resonance fluid-attenuated inversion-recovery imaging revealed a hyperintense lesion in left precuneus. In almost all focal seizures recorded during an invasive EEG evaluation, ictal onset was detected from the inferomesial aspect of the lesion, but fast paroxysmal discharges from the ipsilateral supplementary motor area (SMA) were observed just before the clinical onset. After surgical excision of the EEG onset zone, including the lesion, seizure frequency was markedly (> 95%) reduced. By the 20th month after surgery, there were only brief nocturnal seizures involving slight elevation of both shoulders and slight abduction of both arms, with preservation of consciousness occurring once every few days. Invasive EEG findings and surgical outcome suggested that the epileptic activity originating from the epileptogenic zone may have propagated to the symptomatogenic zone including mainly the ipsilateral SMA. In summary, we report an interesting case of bilateral symmetric tonic posturing suggesting propagation to the SMA. MRI and invasive EEG confirmed the epileptogenic focus as a precuneate cortical dysplasia lesion.[Published with video sequences].