Specificity of sulfated polysaccharides to accelerate the inhibition of activated protein C by protein C inhibitor

The ability of various sulfated polysaccharides to activate protein C inhibitor (PCI) and the effect of molecular weight (Mr) and sulfur content of dextran sulfates were investigated. Besides dextran sulfate, highly sulfated polysaccharides such as chondroitin polysulfates 1 and 5, and pentosan polysulfate were more active than heparin in enhancing the activated protein C inhibition by PCI. The molecular weight and the sulfur content of dextran sulfate were critical for the second-order rate constant of the reaction and for the optimal concentration of the polysaccharide, respectively. These results suggest that the carboxyl groups of polysaccharides are not necessarily required, but some sulfate groups within polymers may play a critical role in the interaction with PCI.     

AMP deaminase activity of skeletal muscle in neuromuscular disorders in childhood. Histochemical and biochemical studies

We studied the histochemical staining and biochemical activity of AMP deaminase in biopsied muscle in Becker-type muscular dystrophy (BMD), Fukuyama-type congenital muscular dystrophy (FCMD), Duchenne-type muscular dystrophy (DMD), Werdnig-Hoffmann disease (WH) in order to elucidate the change of AMP deaminase activity in muscle with neuromuscular disorders in childhood. The intensity of AMP deaminase staining did not decrease in BMD with mild pathologic change, but in DMD, FCMD and WH it decreased in parallel with the severity of the pathologic change. The biochemical activity of AMP deaminase did not decrease in muscle with mild pathologic change in patients with DMD and tended to decrease according to the progress of the disease. The activity of AMP deaminase in muscle of patients with FCMD and WH which showed severe pathologic change was remarkably low. It was demonstrated that the decrease in the activity of AMP deaminase was related to the intensity of pathologic change rather than diagnosis of a neuromuscular disorder.     

Reversal of multidrug resistance by new dihydropyridines with lower calcium antagonistic activity

Summary BS compounds, a series of new dihydropyridines, successfully overcame multidrug resistance in P388/ADR cells in vitro. These agents synergistically potentiated the cytotoxicity of Adriamycin to P388/ADR cells at a concentration of 1–2 M, whereas they showed hardly any synergistic effect in the parental cell line (P388/S) at the same concentration. They inhibited the active drug efflux in P388/ADR cells as well as the binding of [G-³H]-vinblastine to membrane vesicles from P388/ADR, which was increased in resistant P388 cells as compared with parental cells. Besides, unlike the activity of clinically used calcium antagonists, the calcium antagonistic activity associated with BS compounds was very weak: their arterial relaxation activity was <21% of that of verapamil. These data suggest that BS compounds specifically overcome multidrug resistance without the serious hypotensive side effects that accompany the use of verapamil orother calcium antagonists.     

Basic and clinical evaluation of an immunoradiometric competitive inhibition assay for 2----6 sialyl Lewis a antigen--1. Evaluation of assay conditions and normal values

We describe an immunoradiometric competitive inhibition assay of the serum levels of the 2----6 sialyl Lewisa antigen, using "SLA 2-6 Otsuka" kits. The assay required only duplicate 50-microliters samples, and the concentration of 2----6 sialyl Lewisa antigen in serum was determined by reference to a standard curve ranging from 0 to 160 arbitrary U/ml. The intra- and inter-assays reproducibilities were good and analytical recovery of antigen were excellent. The serum levels of the antigen were highly dependent on the Lewis blood types of the tested individuals; i.e., the levels of the antigen in the sera of the Lewisa-b- individuals were significantly lower than those of the antigen obtained with the Lewisa+b- and Lewisa-b+ individuals. The cut-off value (42 U/ml) was obtained as mean + 2SD, which was carefully calculated from the antigen levels in sera of the non-Lewisa-b- individuals.     

Diazepam reduces both arterial blood pressure and muscle sympathetic nerve activity in human

It is known that benzodiazepines have a hypotensive effect, but the mechanism has not been well elucidated yet. To clarify whether this effect is due to central or peripheral mechanism, we administered 5 mg of diazepam or saline intravenously to healthy volunteers and assessed the change in blood pressure, heart rate, muscle sympathetic nerve activity and heart rate variability. After diazepam administration, systolic and mean blood pressure decreased significantly. Muscle sympathetic nerve activity was also significantly reduced but heart rate did not change, whereas the variables of spectral analysis of heart rate variability did not show significant change. We concluded that the hypotensive effect of diazepam in human is mainly due to the central mechanism.     

A population cytogenetic study of a common fragile site, fra(3)(p14), in a healthy population

A population survey of a common folate-sensitive fragile site, fra(3)(p14), was carried out on PHA-stimulated peripheral lymphocytes of 1,078 healthy subjects. Fra(3)(p14) was expressed more frequently in the younger than in the older, and in males than in females. It also showed some seasonal variation. The age difference of the expression frequency was also observed by aphidicolin treatment. A positive correlation of the expression frequency was found, though not so strongly, between both culture conditions of folate deprivation and aphidicolin treatment, These findings suggest that the inter-individual variation in the expressivity of common fragile sites is not only ascribable to chance, but to some physiological conditions of blood donors such as response rate of lymphocyte to PHA stimulation and blood concentration of folic acid.