Himematsutake (Iwade Strain 101) extract (ABM-FD): genetic toxicology and a 3-month dietary toxicity study in rats.

Agaricus blazei Murrill, an edible mushroom, is used as a functional food due to medicinal effects of (1-->6)-beta-D-glucan protein complex which has been shown to have anti tumour activity in mice. A 13week oral subchronic study in rats performed at 500, 1000 or 2000mg/kg/day caused, at the highest dose, reduced erythrocyte numbers and high mean cell volume in males, high creatinine and urea concentrations in both sexes and low spleen weights in females, but no histopathological change. The findings suggested low level chronic toxicity at 2000mg/kg/day and a no observed adverse effect level (NOAEL) of 1000mg/kg/day. Genotoxicity tests on the aqueous extract were negative in the bacterial reverse mutation test, either with or without S9 mix, up to 5000microg/plate and in a rat bone marrow micronucleus test up to 2g/kg bodyweight. The extract was positive at acceptable levels of toxicity in an L5178Y mouse lymphoma assay following 24h exposure in the absence of S9 and this was associated with an increase in the number of small colonies, suggesting possible clastogenic activity or aneuploidy, rather than point mutation. The aqueous extract of A. blazei is therefore of low subchronic toxicity and did not cause any direct effect upon the DNA molecule and the weak positive in the L5178 mouse lymphoma test was likely due to large deletions or the loss of the whole chromosomes rather than to direct damage to the DNA.

Relationships among biological growth parameters for body weight in Japanese children.

Longitudinal weight records for 360 boys and 345 girls from birth to young adulthood are used. The Count-Gompertz growth curve is fitted to individual growth records in order to characterize individual body weight growth. The authors present the mean-constant growth curves of boys and girls divided by weight at the peak weight velocity for boys and girls, and also girls are subdivided by their weight at menarche. Adult weight has no simple relationship with the timing of adolescence and menarcheal age. Adult weight is, nevertheless, negatively correlated with the timing of adolescence (or menarcheal age) when weight at the timing of adolescence (or menarcheal weight) and/or age at growth completion are held constant. Age at growth completion also negatively correlated with weight at menarche when adult weight and menarcheal age are held constant. Even if it is difficult to find a simple biological relationship among these parameters, for researchers looking for relationships and structures among biological parameters, this partial correlation may be useful. A contra-pair of biological parameters, age and weight, at two growth epochs of weight is introduced, and its properties are discussed in detail.

Sphingomyelin inhibits platelet 12-lipoxygenase activity.

The effect of sphingomyelin on the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), thromboxane B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) in washed rabbit platelets was examined. Sphingomyelin had a powerful inhibitory effect on 12-HETE formation, while it produced only a small increase in thromboxane B2 and HHT formation. The sphingomyelin metabolite ceramide did not affect the formation of 12-HETE, thromboxane B2 and HHT. These results suggest that sphingomyelin is a selective inhibitor of platelet 12-lipoxygenase and may have functional effects in platelets.

Effects of monatepil maleate, a new Ca2+ channel antagonist with alpha1-adrenoceptor antagonistic activity, on cholesterol absorption and catabolism in high cholesterol diet-fed rabbits.

The mechanism of the prophylactic effect against hyperlipidemia by monatepil maleate was investigated in animal models. Monatepil maleate is an antihypertensive agent with Ca2+-channel antagonistic, alpha1-adrenergic receptor-blocking, and lipid peroxidation inhibitory activity. In high cholesterol diet-fed rabbits, monatepil maleate (30 mg/kg, p.o., once daily for 9 weeks) showed a prophylactic effect against increases in total cholesterol and beta-lipoprotein. Monatepil maleate significantly accelerated the clearance of radioactivity from the blood after intravenous injection of low-density lipoprotein (LDL) labeled with [1alpha,2alpha (n)-3H]cholesterol, increasing biliary excretion of [3H]-bile acids without modifying bile acid composition. Furthermore, monatepil maleate tended to inhibit the absorption of orally administered [1alpha,2alpha (n)-3H]cholesterol from the gastrointestinal tract in these rabbits. In Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of hepatic LDL receptor deficiency, monatepil maleate (30 mg/kg, p.o., once daily for 6 months) did not suppress the increase in plasma lipids. These results suggest that the plasma lipid lowering effect of monatepil maleate requires the presence of hepatic LDL receptors. It is also suggested that monatepil maleate improves plasma lipid metabolism through two mechanisms: enhancement of clearance of plasma LDL, which may be mediated by up-regulation of hepatic LDL receptors, and acceleration of conversion of free cholesterol to bile acids in the liver.

Sensing stability and dynamic response of the F-Scan in-shoe sensing system: a technical note.

The objective of this study was to gain a better understanding of the F-Scan to determine its appropriate clinical application. Vertical pressure was applied to a sensor foil over the range of 10-80 kPa with or without the intervention of 0.2-0.8 mm thick felt. Sensor sensitivity reached a maximum without the felt, and decreased with increasing felt thickness, stabilizing at 48-74% of the maximum level when felt thickness exceeded 0.4 mm. This sensitivity change was caused by the slight difference in thickness of sensing areas from that of non-sensing areas. Dynamic response time was delayed by a mean of 0.32 s. Although the cause of this dynamic response delay remains unclear, it was considered to be inappropriate for accurate dynamic measurements. Therefore, rather than using F-Scan measurement to accurately obtain actual values, it should be used for relative comparisons of the plantar pressure distributions under constant conditions.

Genetic analysis of the chitinase system of Serratia marcescens 2170.

To carry out a genetic analysis of the degradation and utilization of chitin by Serratia marcescens 2170, various Tn5 insertion mutants with characteristic defects in chitinase production were isolated and partially characterized. Prior to the isolation of the mutants, proteins secreted into culture medium in the presence of chitin were analyzed. Four chitinases, A, B, C1, and C2, among other proteins, were detected in the culture supernatant of S. marcescens 2170. All four chitinases and a 21-kDa protein (CBP21) lacking chitinase activity showed chitin binding activity. Cloning and sequencing analysis of the genes encoding chitinases A and B of strain 2170 revealed extensive similarities to those of other strains of S. marcescens described previously. Tn5 insertion mutagenesis of strain 2170 was carried out, and mutants which formed altered clearing zones of colloidal chitin were selected. The obtained mutants were divided into five classes as follows: mutants with (i) no clearing zones, (ii) fuzzy clearing zones, (iii) large clearing zones, (iv) delayed clearing zones, and (v) small clearing zones. Preliminary characterization suggested that some of these mutants have defects in chitinase excretion, a negatively regulating mechanism of chitinase gene expression, an essential factor for chitinase gene expression, and a structural gene for a particular chitinase. These mutants could allow researchers to identify the genes involved in the degradation and utilization of chitin by S. marcescens 2170.

A survey of wheelchair use by paraplegic individuals in Japan. Part 1: Characteristics of wheelchair cushions.

The characteristics of wheelchair cushions used by 218 paraplegic patients who lived independent lives were surveyed to clarify the present state of wheelchair cushioning for pressure sore prevention in Japan. Out of 586 cushions surveyed, 91.0% were ready-made and the rest were custom-made. The outstanding popularity of polyurethane foam ready-made cushions (76.3%) suggested that insufficient consideration was taken in the selection of cushions. Custom-made cushions displayed unique modifications to relieve contact pressure or to stabilize sitting posture, which should be systematically provided for all patients. The variety of cushion types and the frequent dissatisfaction with cushions seen in patients with current pressure sores suggested a strong demand for the effective prescription of cushions. Furthermore, 30% of all cushions had had an excessively prolonged use, indicating insufficient follow-up. A medical system including deliberate prescription and regular follow-up of wheelchair cushions should be established for the effective prevention of pressure sores.

A survey of wheelchair use by paraplegic individuals in Japan. Part 2: Prevalence of pressure sores.

A cross-sectional survey was done to clarify the incidence of pressure sores in 218 self-supported Japanese paraplegic patients and to determine effective measures for prevention. The majority of patients (85.7%) had previous pressure sores, and 46.3% had undergone multiple surgeries. Some patients (17.9%) were still suffering from persistent sores which commonly developed at the ischial tuberosities, suggesting insufficiency of self-care practice during wheelchair activities. Sensory disturbance over the seating surface, urinary incontinence, and general complications were seen in 85.8%, 49.5%, and 18.8% of total subjects, respectively. They were seen as risk factors for pressure sores, but only urinary incontinence clearly increased the current pressure sore prevalence. Nevertheless, both self-care practice and sports activities, seen in 85.3% and 36.2% of total subjects, respectively, contributed to greatly reduce the incidence. A patient education system including acquisition of basic knowledge and proper technique should be established to promote effective prevention of pressure sores in Japan.

Instantaneous centers of rotation in dorsi/plantar flexion movements of posterior-type plastic ankle-foot orthoses.

Hingeless plastic ankle-foot orthoses (PAFOs) achieve ankle motion by flexing about the ankle joint. Instantaneous centers of rotation (ICRs) in dorsi- and plantarflexion movements, used as a measure of PAFO axes of movement, were measured to evaluate their fit to ankle motion. Thirty different PAFOs were fabricated and their stiffness modified in three stages. They were dorsi- and plantarflexed 16 degrees at 2 degrees-intervals using an original device. Displacement of two marks on the lateral calf-cuff were traced photographically, and ICRs were determined by plotting intersections of vertical bisectors for each displacement. The ICRs converged on the junction between the calf shell and the shoe insert. They deviated posteriorly from the anatomical ankle axis and caused the calf-cuff to move up-down during dorsi- and plantarflexion movements. However, this poor fit of the PAFO to ankle motion can be sufficiently compensated for by fastening straps more loosely.

Inhibitory effect of monatepil maleate on acyl-CoA:cholesterol acyltransferase activity in the liver of cholesterol-fed Japanese monkeys.

We have previously demonstrated that monatepil maleate, AJ-2615, a new calcium antagonist endowed with alpha1-adrenoceptor blocking property, has antiatherosclerotic and plasma lipid-lowering effects in Japanese monkeys fed on a cholesterol-rich diet. To clarify the mechanisms on plasma lipid-lowering action, we investigated the effect of monatepil maleate in these monkeys on hepatic acyl-CoA:cholesterol acyltransferase (ACAT) activity. Both ACAT activity and esterified cholesterol content in the livers of monkeys fed on a cholesterol-rich diet for 6 months significantly increased about 7- and 16-fold, respectively, as compared with those in monkeys fed on a standard diet. Monatepil maleate (30 mg/kg/day for 6 months, orally) inhibited the increases of ACAT activity and esterified cholesterol content by 51% and 71%, respectively. In in vitro experiments, monatepil maleate inhibited ACAT activity in a concentration-dependent manner, whereas it did not affect 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity. A kinetic analysis revealed that monatepil maleate was a noncompetitive type inhibitor of ACAT. Hepatic ACAT activity was significantly correlated to hepatic esterified cholesterol content (r = 0.775, P < .0001), to plasma very low density lipoprotein (VLDL) content (r = 0.765, P < .0001) and to plasma total cholesterol content (r = 0.573, P < .005) in the monkeys. These results suggest that ACAT-inhibiting effect of monatepil maleate plays an important role in the reduction of hyperlipidemia.

Stiffness control in posterior-type plastic ankle-foot orthoses: effect of ankle trimline. Part 2: Orthosis characteristics and orthosis/patient matching.

The hingeless plastic ankle-foot orthosis (AFO) changes stiffness largely depending on how much plastic is trimmed around the ankle. To support proper selection of the orthosis and final adjustment of the orthotic stiffness, the correlation between the posterior upright width and the resistance to dorsi- and plantar flexion movements was measured in 30 posterior-type plastic AFOs. The posterior upright width was varied by regularly trimming around the ankle in nine stages. The resistance to dorsi- and plantar flexion movements was measured by bending the plastic AFOs 15 degrees with the measuring device described in Part 1. All the plastic AFOs decreased in their resistance to both movements in proportion to the reduction of the posterior upright width. The maximum resistance to plantar flexion movement was about 28 Nm, which was strong enough to assist dorsiflexion in patients with severe spasticity. On the other hand, the maximum resistance to dorsiflexion movement measured was about 10 Nm, which was insufficient to stabilise the ankle in patients who lacked in plantar flexion strength. These findings suggested that this type of plastic AFO should be prescribed for patients who predominantly require dorsiflexion assist, and that the orthotic stiffness could be finally adjusted by trimming to exactly meet individual requirements.

Stiffness control in posterior-type plastic ankle-foot orthoses: effect of ankle trimline. Part 1: A device for measuring ankle moment.

A device was developed to measure the dorsi- and plantar flexion moment of plastic ankle-foot orthoses when deflected. It is operated by manually controlling a lever which is used to apply a nearly static force. Various orthoses can be classified according to the characteristics of the correcting force measured by this device. Simplicity and high reproducibility are the major advantages. However, to obtain measurements approximating the characteristics of orthoses under wearing conditions its use is restricted to orthoses made of low-viscosity materials.

Effects of fatty acyl coenzyme A esters on lipoxygenase and cyclooxygenase metabolism of arachidonic acid in rabbit platelets.

The effects of fatty acyl coenzyme A (CoA) esters (palmitoyl-, stearoyl-, oleoyl-, linoleoyl- and arachidonoyl--CoA) on the activities of lipoxygenase and cyclooxygenase in rabbit platelets were examined. Palmitoyl-, stearoyl-, oleoyl- and linoleoyl- CoA were potent inhibitors of platelet lipoxygenase activity. In addition to the lipoxygenase, the four fatty acyl-CoA esters elicited inhibitory activity on platelet cyclooxygenase, although the inhibition was a little weaker. The CoA derivative of the icosanoid precursor arachidonic acid (AA) showed little inhibition on lipoxygenase and cyclooxygenase. Palmitic, stearic and oleic acids had little or no effect on lipoxygenase and cyclooxygenase, in contrast with their CoA derivatives. Linoleic acid was more potent than linoleoyl-CoA as an inhibitor of the cyclooxygenase, but it was a weak inhibitor of the lipoxygenase. These results suggest that the CoA derivatives of palmitic, stearic, oleic and linoleic acids have the potential to modulate both platelet lipoxygenase and cyclooxygenase activities and may have functional effects within platelets.

Effect of 13-hydroperoxy-9,11-octadecadienoic acid (13-HPODE) on arachidonic acid metabolism in rabbit platelets.

1. The effect of 13-hydroperoxy-9,11-octadecadienoic acid (13-HPODE) on the formation of thromboxane (TX) B2, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) from exogenous arachidonic acid in washed rabbit platelets was examined. 2. 13-HPODE inhibited TXB2 and HHT formation without affecting 12-HETE production. 3. 13-Hydroxy-9,11-octadecadienoic acid which was produced rapidly from 13-HPODE, did not suppress the formation of TXB2 and HHT, indicating the requirement of the hydroperoxy moiety for the inhibitory effect of 13-HPODE on TXB2 and HHT formation. 4. Experiments utilizing mannitol and dimethyl sulfoxide (hydroxy radical scavengers) revealed that the action of 13-HPODE is not due to hydroxy radicals which are expected to be formed from 13-HPODE. 5. These results suggest that 13-HPODE is a selective inhibitor of platelet cyclo-oxygenase and may have functional effects within platelets.

Fractionation and Antitumor Activity of Polysaccharides from Grifola frondosa Mycelium.

We developed a method for the fractionation and purification of antitumor polysaccharides, considered to be a type of immuno-potentiator or BRM (biological response modifier), from the mycelium of liquid cultured Grifola frondosa. The active polysaccharide fractions that showed higher antitumor activity were considered to be heteroglycans or their protein complexes as follows, in water-soluble fractions: FI0-a-α: fucoga-lactomannan-protein complex; FI0-a-ß: mannogalactofucan; FA-1: galactoglucomannofucan-protein complex; FA-2-b-α: glucogalactomannan-protein complex; in water-insoluble fractions: FIII-1-a: mannofucoglucoxylan; FIII-1-b: mannoglucofucoxylan-protein complex; FIII-2-a: mannofucoglucoxylan-protein complex; FIII-2-b: glucomannofucoxylan-protein complex.

Effects of reactive oxygen species on arachidonic acid metabolism in rabbit platelets.

Rabbit platelets were exposed to a reactive oxygen species (ROS) generating system (xanthine plus xanthine oxidase) to explore the effect of ROS on the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), thromboxane (TX) B2, and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) from exogenous arachidonic acid. Xanthine plus xanthine oxidase suppressed the production of 12-HETE, TXB2, and HHT by 65-69%. This effect was reversed by addition of catalase to the ROS generating system but not by superoxide dismutase, mannitol, or dimethylsulfoxide, indicating that H2O2 is the responsible metabolite. These results suggest that H2O2 plays an important role in the regulation of platelet cyclo-oxygenase and lipoxygenase activities.

Effect of tert-butyl hydroperoxide on cyclooxygenase and lipoxygenase metabolism of arachidonic acid in rabbit platelets.

The effect of tert-butyl hydroperoxide (t-BOOH) on the formation of thromboxane (TX) B2, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) from exogenous arachidonic acid (AA) in washed rabbit platelets was examined. t-BOOH enhanced TXB2 and HHT formation at concentrations of 8 microM and below, and at 50 microM it inhibited the formation, suggesting that platelet cyclooxygenase activity can be enhanced or inhibited by t-BOOH depending on the concentration. t-BOOH inhibited 12-HETE production in a dose-dependent manner. When the platelets were incubated with 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) instead of AA, t-BOOH failed to inhibit the conversion of 12-HPETE to 12-HETE, indicating that the inhibition of 12-HETE formation by t-BOOH occurs at the lipoxygenase step. Studies utilizing indomethacin (a selective cyclooxygenase inhibitor) and desferrioxamine (an iron-chelating agent) revealed that the inhibitory effect of t-BOOH on the lipoxygenase is not mediated through the activation of the cyclooxygenase and that this effect of t-BOOH is due to the hydroperoxy moiety. These results suggest that hydroperoxides play an important role in the control of platelet cyclooxygenase and lipoxygenase activities.

The effects of xanthoangelol E on arachidonic acid metabolism in the gastric antral mucosa and platelet of the rabbit.

The effects of a new chalcone derivative, xanthoangelol E, isolated from Angelica keiskei Koidzumi, on arachidonic acid metabolism in the gastric antral mucosa and platelet of the rabbit were examined. When gastric antral mucosal slices were incubated with xanthoangelol E (0.05-1.0 mM), there was no significant effect on the production of prostaglandin (PG) E2, PGF2 alpha and their metabolites. On the other hand, this compound inhibited effectively the production of thromboxane B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid from exogenous arachidonic acid in platelets, and the concentration required for 50% inhibition (IC50) was approximately 5 microM. The formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid was also reduced by this drug (IC50, 50 microM). These results suggest that xanthoangelol E has the potential to modulate arachidonic acid metabolism in platelets and that this action may participate in some pharmacological effect of the plant.

Inhibition of prostaglandin delta 13 reductase activity in rabbit kidney cortex by glutathione disulfide.

t-Butyl hydroperoxide and H2O2-Fe(2+)-EDTA-glutathione system which produces hydroxyl radicals did not affect the 15-hydroxy prostaglandin dehydrogenase activity in rabbit kidney cortex. On the other hand, H2O2-Fe(2+)-EDTA-glutathione system inhibited the prostaglandin delta 13 reductase activity. Mannitol, a scavenger of hydroxyl radicals, had no effect on the inhibitory action of this system, indicating that the effect of H2O2-Fe(2+)-EDTA-glutathione system on the prostaglandin delta 13 reductase may not be due to produced hydroxyl radicals. As a result of further investigation, it was shown that glutathione disulfide, which is synthesized concomitantly with hydroxyl radicals from H2O2-Fe(2+)-EDTA-glutathione, inhibited the prostaglandin delta 13 reductase activity. These results suggest that hydroperoxides and hydroxyl radicals may not be likely candidates for the modulator of the catabolism of prostaglandins in the kidney cortex, and that glutathione disulfide has the potential to modulate the prostaglandin catabolism by affecting the prostaglandin delta 13 reductase activity.

A case of abdominal cystic lymphangioma: cobweb appearance on ultrasonography.

A case of abdominal cystic lymphangioma is described. Our sonographic examination showed a large multilocular cyst with a cluster of honeycomb cysts revealing a cobweb appearance, which correlated with the pathologic specimen, and revealed characteristics of the disease. Sonographic appearance may be helpful in differentiating abdominal cystic lymphangioma from other multilocular cystic tumors.