Strain- and age-dependent loss of sarcoglycan complex in cardiomyopathic hamster hearts and its re-expression by delta-sarcoglycan gene transfer in vivo

We found that 5-S-GAD, an insect-derived antibacterial peptide, inhibited murine osteoclast formation in vitro. We examined the specific time point of the inhibitory action of 5-S-GAD on osteoclast formation and found that it mainly suppressed differentiation of osteoclasts in the middle of the culture period. Using HL60 cells that are able to differentiate into multinucleated macrophage-like cells, we found that 5-S-GAD induced apoptosis of HL60 cells by producing H(2)O(2). Thus, the inhibition of osteoclast formation by 5-S-GAD could be, in part, due to apoptosis of the cells of an osteoclast lineage.     

Contamination of public facilities with Dermatophagoides mites (Acari: Phyroglyphidae) in Japan

The distribution of allergenic mites, Dermatophagoides farinae and Dermatophagoides pteronyssinus, was surveyed among public facilities in Japan, in order to assess the risk of people, including allergic patients, being exposed to mite allergens outside homes. Dust samples were collected using a vacuum cleaner from bedclothes, floors and other materials in four hospitals, two hotels, two ryokans, one film theatre and four office buildings. Fine dust fractions of these samples were examined for mite antigens by enzyme-linked immunosorbent assay. Overall, clinically important antigen levels of 50 g m–2 (corresponding to approximately 500 mites m–2) or more were detected in 71% of samples from chairs in a film theatre and 42% of samples from tatami and carpet floors of ryokans, whereas such serious mite contamination was not observed in samples from hospitals, hotels and offices. High mean antigen levels were observed in chairs in a film theatre (98.2 g m–2) and floors of ryokans (81.4 g m–2), whereas samples from other facilities showed mean antigen levels of <11 g m–2. Hospitals had individual antigen levels of 50 g m–2 in 2% of mattresses and 5% of painted and tiled floors but not in comforters, futons and pillows. No samples obtained from bedclothes in hotels and ryokans had antigen levels of 50 g m–2. In office buildings where the air was fully controlled by a central air-conditioning system all the year round, 99% of samples showed low antigen levels of <10 g m–2. © Rapid Science Ltd. 1998     

Decreased mRNA expression of the PTH/PTHrP receptor and type II sodium-dependent phosphate transporter in the kidney of rats fed a high phosphorus diet accompanied with a decrease in serum calcium concentration

This study investigates the phosphorus (P) homeostasis in the process of an altered parathyroid hormone (PTH) action in the kidney of rats fed a high P diet. Four-week-old male Wistar strain rats were fed diets containing five different P levels (0.3, 0.6, 0.9, 1.2 and 1.5%) for 21 days. The serum PTH concentration and urinary excretion of P were elevated with increasing dietary P level. Compared to rats fed the 0.3% P diet, the serum calcium (Ca) concentration remained unchanged, while the serum 1,25(OH)(2)D(3) concentration and urinary excretion of cAMP were elevated with increasing dietary P level in rats fed the high P diets containing 0.6-0.9% P. On the other hand, a lower serum Ca concentration was observed in rats fed the high P diets containing 1.2% or greater P. The serum 1,25(OH)(2)D(3) concentration remained unchanged in rats fed the high P diets containing 1.2% or greater P, comparison with rats fed the 0.3% P diet. The urinary excretion of cAMP and PTH/PTH-related peptide (PTHrP) receptor and type II sodium-dependent phosphate transporter (NaPi-2) mRNA in the kidney were both decreased in rats fed the high P diets containing 1.2% or greater P. In conclusion, a high P diet with subsequent decrease in serum Ca concentration suppressed the PTH action in the kidney due to PTH/PTHrP receptor mRNA down-regulation. Furthermore, an increase in the urinary excretion of P might have been caused by decreased NaPi-2 mRNA expression without the effects of PTH and 1,25(OH)(2)D(3).     

Electron acquisition system constructed from an NAD-independent D-lactate dehydrogenase and cytochrome c2 in Rhodopseudomonas palustris No. 7

The activities of NAD-independent D- and L-lactate dehydrogenases (D-LDH, L-LDH) were detected in Rhodopseudomonas palustris No. 7 grown photoanaerobically on lactate. One of these enzymes, D-LDH, was purified as an electrophoretically homogeneous protein (M(r), about 235,000; subunit M(r) about 57,000). The pI was 5.0. The optimum pH and temperature of the enzyme were pH 8.5 and 50 degrees C, respectively. The Km of the enzyme for D-lactate was 0.8 mM. The enzyme had narrow substrate specificity (D-lactate and DL-2-hydroxybutyrate). The enzymatic activity was competitively inhibited by oxalate (Ki, 0.12 mM). The enzyme contained a FAD cofactor. Cytochrome c(2) was purified from strain No. 7 as an electrophoretically homogeneous protein. Its pI was 9.4. Cytochrome c(2) was reduced by incubating with D-LDH and D-lactate.     

Phase 1 study of multiple biomarkers for metabolism and oxidative stress after one-week intake of broccoli sprouts

Little is known about the direct effect of broccoli sprouts on human health. So we investigated the effect of broccoli sprouts on the induction of various biochemical oxidative stress markers. Twelve healthy subjects (6 males and 6 females) consumed fresh broccoli sprouts (100 g/day) for 1 week for a phase 1 study. Before and after the treatment, biochemical examination was conducted and natural killer cell activity, plasma amino acids, plasma PCOOH (phosphatidylcholine hydroperoxide), the serum coenzyme Q(10), urinary 8-isoprostane, and urinary 8-OHdG (8-hydroxydeoxyguanosine) were measured. With treatment, total cholesterol and LDL cholesterol decreased, and HDL cholesterol increased significantly. Plasma cystine decreased significantly. All subjects showed reduced PCOOH, 8-isoprostane and 8-OHdG, and increased CoQ(10)H(2)/CoQ(10) ratio. Only one week intake of broccoli sprouts improved cholesterol metabolism and decreased oxidative stress markers.     

Effects of gender on kidney function in magnesium-deficient rats

This study investigated the gender differences in the kidney function of magnesium (Mg)-deficient rats. Male and female rats were fed a control diet or a Mg-deficient diet for 21 d. Mg-deficient diet had no significant effect on kidney calcium (Ca) or phosphorus (P) concentration in male rats, while Ca and P concentrations in female rats were significantly higher in Mg-deficient rats than in the control rats. With regard to indicators of kidney function, no significant differences in creatinine clearance and serum urea nitrogen concentration were observed among the groups. Serum albumin concentrations were significantly lower in rats fed the Mg-deficient diet than in rats fed the control diet. In both sexes, urinary albumin excretion was significantly higher in rats fed the Mg-deficient diet than in rats fed the control diet. Gender differences had no significant influence on creatinine clearance, serum urea nitrogen concentration, serum albumin concentration and urinary albumin excretion. These results suggest that gender differences have no effect on kidney function in Mg-deficient rats under the condition used.     

A double classification tree search algorithm for index SNP selection

Background  

In population-based studies, it is generally recognized that single nucleotide polymorphism (SNP) markers are not independent. Rather, they are carried by haplotypes, groups of SNPs that tend to be coinherited. It is thus possible to choose a much smaller number of SNPs to use as indices for identifying haplotypes or haplotype blocks in genetic association studies. We refer to these characteristic SNPs as index SNPs. In order to reduce costs and work, a minimum number of index SNPs that can distinguish all SNP and haplotype patterns should be chosen. Unfortunately, this is an NP-complete problem, requiring brute force algorithms that are not feasible for large data sets.     

Continuous subcutaneous injection reduces polymorphonuclear leukocyte activation by granulocyte colony-stimulating factor

The use of granulocyte colony stimulating factor (G-CSF) for recovery from neutropenia has been established; however, acute lung injury due to G-CSF-induced polymorphonuclear leukocyte (PMN) activation is a serious complication. This study was designed to compare the activation of PMN with single bolus administration and continuous administration of G-CSF. Healthy volunteers (age 33.8 +/- 1.4 yr; n = 6) received a single bolus injection of 50 microm/m2 of G-CSF (SI; n = 6) or continuous subcutaneous injection of 50 microm/m2 of G-CSF for 24 h (CI; n = 6) and were followed for 48 h. Circulating leukocyte counts, markers of activation on PMN, and circulating levels of G-CSF, IL-6, and PMN elastase were measured. SI rapidly increased serum G-CSF levels, which peaked at 4 h, whereas CI gradually increased G-CSF levels, which remained at a steady level from 8 to 24 h. SI caused a rapid decrease in PMN counts at 0.5 h followed by sustained increase to peak at 12 h. CI gradually increased PMN counts, which peaked at 24 h, but the peak values were not significantly different between the groups. SI-induced activation of PMN, which was characterized by increased expression of CD11b, decreased expression of L-selectin, and increased F-actin content, led to increases in serum IL-6 and PMN elastase level. Such changes were all attenuated with CI (P < 0.05). We conclude that continuous subcutaneous injection of G-CSF resulted in a marrow response similar to that to a single injection but yielded reduced PMN activation.     

Possible functional roles of phase resetting during walking

The walking rhythm is known to show phase shift or "reset" in response to external impulsive perturbations. We tried to elucidate functional roles of the phase reset possibly used for the neural control of locomotion. To this end, a system with a double pendulum as a simplified model of the locomotor control and a model of bipedal locomotion were employed and analyzed in detail. In these models, a movement corresponding to the normal steady-state walking was realized as a stable limit cycle solution of the system. Unexpected external perturbations applied to the system can push the state point of the system away from its limit cycle, either outside or inside the basin of attraction of the limit cycle. Our mathematical analyses of the models suggested functional roles of the phase reset during walking as follows. Function 1: an appropriate amount of the phase reset for a given perturbation can contribute to relocating the system's state point outside the basin of attraction of the limit cycle back to the inside. Function 2: it can also be useful to reduce the convergence time (the time necessary for the state point to return to the limit cycle). In experimental studies during walking of animals and humans, the reset of walking rhythm induced by perturbations was investigated using the phase transition curve (PTC) or the phase resetting curve (PRC) representing phase-dependent responses of the walking. We showed, for the simple double-pendulum model, the existence of the optimal phase control and the corresponding PTC that could optimally realize the aforementioned functions in response to impulsive force perturbations. Moreover, possible forms of PRC that can avoid falling against the force perturbations were predicted by the biped model, and they were compared with the experimentally observed PRC during human walking. Finally, physiological implications of the results were discussed.     

Differential influence of increased polyol pathway on protein kinase C expressions between endoneurial and epineurial tissues in diabetic mice

To explore the relationship between polyol pathway and protein kinase C (PKC), we examined PKC activities and expressions of PKC isoforms separately in endoneurial and vessel-rich epineurial tissues in diabetic mice transgenic for human aldose reductase (Tg). Tg and littermate control mice (Lm) were made diabetic by streptozotocin at 8 weeks of age and treated orally with aldose reductase inhibitor (ARI) (fidarestat 3-5 mg/kg/day) or placebo for 12 weeks. At the end, compared with non-diabetic state, sorbitol contents were increased 6.4-fold in endoneurium and 5.1-fold in epineurium in diabetic Tg, whereas the increase was detected only in endoneurium in diabetic Lm. Endoneurial PKC activity was significantly reduced in diabetic Tg. By contrast, epineurial PKC activity was increased in both diabetic Lm and diabetic Tg and there was no significant difference between the two groups. These changes were all corrected by ARI treatment. Consistent with the changes of PKC activities, diabetic Tg showed decreased expression of PKC alpha in endoneurium, whereas there was an increased expression of PKC beta II in epineurium in both diabetic Tg and diabetic Lm. These findings suggest the presence of dichotomous metabolic pathway between neural and vascular tissues in the polyol-PKC-related pathogenesis of diabetic neuropathy.