Lack of nocturnal blood pressure fall in elderly bedridden hypertensive patients with cerebrovascular disease

To prevent recurrence of cerebrovascular disease (CVD), adequate control of blood pressure (BP) is extremely important for the treatment of hypertensive CVD patients. As absence of the nocturnal fall of BP by the expected 10-20% from daytime levels is reported to exaggerate target organ injury, 24-h ambulatory blood pressure monitoring (ABPM) was conducted, especially to obtain data during nighttime sleep. Forty-eight elderly bedridden chronic phase CVD hypertensive patients (assessed 1-3 mo after CVD accident) participated. As a group, nocturnal BP was higher than diurnal BP, whereas nocturnal pulse rate was lower than diurnal pulse rate. The nocturnal BP fall was blunted in most (～90%) of the patients. These results suggest that to perform a rational drug treatment, it is essential to do 24-h ABPM before initiation of antihypertensive therapy in elderly bedridden hypertensive CVD patients.     

The involvement of the 67 kDa laminin receptor-mediated modulation of cytoskeleton in the degranulation inhibition induced by epigallocatechin-3-O-gallate

Recently, we have reported that (-)-epigallocatechin-3-O-gallate (EGCG) acts as an inhibitor of degranulation. However, the inhibitory mechanism for degranulation is still poorly understood. Here we show that suppression of exocytosis-related myosin II regulatory light chain phosphorylation and alteration of actin remodeling are involved in the inhibitory effect of EGCG on the calcium ionophore-induced degranulation from human basophilic KU812 cells. Surface plasmon resonance assay also revealed that EGCG binds to the cell surface, and the disruption of lipid rafts resulted in reduction of EGCG's ability. We have previously identified the raft-associated 67kDa laminin receptor (67LR) as an EGCG receptor on the cell surface. Treatment of the cells with anti-67LR antibody or RNA interference-mediated downregulation of 67LR expression abolished the effects of EGCG. These findings suggest that EGCG-induced inhibition of the degranulation includes the primary binding of EGCG to the cell surface 67LR and subsequent modulation of cytoskeleton.     

The murine homolog of SALL4, a causative gene in Okihiro syndrome, is essential for embryonic stem cell proliferation, and cooperates with Sall1 in anorectal, heart, brain and kidney development

Mutations in SALL4, the human homolog of the Drosophila homeotic gene spalt (sal), cause the autosomal dominant disorder known as Okihiro syndrome. In this study, we show that a targeted null mutation in the mouse Sall4 gene leads to lethality during peri-implantation. Growth of the inner cell mass from the knockout blastocysts was reduced, and Sall4-null embryonic stem (ES) cells proliferated poorly with no aberrant differentiation. Furthermore, we demonstrated that anorectal and heart anomalies in Okihiro syndrome are caused by Sall4 haploinsufficiency and that Sall4/Sall1 heterozygotes exhibited an increased incidence of anorectal and heart anomalies, exencephaly and kidney agenesis. Sall4 and Sall1 formed heterodimers, and a truncated Sall1 caused mislocalization of Sall4 in the heterochromatin; thus, some symptoms of Townes-Brocks syndrome caused by SALL1 truncations could result from SALL4 inhibition.     

The effects of hydrogen peroxide on metabolism in the coral Goniastrea aspera

Coral metabolism reflects the physiological condition of a coral colony. We studied coral metabolism using a continuous-flow, complete mixing (CFCM) experimental system. Small-size Goniastrea aspera coral colonies were incubated in the CFCM system with and without hydrogen peroxide (H₂O₂) added to the supplied seawater (0 µM H₂O₂ for 12 days; 0, 0.3, 3.0, and 30 µM H₂O₂ for 3 days, for each treatment) Without addition of H₂O₂, coral metabolism, including photosynthesis (gross primary productivity) and calcification, was relatively stable and there were no significant metabolic changes, suggesting that, without H₂O₂ added to the CFCM system, the corals did not suffer significant stress from the experimental system over a 12-day incubation period. When H₂O₂ was added, large decreases in photosynthesis and calcification were observed. The non-parametric Mann–Whitney U-test showed that there were statistically significant differences in photosynthesis after addition of 3.0 µM and 30 µM H₂O₂, compared with the control. We also found statistically significant differences in net calcification after addition of 30 µM H₂O₂. Thus, the incubation experiments suggest that higher H₂O₂ concentrations in seawater clearly influence coral metabolism. However, the results also suggest that the current seawater H₂O₂ level in Okinawa is not likely to pose significant acute effects on the metabolic activities of corals.     

QTL mapping of clubroot resistance in radish (Raphanus sativus L.)

A QTL analysis for clubroot resistance (CR) of radish was performed using an F₂ population derived from a crossing of a CR Japanese radish and a clubroot-susceptible (CS) Chinese radish. F₃ plants obtained by selfing of F₂ plants were used for the CR tests. The potted seedlings were inoculated and the symptom was evaluated 6 weeks thereafter. The mean disease indexes of the F₃ plants were used for the phenotype of the F₂. The results of two CR tests were analyzed for the presence of QTL. A linkage map was constructed using AFLP and SSR markers; it spanned 554 cM and contained 18 linkage groups. A CR locus was observed in the top region of linkage group 1 in two tests. Therefore, the present results suggest that a large part of radish CR is controlled by a single gene or closely linked genes in this radish population, although minor effects of other genomic areas cannot be ruled out. The CR locus was named Crs1. Markers linked to Crs1 showed sequence homology to the genomic region of the top of chromosome 3 of Arabidopsis, as in the case of Crr3, a CR locus in Brassica rapa. These markers should be useful for breeding CR cultivars of radish. As Japanese radishes are known to be highly resistant or immune to clubroot, these markers may also be useful in the introgression of this CR gene to Brassica crops.     

Genotyping of Mycobacterium tuberculosis isolates from a low-endemic setting in northwestern state of Paraná in Southern Brazil

The purpose of this study was to provide information about the genetic diversity and prevalent genotype of Mycobacterium tuberculosis in a low-endemic setting in northwestern state of Paraná in Southern Brazil. We employed spoligotyping and mycobacterial interspersed repetitive units-variable number tandem repeat (MIRU-VNTR) techniques to genotype M. tuberculos isisolates from patients with pulmonary tuberculosis (TB). The 93 isolates analyzed by spoligotyping were divided into 36 different patterns, 30 of which were described in the SITVIT database. Latin American and Mediterranean, Haarlem and T families were responsible for 26.9%, 17.2% and 11.8% of TB cases, respectively. From the 84 isolates analyzed by MIRU-VNTR, 58 shared a unique pattern and the remaining 26 belonged to nine clusters. The MIRU loci 40, 23, 10 and 16 were the most discriminatory. A combination of MIRU-VNTR and spoligotyping resulted in 85.7% discriminatory power (Hunter-Gaston index = 0.995). Thus, combining spoligotyping and MIRU-VNTR typing proved to be most useful for epidemiological study in this low-endemic setting in Southern Brazil. The current study demonstrated that there is significant diversity in circulating strains in the city of Maringá and the surrounding regions, with no single genotype of M. tuberculosis predominating.     

Vitamin E as a novel enhancer of macroautophagy in rat hepatocytes and H4-II-E cells

Autophagy is an intracellular bulk degradation process induced by nutrient starvation, and contributes to macromolecular turnover and rejuvenation of cellular organelles. We demonstrated that vitamin E was a novel nutritional enhancer of autophagy in freshly isolated rat hepatocytes and rat hepatoma H4-II-E cells. Supplementation of fresh hepatocytes with vitamin E (up to 100 μM) increased proteolysis significantly in the presence or absence of amino acids in a dose-dependent manner. The cytosolic LC3 ratio, a newly established index of autophagic flux, was significantly increased by vitamin E, strongly suggesting that the possible site of action is the LC3 conversion step, an early step in autophagosome formation. A typical antioxidant, α-lipoic acid, exerted autophagy suppression, while H₂O₂ stimulated autophagy. It is conceivable that autophagy was stimulated by oxidative stress and this stimulation was cancelled by cellular antioxidative effects. However, in our studies, vitamin E could have enhanced autophagy over-stimulation by H₂O₂, rather than suppress it. From these results, using a new cytosolic LC3 ratio, vitamin E increases autophagy by accelerating LC3 conversion through a new signaling pathway, emerging as a novel enhancer of autophagy.