Interaction of Necl‐4/CADM4 with ErbB3 and integrin α6β4 and inhibition of ErbB2/ErbB3 signaling and hemidesmosome disassembly

Nectin‐like molecule 4 (Necl‐4)/CADM4, a transmembrane cell–cell adhesion molecule with three Ig‐like domains, was shown to serve as a tumor suppressor, but its mode of action has not been elucidated. In this study, we showed that Necl‐4 interacted in cis with ErbB3 through their extracellular regions, recruited PTPN13 and inhibited the heregulin‐induced activation of the ErbB2/ErbB3 signaling. In addition, we extended our previous finding that Necl‐4 interacts in cis with integrin α₆β₄ through their extracellular regions and found that Necl‐4 inhibited the phorbol ester‐induced disassembly of hemidesmosomes. These results indicate that Necl‐4 serves as a tumor suppressor by inhibiting the ErbB2/ErbB3 signaling and hemidesmosome disassembly.     

Inhibition of enamel demineralization by buffering effect of S‐PRG filler‐containing dental sealant

The buffering capacity and inhibitory effects on enamel demineralization of two commercially available dental sealants were evaluated in this study. The effects of filler particles were also examined. Disks of enamel and cured sealant materials of BeautiSealant (silica or S‐PRG filler) or Teethmate F‐1 were incubated in lactic acid solutions (pH 4.0) for 1–6 d. The pH changes and amounts of ions released in the solutions were assessed, and enamel surfaces were observed using a scanning electron microscope. The pH of the solution with BeautiSealant (S‐PRG filler) was neutralized from pH 4.0 to pH 6.1 (after incubation for 1 d) and from pH 4.0 to pH 6.7 (after incubation for 6 d). In addition, no release of calcium ions was detected and the enamel surface was morphologically intact in scanning electron microscopy images. However, the pH of the solution with Teethmate F‐1 remained below pH 4.0 during incubation from days 1 to 6. Calcium release was increased in solutions up to and after 6 d of incubation. Scanning electron microscopy images showed that the structures of hydroxyapatite rods were exposed at the specimen surfaces as a result of demineralization. Ions released from S‐PRG filler‐containing dental sealant rapidly buffered the lactic acid solution and inhibited enamel demineralization.     

Efficacy of plasma exchange therapy for Kawasaki disease intractable to intravenous gamma-globulin

Kawasaki disease (KD) causes coronary artery lesions (CALs) in 500 Japanese children each year. Intravenous gamma-globulin (IVGG) decreases the incidence of these lesions from 25% to 8% of the total KD cases. We examined whether plasma exchange is a safe and effective prophylaxis against CALs in children with KD intractable to IVGG therapy. Eighty-nine children with KD at high risk of CALs were selected on the basis of increases in fractional changes in inflammatory markers such as white blood cell count, neutrophil count, and C-reactive protein between the baseline and 1–2 days after IVGG treatment. Of 105 children who received a second course of IVGG therapy because the initial course was ineffective, plasma exchange (PE) was performed in 46 children who had not responded to the second IVGG treatment. The outcome was compared with the results when a third course of IVGG therapy was given to the other 59 children. No complications occurred with the plasma exchange therapy. CALs developed in only 8 of the 46 children (17.3%) who underwent plasma exchange, but they occurred in 24 of the 59 (40.7%) who had received a third course of IVGG therapy (P 0.0012). We concluded that PE was a safe, effective prophylactic measure against CALs in children with KD intractable to IVGG therapy. PE should be performed at an early stage, as soon as fractional increases in inflammatory markers are found after IVGG therapy.     

Action of aspirin on whole blood-aggregation evaluated by the screen filtration pressure method.

BACKGROUND: There are few monitoring systems widely used in clinical practice for evaluating the effectiveness of aspirin therapy, so in the present study aspirin's antiplatelet effects we investigated with a whole blood aggregometer using a screen filtration pressure (SFP) method. METHODS AND RESULTS: Thirty-five healthy male volunteers took 100 mg/day aspirin for 14 days. Whole-blood aggregation was analyzed at baseline and on days 7 and 14, using collagen and adenosine diphosphate as the stimuli, and compared with the platelet-rich plasma (PRP) aggregation measured by optical aggregometer. The platelet-aggregation threshold index (PATI) for both methods, which was defined as the putative agonist-concentration giving half-maximal aggregation, and the PRP-maximal aggregation rate were analyzed. The maximal aggregation rate induced by 1.6 mg/L collagen decreased from 85.5% (80.8-92.8) [median (interquartile range)] at baseline to 51.5% (39-63.8) on day 14 (p<0.0001). The PRP-PATI and whole-blood PATI for collagen increased from 0.32 (0.28-0.70) to 1.82 mg/L (1.25-2.89) (p<0.0001) and from 0.28 (0.22-0.3) to 1.06 mg/L (1.01-1.29) (p<0.0001) respectively. CONCLUSIONS: The whole-blood PATI and PRP-PATI for collagen, as well as the maximal PRP aggregation rate, clearly distinguish platelet aggregability before and after aspirin intake. However, whole-blood analysis by the SFP-method is easier to perform, and is a promising method of monitoring aspirin's effects.     

The role of mineralocorticoid receptor expression in brain remodeling after cerebral ischemia

Mineralocorticoid receptors (MRs) are classically known to be expressed in the distal collecting duct of the kidney. Recently it was reported that MR is identified in the heart and vasculature. Although MR expression is also found in the brain, it is restricted to the hippocampus and cerebral cortex under normal condition, and the role played by MRs in brain remodeling after cerebral ischemia remains unclear. In the present study, we used the mouse 20-min middle cerebral artery occlusion model to examine the time course of MR expression and activity in the ischemic brain. We found that MR-positive cells remarkably increased in the ischemic striatum, in which MR expression is not observed under normal conditions, during the acute and, especially, subacute phases after stroke and that the majority of MR-expressing cells were astrocytes that migrated to the ischemic core. Treatment with the MR antagonist spironolactone markedly suppressed superoxide production within the infarct area during this period. Quantitative real-time RT-PCR revealed that spironolactone stimulated the expression of neuroprotective or angiogenic factors, such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), whereas immunohistochemical analysis showed astrocytes to be cells expressing bFGF and VEGF. Thereby the incidence of apoptosis was reduced. The up-regulated bFGF and VEGF expression also appeared to promote endogenous angiogenesis and blood flow within the infarct area and to increase the number of neuroblasts migrating toward the ischemic striatum. By these beneficial effects, the infarct volume was significantly reduced in spironolactone-treated mice. Spironolactone may thus provide therapeutic neuroprotective effects in the ischemic brain after stroke.     

Delayed Gastric Emptying by Helicobacter pylori Lipopolysaccharide in Conscious Rats

The present study was carried out to investigatethe possibility that lipopolysaccharide deprived fromHelicobacter pylori may alter gastric motility. Toaddress the question, we examined the effect of H. pylori lipopolysaccharide on gastricemptying in conscious rats. Gastric emptying wasevaluated by the phenol red method. Time-course anddose-related effects of intraperitoneal administrationof H. pylori lipopolysaccharide were investigated.Intraperitoneal injection of H. pylorilipopolysaccharide significantly suppressed gastricemptying of a liquid meal in a dose-dependent manner.The inhibitory action of H. pylori lipopolysaccharide wasobserved 2, 4, 8, or 12 hr after the injection. Theseresults suggest for the first time that H. pylorilipopolysaccharide may suppress gastric emptying in along-lasting fashion. It is also suggested that H. pylorimay influence gastric function through its cell wallstructure named lipopolysaccharide.