Characteristic hydrolyzing of megalosaccharide by human salivary α-amylase and small intestinal enzymes,and its bioavailability in healthy subjects

The digestibility of Megalosaccharide® (newly developed carbohydrate comprising α-1,4-glucosaccharide) was investigated in vitro and in vivo. Isomaltosyl-megalosaccharide® (IMS) and nigerosyl-megalosaccharide® (NMS) contain 20% and 50% of the megalosaccharide fraction (degree of polymerization (DP) 10–35), respectively. IMS was hydrolyzed readily by α-amylase to oligosaccharides (DP?≤?7), and a small amount of glucose was produced from oligosaccharides by small intestinal enzymes (SIEs). NMS was partially hydrolyzed by α-amylase to oligosaccharides, and a small amount of glucose produced by SIEs. When IMS and NMS were treated by SIEs after treatment with human saliva α-amylase for a few minutes, IMS and NMS were hydrolyzed readily to glucose. Plasma levels of glucose and insulin upon ingestion of 50?g of IMS or NMS were elevated the same as those for 50?g of glucose, and breath hydrogen was not excreted. These results suggest that IMS and NMS are digestible carbohydrates.     

Negative regulation of cell motile and invasive activities by lysophosphatidic acid receptor-3 in colon cancer HCT116 cells

Lysophosphatidic acid (LPA) mediates a wide range of biological responses with G protein-coupled transmembrane receptors (LPA receptors). So far, at least six types of LPA receptors (LPA receptor-1 (LPA₁) to LPA₆) have been identified. Recently, it has been reported that LPA₃ indicates opposite effects on cellular functions of cancer cells. In the present study, to assess a biological role of LPA₃ on cell migration ability of colon cancer cells, we generated LPA receptor-3 (LPAR3) knockdown (HCT-sh3-3) cells from HCT116 and measured cell motile and invasion activities. In motility assay with a cell culture insert, HCT-sh3-3 cells showed significantly high cell motile activity, compared with control cells. For invasion assay, the filter was coated with Matrigel. The invasive activity of HCT-sh3-3 cells was significantly higher than that of control cells. Furthermore, we also examined the effects of LPAR3 knockdown on the interaction between colon cancer cells and endothelial F-2 cells. When F-2 cells were cultured with serum-free DMEM containing a supernatant from HCT-sh3-3 cells, the cell growth rate and migration activity of F-2 cells were significantly stimulated, associating with the elevated expressions of vascular endothelial growth factor (VEGF)-A and VEGF-C genes in HCT-sh3-3 cells. These results suggest that LPA₃ may act as a negative regulator on cell motile and invasive abilities of colon cancer HCT116 cells.     

Distinct ontogenic and regional expressions of newly identified Cajal-Retzius cell-specific genes during neocorticogenesis

Cajal-Retzius (CR) cells are early-generated transient neurons and are important in the regulation of cortical neuronal migration and cortical laminar formation. Molecular entities characterizing the CR cell identity, however, remain largely elusive. We purified mouse cortical CR cells expressing GFP to homogeneity by fluorescence-activated cell sorting and examined a genome-wide expression profile of cortical CR cells at embryonic and postnatal periods. We identified 49 genes that exceeded hybridization signals by >10-fold in CR cells compared with non-CR cells at embryonic day 13.5, postnatal day 2, or both. Among these CR cell-specific genes, 25 genes, including the CR cell marker genes such as the reelin and calretinin genes, are selectively and highly expressed in both embryonic and postnatal CR cells. These genes, which encode generic properties of CR cell specificity, are eminently characterized as modulatory composites of voltage-dependent calcium channels and sets of functionally related cellular components involved in cell migration, adhesion, and neurite extension. Five genes are highly expressed in CR cells at the early embryonic period and are rapidly down-regulated thereafter. Furthermore, some of these genes have been shown to mark two distinctly different focal regions corresponding to the CR cell origins. At the late prenatal and postnatal periods, 19 genes are selectively up-regulated in CR cells. These genes include functional molecules implicated in synaptic transmission and modulation. CR cells thus strikingly change their cellular phenotypes during cortical development and play a pivotal role in both corticogenesis and cortical circuit maturation.     

Incidence of thrombotic stent occlusion during the first three months after sirolimus-eluting stent implantation in 500 consecutive patients

Sirolimus-eluting stents have been used in our institution for all percutaneous interventions, without clinical or anatomic exclusion criteria, as part of the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital registry. We analyzed the incidence of (sub)acute stent thrombosis after sirolimus-eluting stent implantation in an unselected population of 510 consecutive patients. At 3-month follow-up, (sub)acute stent thrombosis was diagnosed in 2 patients (0.4%) 6 hours and 11 days after the procedure, respectively. These cases occurred in diabetic women with complex coronary lesions. Intravascular ultrasound examination showed inadequate stent expansion and uncovered distal dissection as possible mechanical explanations for the thrombosis.     

The management of bleeding peptic ulcer in the elderly with heater probe thermocoagulation

BACKGROUND/AIMS: The aim of this study was to compare the clinical characteristics of bleeding peptic ulcers in the elderly with those in younger patients, retrospectively. METHODOLOGY: Between 1986 and 1994, 274 patients with bleeding peptic ulcers were treated with heater probe endoscopically. They were divided into 2 groups: 48 in the elder group (70 years of age or older) and 226 in the younger group (<70). We evaluated the rate of concomitant disease, rebleeding rate, incidence of emergency surgery, mortality and blood transfusion requirement between the 2 groups. RESULTS: The incidence of concomitant disease was significantly higher in the elderly group (83.3%) than in the younger group (33.3%) (p<0.01). The rate of rebleeding (younger group 23.5% vs. elderly group 31.3%), the incidence of emergency surgery (5.8% vs. 6.3%, respectively) and the rate of mortality due to hemorrhage (2.2% vs. 4.2%, respectively) were similar in the 2 groups. There was no significant difference in the mean volume of blood transfused. CONCLUSIONS: It was revealed that aggressive endoscopic hemostasis improved the mortality rate and the incidence of emergency surgery in elderly patients as well as in younger patients, provided that their general condition was monitored carefully.     

Galpha(12/13) mediates alpha(1)-adrenergic receptor-induced cardiac hypertrophy

In neonatal cardiomyocytes, activation of the G(q)-coupled alpha(1)-adrenergic receptor (alpha(1)AR) induces hypertrophy by activating mitogen-activated protein kinases, including c-Jun NH(2)-terminal kinase (JNK). Here, we show that JNK activation is essential for alpha(1)AR-induced hypertrophy, in that alpha(1)AR-induced hypertrophic responses, such as reorganization of the actin cytoskeleton and increased protein synthesis, could be blocked by expressing the JNK-binding domain of JNK-interacting protein-1, a specific inhibitor of JNK. We also identified the classes and subunits of G proteins that mediate alpha(1)AR-induced JNK activation and hypertrophic responses by generating several recombinant adenoviruses that express polypeptides capable of inhibiting the function of specific G-protein subunits. alpha(1)AR-induced JNK activation was inhibited by the expression of carboxyl terminal regions of Galpha(q), Galpha(12), and Galpha(13). JNK activation was also inhibited by the Galpha(q/11)- or Galpha(12/13)-specific regulator of G-protein signaling (RGS) domains and by C3 toxin but was not affected by treatment with pertussis toxin or by expression of the carboxyl terminal region of G protein-coupled receptor kinase 2, a polypeptide that sequesters Gbetagamma. alpha(1)AR-induced hypertrophic responses were inhibited by Galpha(q/11)- and Galpha(12/13)-specific RGS domains, C3 toxin, and the carboxyl terminal region of G protein-coupled receptor kinase 2 but not by pertussis toxin. Activation of Rho was inhibited by carboxyl terminal regions of Galpha(12) and Galpha(13) but not by Galpha(q). Our findings suggest that alpha(1)AR-induced hypertrophic responses are mediated in part by a Galpha(12/13)-Rho-JNK pathway, in part by a G(q/11)-JNK pathway that is Rho independent, and in part by a Gbetagamma pathway that is JNK independent.