Modulation of individual components of gastric motor response to duodenal glucose

AIM:To evaluate individual components of the antro-pyloro-duodenal(APD)motor response to graded small intestinal glucose infusions in healthy humans.METHODS:APD manometry was performed in 15healthy subjects(12 male;40±5 years,body mass index 26.5±1.6 kg/m2)during four 20-min intraduodenal infusions of glucose at 0,0.5,1.0 and 1.5 kcal/min,in a randomised double-blinded fashion.Glucose solutions were infused at a rate of 1 mL/min and separated by 40-minwash-outperiod.Data are mean±SE.Inferential analyses are repeated measure analysis of variance with Bonferroni post-hoc testing.RESULTS:At 0 kcal/min frequency of pressure waves were:antrum(7.5±1.8 waves/20 min)and isolated pyloric pressure waves(IPPWs)(8.0±2.3 waves/20min)with pyloric tone(0.0±0.9 mmHg).Intraduodenal glucose infusion acutely increased IPPW frequency(P<0.001)and pyloric tone(P=0.015),and decreased antral wave frequency(P=0.007)in a dosedependent fashion.A threshold for stimulation was observed at 1.0 kcal/min for pyloric phasic pressure waves(P=0.002)and 1.5 kcal/min for pyloric tone and antral contractility.CONCLUSION:There is hierarchy for the activation of gastrointestinal motor responses to duodenal glucose infusion.An increase in IPPWs is the first response observed.     

食管球囊联合超细胃镜扩张贲门失弛缓症1例

对1例中年贲门失弛缓症患者于超细胃镜直视下应用食管球囊预扩张一次的基础上,将胃镜插至胃底反转对球囊定位后再次扩张.扩张口径满意,无穿孔；症状缓解,随访1mo无复发.     

三叶因子基因表达调控相关因子

三叶因子在黏膜修复与重建及肿瘤的发生、发展过程中发挥了重要的作用,对其结构与功能及基因表达调控的研究一直是近20余年来黏膜保护及肿瘤研究领域的热点．目前的研究发现,许多转录因子如C／EBPβ、GATA家族、NF-κB等,调节蛋白质如雌激素、EGF及TGFα等,及其他化学物质如NSAIDs、TPA、硫氨素等均参与了三叶因子基因的表达调控过程．通过调节这些相关因子,我们可以充分发挥三叶因子生物学作用中的有利方面,避免其不利方面,为临床应用创造条件．     

Noggin haploinsufficiency differentially affects tissue responses in destructive and remodeling arthritis

OBJECTIVE: The balance between destruction and homeostatic or reparative responses determines the outcome of arthritis. Increasing evidence suggests a role for signaling pathways, essential for development and growth, in the maintenance of tissue homeostasis and attempts at repair. Inappropriate activation of such pathways may also have a role in disease progression. We undertook this study to determine the effect of shifting the balance in bone morphogenetic protein (BMP) signaling in different mouse models of arthritis. METHODS: Endogenous levels of noggin, a BMP antagonist, were reduced using heterozygous noggin(+/LacZ) mice in a model of inflammation-driven destruction (methylated bovine serum albumin [mBSA]-induced monarthritis), a model of systemic autoimmune arthritis (collagen-induced arthritis [CIA]), and a model of joint ankylosis (spontaneous arthritis in DBA/1 mice). In addition, we studied BMP inactivation by adenoviral noggin overexpression in destructive arthritis. Cartilage damage and activation of BMP signaling were studied by digital image analysis using Safranin O sulfated glycosaminoglycan staining and immunohistochemistry for phosphorylated Smads (Smads 1, 5, and 8), respectively. RESULTS: Noggin haploinsufficiency provided protection for articular cartilage against destruction in mBSA-induced arthritis. Antagonist overexpression rendered cartilage more vulnerable in this model. Noggin gene transfer in knees affected by CIA also enhanced cartilage damage. Haploinsufficiency did not affect CIA, but noggin(+/LacZ) mice had an increased number of CD4-positive cells with normal immune responses. In noggin(+/LacZ) DBA/1 mice with spontaneous arthritis, we observed delayed progression from cartilage to bone formation. CONCLUSION: Tight spatiotemporal control of BMP signaling appears to be critical in the response of joint tissues in models of arthritis.     

Relationship between human development and disappearance of unusually large von Willebrand factor multimers from plasma

von Willebrand factor (vWF) multimers were examined in fetal, umbilical cord, and neonatal platelet-poor plasma (PPP) specimens. Sixty-five of 65 (100%) fetal PPP samples aged less than 35 weeks and seven of ten (70%) fetal samples aged greater than 35 weeks had unusually large vWF (ULvWF) multimers. Thirty of 46 (65%) cord PPP samples from neonates ranging in gestational age from 34 to 41 weeks had ULvWF. There was no significant relationship between either gestational age at time of delivery or birth weight and likelihood of finding ULvWF multimers in cord PPP samples. No maternal PPP sample contained ULvWF multimers. Serial heelstick samples from 16 preterm and term neonates were analyzed for 8 weeks. ULvWF multimers disappeared from the PPP of ten of the neonates during this time. The PPP of four neonates had vWF patterns similar to those in normal adult PPP throughout the sampling period. The ULvWF multimeric forms of fetal and neonatal PPP samples were similar to those constitutively released from endothelial cells. They were not as slowly migrating in a very porous 0.5% agarose gel system as the ULvWF multimers released from Weibel-Palade bodies in response to the calcium ionophore A23187. A vWF protomer was present in 97% of fetal samples, 83% of cord blood specimens, and 11% of neonatal heelstick samples, but was not found in any maternal sample. These results indicate that control mechanisms operative in older children and adults to prevent circulation of ULvWF multimers and vWF protomeric forms are normally acquired late in uterine life or during the neonatal period. ULvWF multimers, which are normal components of fetal, most cord, and some neonatal plasma samples, may contribute to in utero and postnatal hemostasis.     

Effects of an antiplatelet glycoprotein Ib antibody on hemostatic function in the guinea pig

Previous studies in the guinea pig model system have established a close structural homology between human and guinea pig glycoproteins Ib (GPIb) and IIb/IIIa (GPIIb/IIIa). Moreover, the murine monoclonal antibody (MoAb) PG-1, which recognizes GPIb in guinea pig platelets and megakaryocytes, exerted full inhibition on von Willebrand factor (vWF)- dependent platelet agglutination without inhibiting aggregation induced by ADP, collagen, or thrombin. The present research extends this animal model system to study of the effects on hemostatic function following the in vivo injection of MoAb PG-1 or its F(ab')2 fragments. A hind limb template bleeding time methodology was developed for use in guinea pigs. Normal bleeding time was determined to be 2.7 +/- 0.5 minutes (mean +/- SD), with an observed range of two to four minutes. Platelet counts in these same animals were 501 +/- 82 x 10(3)/microL. After intraperitoneal (IP) injection of busulfan, guinea pigs became increasingly thrombocytopenic. As long as the platelet count remained above approximately 150 x 10(3)/microL, the bleeding time was not more than five minutes; however, further decrease in the platelet count was accompanied by more marked prolongations of the bleeding time. For 14 to 72 hours after IP injection of 1.3 mg/kg intact PG-1 MoAb, a hemorrhagic state was produced with a bleeding time greater than 20 minutes. The platelet count concurrently decreased to approximately 50% of its baseline value but could not be further decreased either by raising the initial PG-1 dosage tenfold or by administering a second, equal dose 24 hours after the initial injection. This finding may reflect a heterogeneity of circulating platelets with respect to GPIb, to Fc receptors, or to an interaction between them. After IP injection of 0.63 to 2.5 mg/kg PG-1 F(ab')2 fragment, platelet counts did not decrease more than 21% below baseline levels in a 72-hour period, and bleeding times never increased by more than one minute over baseline values. Nevertheless, platelets obtained from animals 24 hours after injection of 2.5 mg/kg PG-1 F(ab')2 showed full inhibition of agglutination induced by ristocetin. The response of these platelets to aggregation by asialo-vWF was also severely inhibited as compared with control platelets. PG-1 F(ab')2 produced no effect on aggregation induced by ADP. These studies show that virtually complete functional block of the vWF receptor by F(ab')2 fragments of the anti-GPIb MoAb PG- 1 is not sufficient to produce a hemorrhagic state in the guinea pig animal model system.(ABSTRACT TRUNCATED AT 400 WORDS)     

Amylose ostéoarticulaire et dysglobulinémie: à propos de deux cas

Amyloidosis of bone and joint related to plasma cell dyscrasia.We report two cases of bone and joint amyloidosis involvement related to plasma cell dyscrasia. The radiographie appearances mimic numerous benign or malignant diseases. MR imaging shows a diffuse low signal in TI and an heterogenous low or mild low signal in T2 weighted spin-echo sequence.