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Marlene L Cohen - One of the best experts on this subject based on the ideXlab platform.
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m1 receptor mediated nitric oxide dependent relaxation unmasked in Stomach Fundus from m3 receptor knockout mice
Journal of Pharmacology and Experimental Therapeutics, 2003Co-Authors: Peter W Stengel, Marlene L CohenAbstract:Muscarinic receptors can mediate both contractile and relaxant responses in smooth muscle. The Stomach Fundus from wild-type mice possesses a neuronal M1 receptor that mediates relaxation to carbamylcholine and (4-hydroxy-2-butynyl)-1-trimethylammonium-3-chlorocarbanilate chloride (McN-A-343) but is masked by M3 receptor-mediated contraction to both agonists. When the M3 receptor was deleted, cholinergic-induced relaxation was unmasked. M1receptor antagonism with pirenzepine, nitric oxide (NO) synthase inhibition with N ω-nitro-l-arginine methyl ester hydrochloride, and inhibition of neuronal activation with tetrodotoxin abolished relaxation to McN-A-343 in tissues from M3 receptor knockout mice, supporting the neuronal localization of an M1 receptor that activated NO release to effect relaxation. However, the cyclooxygenase inhibitor indomethacin did not affect contraction or relaxation to carbamylcholine in Stomach Fundus from wild-type or M3 receptor knockout mice, indicating that cyclooxygenase products played no role in these responses. The neuronal M1 receptor modulated relaxation induced by carbamylcholine and McN-A-343 but not relaxation induced by electric field stimulation of the Stomach Fundus. These data support the presence of M1 receptor-mediated relaxation in the Stomach and suggest that when the M3 receptor is eliminated or blocked, M1 receptor-mediated gastric relaxation may be enhanced, possibly leading to alterations in gastric emptying and subsequent effects on body weight.
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m3 receptor knockout mice muscarinic receptor function in atria Stomach Fundus urinary bladder and trachea
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2002Co-Authors: Peter W Stengel, Jurgen Wess, Masahisa Yamada, Marlene L CohenAbstract:Negative chronotropic and smooth muscle contractile responses to the nonselective muscarinic agonist carbamylcholine were compared in isolated tissues from M3-muscarinic receptor knockout and wild-...
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m2 and m4 receptor knockout mice muscarinic receptor function in cardiac and smooth muscle in vitro
Journal of Pharmacology and Experimental Therapeutics, 2000Co-Authors: Peter W Stengel, Jurgen Wess, Jesus Gomeza, Marlene L CohenAbstract:Peripheral muscarinic receptors play key roles in the control of heart rate and smooth muscle activity. In this study, bradycardic and smooth muscle contractile responses to the muscarinic agonist carbamylcholine were compared in isolated tissues from M2 and M4 muscarinic receptor knockout mice and their wild-type littermates. Carbamylcholine (1 × 10−8-3 × 10−5 M) produced similar concentration-dependent bradycardia in spontaneously beating atria from M4 receptor knockout and wild-type control mice. In contrast, carbamylcholine did not produce bradycardia in atria derived from M2 receptor knockout mice, whereas such atria were responsive to adenosine-induced bradycardia. Carbamylcholine-induced contractile responses were similar in Stomach Fundus, urinary bladder, and tracheal preparations from M4 receptor knockout mice and their wild-type littermates for each tissue (−logEC50 values ranging from 6.20 ± 0.10 to 6.76 ± 0.08), suggesting that M4 receptors do not participate in smooth muscle contraction in these tissues. In contrast, ∼2-fold higher carbamylcholine concentration was required for contraction of Stomach Fundus, urinary bladder, and trachea from M2 receptor knockout mice (−logEC50 = 6.39 ± 0.05, 6.07 ± 0.06, and 6.27 ± 0.12, respectively) than from wild-type littermates (−logEC50 = 6.68 ± 0.07, 6.27 ± 0.07, and 6.56 ± 0.06, respectively). Furthermore, the affinity of the M2 “selective” receptor antagonist AF-DX116 in inhibiting carbamylcholine-induced smooth muscle contraction was significantly reduced in M2 receptor knockout mice compared with tissues from wild-type littermates. Collectively, these results provide direct and unambiguous evidence that M2 receptors mediate muscarinic receptor-induced bradycardia and play a role in smooth muscle contractility, whereas M4 receptors are not involved in Stomach Fundus, urinary bladder, or tracheal contractility.
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Beta3 receptors mediate relaxation in Stomach Fundus whereas a fourth beta receptor mediates tachycardia in atria from transgenic beta3 receptor knockout mice.
Receptors & channels, 2000Co-Authors: Marlene L Cohen, Bloomquist W, Ito M, Bradford B. LowellAbstract:Pharmacological studies have revealed a non-beta1, beta2 or beta3 adrenergic receptor that mediates tachycardia in rat and human atria. The present studies utilized transgenic mice that lack the rodent beta3 receptor to explore, in a more definitive fashion, whether a non-beta1, beta2 or beta3 receptor can mediate atrial tachycardia. Insofar as the rat Stomach Fundus possesses a beta3 receptor mediating relaxation, we examined the Stomach Fundus from beta3 receptor knockout mice for the presence or absence of the beta3 relaxant receptor. Contractile responses to carbamylcholine were similar in potency and magnitude between mouse Stomach Fundus from wild type and beta3 receptor knockout animals. However, the classical beta3 receptor agonist CL316243, (10(-8)-10(-6)M) relaxed Stomach Fundus from wild type mice, but not from the beta3 receptor knockout animals. These data provide functional evidence for the absence of the beta3 receptor in beta3 receptor knockout animals and support the role of beta3 receptors mediating relaxation in mouse Stomach Fundus. Atria from mice lacking the beta3 receptor responded similarly (in potency and maximal increase in heart rate) to isoproterenol (10(-9)-10(-6)M) as atria from wild type mice. Furthermore, propranolol (3 x 10(-7) M) produced a dextral shift in the concentration response to isoproterenol in atria from both the beta3 receptor knockout and wild type mice with negative log K(B) values of 8.03 and 8.09, respectively. Thus, beta receptors mediating tachycardia to isoproterenol are intact and respond similarly in atria from both knockout and wild type mice. Furthermore, CGP12177, a prototypic 'atypical' beta receptor agonist produced tachycardia with a similar EC50 and maximal response in atria from both the wild type and beta3 receptor knockout mice. Cyanopindolol was a partial agonist relative to CGP12177 in both wild type and beta3 receptor knockout mice. Tachycardia to CGP12177 and cyanopindolol was not blocked by propranolol (3 x 10(-7) M) in atria from either group. These data provide definitive evidence that the receptor mediating tachycardia to CGP12177 and to cyanopindolol in atria from the transgenic beta3 receptor knockout mice is neither the beta1, beta2, nor beta3 adrenergic receptor.
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bradykinin and phorbol ester but not 5 ht2b receptor activation stimulate phospholipase d activity in the rat Stomach Fundus
Progress in Neuro-psychopharmacology & Biological Psychiatry, 1999Co-Authors: David A Cox, David K Blase, Marlene L CohenAbstract:Abstract 1. 1. Serotonin has been implicated as a mediator involved in migraine headache, an effect that may involve central 5-HT;B receptor activation. 5-HT2B receptor signal transduction is controversial. 2. 2. Rat Stomach Fundus contraction to serotonin has been used as a model for 5-HT2B receptor activation. Serotonin-induced contractility involves intracellular calcium release and activation of protein kinase C without stimulation of phosphoinositide (PI) hydrolysis. 3. 3. Since phospholipase D (PLD) activation results in phosphatidic acid production, which can release intracellular calcium and provide diacylglycerol for PKC activation, the purpose of this study was to determine whether the 5-HT2B receptor coupled to PLD activation using the rat Stomach Fundus as a model system. 4. 4. Using phosphatidylethanol production to measure PLD activity, both bradykinin (0.01–1 μM) and phorbol dibutyrate (PDBu, 1 μM) stimulated PLD activity in rat Stomach fimdal strips, indicating that this tissue possesses an active PLD system. 5. 5. Under identical conditions, 5-hydroxytryptamine (5-HT) failed to stimulate PLD activity over a concentration range (1 nM–1 μM) documented to induce 5-HT2B receptor-mediated contraction in rat Stomach Fundus. Thus, the 5-HT2B contractile receptor in rat Stomach Fundus is not coupled to PLD activation, whereas both bradykinin and phorbol ester do couple to PLD.
Thomas J. Eddinger - One of the best experts on this subject based on the ideXlab platform.
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Tonic and Phasic Smooth Muscle Contraction Is Not Regulated by the PKCa- CPI-17 Pathway in Swine
2016Co-Authors: Yu Zhang, Meghan E. Hermanson, Thomas J. Eddinger, Stomach AntrumAbstract:Regulation of myosin light chain phosphatase (MLCP) via protein kinase C (PKC) and the 17 kDa PKC-potentiated inhibitor of myosin light chain phosphatase (CPI-17) has been reported as a Ca2+ sensitization signaling pathway in smooth muscle (SM), and thus may be involved in tonic vs. phasic contractions. This study examined the protein expression and spatial-temporal distribution of PKCa and CPI-17 in intact SM tissues. KCl or carbachol (CCh) stimulation of tonic Stomach Fundus SM generates a sustained contraction while the phasic Stomach antrum generates a transient contraction. In addition, the tonic Fundus generates greater relative force than phasic antrum with 1 mM phorbol 12, 13-dibutyrate (PDBu) stimulation which is reported to activate the PKCa – CPI-17 pathway. Western blot analyses demonstrated that this contractile difference was not caused by a difference in the protein expression of PKCa or CPI-17 between these two tissues. Immunohistochemical results show that the distribution of PKCa in the longitudinal and circular layers of the Fundus and antrum do not differ, being predominantly localized near the SM cell plasma membrane. Stimulation of either tissue with 1 mM PDBu or 1 mM CCh does not alter this peripheral PKCa distribution. There are no differences between these tw
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Tonic and phasic smooth muscle contraction is not regulated by the PKCα - CPI-17 pathway in swine Stomach antrum and Fundus.
PloS one, 2013Co-Authors: Yu Zhang, Meghan E. Hermanson, Thomas J. EddingerAbstract:Regulation of myosin light chain phosphatase (MLCP) via protein kinase C (PKC) and the 17 kDa PKC-potentiated inhibitor of myosin light chain phosphatase (CPI-17) has been reported as a Ca2+ sensitization signaling pathway in smooth muscle (SM), and thus may be involved in tonic vs. phasic contractions. This study examined the protein expression and spatial-temporal distribution of PKCα and CPI-17 in intact SM tissues. KCl or carbachol (CCh) stimulation of tonic Stomach Fundus SM generates a sustained contraction while the phasic Stomach antrum generates a transient contraction. In addition, the tonic Fundus generates greater relative force than phasic antrum with 1 µM phorbol 12, 13-dibutyrate (PDBu) stimulation which is reported to activate the PKCα – CPI-17 pathway. Western blot analyses demonstrated that this contractile difference was not caused by a difference in the protein expression of PKCα or CPI-17 between these two tissues. Immunohistochemical results show that the distribution of PKCα in the longitudinal and circular layers of the Fundus and antrum do not differ, being predominantly localized near the SM cell plasma membrane. Stimulation of either tissue with 1 µM PDBu or 1 µM CCh does not alter this peripheral PKCα distribution. There are no differences between these two tissues for the CPI-17 distribution, but unlike the PKCα distribution, CPI-17 appears to be diffusely distributed throughout the cytoplasm under relaxed tissue conditions but shifts to a primarily peripheral distribution at the plasma membrane with stimulation of the tissues with 1 µM PDBu or 1 µM CCh. Results from double labeling show that neither PKCα nor CPI-17 co-localize at the adherens junction (vinculin/talin) at the membrane but they do co-localize with each other and with caveoli (caveolin) at the membrane. This lack of difference suggests that the PKCα - CPI-17 pathway is not responsible for the tonic vs. phasic contractions observed in Stomach Fundus and antrum.
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rhoa kinase and protein kinase c participate in regulation of rabbit Stomach Fundus smooth muscle contraction
British Journal of Pharmacology, 2002Co-Authors: Paul H Ratz, Joel T Meehl, Thomas J. EddingerAbstract:The degree to which the RhoA kinase (ROK) blockers, Y-27632 (1 μM) and HA-1077 (10 μM), and the PKC blocker, GF-109203X (1 μM), reduced force produced by carbachol, a muscarinic receptor agonist, and phenylephrine, an α-adrenoceptor agonist, was examined in rabbit Stomach Fundus smooth muscle. When examining the effect on cumulative carbachol concentration-response curves (CRCs), ROK and PKC blockers shifted the potency (EC50) to the right but did not reduce the maximum response. In a single-dose carbachol protocol using moderate (∼EC50) and maximum carbachol concentrations, Y-27632 and HA-1077 reduced peak force, but GF-109203X had no effect. By contrast, all three agents inhibited the carbachol contractions of rabbit bladder (detrusor) smooth muscle. Compared to carbachol, phenylephrine produced a weaker maximum response that was not inhibited by phentolamine, atropine nor capsaicin but was inhibited by Y-27632 , HA-1077 and GF-109203X. In detrusor, classical down-regulation occurred, but in Fundus, up-regulation of responsiveness occurred. This up-regulation in Fundus may have been a post-receptor event, because a KCl-induced contraction produced after a carbachol CRC was stronger than one produced before the carbachol stimulus. In conclusion, these data suggest that ROK plays a critical role in the regulation of rabbit Fundus smooth muscle contraction, which is distinct from chicken gizzard smooth muscle, where ROK is reported to exist but to not play a role in muscarinic receptor-induced contraction. Additional unique findings are that PKC participates in phenylephrine- but not carbachol-induced contraction in Fundus, that carbachol does not activate identical subcellular signalling systems in Fundus and detrusor, and that Fundus, unlike detrusor, responds to carbachol stimulation with post-receptor up-regulation of contraction. Keywords: Signal transduction, Stomach Fundus, detrusor, smooth muscle, Ca2+-sensitization, RhoA kinase inhibitors Introduction Several reports published just over a decade ago revealed that smooth muscle contractile proteins could be ‘sensitized' to Ca2+ (Nishimura et al., 1988; Fujiwara et al., 1989; Kitazawa et al., 1989). In a review, Karaki (1989) described Ca2+ sensitization as a mechanism by which receptor agonists produce greater increases in force for a given increase in [Ca2+]i than a stimulus such as KCl. This model remains valid, except that recent reports indicate that KCl can also modulate the degree of Ca2+ sensitivity (Yanagisawa & Okada, 1994; Ratz, 1995; Mita et al., 2002), although to a lesser degree (Ratz, 1999). The precise mechanisms that cause Ca2+ sensitization are still being investigated. However, in general terms, Ca2+ sensitization may be due to an alteration in the sensitivity of myosin light chain (MLC) phosphorylation to Ca2+, principally through inhibition of MLC phosphatase by RhoA kinase (ROK) and protein kinase C (PKC), and to thin filament regulation (Hori & Karaki, 1998; Somlyo & Somlyo, 2000). Y-27632 and HA-1077 have recently proven invaluable in identification of the relative role that Ca2+ sensitization plays in regulation of contraction of intact smooth muscles of different organ systems. In permeabilized guinea-pig ileum, the ROK inhibitors, Y-27632 and HA-1077, inhibit GTPγS-induced Ca2+ sensitized contraction with IC50 values of, respectively, 1.7 μM and 2.7 μM (Sward et al., 2000). In arterial tissue, Y-27632 is reported to inhibit tonic contraction with an IC50 value of 0.7 μM (Uehata et al., 1997). These values are similar to Ki values reported for inhibition of ROK activity by these agents (Uehata et al., 1997; Davies et al., 2000; Sward et al., 2000), and a recent thorough study documenting the specificity of 28 commercially available kinase inhibitors indicates that Y-27632 and HA-1077 are highly selective for inhibition of ROK when used at appropriate concentrations (Davies et al., 2000). To date, Y-27632 or HA-1077 is reported to inhibit vascular (Uehata et al., 1997), respiratory (Chiba et al., 1999), ileal (Sward et al., 2000), bladder (Jezior et al., 2001) and myometrial (Kupittayanant et al., 2001) smooth muscle contractions. However, the degree to which these agents inhibit, and thus, the extent by which ROK participates in contractions appears to differ in different smooth muscle types. For example, 10 μM Y-27632 only modestly reduces spontaneous human myometrial contractions (Kupittayanant et al., 2001), but abolishes tonic α-adrenoceptor-induced contraction of rabbit aorta (Uehata et al., 1997). Muscarinic receptor stimulation induces a biphasic contraction of ileum, bladder and chicken gizzard consisting of a rapid, peak contraction (phasic component) followed by a tonic component that is weaker than the peak response. ROK blockade by Y-27632 or HA-1077 abolishes the tonic component but leaves the phasic component nearly intact in ileum (Sward et al., 2000), while in bladder, both components are greatly diminished (Jezior et al., 2001). Interestingly, despite the finding that GTPγS induces ROK activation and Ca2+ sensitization in chicken gizzard smooth muscle, muscarinic receptor stimulation does not cause ROK-dependent Ca2+ sensitization in this muscle type (Anabuki et al., 2000). However, Y-27632 does reduce gastric antrum motility in conscious rats (Tomomasa et al., 2000). The present study was designed to determine whether the selective ROK inhibitors, Y-27632 and HA-1077, inhibit contractions produced in isolated rabbit Stomach Fundus smooth muscle. For a comparison, the ability of GF-109203X, an inhibitor of conventional and novel PKC isotypes (Gailly et al., 1997), to inhibit Fundus contraction was examined, and the effects of each agent on muscarinic receptor-induced contraction of rabbit bladder wall (detrusor) smooth muscle was tested.
Xiangfu Zhang - One of the best experts on this subject based on the ideXlab platform.
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prognosis analysis of surgical treatment for cancer of Stomach Fundus and cardia with invasion to body and tail of the pancreas
Chinese Journal of Gastrointestinal Surgery, 2008Co-Authors: Changming Huang, Bijuan Lin, Jianwei Xie, Xiangfu ZhangAbstract:Objective To investigate the prognostic factors of surgical treatment for the cancer of Stomach Fundus and cardia with invasion to body and tail of the pancrea.Methods A total of 135 patients with cancer of Stomach Fundus and eardia invading body and tail of the pancrea undergone surgical treatment were enrolled in this study.Twenty of them underwent iaparotomy,while 115 underwent gastrectomy with panereaticosplenectomy,even combined with the resection of other organs for macroscopic invasion to adjacent organs during surgery. The 3-,5-year survival rates,morbility of postoperative complications and mortality were foUowed up. The prognostic factors were evaluated by univariate and multivariate analyses. Results The median survival time of the patients undergone laparotomy was 4.7 months,of patients treated by gastrectomy combined with pancreaticosplenectomy was 30.5 months,and the difference was significant (X2=403.8,P＜0.01 ).The cumulative 3- and 5-year survival rates of the patients treated by gastrectomy combined with pancreatieosplenectumy were 48.3% and 26.6% respectively.Univariate analysis revealed that significant differences in prognosis of 115 patients undergone combined resection were demonstrated for the following factors: maximal dimension of tumor, macroscopic type, extent of lymph node metastasis according to the Japanese classification, No.10 or No.11 lymph node metastasis,curability and number of invaded organs.And histological depth of invasion, extent of lymph node metastasis according to the Japanese classification,number of invaded organs and curability were significant prognostic factors, examined as variables by multivariate analysis (Cox's proportional hazard model,forward stepwise selection LR method).The postoperative complication rate and mortality of 135 patients were 20.0% and 3.5% respectively.Conclusions For cancer located in Stomach Fundus and cardia with limited invasion to distal pancreas, gastrectomy combined with pancreaticosplenectomy should be performed to improve long-term outcomes. Best long-term survival outcomes would be attained if there are no lymph node metastases,or no incurable factors,or no other organ invasions. Key words: Stomach neoplasms; Surgical procedures,digestive system; Pancrea; Survival rates
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impact of negative lymph node number on prognosis advanced cancer of cardiac and Stomach Fundus
National Medical Journal of China, 2008Co-Authors: Changming Huang, Xiangfu Zhang, Bijuan Lin, Jianwei XieAbstract:Objective To analyze the impact of negative lymph node number on the prognosis of advanced cancer of the cardia and Stomach Fundus. Methods 236 patients with advanced cancer of the cardia and Stomach Fundus underwent D2 radical resection. 5-year survival rate and recurrence rate were followed up and the relationships of lymph node (LN) number to 5-year survival rate and recurrence rate were analyzed respectively, according to LN count subgroups. Results The 5-year survival rate of the entire cohort was 37.5%. The number of metastasis negative LNs was positively correlated with the LNs examined ( P ＜ 0. 05 ). For the cancer at the same stage, the higher the number of metastasis negative LNs the higher the 5-year survival rate ( P ＜ 0. 05 ). Linear correlation analysis showed that along with the increase of the number of negative LNs the post-operative survival rate increased. In the cancers at the stages Ⅲ and Ⅳ, the 5-year survival rate increased by 6.09% and 7.65% respectively compared to the predicted values ( P =0. 013 and P =0. 035). The overall recurrence rate was 61.0% within 5 years after surgery. For the cancers at the stages Ⅲ and Ⅳ, the more the number of negative LNs the higher the 5-year survival rates ( P ＜0. 05 ). In the cancers at the stages Ⅲ and Ⅳ there were significant differences in the recurrence rates among the subgroups with different numbers of negative LNs ( all P ＜ 0. 002 ). Conclusion Number of negative LNs has a close relation with stage-based survival prediction. Dissection of sufficient lymph nodes in the procedure of Dz dissection should be recommended so as to improve the long-term therapeutic effects and reduce the recurrence rate. Key words: Stomach neoplasms; Lymph nodes; Neoplasm metastasis; Lymph node excision; Prognosis
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impact of dissected lymph node number on the prognosis of advanced cancer of cardiac and Stomach Fundus
Chinese Journal of Gastrointestinal Surgery, 2008Co-Authors: Bijuan Lin, Changming Huang, Xiangfu Zhang, Jianwei XieAbstract:Objective To investigate the impact of dissected lymph node number on the prognosis of patients with advanced cancer of cardia and Stomach Fundus. Methods Clinical data of 236 patients with advanced cancer of cardia and Stomach Fundus undergone D2 radical resection were reviewed retrospectively. Five-year survival rate and post-operative complication rate were followed up and their relationships with dissected lymph node number were analyzed respectively. Results The 5year survival rate of the entire cohort was 37.5%. Among those patients with the same stage, the more lymph nodes (LNs) resected, the better survival outcomes achieved(Log-rank trend test P=0.0013).A cut point analysis yielded the ability to detect the significant survival differences. The best long-term survival outcomes were observed with LN counts of more than 20 for stage Ⅱ (P=0.0136), more than 25 for stage Ⅲ (P＜0.0001), more than 30 for stage Ⅳ (P=0.0002) or more than 15 for the entire cohort (P=0.0024), with greatest comparative discrepancies. The post-operative complication rate was 15.7% and was not significantly correlated with dissected lymph node number(P=0.101 ). Conclusions The prognosis of patients with advanced cancer of cardia and Stomach Fundus is associated with the number of resected LNs when D2 lymphadenectomy is carried out. Suitable increment of dissected lymph node number would not increase the post-operative complication rate. Key words: Stomach neoplasms; Lymph node metastasis ; Lymphadenectomy; Postoperativecomplications
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long term therapeutic effects of total gastrectomy in cancer of the cardia and Stomach Fundus
Chinese journal of surgery, 2003Co-Authors: Changming Huang, Xiangfu Zhang, Jianzhong Zhang, Guoxian Guan, Chuan WangAbstract:Objective To evaluate total gastrectomy for the treatme nt of cancer of the cardia and Stomach Fundus. Methods Five hundred and thirteen patients with cancer of the cardia and Stomach Fundus underwent radical resection. Of them, 326 were treated using total gastrectomy(group TG); and 187, using proximal gastrectomy(group PG). The 5 year and 10 year survival rates and the postoperative complication rate and mortality rate were followed up and compared in the two groups. Results The 5 year and 10 year survival rates of group TG were 43 6% and 24 5%, of group PG were 33 9% and 14 1%, respectively, and the difference was statistically significant (χ 2=4 421,P0 05,χ 2=5 726, P0 05). The postoperative complication rate and mortality rate of group TG were 14 7% and 3 1%, of group PG were 10 2% and 2 1%, respectively, and the difference was not statistically significant (χ 2=1 796,P0 05,χ 2=0 082,P0 05). Conclusions To improve long term therapeutic effects, total gastrectomy should be recommended for stage Ⅲ patients with cancer of the cardia and Stomach Fundus when tumor size is bigger than 3 0 cm or lymph node metastasis occur. The postoperative complication rate and mortality rate should not be increased and the esophagitis of gastroesophageal reflux should be avoided in the patients treated using total gastrectomy.
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therapeutic effects of operation in tumor invades adjacent structures cancer of cardia and Stomach Fundus
Chinese journal of surgery, 2003Co-Authors: Shaoping Lan, Changming Huang, Xiangfu Zhang, Guoxian Guan, Chuan WangAbstract:OBJECTIVE To study the best style of operation in the treatment of tumor invades adjacent structures (T(4)) cancer of the cardia and Stomach Fundus. METHODS Two hundred and one patients with T(4) cancer of the cardia and Stomach Fundus underwent operation. Of them, 31 were treated by laparotomy, and 170 by combined resection of the involved organs. The 3- and 5-year survival rates and the postoperative complication rate and mortality rate were analyzed in the patients who had under gone combined resection of the involved organs. RESULTS The median survival of the patients undergoing combined resection of the involved organs (29.3 months) was significantly longer than that of those receiving laparotomy (4.9 months). The 3- and 5-year survival rates of 170 patients who had under gone combined resection of the involved organs were 46.2% and 22.8%, respectively. The 3- and 5-year survival rates of patients undergoing total gastrectomy and proximal gastrectomy were 54.9% and 29.2% and 32.2% and 12.5%, respectively, and the difference was statistically significant (chi(2) = 7.589, P < 0.01;chi(2) = 5.792, P < 0.05).The postoperative mortality rate and complication rate were 4.1% and 24.1%, respectively. CONCLUSIONS The patients without liver metastasis, widespread nodal involvement, peritoneal dissemination and local focus allowed by an en bloc combined resection in T(4) cancer of cardia and Stomach Fundus should undergo gastrectomy with a combined resection of the involved organs. Total gastrectomy should be performed to improve the curative effect.
Uy Dong Sohn - One of the best experts on this subject based on the ideXlab platform.
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Signaling pathways underlying changes in the contractility of the Stomach Fundus smooth muscle in diabetic rats
Archives of Pharmacal Research, 2020Co-Authors: Dong Min Kim, Tin Myo Khing, Wynn Thein, Won Seok Choi, Chang Yell Shin, Uy Dong SohnAbstract:Dysfunction of gastrointestinal (GI) motility is a common complication in patients with diabetes mellitus (DM). Studies related to changes in Fundus contraction induced by inhibitors in DM are not well known. Therefore, this study aimed to investigate the signaling pathways involved in the changes in the contraction of Fundus smooth muscle obtained from control and DM rats. DM was induced by injecting streptozotocin (65 mg/kg) into Sprague–Dawley rats. The rats were sacrificed after 14 days. Fundus smooth muscle contraction was stimulated using electrical field stimulation (amplitude, 50 V; duration, 1 min; frequency, 2–20 Hz) and acetylcholine (0.1 mM). The inhibitor-mediated cell membrane was pre-treated with atropine, verapamil, methysergide, ketanserin, ondansetron, and GR 113808. Inhibitors related to intracellular signaling, such as U73122, chelerythrine, l -NNA, were also used. ML-9 and Y-27632 were identified as inhibitors of factors of myosin light chain (MLC). The contractility was observed to be lower in the DM group than in the control group. Further, the activities of phospholipase C (PLC), protein kinase C (PKC), and myosin light chain kinase (MLCK) were decreased in the DM group. DM reduced the activity of PLC, PKC, and MLCK, which resulted in a decrease in the contractility of the Fundus smooth muscle. Therefore, our results present the mechanism of this DM-mediated GI disorder.
Hermann Lubbert - One of the best experts on this subject based on the ideXlab platform.
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cloning and functional characterization of the rat Stomach Fundus serotonin receptor
The EMBO Journal, 1992Co-Authors: M Foguet, Daniel Hoyer, Luis A Pardo, Anant B Parekh, F W Kluxen, H O Kalkman, Walter Stuhmer, Hermann LubbertAbstract:A DNA segment homologous to the third exons of the serotonin 1C and 2 receptor genes was isolated from a mouse genomic library. The positions of the introns flanking these exons were conserved in the three genes. To examine whether the new fragment was part of an active gene, we used a quantitative PCR protocol to analyse rat RNAs from different tissues and ages. The gene was expressed in Stomach Fundus at an abundance of 1 x 10(5) mRNA molecules. This tissue contracts in response to serotonin via a receptor that has previously resisted classification. We constructed a cDNA library from rat Stomach Fundus and isolated clones containing 2020 bp inserts with open reading frames of 465 amino acids comprising seven putative membrane-spanning regions. The protein was transiently expressed in COS cells and binding of serotonergic ligands to the membranes was analysed. The pharmacological profile resembled that described for the serotonin-stimulated contraction of the Stomach Fundus. After expression of this receptor in Xenopus oocytes, the application of serotonin triggered the typical chloride current which presumably results from the activation of phospholipase C. The coupling to this response system was less efficient than that of the 5-HT1C or 5-HT2 receptors.
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structure of the mouse 5 ht1c 5 ht2 and Stomach Fundus serotonin receptor genes
Neuroreport, 1992Co-Authors: M Foguet, H Nguyen, Hermann LubbertAbstract:By analysis of the mouse 5-HT1C receptor gene we found that its coding region contains three introns. We next isolated cDNA and genomic clones for the closely related 5-HT2 receptor using a probe derived from the 5-HT1C receptor sequence. This probe also hybridized to an additional gene, called SRL (Serotonin Receptor Like). We have evidence demonstrating that it encodes the Stomach Fundus 5-HT receptor. Two introns are present within the coding regions of the mouse 5-HT2 receptor gene and the SRL gene at positions which correspond to those of introns in the 5-HT1C receptor gene. This intron distribution is unique and distinguishes these receptors from other members of the family of receptors coupled to G-proteins.