Magnesium sulfate inhibits the oxytocin-induced production of inositol 1,4,5-trisphosphate in cultured human myometrial cells

OBJECTIVE: The purpose of this study was to determine the effects of magnesium sulfate on inositol trisphosphate production and the mechanism of these effects. STUDY DESIGN: Myometrium was obtained at the time of cesarean delivery from women before labor at term. Inositol trisphosphate was measured in the primary myometrial cell cultures after stimulation with oxytocin, sodium fluoride, or Bay K 8644 with or without preincubation with magnesium sulfate or nifedipine. Experiments were performed in either calcium-containing or calcium-free medium that contained egtazic acid and after preincubation with the intracellular calcium chelator BAPTA-acetoxymethylester. Inositol trisphosphate production was measured by radioreceptor assay. In separate experiments, changes in intracellular calcium concentrations ([Ca(2+)](i)) were measured with the use of Fura-2 and spectrophotofluorometry. RESULTS: Oxytocin, sodium fluoride, and Bay K 8644 increased inositol trisphosphate production 2- to 4-fold. Preincubation with magnesium sulfate (3 x 10(-3) mol/L) for > or = 5 minutes decreased oxytocin-, sodium fluoride-, and Bay K 8644-induced inositol trisphosphate production in either calcium-containing or calcium-free media. Preincubation with BAPTA-acetoxymethylester decreased oxytocin-stimulated inositol trisphosphate production by 78% in calcium-containing media and completely prevented the oxytocin response in calcium-free media. Magnesium sulfate decreased inositol trisphosphate production in calcium-containing media but had no additional effect in calcium-free media. Oxytocin and Bay K 8644 increased [Ca(2+)](i) in either calcium-containing or calcium-free media, and magnesium sulfate reduced this in both cases. CONCLUSION: Magnesium sulfate appears to inhibit phosphatidylinositol-4, 5-bisphosphate-specific phospholipase C activity and subsequent calcium release in cultured myometrial cells by a direct effect on phospholipase C.     

Mammographic and clinical predictors of drainage patterns in breast lymphoscintigrams obtained during sentinel node procedures

PURPOSE: The authors' purpose was to explore the association between mammographic findings and drainage patterns on lymphoscintigrams obtained during sentinel node procedures for breast carcinoma. MATERIALS AND METHODS: From July 1997 to March 2000, 132 patients with breast cancer who were included in a prospective mammography-pathology correlation and staging database were imaged 2 hours after perilesional injection of 1 mCi filtered (0. 22 microm) Tc-99m sulfur colloid (4 ml volume) before sentinel node procedures. RESULTS: Sixty-four percent of the scans showed axillary drainage only, 9% showed axillary and internal mammary drainage, and 4% revealed internal mammary drainage only. Twenty-three percent of scans showed no drainage. Of the patients who showed drainage, 17% showed drainage to the internal mammary basin, and 5% showed this exclusively. Internal mammary drainage was seen in 18% (10 of 57) of lateral, 21% (6 of 29) of medial, and 14% (1 of 7) of subareolar lesions (P = NS). No drainage was seen in 22% of patients with predominantly fatty mammographic parenchymal density (>50%) compared with only 8% of patients with predominantly dense (>50%) parenchyma (P < 0.05). Failure to show drainage was more common in women older than 50 years (P < 0.05). Axillary sentinel nodes were identified surgically in 73% of patients with negative scan findings. There was no significant association between scintigraphic drainage and mammographic soft tissue tumor size and appearance, histologic findings, or axillary node status. CONCLUSIONS: Dense mammographic parenchyma and age less than 50 years are associated with identification of lymphatic drainage on lymphoscintigrams performed before sentinel node procedures in 91% to 92% of patients. Internal mammary drainage, present in 18% of lateral and 21% of medial lesions, may direct therapy to include internal mammary lymph nodes.     

A phase III,randomized, double-blind,placebo-controlled,multinational trial of iseganan for the prevention of oral mucositis in patients receiving stomatotoxic chemotherapy (PROMPT-CT trial)

Microfloral invasion and colonization of oral cavity mucosal tissues contribute to the pathophysiology of ulcerative oral mucositis (UOM). Iseganan is an analog of Protegrin-1, a naturally occurring peptide with broad-spectrum microbicidal activity. A randomized, double-blind, placebo-controlled study was conducted to evaluate iseganan in preventing UOM after stomatotoxic therapy. Patients received an oral rinse of iseganan 9 mg or placebo, swished/swallowed 6 times daily, starting with stomatotoxic therapy and continuing for 21-28 days. One hundred sixty three and 160 patients, respectively, were randomized to receive iseganan or placebo. One hundred and two patients (32%) were affected by a drug dispensing error, caused by a flawed computerized allocation system. Among all 323 patients, analyzed according to randomization assignment, 43% and 33% of iseganan and placebo patients, respectively, did not develop UOM (P = 0.067). On an 11-point scale, iseganan patients experienced less mouth pain (3.0 and 3.8 (P = 0.041), throat pain (3.8 and 4.6 (P = 0.048)), and difficulty swallowing (3.9 and 4.7 (P = 0.074)), compared to placebo patients. On the 5-point NCI CTC scale, iseganan patients experienced lower stomatitis scores (1.6 and 2.0 (P = 0.0131). Iseganan was well tolerated; no systemic absorption was detected. Iseganan is safe and may be effective in reducing UOM and its clinical sequelae.     

Variation of the prognostic significance of HER-2 expression in breast cancer according to tumor size

The prognostic importance of HER-2 status in breast cancer has been investigated extensively, but findings have not been uniform across immunohistochemical studies using fixed, paraffin-embedded specimens. We speculate that studies with an overrepresentation of large tumors might not produce evidence for an independent effect of a single marker because breast tumors of larger size tend to exhibit multiple adverse attributes as the malignancy advances through the metastatic cascade. Further, it has been posited that results from certain studies of biologic markers might be generalizable only to larger tumors because tumor repositories tend to house a disproportionate number of larger tumors. To test our hypothesis that the prognostic effect of HER-2 status might be modified by the size of the tumor, we conducted a survival analysis of a nested case-case sample of 156 women diagnosed with primary breast cancer from 1983 to 1995. Relative risks (RRs) and confidence intervals (CIs) for recurrence in relation to HER-2 status were estimated using a multivariate Cox proportional hazards model. Immunohistochemistry of archival tissue was used to detect HER-2 expression. Positive HER-2 status was associated with recurrence (RR = 4.24, 95% CI 1.30-13.78) among patients with axillary lymph node-positive involvement. This analysis identified an interaction (p < 0.01) between tumor size and overexpression. Stratification by tumor size revealed an increased risk of recurrence associated with HER-2-positive tumors that were 相似文献   

Neurokinin 1 receptor and relative abundance of the short and long isoforms in the human brain

Substance P exerts its various biochemical effects mainly via interactions through neurokinin-1 receptors (NK1). Recently, the NK1 receptor has attracted considerable interest for its possible role in a variety of psychiatric disorders including depression and anxiety. However, little is known regarding the anatomical distribution of NK1 in the human central nervous system (CNS). Riboprobe in situ hybridization, quantitative PCR and in vitro autoradiography were performed. Highest NK1 mRNA levels were localized in the locus coeruleus and ventral striatum, while moderate hybridization signals were observed in the cerebral cortex (most abundant in the visual cortex), hippocampus and different amygdaloid nuclei. Very low levels of the NK1 mRNA were detected in the cerebellum and thalamus. In view of the existence of a long and short isoform of the NK1 receptor, it was of interest to assess whether there was a differential distribution of the two splice variants in the human CNS and peripheral tissues. A quantitative TaqMan PCR analysis showed that the long NK1 isoform was the most prevalent throughout the human brain, while in peripheral tissues the truncated form was the most represented. 3H-Substance P autoradiography revealed a good correlation between receptor binding sites and NK1 mRNA expression throughout the brain, with the highest levels of binding in the locus coeruleus. These results provide the anatomical evidence that the NK1 receptors have a strong association with neuronal systems relevant to mood regulation and stress in the human brain, but do not suggest a region-specific role of the two isoforms in the CNS.     

Expression of protein kinase C isozymes in nonpregnant and pregnant human myometrium

OBJECTIVE: The aim of this study was to compare the distributions of protein kinase C isozymes in human nonpregnant and pregnant myometrial tissues and primary cell cultures. STUDY DESIGN: Myometrial tissues were obtained at hysterectomy from nonpregnant women and at cesarean delivery from women both before and during early labor at term. Western immunoblot analysis was performed on homogenates of myometrial tissues and primary cell cultures with monoclonal antibodies specific for protein kinase C isozymes. Redistribution and translocation of protein kinase C were examined by means of immunocytochemical methods. RESULTS: Nonpregnant myometrial tissues contained protein kinase C isozymes alpha, gamma, delta, mu, iota, and zeta but not beta(1), beta(2), theta, or epsilon. Pregnant myometrial tissues both before and during early labor contained the same protein kinase C isozymes and also beta(1) and beta(2). The protein kinase C isozyme distribution in primary myometrial cell cultures was identical to that in the myometrial tissues. Protein kinase C redistribution and translocation were demonstrated in these cultured myometrial cells. CONCLUSION: Both human myometrial tissues and primary cell cultures expressed a broad range of protein kinase C isozymes. Protein kinase C isozymes beta(1) and beta(2) were absent in nonpregnant myometrium but were induced during pregnancy. Labor at term did not alter protein kinase C isozyme expression.     

唐古特大黄提取物不同成分泻下作用的比较研究

目的：研究唐古特大黄提取物不同成分的泻下作用。方法：采用炭末推进方法、酚红排空方法进行肠推进实验,观察大黄提取物各成分(15 g·kg^-1)对小鼠小肠推进和肠水分吸收、大鼠大肠运动的影响。结果：唐古特大黄提取物不同成分与对照组相比,对小鼠小肠推进和肠水分吸收、大肠推进作用均有显著性差异(P<0.01)；与大黄水煎液、醇提液相比,泻下活性存在一些差异。结论：唐古特大黄提取物不同成分均有显著的泻下作用,但与大黄水煎液和醇提液相比有一些差异。