Improved survival after retrieval of 12 or more regional lymph nodes in appendiceal cancer.

BACKGROUND: To evaluate the role of regional lymph node (RLN) retrieval on stage migration, overall (OS), and cancer-specific survival (CSS) in appendiceal cancer. METHODS: Between 2004 and 2012, 1046 patients with primary stage I-III carcinoma of the appendix were identified in the Surveillance, Epidemiology and End Results database. The impact of the number of RLN removed on OS and CSS was assessed using joinpoint regression, Cox regression, and propensity score methods. RESULTS: The rate of node-positive cancer increased with the number of retrieved RLN from 10.5% in patients with one RLN removed to 30.6% in patients with 10 RLNs removed. This leveling off at 10 RLN was confirmed by joinpoint regression analysis (p = 0.023). Despite the finding that retrieval of 10 RLN should be sufficient for appendiceal cancer, for the survival analysis the somewhat higher cutoff of 12 RLN was applied, since this cutoff is recommended by the guidelines for colorectal cancer. Retrieval of 12 or more RLN was beneficial compared to less than 12 RLN retrieved for OS (HR = 0.60, p < 0.001) and CSS (HR = 0.67, p = 0.020) in multivariable analysis, as well as in propensity score matched analysis (OS: HR = 0.58, p = 0.001, CSS: HR = 0.61, p = 0.005). CONCLUSION: The rate of node-positive cancer increased with the number of retrieved RLN up to about 10 RLN (95%CI: 3.6-16.3, p = 0.023). Over 10 retrieved RLN, the node-positive cancer rate no longer increased. This correlates with the recommended number of 12 RLN to be retrieved in colorectal cancer, but differs from the guideline for neuroendocrine tumors.

Mushroom bodies and post-mating behaviors of Drosophila melanogaster females.

After mating, Drosophila melanogaster females lay substantially more eggs and mate rarely. Central to these changes is Sex peptide (SP), a male peptide transferred into the female during copulation. Injected into virgins, SP induces the same post mating response as observed after mating. In this study we investigated the role of the mushroom body (MB) in the SP response system. The SP response of females with either chemically ablated or mutant MBs was analyzed. After injection of SP, females with chemically ablated MBs reduce their receptivity and increase their ovulation and oviposition to the level of females with intact MBs. Virgin females with ablated MBs, however, show a constitutively elevated oviposition rate. Hence in untreated females, MBs are not implicated in the SP-induced reduction of receptivity and increase of ovulation. However, they depress the oviposition rate of virgins. Thus, SP has two functions for oviposition: it de-represses the MB-dependent block on the egg laying activity of virgins and additionally stimulates oviposition. SP-injected mushroom body miniature (mbm) females lay fewer eggs, ovulate less frequently, and mate more often than wild-type females. A model of the putative role of MBs and the gene product of mbm in SP-induced oviposition is presented.

Is l-arginine infusion an adequate tool to assess endothelium-dependent vasodilation of the human renal vasculature?

Systemic administration of L-arginine alters renal haemodynamics in humans. We examined whether L-arginine-induced vasodilation of the renal vasculature is related to an increased production and release of NO by comparing the effects of L- and D-arginine on renal endothelium-dependent vasodilation. In a double-blind randomized cross-over study including 20 young, healthy male white subjects (age 26+/-2 years), we determined the effects of intravenous administration of L-arginine or its enantiomer D-arginine, at doses of 100 mg/kg body weight for 30 min or 500 mg/kg for 30 min, on renal haemodynamics. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were assessed by a constant-infusion input-clearance technique (using p-aminohippuric acid and inulin respectively). In addition, changes in blood pressure, heart rate, urinary sodium excretion (U(Na)) and urinary cGMP were measured. HPLC was used to determine L- and D-arginine concentrations. Intravenous infusion of L-arginine at 100 mg/kg for 30 min increased RPF from 641+/-87 to 677+/-98 ml/min (P=0.019), whereas infusion of D-arginine did not (from 642+/-74 to 657+/-86 ml/min; not significant). The change in RPF was more marked during the infusion of L-arginine than during the infusion of D-arginine (+36+/-61 versus +16+/-57 ml/min; P=0.037). Infusion of both L- and D-arginine at doses of 500 mg/kg for 30 min increased RPF from baseline [from 641+/-87 to 762+/-133 ml/min (P<0.001) and from 642+/-74 to 713+/-120 ml/min (P=0.004) respectively], but the change in RPF again was greater in response to L-arginine infusion than to infusion with D-arginine (+121+/-97 versus +71+/-94 ml/min; P=0.018). In accordance, changes in renal vascular resistance (RVR) were higher in response to L-arginine compared with D-arginine for both doses (P<0.05 and P<0.001 respectively). U(Na) increased only with L-arginine (change in U(Na), +0.33+/-0.26 mmol/min; P<0.01) but not with D-arginine (change in U(Na), +0.11+/-0.17 mmol/min; not significant). The change in U(Na) was more pronounced during infusion of L-arginine compared with infusion of D-arginine (P=0.023). In parallel, urinary excretion of cGMP only increased in response to L-arginine (+676+/-272 pmol/l; P=0.038) and not during D-arginine infusion (+185+/-153 pmol/l; not significant). L-Arginine-induced changes in RPF, RVR, U(Na) and cGMP excretion differed significantly from those induced by D-arginine. Thus although no direct measurements of NO synthesis were performed, putative markers of NO synthesis suggest that the renal vasodilatory response to L-arginine, at least in part, was due to increased production and release of NO. The dose of L-arginine at 100 mg/kg for 30 min emerged as the most suitable, because of the absence of systemic haemodynamic changes. The effects of infusion of L-arginine at 500 mg/kg for 30 min on renal endothelium-dependent vasodilation need to be corrected for the effects of D-arginine before conclusions can be drawn.

Sex-peptide activates juvenile hormone biosynthesis in the Drosophila melanogaster corpus allatum.

Mating elicits two well-defined reactions in sexually matured females of many insects: reduction of receptivity and increased oviposition. These post-mating responses have been shown to be induced by factors synthesized in the reproductive tract of the adult male and transferred in the seminal fluid to the female during copulation. One of these factors, named sex-peptide (SP), has been identified in Drosophila melanogaster. Using an in vitro radiochemical assay, we show that synthetic sex-peptide considerably activates juvenile hormone III-bisepoxide (JHB3) synthesis in corpus allatum (CA) excised from Days 3 and 4 post-eclosion virgin females. Base levels are significantly lower at emergence (Day 0) than on subsequent days, and only weak stimulation is obtained on Day 1, while none is obtained on Day 2, where maximal basal synthesis occurs. The CA of mated females cannot be stimulated further for at least 7 days, but regain responsiveness by Day 10 after mating. Synthesis of JHB3 stimulated by SP in vitro persists for at least 4 h after removal of the peptide. Development of responsiveness of the CA to SP in vitro is compared with development of the post-mating reactions of sex-peptide injected virgin females. Our results suggest that the CA is a direct target for SP in vivo and that sexual maturity is established separately for the two post-mating reactions.

Ectopic expression of sex peptide alters reproductive behavior of female D. melanogaster.

Sex peptide, a secreted component of the male accessory glands, has been shown to induce behavioral and physiological changes in mated Drosophila. We transformed flies with a hybrid gene containing an hsp70 promoter fused to a cDNA encoding sex peptide. Heat-induced ectopic expression of the peptide in transgenic virgin females altered their reproductive behavior, in the presence of courting males, to that observed in mated females. This demonstrates that the peptide is functional as expected. Time course studies revealed that the behavioral change appeared earlier than the stimulated ovulation. We have also introduced a modified sex peptide gene that is driven by the yp1 enhancer, conferring expression in adult females, and shown that these flies refuse mating constitutively in the presence of courting males and lay unfertilized eggs at the rate of mated females.