Sex-specific mating pheromones in the nematode Panagrellus redivivus

Nematodes use an extensive chemical language based on glycosides of the dideoxysugar ascarylose for developmental regulation (dauer formation), male sex attraction, aggregation, and dispersal. However, no examples of a female- or hermaphrodite-specific sex attractant have been identified to date. In this study, we investigated the pheromone system of the gonochoristic sour paste nematode Panagrellus redivivus, which produces sex-specific attractants of the opposite sex. Activity-guided fractionation of the P. redivivus exometabolome revealed that males are strongly attracted to ascr#1 (also known as daumone), an ascaroside previously identified from Caenorhabditis elegans hermaphrodites. Female P. redivivus are repelled by high concentrations of ascr#1 but are specifically attracted to a previously unknown ascaroside that we named dhas#18, a dihydroxy derivative of the known ascr#18 and an ascaroside that features extensive functionalization of the lipid-derived side chain. Targeted profiling of the P. redivivus exometabolome revealed several additional ascarosides that did not induce strong chemotaxis. We show that P. redivivus females, but not males, produce the male-attracting ascr#1, whereas males, but not females, produce the female-attracting dhas#18. These results show that ascaroside biosynthesis in P. redivivus is highly sex-specific. Furthermore, the extensive side chain functionalization in dhas#18, which is reminiscent of polyketide-derived natural products, indicates unanticipated biosynthetic capabilities in nematodes.     

Definitive chemoradiotherapy of limited-disease small cell lung cancer: Retrospective analysis of new predictive factors affecting treatment results

The aim of this study was to evaluate potential predictive factors in the treatment of limited-disease small cell lung cancer (LD-SCLC). A total of 33 patients with LD-SCLC who underwent definitive chemoradiotherapy at our institute between April 1996 and May 2007 were enrolled in our retrospective study. The relationship between a range of potential predictive factors and the initial response, time to progression and pattern of failure was analyzed. The factors evaluated included the tumor markers Pro-gastrin-releasing peptide (Pro-GRP) and neuron-specific enolase; net tumor size (sum of each lesion mass on computed tomography at 1-cm intervals); total radiation dose; biological effective dose (BED); overall treatment time (OTT); time between the start of any type of treatment and the end of radiation therapy (SER). In addition, the novel factors of radiation dose-intensity (RDI = BED/OTT) and RDI/NTS (= RDI/net tumor size) were defined. Of the 33 patients evaluated in our study, 22 (67%) achieved a complete response (CR) and 27 (82%) experienced treatment failure or recurrence. High RDI/NTS values showed a significant correlation with CR (P=0.043). Prolonged OTT and lower values of RDI and RDI/NTS showed a significant correlation with recurrence within 12 months (P=0.022, 0.033 and 0.015, respectively). The lower values of RDI and RDI/NTS showed a significant correlation with distant metastasis as a first failure site (P=0.038 and 0.044, respectively). Patients with RDI/NTS ≥0.08 had a more favorable prognosis (P=0.045). Thus, RDI and RDI/NTS may become beneficial predictive factors in the treatment of LD-SCLC. However, further studies are required to confirm our preliminary results.     

A nonfunctioning islet cell carcinoma with tumor thrombus in both the portal and splenic veins — a case report of successful resection

A rare case of nonfunctioning islet cell carcinoma associated with tumor thrombi in both the portal and splenic veins is reported. The patient, a 49-year-old male, had a 2-year history of occasional abdominal pain. Computed tomography (CT) disclosed a huge mass in the body of the pancreas, and celiac arteriogram showed a tumor stain in the body and tail of the pancreas. Percutaneous transhepatic portography (PTP) demonstrated an irregular filling defect, indicating intraportal tumor growth. Curative surgery, which included total pancreatectomy with combined resection (50 mm in length) and reconstruction of the portal vein, distal gastrectomy, and partial resection of the transverse colon, was performed. Histological examination of the surgical specimen led to a diagnosis of nonfunctioning islet cell carcinoma with a negative immunohistochemical stain for insulin, glucagon, somatostatin, and adrenocorticotropic hormone. The patient has been well for 38 months to date without any sign of tumor recurrence. Our experience with this case has introduced a radical resection for islet cell tumor of the pancreas, even if the tumor has extended into the portal vein.     

Radial augmentation index is related to cardiovascular risk in hemodialysis patients

Cardiovascular accidents related to atherosclerosis are the leading cause of death among hemodialysis patients, which makes continuous monitoring of their cardiovascular status crucial. Recently, a handy device for monitoring the augmentation index (AIx) in the radial artery was introduced in Japan, enabling the use of the AIx in addition to pulse wave velocity (PWV) in the management of hemodialysis patients. In this study the AIx, PWV, abdominal aortic calcification index (ACI), and left ventricular mass index (LVMI) were serially assessed in 108 hemodialysis patients. The radial AIx was monitored using a newly introduced tonometer (HEM-9010AI), and the interrelationships among the measured parameters and their contributions to the risk of cardiovascular accidents were evaluated. The radial AIx was significantly higher in hemodialysis patients than in healthy subjects (N = 50) and was well correlated with risk markers such as LVMI (r = 0.30, P = 0.019) and ACI (r = 0.38, P < 0.001), but not with PWV. Multiregression analysis showed that radial AIx was also significantly associated with LVMI, ACI and blood pressure; PWV was associated with other parameters such as age, blood pressure, and ACI. The AIx and ACI were both significantly increased in patients with cardiovascular complications. Although PWV was strongly increased in the hemodialysis patients, it failed to discriminate between these subgroups of high-risk patients. The radial AIx is closely associated with aortic calcification, cardiac hypertrophy, and a history of cardiovascular accidents in hemodialysis patients, and could be a useful marker for management of these patients.