Association mapping of Stagonospora nodorum blotch resistance in modern European winter wheat varieties.

Association mapping in populations relevant for wheat breeding has a large potential for validating and fine-mapping QTLs identified in F2- or DH (double haploid)-derived populations. In this study, associations between markers in the region of QSng.sfr-3BS, a major QTL for resistance to Stagonospora nodorum glume blotch (SNG), and SNG resistance were investigated by linkage and association analyses. After increasing marker density in 240 F(5:7) recombinant inbred lines (RILs), QSng.sfr-3BS explained 43% of the genetic variance and peaked 0.6 cM proximal from the marker SUN2-3B. Association between SNG resistance and markers mapped in the region of QSng.sfr-3BS was investigated in a population of 44 modern European winter wheat varieties. Two genetically distinct subpopulations were identified within these lines. In agreement with linkage analyses, association mapping by a least squares general linear model (GLM) at marker loci in the region of QSng.sfr-3BS revealed the highest association with SNG resistance for SUN2-3B (p < 0.05). Association mapping can provide an effective mean of relating genotypes to complex quantitative phenotypes in hexaploid wheat. Linkage disequilibrium (r (2)) in chromosome 3B extended less than 0.5 cM in 44 varieties, while it extended about 30 cM in 240 RILs, based on 91 SSR and STS marker-pair comparisons. This indicated that the association mapping population had a marker resolution potential at least 390-fold higher compared to the RIL population.

Detection of QTLs for Stagonospora glume blotch resistance in Swiss winter wheat.

Stagonospora nodorum is the causal agent of the Stagonospora glume blotch disease in hexaploid wheat. The Swiss winter bread wheat cv. 'Arina' has a highly effective, durable and quantitative glume blotch resistance. We studied 240 single seed descent (SSD)-derived lines of an 'Arina x Forno' F(5:7) population to identify and map quantitative trait loci (QTLs) for glume blotch resistance under natural infestation. Using composite interval mapping (CIM) and LOD>4.5, we detected two chromosomal regions on chromosome arms 3BS and 4BL which were specifically associated with glume blotch resistance. These identified QTLs were designated QSng.sfr-3BS and QSng.sfr-4BL, respectively. QSng.sfr-3BS peaked at the locus Xgwm389 in the telomeric region of the short arm of chromosome 3B and explained 31.2% of the observed phenotypic variance for the resistance within the population. The responsible QSng.sfr-3BS allele originated from the resistant parent 'Arina'. The QTL QSng.sfr-4BL (19.1%) mapped to chromosome arm 4BL ('Forno' allele) very close to two known genes, TaMlo and a catalase ( Cat). Both QTL alleles combined could enhance the resistance level by about 50%. Additionally, they showed significant epistatic effects (4.4%). We found PCR-based microsatellite markers closely linked to QSng.sfr-3BS (gwm389) and QSng.sfr-4BL (gwm251) which make marker-assisted selection (MAS) for Stagonospora glume blotch resistance feasible. We also found one resistance QTL, QSng.sfr-5BL, on the long arm of chromosome 5B which overlapped with QTLs for plant height as well as heading time.

Prevalence and drug susceptibility of pathogens causing bloodstream infections in northern Italy: a two-year study in 16 hospitals.

The epidemiology of bacterial pathogens causing bloodstream infection was studied in 16 hospitals in Lombardy (northern Italy) over a 2-year period (1999 and 2000). Overall, 2924 microorganisms causing significant bacteremia were collected. The most frequent isolates were Escherichia coli ( n=663; 22.7%), Staphylococcus aureus ( n=534; 18.3%), Staphylococcus epidermidis ( n=242; 8.2%), and Pseudomonas aeruginosa ( n=176; 6.0%). Unlike Escherichia coli, which was usually acquired from the community, Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa were usually acquired in hospitals. Rates of resistance to oxacillin and its associated traits were significantly higher among hospital-acquired staphylococci as compared to those of isolates from the community. Escherichia coli was highly susceptible to extended-spectrum cephalosporins, with a very low percentage of strains producing extended-spectrum ss-lactamases (ESBLs). On the contrary, production of ESBL appeared to be an important mechanism of resistance among nosocomial isolates of Klebsiella pneumoniae. Resistance to ciprofloxacin was widespread in several members of the family Enterobacteriaceae, with rates often exceeding 10%. Moreover, with regard to ciprofloxacin, there were no significant differences between rates of resistance among Enterobacteriaceae causing hospital-acquired infections versus those causing community-acquired infections. Multidrug resistance was commonly observed in Pseudomonas aeruginosa, indicating the need for new antimicrobial agents that are more active against nonfermentative gram-negative bacteria. In conclusion, epidemiological studies of the prevalence and antimicrobial susceptibility patterns of blood isolates in northern Italy appear to provide useful information for both empirical treatment of suspected infections and better management of patients.

Area under pH 4: a more sensitive parameter for the quantitative analysis of esophageal acid exposure in adults.

OBJECTIVE: Traditional quantitative analysis of 24-h esophageal pH monitoring data does not include the pH of reflux episodes. Area under pH 4 (AU4) is a recently introduced parameter that describes the acid exposure rate through both duration and depth of pH falls. METHODS: In Study A, we enrolled 20 healthy controls and 42 patients (18 without esophagitis, 24 with Savary I-III esophagitis) in a study evaluating reference values for 24-h reflux time at pH <4 (RT) and 24-h AU4 by means of receiver operating characteristic (ROC) discriminant analysis. For Study B, we next prospectively applied the resulting cutoffs to 16 healthy controls and to 110 gastroesophageal reflux (GERD) patients (55 with esophagitis) to adjust sensitivity, specificity, and predictive values of both RT and AU4. RESULTS: In Study A, the best cutoff values were 5.1% for RT (Area Index +/- SE, 0.899 +/- 0.038; 95% confidence interval [C.I.], 0.796 +/- 0.961) and 36.1 pH x min for AU4 (Area Index +/- SE, 0.935 +/- 0.03; 95% C.I., 0.842 +/- 0.981); AU4 gave the best performance (p = 0.038 vs RT) in discriminating controls and GERD patients. In Study B, RT was abnormal in three controls and 79 patients; AU4 identified all the controls and patients with abnormal RT and also 10/31 patients (32.3%) with so-called "normal" acid exposure (according to RT). In the whole GERD group of patients, AU4 and RT specificity was 81.2%, whereas sensitivity was 71.8% for RT and 80.9% for AU4 (chi2, 61.831; DF, 1; p < 0.005); PPV/NPV were 96.3%/29.5% for RT, and 96.7%/38.2% for AU4. CONCLUSIONS: AU4 appears to be a simple and sensitive quantitative parameter to measure the esophageal acid exposure in adults submitted to 24-h pH monitoring, and it could be an useful clinical aid in evaluating normal RT tests where, from a clinical point of view, a reflux disease is highly likely.

Immunotherapy with subcutaneous low-dose interleukin-2 and the pineal indole melatonin as a new effective therapy in advanced cancers of the digestive tract.

The advanced tumours of the digestive tract are generally less responsive to conventional chemotherapies. Moreover, preliminary results with IL-2 immunotherapy also seem to show a low efficacy. On the basis of our previous studies suggesting s synergistic action between IL-2 and some neurohormones, such as the pineal indole MLT, a clinical trial was performed to investigate the clinical efficacy and tolerability of an immunotherapy with IL-2 plus MLT in patients with advanced neoplasms of the digestive tract. The study included 35 patients (colorectal cancer: 14; gastric cancer: 8; hepatocarcinoma: 6; pancreas adenocarcinoma: 7). Distant organ metastases were present in 31/35 patients. MLT was given orally at a daily dose of 50 mg at 8.00 p.m., starting 7 days before IL-2, which was given subcutaneously at a dose of 3 million IU/day at 8.00 p.m. for 6 days/week for 4 weeks, corresponding to one cycle of immunotherapy. In nonprogressed patients, a second cycle was given after a 21-day rest period. A complete response was achieved in two patients (gastric cancer: 1; hepatocarcinoma: 1). Six other patients obtained a partial response: (gastric cancer: 2; hepatocarcinoma: 2; colon cancer: 1; pancreas cancer: 1). Therefore, the overall response rate was 8/35 (23%). Stable disease was obtained in 11/35 (31%) patients, whereas the remaining 16 patients (46%) progressed. The response rate was significantly higher in untreated patients than in those previously treated with chemotherapy. Toxicity was low in all patients, who received the treatment as a home therapy. This study shows that the immunotherapy with low-dose IL-2 plus the pineal hormone MLT is a new well tolerated and effective therapy of advanced tumours of the digestive tract, mainly in gastric cancer and hepatocarcinoma.