The mode of binding of sperm and somatic H1 histones to DNA has been investigated by analyzing the effect of their addition on the electrophoretic mobility of linear and circular plasmid molecules. Low concentrations of sperm histones do not appear to alter the electrophoretic mobility of DNA, whereas at increasing concentrations, an additional DNA band is observed near the migration origin. This band then becomes the only component at higher values. In contrast, somatic histones cause a gradual retardation in the mobility of the DNA band at low concentrations and aggregated structures are observed only at higher values. Experiments on the H1 globular domain obtained by limited proteolysis indicate that the mode of binding to DNA depends on the H1 globular domain. The arginine residues appear to be relevant for the different effects as indicated by experiments on sperm histone and on protamine with arginines deguanidinated to ornithines. The modified molecules influence DNA mobility like somatic H1s, indicating that the positive guanidino groups of arginines cannot be substituted by the positive amino groups of ornithines. Modifications of the amino groups of lysines show that these residues are necessary for the binding of H1 histones to DNA but they have no influence on the binding mode.

BACKGROUND:The body composition in overweight and obese hemodialyzed patients (HD) remains ill-de®ned. This study evaluates in HD patients the in¯uence of body size, as indicated by body mass index (BMI, kgam 2 ), on body composition by measuring bioimpedance analysis (BIA)-derived variables (phase angle (PA), fat-free mass (FFM) and body cell mass (BCM). METHODS: We studied 50 Caucasian patients (mean age 62.8 AE 9.2 y) on standard bicarbonate hemodialysis for at least 12 months who regularly achieved dry weight in post-HD, received similar dialysis doses and were free from in¯ammationainfec-tion. Thirty-eight gender-and age-matched healthy subjects were included as controls (CON). Both HD and CON were divided into three groups on the basis of their BMI(kgam 2 ) 18.5 ± 24.9, normal-weight (NW); 25 ± 29.9, overweight (OW); and !30, obese (OB). In HD patients, BIA was performed 30 min after the end of dialysis. RESULTS: Seven patients were obese (12%) while 16 were overweight (32%); in CON, 12 were obese (31%) and 12 overweight (31%). BIA-measured extracellular water was comparable in all groups. PA, which was similar in normal-weight HD and CON (6.2 AE 0.9 and 6.3 AE 0.8 ), decreased in OW-and OB-HD patients (5.3 AE 1.0 and 5.2 AE 0.6 , respectively; P`0.05 vs NW-HD) while it was unchanged in OW-and OB-CON (6.1 AE 0.8 and 5.9 AE 0.5 , P`0.05 vs respective HD groups). In OW and OB patients, the lower PA values were coupled with a major reduction of BIA-derived percentage BCM and FFM (P`0.05 vs NW-HD, and vs OW-and OB-CON). In patients, PA and BCM correlated with anthropometry-measured FFM. Of note, serum albumin and protein catabolic rate were signi®cantly reduced in OB patients. CONCLUSION: In overweight and obese HD patients, BIA-derived FFM, BCM and PA are signi®cantly lower with respect to normal-weight patients and BMI-matched controls. These abnormalities of body composition are coupled with reduction of anthropometric measures of lean mass and a decrease of protein intake that, however, becomes signi®cant only in the obese. We therefore suggest that overweight and obese HD patients are at risk of protein malnutrition in spite of excessive energy intake. BIA may be considered as a useful diagnostic tool to detect such a condition early.

Objectives. Serum cystatin C seems to be an accurate marker of glomerular filtration rate (GFR) compared to serum creatinine. The aim of this work was to explore the possibility of using serum cystatin C instead of serum creatinine to early predict renal failure in cancer patients who received platinum based chemotherapy. Design and Methods. Serum creatinine, serum cystatin C concentrations, and GFR were determined simultaneously in 52 cancer patients received carboplatin-based or cisplatin-based chemotherapy. Serum creatinine was assayed on Cobas C6000-Roche, serum cystatin C assay was performed on AIA 360-Tosoh, and GFR was determined in all patients, before the first cycle of chemotherapy and before the subsequent administrations. Results. In the overall series, for the prediction of a fall of GFR < 80 mL/min/1.73 m2, the AUC of the ROC curve for cystatin C was 0,667 and the best threshold was 1.135 mg/L (sensitivity 90.5%, specificity 61.1%). For a GFR fall < 60 mL/min/1.73 m2, the AUC of ROC curve for cystatin C was 74.3% and the best threshold was 1.415 mg/L (sensitivity 66.7%, specificity 73.2%). Conclusions. Baseline cystatin C values were not able to predict renal failure during subsequent treatment. In conclusion, serum cystatin C is not a reliable early marker to efficiently predict renal failure in patients receiving chemotherapy.

Genomic and trascriptomic profiling has recently contributed details to the characterization of luminal B breast cancer. We explored the contribution of anthropometric, metabolic, and molecular determinants to the multifaceted heterogeneity of this breast cancer subtype, with a specific focus on the association between body mass index (BMI), pre-treatment fasting glucose, hormone receptors, and expression of human epidermal growth factor receptor 2 (HER2). Extensively annotated specimens were obtained from 154 women with luminal B breast cancer diagnosed at two Italian comprehensive cancer centres. Participants' characteristics were descriptively analyzed overall and by HER2 status (positive vs. negative). BMI (<25 vs ≥25), pre-treatment fasting glucose (

Intestinal‑type gastric adenocarcinomas are preceded by precancerous lesions, which begin with chronic atrophic gastritis. Over the last few years, multiple serological screening techniques have been performed and commercialized for the diagnosis of chronic atrophic gastritis. In the present study, 123 patients were recruited at the International Cancer Institute 'G. Pascale' Foundation (Naples, Italy) to test commercial kits for the serological determination of chronic atrophic gastritis, supported by histological analysis, according to the International Group of Gastroenterologists 'Operative Link for Gastritis Assessment Staging System'. The results revealed a significant discrepancy between serological screening and histological evaluation in 10.6% of patients, which highlighted the dubious positive predictive value of commercial serological screening kits.

Endotoxin Activity Assay is a novel and rapid test capable of differentiating Gram-negative sepsis from infections carried by other bacteria. The test, moreover, represents a useful tool in the management of the septic patient. We show the data collected during a 6-year period experience, related to samples from septic patients admitted in ICU; for each patient we performed an EAA test and a blood culture with an automated system. Our aim was to evaluate the effectiveness of the EAA test, alone or in combination with blood cultures, in ICU setting. Our experience confirms that the measure of the endotoxin levels, along with the execution of a traditional blood culture, provides a useful tool in the management of the critical patient. The high predictive negative value of the EAA test, moreover, allow to rule-out a Gram-negative bloodstream infection.

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