Provision of 4-1BB ligand enhances effector and memory CTL responses generated by immunization with dendritic cells expressing a human tumor-associated antigen

Up-regulation of receptor-ligand pairs during interaction of an MHC-presented epitope on dendritic cells (DCs) with cognate TCR may amplify, sustain, and drive diversity in the ensuing T cell immune response. Members of the TNF ligand superfamily and the TNFR superfamily contribute to this costimulatory molecule signaling. In this study, we used replication deficient adenoviruses to introduce a model tumor-associated Ag (the E7 oncoprotein of human papillomavirus 16) and the T cell costimulatory molecule 4-IBBL into murine DCs, and monitored the ability of these recombinant DO to elicit E7-directed T cell responses following immunization. Splenocytes from mice immunized with DCs expressing E7 alone elicited E7-directed effector and memory CTL responses. Coexpression of 4-1BBL in these E7-expressing DO increased effector and memory CTL responses when they were used for immunization. 4-1BBL expression up-regulated CD80 and CD86 second signaling molecules in DO. We also report an additive effect of 4-IBBL and receptor activator of NF-kappaB/receptor activator of NF-kappaB ligand coexpression in E7-transduced DC inummogens on E7-directed effector and memory CTL responses and on MHC class II and CD80/86 expression in DCs. Additionally, expression of 4-1BBL in E7-transduced DCs reduced nonspecific T cell activation characteristic of adenovirus vector-associated immunization. The results have generic implications for improved or tumor Ag-expressing DC vaccines by incorporation of exogenous 4-1BBL. There are also specific implications for an improved DC-based vaccine for human papillomavirus 16-associated cervical carcinoma.

Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis

Background The mechanisms responsible for disturbed iron homoeostasis in hereditary haemochromatosis are poorly understood. However, results of some studies indicate a link between hepcidin, a liver-derived peptide, and intestinal iron absorption, suggesting that this molecule could play a part in hepatic iron overload. To investigate this possible association, we studied the hepatic expression of the gene for hepcidin (HAMP) and a gene important in iron transport (IREG1) in patients with haemochromatosis, in normal controls, and in Hfe-knockout mice. Methods We extracted total RNA from the liver tissue of 27 patients with HFE-associated haemochromatosis, seven transplant donors (controls), and Hfe-knockout mice. HAMP and IREG1 mRNA concentrations were examined by ribonuclease protection assays and expressed relative to the housekeeping gene GAPD. Findings There was a significant decrease in HAMP expression in untreated patients compared with controls (5.4-fold, 95% CI 3.3-7.5; p

Link invariants associated with gauge equivalent solutions of the Yang-Baxter equation: The one-parameter family of minimal typical representations of Uq[gl(2|1)]

In this paper we investigate the construction of state models for link invariants using representations of the braid group obtained from various gauge choices for a solution of the trigonometric Yang-Baxter equation. Our results show that it is possible to obtain invariants of regular isotopy (as defined by Kauffman) which may not be ambient isotopic. We illustrate our results with explicit computations using solutions of the trigonometric Yang-Baxter equation associated with the one-parameter family of minimal typical representations of the quantum superalgebra U-q,[gl(2/1)]. We have implemented MATHEMATICA code to evaluate the invariants for all prime knots up to 10 crossings.

Acquired myasthenia gravis associated with a non-invasive thymic carcinoma in a dog

An 8 1/2-year-old neutered male Beagle was diagnosed with acquired myasthenia gravis associated with a non-invasive thymic carcinoma. The thymic mass was surgically excised and the dog was treated with pyridostigmine, prednisolone and azathioprine. Serial acetylcholine receptor antibody titres were increased initially but slowly declined to normal values over a period of 24 weeks. Improved exercise tolerance was seen following therapy, however, oesophageal dysfunction persisted. The dog was euthanased 26 weeks after initial presentation due to a complicating illness. A necropsy showed no regrowth or metastasis of the thymic carcinoma.

In overweight patients with chronic hepatitis C, circulating insulin is associated with hepatic fibrosis: implications for therapy

Background/Aims: Host factors such as increased body mass index (BMI) and genotype-specific viral factors contribute to the development of steatosis in patients with chronic hepatitis C (HCV). We hypothesized that host metabolic factors associated with increased BMI may play a role in disease progression. Methods: Fasting serum was collected from 160 patients with chronic HCV at the time of liver biopsy and 45 age, gender and BMI matched controls, and assessed for levels of insulin, c-peptide and leptin. Results: Patients with viral genotype 3 had more severe steatosis (P = 0.0001) and developed stages 1 and 2 fibrosis at a younger age (P < 0.05) than patients with genotype 1. For both genotypes, overweight patients had significantly more steatosis and increased insulin and leptin levels. In contrast to lean patients, there was a statistically significant increase in circulating insulin levels with increasing fibrosis in overweight patients with chronic HCV (P = 0.03). Following multivariate analysis, insulin was independently associated with fibrosis (P = 0.046) but not inflammation (P = 0.83). There was no association between serum leptin levels and stage of fibrosis. Conclusions: Increasing circulating insulin levels may be a factor responsible for the association between BMI and fibrosis in patients with HCV, irrespective of viral genotype. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Obesity is associated with worse peritoneal dialysis outcomes in the Australia and New Zealand patient populations

Although obesity is associated with increased risks of morbidity and death in the general population, a number of studies of patients undergoing hemodialysis have demonstrated that increasing body mass index (BMI) is correlated with decreased mortality risk. Whether this association holds true among patients treated with peritoneal dialysis (PD) has been less well studied. The aim of this investigation was to examine the association between BMI and outcomes among new PD patients in a large cohort, with long-term follow-up monitoring. Using data from the Australia and New Zealand Dialysis and Transplant Registry, an analysis of all new adult patients (n = 9679) who underwent an episode of PD treatment in Australia or New Zealand between April 1, 1991, and March 31, 2002, was performed. Patients were classified as obese (BMI of greater than or equal to30 kg/m(2)), overweight (BMI of 25.0 to 29.9 kg/m(2)), normal weight (BMI of 20 to 24.9 kg/m(2)), or underweight (BMI of

Gender differences in CF phenotype associated with low bone mineral density

Adolescents and adults with CF have lower bone mineral density (BMD) than normal, but its relationship with phenotype is not well understood. Point FEV1% predicted (FEV) and rate of change of FEV are biased estimates of disease severity, because progressively older subjects represent a selected survivor population, with females at greater risk of death than males. To investigate the relationship between BMD and phenotype we used an index (predicted age at death) derived from Bayesian estimates of slope and intercept of FEV, age at last measurement and survival status. Predictive equations for the index were derived from 97 subjects (78 survivors) from the RCH CF clinic, and applied to a group of 102 comparable subjects who had BMD measured, classified as having‘mild’ ()75th), ‘moderate’ (25– 75th), or ‘severe’ (-25th centile) phenotype. Total body (TB) and lumbar spine (LS) BMD z-scores (Z) were compared, adjustingfor gender effects, using 2-way ANOVA. Annual mean change in FEV segregated, as expected, according to phenotype, ‘severe’ (ns25), ‘moderate’ (ns51) and ‘mild’ (ns25) y3.01(y3.73 to y2.30)%, y0.85(y1.36 to y0.35)%, 2.70(1.92 to 3.46)%, respectively, with no gender difference. LS and TB BMDZ were different in each phenotype (P-s 0.002), LS BMDZ for ‘severe’, ‘moderate’ and ‘mild’ y1.63(CI: y2.07 to y 1.19), y0.86(CI: y1.17 to y0.55), y0.06(CI: y0.54 to 0.41). Males had lower LS BMDZ than females overall (y1.22 (CI: y1.54 to y0.91) vs. y0.48(CI: y 0.84 to y0.12) Ps0.002). In the ‘severe’ group, males had lower TB BMDZ and LS BMDZ (PF0.002). Low BMD is associated with ‘moderate’ and ‘severe’ phenotypes, with relative preservation in females in the ‘severe’ group. Female biology (reproductive fitness) might promote resistance to bone resorption at a critical level of BMD loss.

The main benefits associated with health and safety management systems certification in Portuguese small and medium enterprises post quality management system certification

The purpose of this study is to characterize how Portuguese Small and Medium Enterprises (SMEs) view the Occupational Health and Safety Management Systems (OHSMSs) certification process, after receiving the Quality Management System (QMS) certification. References were based on the ISO 9001 standard for a QMS and OHSAS 18001 for OHSMS. The method used to evaluate the implemented systems, was by form of questionnaire. Those questioned had to have a certified quality management system, an implemented OHSMS and be a SME. The questionnaire was sent to 300 SMEs; 46 responses were received and validated. Of them, only 12 SMEs had the OHSMS certificate according to OHSAS 18001. Within those 12 companies that participated: 7 SMEs are from the industrial sector; 3 belong to the electricity/telecommunications sector and 2 SMEs are from the trade/services activity sector. The size of the sample was small, but corresponds to Portuguese reality. Moreover, 34 SMEs did not have the OHSMS certificate. The questionnaire requested the main reasons for SMEs to opt for non-certification and it was related with high costs, while the main reasons to certificate were, among others, needed to eliminate or minimize risks to workers. The main benefits that Portuguese SMEs have gained from the referred certifications have been, improved working conditions, ensuring compliance with legislation and better internal communication about risks and hazards. Also presented are the main difficulties in achieving an OHSMS certification including high certification costs, difficulties motivating personnel, difficulties in changing the company’s culture and increased bureaucracy.

Inoculation with Azospirillum, associated with nitrogen fertilization in maize

The biological nitrogen fixation is an alternative to supply the nitrogen needed for maize. The objective of this study was to evaluate the development and yield of maize in response to inoculation with Azospirillum associated with nitrogen fertilization. We conducted two field experiments in the summer harvest, the first in the 2000/2001 crop year in the region of Marechal Cândido Rondon, under conventional tillage, and second in the 2002/2003 agricultural year in the region of Cascavel, under no tillage. The experimental design in both experiments was a randomized complete block, with four replications, 2x2x2 factorial, with two levels of nitrogen at sowing (zero and 20 kg ha-1), two levels of inoculum (zero and 200 g ha-1) and two levels of nitrogen in topdressing (zero and 100 kg ha-1). There was evaluated the height of ear insertion, total plant height, leaf N content, shoot dry biomass and grain yield. The height of ear insertion and total plant height were not influenced by the factors under study. Nitrogen fertilization at sowing increased the leaf N content, causing the opposite effect when combined with inoculation. Inoculation with Azospirillum in the absence of nitrogen, provide productivity increases of 15.4% and 7.4% for 2000/2001 and 2002/2003 crops, respectively. The inoculation provided productivity similar to that obtained with 100 kg ha-1 in topdressing in crop 2000/2001, while in association with the topdressing, reduced productivity and shoot dry biomass in crop 2002/2003.

Wound healing and cancer progression in Opisthorchis viverrini associated cholangiocarcinoma

Letter to the editor

Accessing Planktothrix species diversity and associated toxins using quantitative real-time PCR in natural waters

Tese de Doutoramento em Biologia apresentada à Faculdade de Ciências da Universidade do Porto, 2015.

Nutritional status of pregnant women: prevalence and associated pregnancy outcomes

INTRODUCTION: Although obesity is well recognized as a current public health problem, its prevalence and impact among pregnant women have been less investigated in Brazil. The objective of the study was to evaluate the impact of pre-obesity and obesity among pregnant women, describing its prevalence and risk factors, and their association with adverse pregnancy outcomes. METHODS: A cohort of 5,564 pregnant women, aged 20 years or more, enrolled at aproximately 20 to 28 weeks of pregnancy, seen in prenatal public clinics of six state capitals in Brazil were followed up, between 1991 and 1995. Prepregnancy weight, age, educational level and parity were obtained from a standard questionnaire. Height was measured in duplicate and the interviewer assigned the skin color. Nutritional status was defined using body mass index (BMI), according to World Health Organization (WHO) criteria. Odds ratios and 95% confidence interval were calculated using logistic regression. RESULTS: Age-adjusted prevalences (and 95% CI) based on prepregnancy weight were: underweight 5.7% (5.1%-6.3%), overweight 19.2% (18.1%-20.3%), and obesity 5.5% (4.9%-6.2%). Obesity was more frequently observed in older black women, with a lower educational level and multiparous. Obese women had higher frequencies of gestational diabetes, macrosomia, hypertensive disorders, and lower risk of microsomia. CONCLUSIONS: Overweight nutritional status (obesity and pre-obesity) was seen in 25% of adult pregnant women and it was associated with increased risk for several adverse pregnancy outcomes, such as gestational diabetes and pre-eclampsia.

Genus and Braid Index Associated to Sequences of Renormalizable Lorenz Maps

We describe the Lorenz links generated by renormalizable Lorenz maps with reducible kneading invariant (K(f)(-), = K(f)(+)) = (X, Y) * (S, W) in terms of the links corresponding to each factor. This gives one new kind of operation that permits us to generate new knots and links from the ones corresponding to the factors of the *-product. Using this result we obtain explicit formulas for the genus and the braid index of this renormalizable Lorenz knots and links. Then we obtain explicit formulas for sequences of these invariants, associated to sequences of renormalizable Lorenz maps with kneading invariant (X, Y) * (S,W)*(n), concluding that both grow exponentially. This is specially relevant, since it is known that topological entropy is constant on the archipelagoes of renormalization.