Inhibition of antigen-induced T-cell clone proliferation by antigen-specific antibodies.

Attempts to inhibit the recognition of soluble antigens by T lymphocytes using antibodies specific for the antigen in question have been uniformally unsuccessful, in contrast to the observed specific inhibition of antibody generation by B cells. One exception is the unique situation whereby anti-hapten antisera inhibit the T-cell proliferative responses observed when hapten-specific T lymphocytes or clones are cultured with hapten-derivatized cells or proteins. The inability to inhibit T-cell functions by antigen-specific antibodies has been interpreted in several ways: (1) T cells possess a different repertoire from B cells; (2) the antibodies tested recognize epitopes present on the native antigen, whereas T cells recognize non-native (processed) structures; (3) the antigenic determinant(s) recognized by T cells on the surface of antigen presenting cells are either not accessible to antibodies, or are present in low amounts. The development of antigen-specific T-cell clones and monoclonal antibodies both specific for the same antigenic determinants now allows this question to be investigated definitively. Here, we report for the first time the specific inhibition of antigen-induced T-cell clone proliferation by a monoclonal antibody directed against the relevant soluble protein antigen.

Metazoan Parasite Infracommunities in Five Sciaenids from the Central Peruvian Coast

Parasitological analysis of 237 Menticirrhus ophicephalus, 124 Paralonchurus peruanus, 249 Sciaena deliciosa, 50 Sciaena fasciata and 308 Stellifer minor from Callao (Perú) yielded 37 species of metazoan parasites (14 Monogenea, 11 Copepoda, 4 Nematoda, 3 Acanthocephala, 1 Digenea, 1 Aspidobothrea, 1 Eucestoda, 1 Isopoda and 1 Hirudinea). Only one species, the copepoda Bomolochus peruensis, was common to all five hosts. The majority of the components of the infracommunities analyzed are ectoparasites. The Brillouin index (H) and evenness (J´) were applied to the fully sampled metazoan parasite infracommunities. High values of prevalence and mean abundance of infection are associated to the polyonchoinean monogeneans; the low values of J' reinforce the strong dominance of this group in the studied communities. The paucity of the endoparasite fauna may be a consequence of the unstable environment due to an upwelling system, aperiodically affected by the El Niño Southern Oscillation phenomena.

D-JNKi, a peptide inhibitor of c-Jun N-terminal kinase, promotes functional recovery after transient focal cerebral ischemia in rats

The c-Jun-N-terminal kinase (JNK) pathway has been shown to play an important role in excitotoxic neuronal death and several studies have demonstrated a neuroprotective effect of D-JNKi, a peptide inhibitor of JNK, in various models of cerebral ischemia. We have now investigated the effect of D-JNKi in a model of transient focal cerebral ischemia (90 min) induced by middle cerebral artery occlusion (MCAo) in adult male rats. D-JNKi (0.1 mg/kg), significantly decreased the volume of infarct, 3 days after cerebral ischemia. Sensorimotor and cognitive deficits were then evaluated over a period of 6 or 10 days after ischemia and infarct volumes were measured after behavioral testing. In behavioral studies, D-JNKi improved the general state of the animals as demonstrated by the attenuation of body weight loss and improvement in neurological score, as compared with animals receiving the vehicle. Moreover, D-JNKi decreased sensorimotor deficits in the adhesive removal test and improved cognitive function in the object recognition test. In contrast, D-JNKi did not significantly affect the infarct volume at day 6 and at day 10. This study shows that D-JNKi can improve functional recovery after transient focal cerebral ischemia in the rat and therefore supports the use of this molecule as a potential therapy for stroke.

Primary care at Swiss universities--current state and perspective.

BACKGROUND: There is increasing evidence that a strong primary care is a cornerstone of an efficient health care system. But Switzerland is facing a shortage of primary care physicians (PCPs). This pushed the Federal Council of Switzerland to introduce a multifaceted political programme to strengthen the position of primary care, including its academic role. The aim of this paper is to provide a comprehensive overview of the situation of academic primary care at the five Swiss universities by the end of year 2012. RESULTS: Although primary care teaching activities have a long tradition at the five Swiss universities with activities starting in the beginning of the 1980ies; the academic institutes of primary care were only established in recent years (2005 - 2009). Only one of them has an established chair. Human and financial resources vary substantially. At all universities a broad variety of courses and lectures are offered, including teaching in private primary care practices with 1331 PCPs involved. Regarding research, differences among the institutes are tremendous, mainly caused by entirely different human resources and skills. CONCLUSION: So far, the activities of the existing institutes at the Swiss Universities are mainly focused on teaching. However, for a complete academic institutionalization as well as an increased acceptance and attractiveness, more research activities are needed. In addition to an adequate basic funding of research positions, competitive research grants have to be created to establish a specialty-specific research culture.

Cloning and Molecular Characterization of the Schistosoma mansoni Genes RbAp48 and Histone H4

The human nuclear protein RbAp48 is a member of the tryptophan/aspartate (WD) repeat family, which binds to the retinoblastoma (Rb) protein. It also corresponds to the smallest subunit of the chromatin assembly factor and is able to bind to the helix 1 of histone H4, taking it to the DNA in replication. A cDNA homologous to the human gene RbAp48 was isolated from a Schistosoma mansoni adult worm library and named SmRbAp48. The full length sequence of SmRbAp48 cDNA is 1036 bp long, encoding a protein of 308 amino acids. The transcript of SmRbAp48 was detected in egg, cercariae and schistosomulum stages. The protein shows 84% similarity with the human RbAp48, possessing four WD repeats on its C-terminus. A hypothetical tridimensional structure for the SmRbAp48 C-terminal domain was constructed by computational molecular modeling using the b-subunit of the G protein as a model. To further verify a possible interaction between SmRbAp48 and S. mansoni histone H4, the histone H4 gene was amplified from adult worm genomic DNA using degenerated primers. The gene fragment of SmH4 is 294 bp long, encoding a protein of 98 amino acids which is 100% identical to histone H4 from Drosophila melanogaster.

Alcohol-related and hepatocellular cancer deaths by country of birth in England and Wales: analysis of mortality and census data.

BACKGROUND: The incidence of and mortality from alcohol-related conditions, liver disease and hepatocellular cancer (HCC) are increasing in the UK. We compared mortality rates by country of birth to explore potential inequalities and inform clinical and preventive care. DESIGN: Analysis of mortality for people aged 20 years and over using the 2001 Census data and death data from 1999 and 2001-2003. SETTING: England and Wales. MAIN OUTCOME MEASURES: Standardized mortality ratios (SMRs) for alcohol-related deaths and HCC. RESULTS: Mortality from alcohol-related deaths (23 502 deaths) was particularly high for people born in Ireland (SMR for men [M]: 236, 95% confidence interval [CI]: 219-254; SMR for women [F]: 212, 95% CI: 191-235) and Scotland (SMR-M: 187, CI: 173-213; SMR-F 182, CI: 163-205) and men born in India (SMR-M: 161, CI: 144-181). Low alcohol-related mortality was found in women born in other countries and men born in Bangladesh, Middle East, West Africa, Pakistan, China and Hong Kong, and the West Indies. Similar mortality patterns were observed by country of birth for alcoholic liver disease and other liver diseases. Mortality from HCC (8266 deaths) was particularly high for people born in Bangladesh (SMR-M: 523, CI: 380-701; SMR-F: 319, CI: 146-605), China and Hong Kong (SMR-M: 492, CI: 168-667; SMR-F: 323, CI: 184-524), West Africa (SMR-M: 440, CI, 308-609; SMR-F: 319, CI: 165-557) and Pakistan (SMR-M: 216, CI: 113-287; SMR-F: 215, CI: 133-319). CONCLUSIONS: These findings show persistent differences in mortality by country of birth for both alcohol-related and HCC deaths and have important clinical and public health implications. New policy, research and practical action are required to address these differences.This resource was contributed by The National Documentation Centre on Drug Use.

Association of cytokine genetic polymorphism with hepatites B infection evolution in adult patients

The infection by the hepatitis B virus (HBV) has different forms of evolution, ranging from self-limited infection to chronic hepatic disease. The objective of this study was to evaluate the influence of cytokine genetic polymorphisms in the disease evolution. The patients were divided into two groups, one with chronic HBV (n = 30), and the other with self-limited infection (n = 41). The genotyping for TNF (-308), TGFB1 (+869, +915), IL-10 (1082, -819, and -592), IL-6 (-174), and IFNG (+874) was accomplished by the PCR-SSP (polymerase chain reaction with sequence specific primers technique using the One Lambda kit. Although no statistically significant differences were found between the groups, the combination of TNF -308GG and IFNG +874TA was found in a lower frequency in chronic patients than in individuals with self-limited infection (26.7 versus 46.3%; P = 0.079; OR = 0.40; IC95% = 0.14-1.11). In chronic patients with histological alterations it was not observed the genotype TGFB1+869 C/C, against 24.4% in the self limited infection group (100 versus 75.6%; P = 0.096; OR = 7.67; IC95% = 0.42-141.63). Further studies in other populations, and evaluation of a greater number of individuals could contribute for a better understanding of the cytokine genetic polymorphism influence in HBV infection evolution.

U-Pb and Ar-Ar geochronological data from the Pelagonian basement in Evia (Greece): geodynamic implications for the evolution of Paleotethys

High precision U-Pb zircon and Ar-40/Ar-39 mica geochronological data on metagranodiorites, metagranites and mica schists from north and central Evia island (Greece) are presented in this study. U-Pb zircon ages range from 308 to 1912 Ma, and indicate a prolonged magmatic activity in Late Carboniferous. Proterozoic ages represent inherited cores within younger crystals. Muscovite Ar-40/Ar-39 plateau ages of 288 to 297 Ma are interpreted as cooling ages of the magmatic bodies and metamorphic host rocks in upper greenschist to epidote-amphibolite metamorphic conditions. The multistage magmatism had a duration between 308 and 319 hla but some older intrusions, as well as metamorphic events, cannot be excluded. Geochemical analyses and zircon typology indicate calc-alkaline affinities for the granites of central Evia and alkaline to calc-alkaline characteristics for the metagranodiorites from the northern part of the island. The new data point towards the SE continuation, in Evia and the Cyclades, of a Variscan continental crust already recognised in northern Greece (Pelagonian basement). The Late Carboniferous magmatism is viewed as a result of northward subduction of the Paleotethys under the Eurasian margin.

La biblioteca del futur

L'objectiu de la ponència és presentar la primera biblioteca virtual de Catalunya, a partir de l'exposició del desenvolupament de la seva planificació, els serveis bibliotecaris que ofereix i els mitjans amb què compta l'usuari per a rebre'ls.

Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer

BACKGROUND Inflammation has been implicated as an etiological factor in several human cancers, including prostate cancer. Allelic variants of the genes involved in inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. The purpose of this study was to investigate whether single nucleotide polymorphisms of genes that lead to increased levels of pro-inflammatory cytokines and chemokines are associated with an increased prostate cancer risk. METHODS A case-control study design was used to test the association between prostate cancer risk and the polymorphisms TNF-A-308 A/G (rs 1800629), RANTES-403 G/A (rs 2107538), IL1-A-889 C/T (rs 1800587) and MCP-1 2518 G/A (rs 1024611) in 296 patients diagnosed with prostate cancer and in 311 healthy controls from the same area. RESULTS Diagnosis of prostate cancer was significantly associated with TNF-A GA + AA genotype (OR, 1.61; 95% CI, 1.09-2.64) and RANTES GA + AA genotype (OR, 1.44; 95% CI, 1.09-2.38). A alleles in TNF-A and RANTES influenced prostate cancer susceptibility and acted independently of each other in these subjects. No epistatic effect was found for the combination of different polymorphisms studied. Finally, no overall association was found between prostate cancer risk and IL1-A or MCP-1 polymorphisms. CONCLUSION Our results and previously published findings on genes associated with innate immunity support the hypothesis that polymorphisms in proinflammatory genes may be important in prostate cancer development.

VIH-SIDA : proceso asistencial integrado

Publicado en la página web de la Consejería de Igualdad, Salud y Políticas Sociales: www.juntadeandalucia.es/salud (Consejería de Igualdad, Salud y Políticas Sociales/ Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados).

Timing of adequate antibiotic therapy is a greater determinant of outcome than are TNF and IL-10 polymorphisms in patients with sepsis.

INTRODUCTION Genetic variations may influence clinical outcomes in patients with sepsis. The present study was conducted to evaluate the impact on mortality of three polymorphisms after adjusting for confounding variables, and to assess the factors involved in progression of the inflammatory response in septic patients. METHOD The inception cohort study included all Caucasian adults admitted to the hospital with sepsis. Sepsis severity, microbiological information and clinical variables were recorded. Three polymorphisms were identified in all patients by PCR: the tumour necrosis factor (TNF)-alpha 308 promoter polymorphism; the polymorphism in the first intron of the TNF-beta gene; and the IL-10-1082 promoter polymorphism. Patients included in the study were followed up for 90 days after hospital admission. RESULTS A group of 224 patients was enrolled in the present study. We did not find a significant association among any of the three polymorphisms and mortality or worsening inflammatory response. By multivariate logistic regression analysis, only two factors were independently associated with mortality, namely Acute Physiology and Chronic Health Evaluation (APACHE) II score and delayed initiation of adequate antibiotic therapy. In septic shock patients (n = 114), the delay in initiation of adequate antibiotic therapy was the only independent predictor of mortality. Risk factors for impairment in inflammatory response were APACHE II score, positive blood culture and delayed initiation of adequate antibiotic therapy. CONCLUSION This study emphasizes that prompt and adequate antibiotic therapy is the cornerstone of therapy in sepsis. The three polymorphisms evaluated in the present study appear not to influence the outcome of patients admitted to the hospital with sepsis.

Estudio bibliométrico de la revista Nutrición Hospitalaria en el periodo 2001 a 2005: Parte I, Análisis de la producción científica.

OBJECTIVE To assess the scientific activity and information production of the journal Nutrición Hospitalaria, for the period 2001-2005 by means of a Bibliometric study. METHOD Cross-sectional descriptive study of the results obtained from the analysis of the articles published in the journal Nutrición Hospitalaria. The data were obtained by consulting the electronic version through the Web. In those cases in which there was a link breakdown, and thus, the inability to have access to the electronic document the printed version was consulted. All the documental possibilities were taken into account with the exception of communications to congresses. RESULTS A total of 345 articles were published, 187 (54.20%) being original articles. The geographical distribution of the first author was Spanish in 287 articles (83.19%) and Latin American in 27 (7.83%). Most of the articles are from health care centers (172 articles (49.86%)), and the cooperation index being 4.15. Madrid is the most productive province, for both the absolute and adjusted frequencies. The median number of references per article is 18, the mean being 23.52 (95% CI 20.93 - 26.10). The predominant language was Spanish, with 308 articles (89.28%). CONCLUSION Nutrición Hospitalaria may be considered as a reference journal regarding information and scientific communication on Nutrition for both the Spanish and Latin American communities. The bibliometric parameters studied compare with those verified for the remaining top of the list Spanish scientific journals on health sciences.