Partial break in tolerance of NKG2A-/LIR-1- single KIR+ NK cells early in the course of HLA-matched, KIR-mismatched hematopoietic cell transplantation.

Natural killer (NK) cell subpopulations from 8 HLA-matched but killer cell immunoglobulin-like receptor (KIR)/HLA-ligand-mismatched patient-donor pairs were analyzed in the course of allogeneic hematopoietic stem cell transplantation (HCT). The patients' post-transplantation NKG2A-/LIR-1- NK cells, which expressed only inhibitory KIRs for which the patient had no HLA class I ligands, showed higher cytotoxic capacity than the NKG2A-/LIR-1- NK cells lacking any inhibitory KIRs that remained tolerant throughout the course of HCT. The NKG2A+ NK cell subpopulations displayed the highest levels of cytotoxic activation, which appeared to be significantly enhanced in comparison with that in allogeneic graft's donors. LIR-1- NK cells were much more frequent after HCT than LIR-1+ NK cells and LIR-1 expression on NKG2A+ or NKG2A- NK cells was associated with significantly lower cytotoxic activities. Thus NKG2A-/LIR-1- NK cells expressing only HLA-mismatched KIRs show a partial break in tolerance in the first year following HCT. The failure to exclude LIR-1+ cells within the NKG2A- NK cell subset in previous studies could explain the earlier conflicting results. Thus systemic immune activation in patients following HCT augments the GvL effect through both increasing overall NK cell activities and partially breaking tolerance of unlicensed NK cells.

Influence of urban area on the water quality of the Campo River basin, Paraná State, Brazil / Influência da área urbana na qualidade das águas na Bacia do Rio do Campo River, estado do Paraná, Brasil

The Campo River basin is located on the third plateau of the Paraná State or trap plateau of Paraná, at the middle portion between the rivers Ivaí and Piquiri, southern Brazil, between the coordinates 23° 53 and 24° 10’ South Latitude and 52° 15’ and 52° 31’ West Longitude. The basin has 384 Km² area, being 247 km2 in the municipality of Campo Mourão and 137 km2 in the municipality of Peabiru, in Paraná State. The Campo River is a left bank tributary of the Mourão River, which flows into the Ivaí River. The objective of this study was to monitor water quality in the Km 119 River and the Campo River, tributaries of the Mourão River, with monthly collection of water samples to determine pH, temperature, turbidity, biochemical oxygen demand, dissolved oxygen, fecal coliforms, total solids, total nitrogen, ammoniacal nitrogen, nitrite, nitrate and total phosphorus. The results obtained were compared with the indices established by the environmental legislation and applied in the determination of the Water Quality Index (WQI) used by the Water Institute of Paraná State, regulating environmental agency. Poor water quality in these rivers presents a worrying scenario for the region, since this river is the main source of water supply for the public system. Results of organic matter, fecal coliforms and total phosphorus were higher than the limits established by Resolution CONAMA 357/2005 to river class 2, specially at downstream of the Km 119 River and the Campo River, due to the significant influence of the urban anthropic activity by the lack of tertiary treatment and also rural by the lack of basic sanitation in this area. Results of WQI of Km 119 River and do Campo River indicated that water quality can be classified as average in 71% and good in 29% of the sites evaluated.

Resumo A Bacia Hidrográfica Rio do Campo está situada no terceiro planalto paranaense, na porção média entre os rios Ivaí e Piquiri, Sul do Brasil, entre as coordenadas 23° 53’ e 24°10’ de Latitude Sul e 52°15’ e 52°31’ de Longitude Oeste. A bacia ocupa área de 384 Km2, sendo 247 km2 no município de Campo Mourão e 137 km2 no município de Peabiru, no estado do Paraná. O Rio do Campo é um afluente da margem esquerda do Rio Mourão, que deságua no Rio Ivaí. O objetivo deste trabalho foi monitorar a qualidade da água do rio Km 119 e rio do Campo, afluentes do Rio Mourão, com coletas mensais de amostras de água para determinação do pH, temperatura, turbidez, demanda bioquímica de oxigênio, oxigênio dissolvido, coliformes fecais, sólidos totais, nitrogênio total, nitrogênio amoniacal, nitrito, nitrato e fósforo total. Os resultados obtidos foram comparados aos limites estabelecidos na legislação ambiental vigente para poluentes na água e aplicados na determinação do Índice de Qualidade das Águas (IQA) usado pelo Instituto das Águas do Paraná, órgão ambiental fiscalizador. A má qualidade observada nestes rios é preocupante para a região que usufruiu destas águas como principal fonte de abastecimento público. Resultados de matéria orgânica, coliformes totais e fósforo total extrapolaram os padrões estabelecidos na Resolução CONAMA 357/2005 para rio classe 2, especialmente à jusante do rio Km 119 e do Rio do Campo, devido à influência significativa da atividade antrópica urbana pela falta de tratamento terciário e rural pela falta de saneamento básico nesta área. Os resultados do IQA do Rio Km 119 e Rio do Campo indicam que as águas podem ser classificadas com qualidade média em 71% e boa em 29% nos pontos avaliados.

Influence of urban area on the water quality of the Campo River basin, Paraná State, Brazil

The Campo River basin is located on the third plateau of the Paraná State or trap plateau of Paraná, at the middle portion between the rivers Ivaí and Piquiri, southern Brazil, between the coordinates 23° 53 and 24° 10 South Latitude and 52° 15 and 52° 31 West Longitude. The basin has 384 Km² area, being 247 km2 in the municipality of Campo Mourão and 137 km2 in the municipality of Peabiru, in Paraná State. The Campo River is a left bank tributary of the Mourão River, which flows into the Ivaí River. The objective of this study was to monitor water quality in the Km 119 River and the Campo River, tributaries of the Mourão River, with monthly collection of water samples to determine pH, temperature, turbidity, biochemical oxygen demand, dissolved oxygen, fecal coliforms, total solids, total nitrogen, ammoniacal nitrogen, nitrite, nitrate and total phosphorus. The results obtained were compared with the indices established by the environmental legislation and applied in the determination of the Water Quality Index (WQI) used by the Water Institute of Paraná State, regulating environmental agency. Poor water quality in these rivers presents a worrying scenario for the region, since this river is the main source of water supply for the public system. Results of organic matter, fecal coliforms and total phosphorus were higher than the limits established by Resolution CONAMA 357/2005 to river class 2, specially at downstream of the Km 119 River and the Campo River, due to the significant influence of the urban anthropic activity by the lack of tertiary treatment and also rural by the lack of basic sanitation in this area. Results of WQI of Km 119 River and do Campo River indicated that water quality can be classified as average in 71% and good in 29% of the sites evaluated.

Resumo A Bacia Hidrográfica Rio do Campo está situada no terceiro planalto paranaense, na porção média entre os rios Ivaí e Piquiri, Sul do Brasil, entre as coordenadas 23° 53 e 24°10 de Latitude Sul e 52°15 e 52°31 de Longitude Oeste. A bacia ocupa área de 384 Km2, sendo 247 km2 no município de Campo Mourão e 137 km2 no município de Peabiru, no estado do Paraná. O Rio do Campo é um afluente da margem esquerda do Rio Mourão, que deságua no Rio Ivaí. O objetivo deste trabalho foi monitorar a qualidade da água do rio Km 119 e rio do Campo, afluentes do Rio Mourão, com coletas mensais de amostras de água para determinação do pH, temperatura, turbidez, demanda bioquímica de oxigênio, oxigênio dissolvido, coliformes fecais, sólidos totais, nitrogênio total, nitrogênio amoniacal, nitrito, nitrato e fósforo total. Os resultados obtidos foram comparados aos limites estabelecidos na legislação ambiental vigente para poluentes na água e aplicados na determinação do Índice de Qualidade das Águas (IQA) usado pelo Instituto das Águas do Paraná, órgão ambiental fiscalizador. A má qualidade observada nestes rios é preocupante para a região que usufruiu destas águas como principal fonte de abastecimento público. Resultados de matéria orgânica, coliformes totais e fósforo total extrapolaram os padrões estabelecidos na Resolução CONAMA 357/2005 para rio classe 2, especialmente à jusante do rio Km 119 e do Rio do Campo, devido à influência significativa da atividade antrópica urbana pela falta de tratamento terciário e rural pela falta de saneamento básico nesta área. Os resultados do IQA do Rio Km 119 e Rio do Campo indicam que as águas podem ser classificadas com qualidade média em 71% e boa em 29% nos pontos avaliados.

[Differential diagnosis of myeloproliferative neoplasms. Quantitative NF-E2 immunohistochemistry for differentiating between essential thrombocythemia and primary myelofibrosis]. / Differenzialdiagnose myelproliferativer Neoplasien. Quantitative NF-E2-Immunhistochemie zur Unterscheidung zwischen essenzieller Thrombozythämie und primärer Myelofibrose.

BACKGROUND: Besides essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) the myeloproliferative neoplasms (MPN) defined by the World Health Organization (WHO) comprise the entity of unclassifiable MPNs (MPN, U). The exact differential diagnosis of the specific MPN entities can be challenging particularly at early stages of the diseases. So far, pathologists have had to rely only on histomorphological evaluation of bone marrow biopsies in combination with laboratory data because helpful ancillary tests are not yet available. Even molecular tests, such as JAK2 mutation analysis are not helpful particularly in the differential diagnosis of ET and PMF because both entities are associated with the V617F mutation in 50 % of the cases. Recently overexpression of the transcription factor NF-E2 in MPN was described. MATERIALS AND METHODS: A collective of samples consisting of 163 bone marrow biopsies including 139 MPN cases was stained immunohistochemically for NF-E2 and analyzed regarding the subcellular localization of NF-E2 in erythroid progenitor cells. The results were compared between the MPN entities as well as the controls and statistical analyses were conducted. RESULTS AND DISCUSSION: This study showed that NF-E2 immunohistochemistry and analysis of the proportion of nuclear positive erythroblasts of all erythroid precursor cells can help to distinguish between ET and PMF even in early stages of the diseases. An MPN, U case showing a proportion of more than 20 % nuclear positive erythroblasts can be classified as a PMF with 92 % accuracy.

Microarray analysis reveals influence of the sesquiterpene lactone parthenolide on gene transcription profiles in human epithelial cells.

Sesquiterpene lactones are known for their anti-inflammatory activity which has been proven in various assays on DNA, mRNA and protein level. Here we report on the change in the gene expression profile in TNF-alpha stimulated human 293 cells after treatment with parthenolide using a cDNA microarray analysis. Twenty-one of 7028 genes were found to be up- and 18 down-regulated. They encode for chemoattractants, immune system proteins, glycoproteins, metabolism, serine proteinases, and transcription factors. Confirmatory analyses were carried out using quantitative real-time RT-PCR (TaqMan). Additional studies with selected genes revealed the concentration-dependent influence of parthenolide on the expression of these genes.

Molecular, immunological and clinical properties of mutated hepatitis B viruses.

Hepatitis B virus (HBV) is at the origin of severe liver diseases like chronic active hepatitis, liver cirrhosis and hepatocellular carcinoma. There are some groups of patients with high risk of generation of HBV mutants: infected infants, immunosuppressed individuals (including hemodialysis patients), patients treated with interferon and lamivudine for chronic HBV infection. These groups are the target for molecular investigations reviewed in this paper. The emergence of lamivudine- or other antiviral-resistant variants, rises concern regarding long term use of these drugs. Infection or immunization with one HBV subtype confers immunity to all subtypes. However, reinfection or reactivation of latent HBV infection with HBV mutants have been reported in patients undergoing transplant and those infected with HIV. Mutations of the viral genome which are not replicative incompetent can be selected in further course of infection or under prolonged antiviral treatment and might maintain the liver disease. Four open reading frames (ORF) which are called S-gene, C-gene, X-gene and P-gene were identified within the HBV genome. Mutations may affect each of the ORFs. Mutated S-genes were described to be responsible for HBV-infections in successfully vaccinated persons, mutated C-genes were found to provoke severe chronic liver diseases, mutated X-genes could cause serious medical problems in blood donors by escaping the conventional test systems and mutated P-genes were considered to be the reason for chemotherapeutic drug resistance. This paper reviews molecular, immunological and clinical aspects of the HBV mutants.

Effects of acute viral respiratory tract infections in patients with cystic fibrosis.

To determine the effects of acute viral respiratory infections (ARI) in cystic fibrosis (CF) we studied all episodes of ARI in ten patients over a 2 year period. A daily diary card was kept on which they recorded all illnesses, including specific upper and lower respiratory symptoms, antibiotic use, and daily peak flow measurements. Recording of concurrent similar illnesses in other household members aided in confirming the onset of ARI, as did a home viral culturing technique and serial serum antibody levels against specific viral types. A total of 80% of the 35 recorded onsets of ARI (1.75/yr/subject) were confirmed by one or more of these methods. Five subjects with moderate to severe pulmonary function scores at the outset of the study had significantly greater decreases in PEFR during ARI episodes (42.4%) than those with milder disease (15.4%), and it took them significantly longer to recover to their baseline measurements (22 days vs. 15 days respectively). The majority of hospital admissions for pulmonary exacerbations were preceded by viral infections (7/8).

A longitudinal study of bronchodilator responsiveness in cystic fibrosis.

The prevalence of bronchodilator responsiveness was evaluated in 20 outpatients with cystic fibrosis (CF) every 1 to 3 months for a 1-yr period and in 20 patients with CF during a hospital admission. All but 1 subject (95%) showed a significant bronchodilator response at least once on an outpatient basis; nonhospitalized subjects were responsive 49% of the time. Bronchodilator responsiveness was unrelated to long-term pulmonary severity or indexes of atopy but it was significantly influenced by season of the year; 70% of the population was responsive in winter compared with 25% in summer. Bronchodilator responsiveness increased during hospital admission together with improvement in baseline values; 23% of the population was responsive during the first 3 days compared with 80% by the end of the second week of admission. After discharge, a reverse pattern occurred, with decrease in bronchodilator responsiveness and a fall in baseline values. However, in some patients, bronchodilator responsiveness was lost when baseline values were still at their best. Bronchodilator responsiveness in CF tends to undulate with pulmonary exacerbations of the disease.