RESUMO
The identification and location of sources of genetic resistance to plant diseases are important contributions to the development of resistant varieties. The combination of different sources and types of resistance in the same genotype should assist in the development of durably resistant varieties. Using a doubled haploid (DH), mapping population of barley, we mapped a qualitative resistance gene ( Rpsx) to barley stripe rust in the accession CI10587 (PI 243183) to the long arm of chromosome 1(7H). We combined the Rpsx gene, through a series of crosses, with three mapped and validated barley stripe rust resistance QTL alleles located on chromosomes 4(4H) (QTL4), 5(1H) (QTL5), and 7(5H) (QTL7). Three different barley DH populations were developed from these crosses, two combining Rpsx with QTL4 and QTL7, and the third combining Rpsx with QTL5. Disease severity testing in four environments and QTL mapping analyses confirmed the effects and locations of Rpsx, QTL4, and QTL5, thereby validating the original estimates of QTL location and effect. QTL alleles on chromosomes 4(4H) and 5(1H) were effective in decreasing disease severity in the absence of the resistance allele at Rpsx. Quantitative resistance effects were mainly additive, although magnitude interactions were detected. Our results indicate that combining qualitative and quantitative resistance in the same genotype is feasible. However, the durability of such resistance pyramids will require challenge from virulent isolates, which currently are not reported in North America.
Assuntos
Hordeum/genética , Imunidade Inata/genética , Doenças das Plantas , Folhas de Planta/genética , Locos de Características Quantitativas , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Cruzamentos Genéticos , Genótipo , Hordeum/microbiologia , Modelos Genéticos , Fenótipo , Especificidade da EspécieRESUMO
The influence of clofibrate on the stereoconversion of fenoprofen (FPF) was studied in guinea pigs. This hypolipidaemic agent has been related to some biochemical changes in the liver leading to an increase in the chiral inversion process. Two groups of animals (n = 6 per group) were pretreated with oral doses of clofibrate (280 mg/kg per day) for three days and were then given (R)- or (S)-FPF (5 mg/kg, IV). The FPF enantiomers were extracted from the guinea-pigs' plasma using a solid phase procedure and analysed by HPLC with previous derivatization with L-leucinamide. Pretreatment with clofibrate increased the chiral inversion of (R)-FPF in favour of the pharmacologically active (S)-FPF enantiomer. Before this metabolic interaction can be applied to therapy with fenoprofen, the toxic effects of (S)-(+)-FPF on the gastrointestinal and renal tracts and the interference by (R)-(-)-FPF with the metabolism of lipids should be thoroughly evaluated.
Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Clofibrato/farmacologia , Fenoprofeno/química , Fenoprofeno/farmacocinética , Animais , Anti-Inflamatórios não Esteroides/sangue , Área Sob a Curva , Biotransformação/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Clofibrato/administração & dosagem , Fenoprofeno/sangue , Cobaias , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Estrutura Molecular , Estereoisomerismo , Fatores de TempoRESUMO
The effect of thyroid hormone excess on glucose tolerance as well as insulin secretion and its peripheral action has been a matter of debate for many years. Thyrotoxicosis caused by Graves' disease is associated in some patients with impaired glucose tolerance and insulin resistance. The objective of the present study was to investigate if the insulin sensitivity, assessed by the euglycemic insulin clamp technique, increase after correction of hyperthyroidism due to Graves' disease. After four months of medical treatment, patients became euthyroid and insulin sensitivity increased significantly from 3.47 to 6.39 mg/kg/min; therefore it was concluded that insulin resistance could be improved after successful treatment of hyperthyroidism. The precise mechanism underlying the effect of thyroid hormone excess on insulin sensitivity remains to be elucidated.
Assuntos
Antitireóideos/uso terapêutico , Doença de Graves/tratamento farmacológico , Doença de Graves/metabolismo , Resistência à Insulina , Metimazol/uso terapêutico , Adulto , HumanosRESUMO
BACKGROUND: Tight junctions play a critical role in tubular function. In mammalian kidney, the transepithelial electrical resistance and the complexity of the tight junction increase from the proximal to the collecting tubule. The differential expression of three tight junction proteins, ZO-1, ZO-2, and occludin, along isolated rabbit renal tubules is examined in this article. METHODS: Microdissected rabbit renal tubules were processed for immunofluorescence detection of ZO-1, ZO-2, and occludin. The quantitation of these proteins was done by Western blot determinations in Percoll isolated tubules. RESULTS: ZO-1 stained cell boundaries independently of the identity of the tubule. However, the amount found in distal segments was significantly higher than that expressed in proximal regions. ZO-2 in the proximal region was found diffusely distributed in the cytoplasm, with faint staining at cell borders, while a clear signal at cell perimeters was detectable from the Henle's loop to collecting tubules. Nuclear staining of ZO-2 was found along the whole nephron. The presence of occludin at the proximal region was faint and discontinuous, while its expression in the more distant portions was conspicuous. The quantity of ZO-2 and occludin present at the distal region was significantly higher compared with the proximal segment. CONCLUSIONS: The distribution of ZO-1, ZO-2, and occludin follows the increase in junction complexity encountered in renal tubules. The amount of the three proteins found in proximal and distal segments is significantly higher in the latter.
Assuntos
Túbulos Renais/metabolismo , Proteínas de Membrana/metabolismo , Fosfoproteínas/metabolismo , Junções Íntimas/metabolismo , Animais , Western Blotting , Núcleo Celular/metabolismo , Imunofluorescência , Secções Congeladas , Técnicas In Vitro , Masculino , Ocludina , Coelhos , Distribuição Tecidual , Proteína da Zônula de Oclusão-1 , Proteína da Zônula de Oclusão-2Assuntos
Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/genética , Obesidade/etiologia , Obesidade/genética , Composição Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/epidemiologia , Dieta , Exercício Físico , Humanos , México/epidemiologia , Obesidade/epidemiologiaRESUMO
The establishment of the junctional complex in epithelial cells requires the presence of extracellular calcium, and is controlled by a network of reactions involving G-proteins, phospholipase C and protein kinase C. Since potential candidates for phosphorylation are the tight junction associated proteins ZO1, ZO2 and ZO3, in a previous work we specifically explored these molecules but found no alteration in their phosphorylation pattern. To continue the search for the target of protein kinase C, in the present work we have studied the subcellular distribution and phosphorylation of vinculin and alpha-actinin, two actin binding proteins of the adherent junctions. We found that during the junctional sealing induced by Ca2+, both proteins move towards the cell periphery and, while there is a significant increase in the phosphorylation of vinculin, alpha-actinin remains unchanged. The increased phosphorylation of vinculin is due to changes in phosphoserine and phosphothreonine content and seems to be regulated by protein kinase C, since: (1) DiC8 (a kinase C stimulator) added to monolayers cultured without calcium significantly increases the vinculin phosphorylation level; (2) H7 and calphostin C (both protein kinase C inhibitors) completely abolish this increase during a calcium switch; (3) inhibition of phosphorylation during a calcium switch blocks the subcellular redistribution of vinculin and alpha-actinin. These results therefore suggest that vinculin phosphorylation by protein kinase C is a crucial step in the correct assembly of the epithelial junctional complex.
Assuntos
Actinina/metabolismo , Cálcio/farmacologia , Proteína Quinase C/metabolismo , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Vinculina/metabolismo , Animais , Sítios de Ligação , Linhagem Celular , Cães , Microscopia de Fluorescência , Fosforilação , Serina/metabolismo , Frações Subcelulares/metabolismo , Treonina/metabolismoRESUMO
OBJECTIVE: To analyze the association of hypertension and upper body fat distribution on the occurrence of non-insulin-dependent diabetes mellitus in Mexicans. MATERIAL AND METHODS: It was a population-based cross-sectional study in Cuajimalpa, a district of Mexico City. A total of 1066 subjects were home interviewed, and attended our clinic for fasting plasma glucose sampling, blood pressure and anthropometric measurements. Diabetes was defined according to the World Health Organization criteria, and hypertension as a blood pressure equal to or greater than 140/90. The ratio of upper to lower body skinfolds was used to estimate body fat distribution. RESULTS: The prevalence of diabetes was 12.0%. There was a significant positive trend in the age and sex adjusted prevalence of diabetes according to the magnitude of hypertension (p = 0.0006) and upper body fat distribution (p = 0.007). The age and sex adjusted prevalence in normotensive subjects with lower body fat distribution was 7.1% (95% confidence interval 5.9-8.2) whereas it was 19.9% (CI 17.0-22.8) in those with hypertension and upper body fat distribution. The prevalence of diabetes in Mexicans was high and it may be related to a genetic susceptibility for an insulin resistance syndrome. CONCLUSIONS: These results indicate that there is a dose response effect in the association of hypertension and upper body fat distribution with diabetes in Mexicans, and that there may be an interaction in the effect of hypertension and body fat distribution in this syndrome.
Assuntos
Tecido Adiposo/anatomia & histologia , Diabetes Mellitus Tipo 2/epidemiologia , Hipertensão/epidemiologia , Somatotipos , Adulto , Idoso , Glicemia , Pressão Sanguínea , Índice de Massa Corporal , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Hipertensão/genética , Resistência à Insulina , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Dobras Cutâneas , SíndromeRESUMO
The present survey was performed to assess the hepatitis C virus seroprevalence in volunteer blood donors of the National Medical Center, Hospital de Especialidades, Mexico City. Serum samples from 1100 individuals were collected. We selected second generation enzyme-linked immunosorbent assay (ELISA) (Abbott HCV EIA) test for the screening. The antibodies against hepatitis C virus (anti-HCV) in the volunteer blood donors were positive in 0.7%. The second generation ELISA test is useful as a screening test and may lead to decreasing the incidence of posttransfusional hepatitis C virus infection.
Assuntos
Doadores de Sangue , Hepacivirus/isolamento & purificação , Anticorpos Anti-Hepatite/sangue , Hepatite B/epidemiologia , Ensaio de Imunoadsorção Enzimática , Anticorpos Anti-Hepatite C , Hospitais Especializados , Humanos , México/epidemiologia , PrevalênciaRESUMO
The current work was undertaken in order to assess the role of the monoclonal antibodies (Mabs) to lipopolysaccharide (LPS) of Salmonella typhi in the induction of passive protection against the challenge with the bacteria in a mice model. BALB/c mice were immunized with the whole bacteria, mice with high anti-LPS antibody titers were killed, the spleens were removed and splenocytes were fused with the mouse plasmocytoma SP2/0. Two IgM monoclonal antibodies against porins were developed. Each one of these Mabs recognized the polysaccharide region of LPS. Passive immunization with supernatant fluid of mice with one of these monoclonal antibodies did not protect against challenged with 20 LD50 and 100 LD50 of Salmonella typhi. The results suggest that LPS is not valuable immunogen for the induction of a protective status against typhoid fever.