Utilidad del APE libre en el diagnóstico de cáncer de próstata / Use of free PSA ratio in the diagnosis of prostate cancer

El Cáncer de próstata (CaP) constituye una importante causa de muerte en nuestro país. La razón Antígeno Prostático Específico libre/ Antígeno Prostático Específico total (APE-L/T) es una de las medidas descritas para mejorar la pesquisa de la enfermedad. MATERIAL Y MÉTODOS: Se realizó un estudio retrospectivo analítico en el Hospital Naval de Viña del Mar entre enero 2007 a diciembre 2011 que incluyó 588 pacientes con biopsias prostáticas que presentaban APE- T entre 2-10 ng/ml. Se evaluó la edad al diagnóstico, el valor de APE-T y la razón APE-L/T en relación al resultado histológico de las biopsias. Se realizaron curvas de rendimiento diagnóstico (ROC) para APE- T y para la razón APE-L/T. Se calculó sensibilidad y especificidad para diferentes puntos de corte para la razón APE-L/T. RESULTADOS: 33 por ciento de las biopsias fueron positivas para CaP. Los valores de la razón APE-L/T fueron significativamente más bajos en pacientes con CaP (p<0.001), alcanzando un área bajo la curva ROC 0,615. El mejor punto de corte para la razón APE-L/T fue de 15 por ciento con una sensibilidad de 60 por ciento y una especificidad de 58 por ciento. Para la razón APE-L/T > 25 por ciento la sensibilidad es 20 por ciento y la especificidad 91 por ciento. En cambio, el APE-T no mostró diferencias estadísticamente significativas (p=0,1) con un AUC 0,55. CONCLUSIONES: El APE-T por sí solo no parece tener capacidad discriminante para detectar CaP cuando los valores se encuentran entre 2-10 ng/ml. La razón APE-L/T tiene una utilidad limitada frente al paciente para decidir efectuar o no una biopsia de próstata.

Prostate cancer (PCa) is one of the major causes of death in our country. The Free/Total Prostate specific antigen ratio (f/t PSA) is one of the measurements that have been used to improve the diagnosis of this disease. MATERIAL AND METHODS: A retrospective analytic study in the Almirante Nef Hospital in Viña del Mar between January 2007 and December 2011 was made, which included 588 patients with prostate biopsies that had tPSA between 2-10 ng/ml. The age at diagnosis was evaluated and the value of tPSA and the f/t PSA ratio were compared with the histological results of the biopsies. Curves were performed for the diagnostic yield (ROC) for tPSA and the f/t PSA ratio. The sensitivity and specificity for different cut-off points for the f/t PSA ratio in the diagnosis of PCa were also calculated. RESULTS: 33 percent of the biopsies were positive for PCa. The f/t PSA ratio values were significantly lower in patients with CaP (p<0.001), reaching an area under the curve of 0,615. The best cutoff for f/t PSA ratio was 15 percent with 60 percent sensitivity and 58 percent specificity. For f/t PSA ratio > 25 percent sensitivity was 20 percent and specificity was 91 percent. PSA showed no statistically significant differences (p = 0.1) with AUC: 0.55. CONCLUSIONS: tPSA alone does not seem to have discriminatory power to detect PCa in patients when values are between 2-10 ng/ml. The f/t PSA ratio has a limited utility to decide to perform a prostate biopsy or not.

Linkage analysis of a rare alkaloid present in a tetraploid potato with Solanum chacoense background.

The potato genotype ND4382-19 has Solanum chacoense Bitt. in its genetic background. Foliar alkaloid analysis of it and its progeny ND5873 (ND4382-19 × Chipeta) by gas chromatography-mass spectrometry (GC-MS) showed that, in addition to the expected alkaloids (solanidine, leptinidine, and acetyl-leptinidine), there was an aglycone of another rare alkaloid. Its molecular mass and some of the m/z fragment ions were similar to leptinidine, but the major fragment ion was the m/z 150 peak of solanidine. This fragmentation pattern suggested that this alkaloid is a solanidine-based compound with mass equal to leptinidine. Leptinidine differs from solanidine by an extra -OH group, but the GC-MS fragmentation pattern of the rare compound indicated hydroxylation at a different position than the C-23 of leptinidine. The exact chemical structure is still unknown, and further analysis, such as NMR will be necessary to determine the structure. Segregation analysis of ND5873 (ND4382-19 × Chipeta) showed that presence of this rare compound segregated in a 1:1 ratio, indicating that a single gene controlled its synthesis and/or accumulation in foliar tissue. Analysis with AFLP and microsatellite markers indicated that the locus-controlling presence of this alkaloid resided on potato chromosome I, with the nearest flanking AFLP markers 0.6 and 9.4 cM apart. This rare alkaloid was present in the foliage and not detected in potato tubers. Its presence in leaves did not affect resistance/susceptibility to Colorado potato beetle.

Mapping of genes associated with leptine content of tetraploid potato.

High content of leptine glycoalkaloids present in Solanum chacoense has been associated with genetic resistance to Colorado potato beetle (Leptinotarsa decemlineata [Say]). From an unrecorded accession of S. chacoense, the North Dakota State University breeding program has developed a tetraploid genotype, ND4382-19, that contains foliar leptines. In this study, using a segregating population, ND5873 (ND4382-19 x Chipeta), and GC-MS to analyze foliar content of alkaloids, two loci, involved in the synthesis of leptines were identified. They segregated as two complementary epistatic genes that allowed the synthesis of leptinidine (Lep) and acetyl-leptinidine (AL), respectively. Partial AFLP maps for both parents were developed using 97 individuals from population ND5873. The total lengths mapped for ND4382-19 and Chipeta were 1,883 and 1,021 cM, respectively. The marker for Lep was located at the distal end of simplex-coupling linkage group R37. Expansion of the initial mapping population and analysis of Lep-containing individuals allowed us to identify the linkage group (R35) that enabled synthesis of AL. By the use of simple sequence repeat markers, linkage group R37 (Lep) and linkage group R35 (AL) have been identified as homologs of chromosomes II and VIII, respectively.

Resistant potato selections contain leptine and inhibit development of the Colorado potato beetle (Coleoptera: Chrysomelidae).

We recently described a new source of host-plant resistance to the Colorado potato beetle, Leptinotarsa decemlineata (Say), in a tetraploid potato (Solanum tuberosum L.) selection, ND2858-1. This genotype, and selected backcross progeny, had little damage while check cultivars were defoliated in open-choice field assays. To further characterize the observed deterrence, we determined foliar glycoalkaloids and conducted no-choice assays with ND2858-1 backcross progeny genotypes (ND4382-n). Development of neonate L. decemlineata in detached leaf assays on resistant progeny genotypes was delayed and larval weight gain after 4 d was inhibited by 75% relative to larval development and weight gain on susceptible genotypes. Inhibition of larval development in detached leaf assays with the selected progeny genotypes was equivalent to that of high-leptine genotypes of S. chacoense Bitter. Foliar glycoalkaloids of resistant genotypes included low levels of leptines I and II. The unlikely nature of this cross and the presence of leptine in this and resistant progeny selections cast doubt on the recorded pedigree. Molecular analyses were conducted by restriction fragment-length polymorphism and amplified fragment-length polymorphisms. Both methods established a high degree of relatedness to S. tuberososum and S. chacoense but not to S. fendleri. We conclude that ND2858-1 did not originate from a cross with S. fendleri, but is likely derived from S. chacoense. Oviposition and larval survival were reduced when adult L. decemlineata were placed in cages with resistant genotypes; an effect that was enhanced by inclusion of Perillus bioculatus F. Therefore, the nonpreference previously observed in open-choice field defoliation assays is also associated with antibiotic effects on L. decemlineata. The resistance may be caused by leptines, but is greater than would be expected by the leptine content. This source of host plant resistance could be a cost-effective management strategy, especially if combined with other resistance mechanisms or compatible control measures to delay development of resistance in the target insects.

Thiobacillus ferrooxidans tyrosyl-tRNA synthetase functions in vivo in Escherichia coli.

The tyrosyl-tRNA synthetase gene (tyrZ) from Thiobacillus ferrooxidans, an acidophilic, autotrophic, gram-negative bacterium that participates in bioleaching of minerals, was cloned and sequenced. The encoded polypeptide (TyrRZ) is 407 amino acids in length (molecular mass; 38 kDa). The predicted protein sequence has an extensive overall identity (44%) to the sequence of the protein encoded by the Bacillus subtilus tyrZ gene, one of the two genes encoding tyrosyl-tRNA synthetases in this microorganism. Alignment with Escherichia coli TyrRS revealed limited overall identity (24%), except in the regions of the signature sequence for class I aminoacyl-tRNA synthetases. Complementation of an E. coli strain with a thermosensitive mutation in TyrRS showed that the protein encoded by the T. ferrooxidans tyrZ gene is functional and recognizes the E. coli tRNA(Tyr) as a substrate. TyrZ is a single-copy gene as revealed by Southern blot analysis. The gene was localized upstream from the putative promoters of the rrnT2 ribosomal RNA operon. Although no rho-independent transcription terminator was found between the two genes, a 1.3-kb RNA hybridized to a DNA probe derived from the tyrZ gene. The functional relationship between these two transcription units is discussed.