Herein, we describe a novel approach in the search for prostate cancer biomarkers, which relies on the transcriptome within tumour exosomes. As a proof-of-concept, we show the presence of two known prostate cancer biomarkers, PCA-3 and TMPRSS2:ERG the in exosomes isolated from urine of patients, showing the potential for diagnosis and monitoring cancer patients status.

Given the prevalence of relapsing fever (RF) in Senegal, this disease may cause illness and death in other areas of West Africa. We performed a cross-sectional, clinic-based study to investigate the presence of RF in Togo during [2002][2003][2004]. Blood samples from patients with fever were examined for RF spirochetes by microscopy, PCR, and DNA sequencing of amplicons and for antibodies to the glycerophosphodiester phosphodiesterase antigen. Although no spirochetes were seen in blood smears, ≈10% of the patients were positive by PCR and ≈13% were seropositive for spirochetes. DNA sequencing demonstrated that Borrelia crocidurae and B. duttonii were present. Most patients were treated for malaria whether or not plasmodia were observed. Thus, many RF patients originally had a misdiagnosis of malaria, which resulted in ineffective treatment. The inability of microscopic analysis to detect spirochetes compared with PCR demonstrates the need for tests with greater sensitivity.

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A number of factors have been implicated in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN). The lack of a reliable animal model has made it difficult to further examine the role of these factors in the pathogenetic process. In this report, we present a tissue cage model in mice for the study of APSGN. Morphological and immunohistological changes in the kidney, resembling those of APSGN in man, were induced at high frequency in the experimental model after infection with group A streptococcal nephritis isolates. Nephritis‐associated strains induced hypercel‐lularity, occlusion of capillaries, and C3 deposition at high frequencies compared to the changes induced in animals infected with a non‐nephritis‐associated strain and non‐infected controls. In animals infected with a nephritis isolate, hematuria and proteinuria were also detected. If penicillin treatment was initiated on the third day of infection, the development of the nephritis process was prevented. Streptokinase, as well as preabsorbing antigen and streptococcal pyrogenic exotoxin B (SpeB), have been implicated in the pathogenesis of APSGN. These proteins, as well as SpeA and SpeF, were detected in the fluids of the infectious focus, regardless of the origin of the strains and whether or not glomerulonephritis was seen. Antibodies to streptokinase were evoked in the majority of the infected animals. This immune response did not correlate with the nephritic process since hypercellularity was also seen in animals which lacked detectable streptokinase antibodies. The results show that the mouse tissue cage model can be used to study APSGN and to evaluate factors involved in the pathogenesis of the disease.

To investigate the role of allelic variants of streptokinase in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), site-specific integration plasmids were constructed, which contained either the non-nephritis-associated streptokinase gene (skc5) from the group C streptococcal strain Streptococcus equisimilis H46A or the nephritis-associated streptokinase gene (ska1) from the group A streptococcal nephritogenic strain NZ131. The plasmids were introduced by electroporation and homologous recombination into the chromosome of an isogenic derivative of strain NZ131, in which the streptokinase gene had been deleted and which had thereby lost its nephritogenic capacity in a mouse model of APSGN. The introduction of a non-nephritis-associated allelic variant of streptokinase did not rescue the nephritogenic capacity of the strain. The mutant and the wild-type strains produced equivalent amounts of streptokinase. Complementation of the ska deletion derivative with the original ska allele reconstituted the nephritogenicity of wild-type NZ131. The findings support the hypothesis that the role of streptokinase in the pathogenesis of APSGN is related to the allelic variant of the protein.Acute poststreptococcal glomerulonephritis (APSGN) is considered to be immune mediated since C3 and immunoglobulin G (IgG) are found deposited in glomeruli of patients with the disease. The symptoms of kidney injury typically appear 7 to 21 days after infection with group A streptococci (GAS). Occasionally, APSGN also occurs following infections with streptococci of groups C and G (GCS and GGS) (1,7,27,32). Since C3 deposition precedes that of IgG in the disease process (17,25), the initial activation of complement does not appear to be due to IgG deposition or the presence of immune complexes within the glomeruli. Thus, a prevalent hypothesis is that glomerular deposition of streptococcal antigen may precede the tissue damage and lead to non-immune-mediated local activation of the complement system, with subsequent deposition of C3 (8). Several streptococcal products have been suggested to be the so-called nephritogenic factor (5,22,(33)(34)(35)(36), and some of these factors have been demonstrated in glomeruli of APSGN patients (34). Of the implicated factors, streptokinase has received especial attention. Streptokinase is considered a spreading factor for GAS, GCS, and GGS, forming a tight 1:1 stoichometric complex with either plasminogen or plasmin (2). The complex can activate plasminogen to the broad specific serine protease plasmin, which has the potential to activate the complement cascade as well as to degrade fibrin clots and extracellular matrix. The enzymatic activity of the complex cannot be inhibited by the inhibitors normally acting to inhibit plasmin in plasma (3). The streptokinase gene is highly conserved, except for two polymorphic regions, designated variable regions 1 (V1) and 2 (V2) (10). By PCR amplification and restriction enzyme analysis of the V1 region of GAS isolated from patients with differe...