"Papillary Adenoma-like" Renal Tumor with TFE3 Gene Rearrangement, A Potential Precursor to or Early Event in the Development of TFE3 Translocation Renal Cell Carcinoma.

MiT family translocation renal cell carcinomas harbor gene fusion involving members of MiT family of transcription factors. Their precursor lesions have not been identified. Herein, we report the first case of small papillary tumors morphologically resembling papillary adenomas but harboring TFE3 gene alteration. The patient was a 23-year old man with multiple small papillary tumors in the right kidney discovered following a gunshot wound injury. These lesions were < 5 mm, well-circumscribed but not encapsulated tubulopapillary proliferation lined with a single layer of cuboidal cells with WHO/ISUP grade 1 or 2 nuclei. The tumor cells were immunoreactive to PAX8, AMACR, high molecular weight cytokeratin, and keratin 7 and negative for CD10, CA9, TTF1, and cathepsin K. Morphologically and immunohistochemically, these lesions were diagnosed as papillary adenomas. TFE3 gene rearrangement was confirmed by fluorescence in-situ hybridization (FISH) using a TFE3 break-apart probe. We term these tumors "papillary adenoma-like" renal tumor with TFE3 gene rearrangement. These tumors are likely a precursor to or represent an early event in the development of TFE3 translocation renal cell carcinomas. An understanding of such tumors to translocation renal cell carcinoma progression can provide insight into the pathogenic mechanism, and ultimately aid the diagnosis and management of translocation renal cell carcinoma.

Identification of differentially expressed genes from spinal cord after firearm injury to rabbit sciatic nerves.

OBJECTIVE: Peripheral nerve regeneration depends on gene regulation by central neurons. To search for more effective treatment methods to improve the regeneration of wounded peripheral nerves, gene expression profile of spinal cord after firearm injury to rabbit sciatic nerves are studied with DNA micro-array technique. METHODS: A total of 54 rabbits were randomly divided into 4 groups: Groups d1, d3, d7 and normal control group. Lumbar spinal cords were sampled. RNA and mRNA were extracted, labeled by Cy3 and Cy5, and analyzed by mouse_8192S gene chips. RESULTS: A total of 1367, 923, and 61 genes with differential expression were found on day 1, day 3, and day 7 after trauma respectively. Five expressed sequence tag (EST) sequences demonstrated differential expression during 7 days after trauma. CONCLUSIONS: There is complex gene profile with differential expression after firearm nerve injury, among which AW701496, U84291, W13926, X04017 and AW822394 EST sequences may be important regulation factors that involved in regeneration of peripheral nerve injury.

Alterations of myelin basic protein and ultrastructure in the limbic system at the early stage of trauma-related stress disorder in dogs.

BACKGROUND: The secondary injury and related complications after trauma are still the focus of trauma research. However, whether the remote effects on the central nervous system could be induced by high-energy missile extremity impact remains unclear. Also, the possible biomarker for brain damage in traumatic stress disorder has not been determined. METHODS: Forty-two healthy adult dogs were divided into three groups: the control group (n = 12), the high-speed trauma group (n = 15), and the low-speed trauma group (n = 15). Bilateral thighs of dogs were wounded with a smoothbore 6.2-mm rifle at a speed of 1,368 m/s (1.03-g steel bullet) for the high-speed trauma group and 625 m/s for the low-speed trauma group. The expression of myelin basic protein (MBP) in cerebrospinal fluid (CSF), hypothalamus and hippocampus of the limbic system, and temporoparietal cortex was investigated by enzyme-linked immunosorbent assay and dot-blot analysis. Also, the ultrastructure of the above areas was observed with light and electron microscopy. RESULTS: Neuronal degeneration and nerve fiber demyelination were seen in the hypothalamus and hippocampus in the high-speed trauma group at 8 hours after impact. The MBP level was markedly increased in the CSF (p < 0.01) in the two trauma groups, in the hypothalamus of the low-speed trauma group (p < 0.05), and in both the hypothalamus and the hippocampus of the high-speed trauma group (p < 0.01). The expression of MBP mRNA was also significantly enhanced in these areas at the same time. The increase of MBP content in the CSF was positively correlated with the elevation of MBP concentration in the hypothalamus and hippocampus. CONCLUSION: The hypothalamus and hippocampus of the limbic system in the central nervous system are vulnerable to damage after high-energy missile extremity impact, indicating that it might be one of the important pathologic bases involved in the development of trauma-related complications. Meanwhile, the MBP level in the CSF may be a sensitive biological indicator for brain damage at the early stage of trauma-related stress disorder.

[The genotoxic effect of gunshot wounds]. / Genotoksicheskii éffect ognestrel'nykh ran.

Evidence for alterations in chromosomes of experimental animals (rats) and humans after gunshot wounds is presented. The rate of chromatid exchanges induced by gunshot wounds in humans depend on the saturation of body tissues with ascorbic acid. It is assumed that free-radical processes underlie the deleterious effect of gunshot wounds on chromosomes.

Trajectory reconstruction from trace evidence on spent bullets. II. Are tissue deposits eliminated by subsequent impacts?

STR-based individualisation of biological deposits on bullets after perforation of tissue, can identify the person injured or killed by a particular bullet and comparison with the firearms used can identify the weapon and thus possibly the person who did the shooting. In this study, the effect of subsequent impacts on intermediate targets such as loss of cells was investigated by amplification of mitochondrial (mt) DNA. Bovine tissue was perforated and the 9 mm Luger FMJ bullets were recovered from the bullet collector. The mt cytochrome-b (cyt-b) gene could be amplified by the polymerase chain reaction (PCR) from 14 out of 15 bullets. Examination with a scanning electron microscope (SEM) and an energy-dispersive X-ray spectrometer (EDS) demonstrated the presence of minute dried tissue deposits on all bullets (n = 10) but was not able to establish preferential locations. In a series of 25 gunshots, various intermediate targets (glass, wood, car metal, gypsum board, asphalt) were perforated/impacted following perforation of tissue and the cyt-b gene could be typed from all bullets. It is concluded that subsequent impacts on intermediate targets do not eliminate enough biological deposits to render DNA analysis impossible and that the amplification of mtDNA is a useful additional method.

DNA-PCR analysis of bloodstains sampled by the polyvinyl-alcohol method.

Among the usual techniques of sampling gunshot residues (GSR), the polyvinyl-alcohol method (PVAL) includes the advantage of embedding all particles, foreign bodies and stains on the surface of the shooter's hand in exact and reproducible topographic localization. The aim of the present study on ten persons killed by firearms was to check the possibility of DNA-PCR typing of blood traces embedded in the PVAL gloves in a second step following GSR analysis. The results of these examinations verify that the PVAL technique does not include factors that inhibit successful PCR typing. Thus the PVAL method can be recommended as a combination technique to secure and preserve inorganic and biological traces at the same time.

STR analysis on perforating FMJ bullets and a new VWA variant allele.

In three separate shooting incidents involving multiple gunshots, two FMJ bullets and one bullet fragment found at the scene (one from each case) were investigated for the presence of biological material from the victim after perforation. The surface of the missiles, which did not show obvious tissue traces when examined under a macroscope, was swabbed. PCR typing of up to five STR loci was performed on the small amounts of DNA extracted, which were seen below the detection limit of the slot blot quantification in one case. Nevertheless, individualisation of cellular material from the perforating projectiles was successful in each of the three cases presented. Consequently, identification of the victim wounded by a perforating bullet can reliably be achieved if contamination or removal of evidentiary material by improper handling is prevented. This technique is especially useful in cases where more than one person has fired a gun because the bullet carrying DNA can be linked to the firearm by investigation with a comparison microscope. As a by-product of this investigation, a variant allele 14 (14+4) at the VWA locus was detected.

DNA typing of cellular material on perforating bullets.

DNA typing of cellular debris from perforating bullets was investigated following shooting experiments. A total of 14 perforating gunshots were fired into 9 calves. PCR typing of tissue fragments was done using bovine-specific primers flanking a 247 bp segment within the bovine lactoglobulin gene. Positive amplification results were obtained for all 9 hollow point (HP) and all 5 full metal jacket (FMJ) bullets. In contrast to HP bullets the smooth surfaces of the FMJ bullets did not have visible biological material, which resulted in weaker bands in the DNA analysis compared to HP bullets. Tissue seemed to accumulate at the base of the projectiles. Due to the lack of a suitable marker in bovines, only a species identification was carried out on the DNA from tissue on the bullets. The small amount of DNA extract (up to 5%) required for specification is promising for the successful application of a set of short tandem repeat (STR) systems for individualization in humans. By individualizing tissue on perforating bullets, the bullet and the victim it passed through can be linked. This can assist the investigation of gunshot deaths, especially when several persons are involved in a gun fight.

New concepts of the pathogenesis in the healing process of gunshot wounds.

By applying cytogenetic methods to the study of gunshot injuries, the authors showed that disturbances of the chromosomic apparatus integrity occurred. These disturbances are present for a long period and aggravate the severity of the wound-healing process.