Laminin 5 is a pivotal hemidesmosomal protein involved in cell stability, migration, and anchoring filament formation. Protein and gene expression of the alpha3, beta3, and gamma2 chains of laminin 5 were investigated in normal and invasive prostate carcinoma using immunohistochemistry, Northern analysis, and in situ hybridization. Laser capture microdissection of normal and carcinomatous glands, in conjunction with RNA amplification and reverse Northern analysis, were used to confirm the gene expression data. Protein and mRNA expression of all three laminin 5 chains were detected in the basal cells of normal glands. In contrast, invasive prostate carcinoma showed a loss of beta3 and gamma2 protein expression with variable expression of alpha3 chains. Despite the loss of protein expression, there was retention of beta3 and gamma2 mRNA expression as detected by in situ hybridization, Northern and reverse Northern analysis. Our findings imply that an altered mechanism of translation of beta3 or gamma2 mRNAs into functional proteins contributes to failure of anchoring filaments and hemidesmosomal formation. The resultant hemidesmosome instability or loss would suggest a less stable epithelial-stromal junction, increased invasion and migration of malignant cells, and disruption of normal integrin signaling pathways.
Hypothermia deaths are frequently accidental and associated with impairment by alcohol, injuries, mental illness, or natural disease. Hypothermia as a method of suicide is unusual, with only nine case reports in the scientific literature. In the early months of 2014, during one of the coldest winters on record, the Hennepin County Medical Examiner's office investigated and certified two unrelated cases of suicide by hypothermia; we describe the salient features of these cases. A retrospective review of all cases investigated by our office from January 1991-April 2014 identified 146 cases in which “hypothermia” or “environmental cold exposure” was listed as a cause of death, contributing condition, or mechanism of injury. Death investigation narratives and autopsy reports were reviewed to confirm hypothermia and evaluate for the presence or absence of characteristic hypothermia findings. In these cases the manner of death was certified as follows: 116 accident (79.4%), 15 undetermined (10.3%), 8 suicide (5.5%), 6 natural (4.1%), and 1 homicide (0.7%). Further examination of the eight suicide cases revealed that half were female and half were male, and most were younger individuals with only one decedent above 50 years of age. Four of these deaths were associated with drug toxicities, five were associated with additional self-inflicted injuries (blunt force, sharp force, and/or gunshot wounds), and none of them exhibited paradoxical undressing. It is important for medicolegal death investigation professionals to recognize that, while rare, hypothermia deaths may represent intentional injury, and suicide as a manner of death should be considered in all cases.
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