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implicated the proline/argine polymorphism of the codon 72 of the tumor-suppressor gene p53 in the development of cervical cancer (CC) with the observation that the p53 protein is more efficiently inactivated by the E6 oncoprotein of human papillomavirus in p53 arginine as compared with its proline isoform. These authors further noted that in the United Kingdom, individuals homozygous for the arginine allele were several times more susceptible to HPV-associated tumorigenesis that proline/arginine heterozygotes. Subsequent studies in different countries failed to unanimously confirm this association. Motivated by the high incidence of CC in Chile, we undertook a case control study obtaining the following frequencies for genotypes PP, AP and AA in 60 ICC cases and 53 carefully selected controls: 0.067, 0.250, 0.683 and 0.075, 0.453, 0.472 respectively. A significant difference (X 2 = 3.19 p < 0.02) and an odds ratio of 2.62 supported Storey et al (1998)'s results. In addition, rejecting previous hypotheses about the world distribution of the p53 codon 72 polymorphism, we conclude that this distribution most likely represents ancient human dispersal routes. Several methodological and biological explanations for the results obtained in previous negative association studies are briefly discussed.

The reported absence of morphologicafly detectable peroxisomes in liver and kidney tissue cells from patients affected by the autosomic recessive, inherited metabolic disease known as cerebrohepatorenal, or Zeflweger, syndrome was studied in fibroblasts, assuming it to be a generalized defect.Normal cultured fibroblasts were shown to contain peroxisomes according to morphological, biochemical, and subcellular fractionation criteria: particle-bound catalase and fatty acyl-CoA oxidase copurify in subcellular fractionation by differential centrifugation or isopycnic equilibrium in continuous density gradients and peroxidase-positive organelles of =O.1 ,um in diameter are detected in the cytoplasm. In Zellweger cultured fibroblasts, these peroxisomal enzymes are present; however, they behave as cytosolic enzymes in the different subcellular fractionation procedures employed and peroxisomes are not detected cytochemically. These rindings support the hypothesis that the lack of peroxisomes in this genetic disease is the consequence of a defect in the assembly of the peroxisomal constituents. Furthermore, the value offibroblasts for subcellular analysis of peroxisomal defects is illustrated.Recent evidence supports the hypothesis that in some inherited metabolic disorders, defects in peroxisomal function are pathogenic. The initial observation that peroxisomes are absent in liver and kidney from children affected with the cerebrohepatorenal (Zellweger) syndrome (1) later correlated with the greatly reduced plasmalogen content found in their tissues (2), a phenomenon attributed to a lack of peroxisomal enzymes involved in plasmalogen biosynthesis (2, 3). It has also been correlated with the accumulation in fibroblasts of very long-chain fatty acids (4), supposedly the consequence of a defect in the peroxisomal fatty acid oxidation system capable of oxidizing very long-chain fatty acids (5, 6). The lack of peroxisomes would also explain the increased blood level of bile acid precursors (7,8) and possibly of pipecolic acid (9), assuming it reflects a deficiency in glutaryl-CoA oxidation (10). Adrenoleukodystrophy constitutes another hereditary disorder in which the accumulation of very longchain fatty acids (11) and also myelin degeneration (12, 13) apparently reflect a peroxisomal defect. As new findings increase the scope of the possible peroxisomal involvement in metabolic inherited disorders, their participation is being considered for hyperpipecolatemia (8,14), glutaric aciduria (10), dicarboxylic aciduria (15, 16), hyperoxaluria (14, 17), glycinuria (17), testicular feminization (18), and cerebrotendinous xanthomatosis (8,14). A single enzymatic defect might explain some of these conditions; however, in the Zellweger syndrome the whole organelle would be missing, perhaps reflecting the deficit of a protein essential for the assembly of peroxisomes. Consequently, as already suggested (14, 19-24), this pathologic condition would constitute a unique example of a genetic disorder expressed as absence of a cell o...

Human papilloma virus (HPV) has a role in benign and malignant pathology of the larynx. In this review we present the biological and epidemiological aspects related to these issues.

Ten of the 31 samples (32%) were positive for HPV DNA and all of the samples were positive for human beta-globin. The genotypes identified were HPV 16 (n=3), HPV 58 (n=2) and HPV 39, 45, 51, 59, 66 and 69 (n=1 for each). The three samples positive for HPV 16 had lost region E2, meaning that the viral DNA had been integrated into the host genome.