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Biomedical subjects

W J Roy

Publications and source records attributed to W J Roy.

6 recordsLinked to original sources

Loss of heterozygosity on chromosomes 7p, 7q, 9p and 11q is an early event in ovarian tumorigenesis.

Forty early stage malignant and seven borderline ovarian tumours were analysed for loss of heterozygosity (LOH) on chromosomes 6, 7, 9, 11 and 17. LOH involving at least one locus was observed in 32 (80%) early stage and six (86%) borderline tumours. Frequent LOH in the early stage tumours was detected on chromosome arms 7p (31%), 7q (50%), 9p (42%) and 11q (34%) suggesting that these chromosomes harbour tumour suppressor genes which are inactivated early in tumorigenesis. Borderline tumours exhibited a similar pattern of LOH to that observed in the early stage malignant tumours, indicating that the development of both malignant and borderline forms may involve inactivation of the same set of tumour suppressor genes. Together with our previous investigation of benign ovarian tumours this data supports the theory that malignant ovarian tumours may arise from benign and borderline precursors.

Chromosomes, Human, Pair 11↗

Frequent loss of heterozygosity on chromosomes 7 and 9 in benign epithelial ovarian tumours.

It is presently unclear if ovarian cancers arise through malignant transformation of pre-existing benign tumours. The apparent rarity of loss of heterozygosity (LOH) reported for benign tumours has led to speculation that they lack malignant potential and represent a biological entity distinct from ovarian carcinoma. We reasoned that the absence of detectable LOH may be due to the masking of such losses by contamination with normal tissue present in excess in the majority of benign tumour biopsies. Therefore we utilized a microdissection technique to examine for LOH using 14 microsatellite markers on chromosome arms 6q, 7p, 7q, 9p, 11q and 17p in 31 solitary benign epithelial ovarian tumours. LOH was detected on all chromosome arms with the most frequent LOH occurring on 7p (27%) and 9p (26%). In addition, a point mutation in codon 157 of TP53 was detected in one tumour which is the first report of a TP53 mutation in a solitary benign ovarian tumour. In total 48% of tumours harboured genetic alterations which supports the idea that all benign ovarian tumours may carry a genetic predisposition to malignancy and are therefore not inherently different from their malignant counterparts.

Chromosome Deletion↗

Acute hyperglycemia following intraperitoneal irrigation with 10% dextrose in a patient with pseudomyxoma peritonei.

Pseudomyxoma peritonei is a condition characterized by the production of large amounts of mucopolysaccharide by a neoplastic epithelium. Although surgical debulking and removal of the mucinous ascites may be attempted, complete removal of the material is often impossible. Intraperitoneal lavage with 10% dextrose in water (D10W) has been advocated to prevent reaccumulation of the mucus and complications such as bowel obstruction requiring repeat laparotomy. We describe a patient undergoing operation for a large abdominopelvic mass. At laparotomy, a mucinous cystadenocarcinoma of the ovary was found with a great deal of tenacious, mucinous ascites and peritoneal implants. In an effort to more efficiently remove the mucus and prevent subsequent reaccumulation, intraperitoneal irrigation with 10% dextrose in water (D10W) was performed. The patient, who gave no history of prior glucose intolerance, was soon thereafter found to be profoundly hyperglycemic (serum glucose >500 mg/dl). She was treated with insulin and recovered without evident sequelae. Practitioners should be aware of this potentially dangerous complication associated with intraperitoneal dextrose instillation.

Acute Disease↗

Loss of heterozygosity at the alpha-inhibin locus on chromosome 2q is not a feature of human granulosa cell tumors.

The alpha-inhibin gene has been shown in knockout mouse models to be a suppressor of granulosa tumorigenesis in the mouse. To determine if alpha-inhibin has the same function in humans, we have assessed the frequency of loss of heterozygosity (LOH) of the alpha-inhibin gene locus on chromosome 2q in 17 human granulosa cell tumors and 36 epithelial ovarian cancers. LOH was detected in 12 of 36 (33.3%) epithelial tumors but in only 1 of 17 (6%) granulosa cell tumors. These data suggest that in contrast to the suggestions from the mouse model alpha-inhibin does not function as a granulosa cell tumor suppressor gene in the human. Furthermore, analysis of the TP53 gene in the granulosa cell tumors failed to detect either LOH or point mutations, indicating that they have a developmental pathway distinct from that of epithelial ovarian tumors.

Adult↗

Thoracic empyema due to Streptococcus intermedius.

With improved laboratory identification procedures, Streptococcus milleri (intermedius) is becoming recognized as an important human pathogen with the potential to form abscesses in a wide range of organs. The occurrence of a rapidly progressive and toxic empyema due to this organism in an otherwise healthy young adult without a predisposing lower respiratory tract infection allows us to examine the possibility that this microbe may be a significant but frequently unrecognized cause of adult empyema.

Adult↗