Biomedical subjects

Mark A Watson

Publications and source records attributed to Mark A Watson.

39 records · Page 3Linked to original sources

PubMed2002

Differential NF1, p16, and EGFR patterns by interphase cytogenetics (FISH) in malignant peripheral nerve sheath tumor (MPNST) and morphologically similar spindle cell neoplasms.

Malignant peripheral nerve sheath tumors (MPNSTs) are diagnostically challenging neoplasms for which sensitive and specific immunohistochemical markers are lacking. Although limited to date, previous studies have suggested that NF1 (17q), NF2 (22q), p16 (9p), and EGFR (7p) alterations may be involved in MPNST tumorigenesis. To determine whether specific genetic changes differentiate between MPNST and morphologically similar neoplasms, we assessed these chromosomal regions in 22 MPNSTs (9 NF1-associated, 13 sporadic), 13 plexiform neurofibromas, 5 cellular schwannomas, 8 synovial sarcomas, 6 fibrosarcomas, and 13 hemangiopericytomas by 2-color FISH. NF1 deletions, often in the form of monosomy 17, were found in MPNSTs (76%). neurofibromas (31%), hemangiopericytomas (17%), and fibrosarcomas (17%), but not in synovial sarcomas or cellular schwannomas. NF1 losses were encountered more frequently in MPNSTs versus other sarcomas (p < 0.001), as were p16 homozygous deletions (45% vs 0%; p < 0.001), EGFR amplifications (26% vs 0%; p = 0.006), and polysomies for either chromosomes 7 (53% vs 12%; p = 0.003) or 22 (50% vs 4%; p < 0.001). Hemizygous or homozygous p16 deletions were detected in 75% of MPNSTs, but not in benign nerve sheath tumors (p < 0.001). Thus, FISH analysis identifies relatively specific genetic patterns that may be useful in selected cases, for which the differential diagnosis includes low- or high-grade MPNST.

Cytogenetic Analysis↗

PubMed2002

Reduced renin expression and altered gene transcript profiles in multicystic dysplastic kidneys.

PURPOSE: Some patients with multicystic dysplasia experience hypertension in infancy which can be clinically improved with simple nephrectomy. Little is known of the role of renin in multicystic dysplasia and therefore, we studied renin expression in nonhypertensive multicystic dysplasia and compared it with hypertensive multicystic dysplasia. Additionally, global gene transcript profiles were studied in nonhypertensive multicystic dysplasia. MATERIALS AND METHODS: Tissue from 12 patients with multicystic dysplasia without hypertension and 2 patients with hypertensive multicystic dysplasia were compared to normal metanephric mid-term and neonatal kidneys. Renin expression was studied by immunohistochemistry. CD-68, a marker for macrophages, was applied to slides previously stained with renin. GeneChip (Affymetrix, Southern Oaks, California) microarray analysis was performed using total RNA from 2 nonhypertensive multicystic dysplastic kidneys and normal newborn kidney as control. RESULTS: Strong renin staining was present in arteries and arterioles in normal early metanephric kidneys and concentrated in juxtaglomerular cells in neonatal kidneys. Renin was variably decreased in arterioles in multicystic dysplasia and was ectopically expressed in interstitial cells. Renin positive interstitial cells co-expressed CD-68 antigen identifying these cells as macrophages. Ectopic renin production was more pronounced in hypertensive multicystic dysplasia. GeneChip hybridization showed a 60 to 200-fold decrease in expression of renin transcript in multicystic dysplasia relative to normal kidney, concordant with immunohistochemical results. Altered expression of several other candidate transcripts was also identified. CONCLUSIONS: Dramatic renin decrease in multicystic dysplasia suggests that it may participate in the development of dysplastic vessels. Pronounced ectopic renin expression by macrophages in multicystic dysplasia associated with hypertension may be linked to hypertension in multicystic dysplasia. Several other candidate genes whose altered expression may be associated with the pathophysiology of multicystic dysplasia provide intriguing molecular targets for future study.

Antigens, CD↗

PubMed2002

Detection of malondialdehyde DNA adducts in human colorectal mucosa: relationship with diet and the presence of adenomas.

Colorectal biopsies from normal mucosa of participants in the United Kingdom Flexible Sigmoidoscopy Trial and European Prospective Investigation on Cancer (EPIC; n = 162) were analyzed for the presence of malondialdehyde-deoxyguanosine (M(1)-dG), a DNA adduct derived from lipid peroxidation. The aim was to investigate whether dietary factors can modulate M(1)-dG levels and whether M(1)-dG in normal mucosa is a risk factor for colorectal adenomas. Samples were analyzed using a sensitive immunoblot blot assay. This study has shown for the first time that M(1)-dG is present in human colorectal tissue. M(1)-dG levels ranged from undetectable (n = 13) to 12.23 per 10(7) total bases. Mean levels were 4.3 +/- 3 and 4.6 +/- 2.9 per 10(7) total bases in men and women, respectively. In men, there were positive associations of adduct levels with height and age, and inverse associations with body mass index. Legumes, fruit, salad, and whole meal bread were inversely associated with M(1)-dG adducts, whereas consumption of offal, white meat, beer, and alcohol were positively associated with elevated levels. In women, there was an inverse association of the adduct with the ratio of polyunsaturated:saturated fatty acids (P = 0.019) and a weak positive correlation with saturated fat (P < 0.061). When levels of adducts were compared in individuals with and without adenomas, there was a trend for higher levels in individuals presenting with adenomas especially in the highest category of M(1)-dG adducts (P < 0.005).

Adenoma↗