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Biomedical subjects

Mark Payson

Publications and source records attributed to Mark Payson.

4 recordsLinked to original sources

Epidemiology of myomas.

Fibroids are a prevalent disorder occurring in at least half of American reproductive-age women. In general, the incidence and size increases with age. Most women never attribute or report any symptoms from their fibroids, and because of this the actual contribution of disease to symptoms of pelvic pain,menstrual symptoms, and infertility is poorly understood. The presence of fibroids can lead to multiple and disabling difficulties. Fibroids may cause pain and menstrual bleeding to the point of anemia. Fibroids clearly reduce fertility,increase preterm labor and delivery, and markedly increase the risk for cesarean delivery. Because the incidence varies according to population of interest, fibroids may explain some health disparities in different populations. For example,African Americans have a relatively poor outcome with assisted reproductive techniques compared with whites. Controlling for fibroid disease may explain this disparity, at least in part. Fibroids represent a tremendous public health burden on women and economic cost on society. Strategies to prevent, limit growth, and treat nonsurgically are needed. Fundamental and significant questions remain about fibroid disease,such as whether different clinical disease phenotypes (multiple versus single leiomyomas) contribute equally to symptoms and possess an equal likelihood of disease progression. For epidemiologic assessment of disease, a scoring system is urgently needed. Well-designed, controlled, prospective studies are still needed to define the natural history and correlate the presence of disease with symptomatology in women.

Epidemiologic Studies↗

Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids.

Uterine leiomyomas are prevalent estrogen-responsive clonal tumors, but the specific genetic alterations that contribute to their development have not been elucidated. To identify genes involved in the formation of leiomyomas, we used global expression profiling to compare clonal tumors with normal myometrium. Contrary to expectation, genes involved in estrogen action were not differentially expressed between leiomyoma and normal myometrium. Genes encoding extracellular-matrix proteins were prominently featured, suggesting their involvement in formation of a myofibroblast phenotype. Analysis of the extracellular matrix in the leiomyomas revealed a disordered collagen fibril orientation. Expression of the collagen-binding protein dermatopontin was found to be consistently decreased in leiomyoma by both reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR (mean underexpression = 9.41-fold) regardless of leiomyoma size, leiomyoma location, patient race, and patient age. This expression pattern was observed in 11 subjects and a total of 23 leiomyoma:myometrium pairs. Decreased expression of dermatopontin was also associated with keloid formation, a fibrotic disease that shares epidemiologic similarities with leiomyoma. Immunohistochemical studies of leiomyomas and keloids demonstrated reduced levels of dermatopontin in both tissues. In addition, ultrastructural analysis revealed that the orientation of the collagen fibrils in the keloid tissues strongly resembled that in the leiomyomas. Reduction in dermatopontin was associated with an increase in transforming growth factor-beta3 (TGFB3) mRNA levels in leiomyomas, whereas other genes involved in dermatopontin signaling were not differentially expressed. These findings suggest that leiomyoma development involves a myofibroblast cell phenotype characterized by dysregulation of genes encoding extracellular-matrix proteins. In particular, decreased expression of dermatopontin represents a molecular link between the leiomyoma and keloid phenotypes.

Adult↗

Strategy for elucidating differentially expressed genes in leiomyomata identified by microarray technology.

OBJECTIVE: cDNA microarray technology identifies genes that are differentially expressed between tissues. Our previous study identified several genes that might contribute to the fibroid phenotype. We therefore sought to confirm genes involved in three distinct signal transduction pathways. DESIGN: Evaluation of differential mRNA and protein expression of Dlk, Frizzled-2, and CD-24 in fibroids compared with adjacent myometrium. University hospital. PATIENT(S): Five women undergoing medically indicated hysterectomy for symptomatic fibroids. INTERVENTION(S): Microarray analysis of up to 33000 genes, reverse transcriptase-polymerase chain reaction (RT-PCR), real-time RT-PCR, Western blot, and immunohistochemistry. MAIN OUTCOME MEASURE(S): Expression of mRNA transcripts and protein in fibroid compared with myometrium.A more extensive microarray confirmed differential expression of Frizzled-2 and CD-24 but did not confirm Dlk overexpression. RT-PCR and real-time PCR demonstrated equivalent Dlk mRNA expression between fibroid and myometrium (ratio, 1.02), a slight Frizzled-2 overexpression (ratio, 2.09), and robust CD-24 overexpression in fibroids (ratio, 12.35). Western blot and immunohistochemistry confirmed Frizzled-2 overexpression, but did not confirm Dlk overexpression. CONCLUSION(S): Microarray technology is the first phase of tissue evaluation, but changes in gene expression must be confirmed. Confirmed genes can then be used to generate hypotheses testing their involvement in fibroid development.

Antigens, CD↗