Rodney Harris

Bio: Rodney Harris is an academic researcher from St Mary's Hospital. The author has contributed to research in topics: Prenatal diagnosis & Genetic counseling. The author has an hindex of 38, co-authored 171 publications receiving 6296 citations. Previous affiliations of Rodney Harris include University of Manchester.

Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene

Abstract: Waardenburg's syndrome (WS) is an autosomal dominant combination of deafness and pigmentary disturbances, probably caused by defective function of the embryonic neural crest. We have mapped one gene for WS to the distal part of chromosome 2. On the basis of their homologous chromosomal location, their close linkage to an alkaline phosphatase gene, and their related phenotype, we suggested that WS and the mouse mutant Splotch might be homologous. Splotch is caused by mutation in the mouse Pax-3 gene. This gene is one of a family of eight Pax genes known in mice which are involved in regulating embryonic development; each contains a highly conserved transcription control sequence, the paired box. Here we show that some families with WS have mutations in the human homologue of Pax-3. Mutations in a related gene, Pax-6, which, like Pax-3, has both a paired box and a paired-type homeobox sequence, cause the Small-eye mutation in mice and aniridia in man. Thus mutations in the Pax genes are important causes of human developmental defects.

Apparent prevention of neural tube defects by periconceptional vitamin supplementation.

Abstract: An earlier preliminary paper is expanded. Women who had given birth to one or more infants with a neural tube defect were recruited into a trial of per conceptional vitamin supplementation. Two hundred mothers attending five centres were fully supplemented (FS), 50 were partially supplemented (PS), and 300 were unsupplemented (US). Neural tube defect recurrences in the study pregnancies were 1 (0.5%), in FS, none in PS, and 13 (4%) in US mothers. The difference in outcome between FS and US mothers is significant. The most likely explanation is that supplementation has prevented some neural tube defects, but further studies are needed.

Prevention of the First Occurrence of Neural-Tube Defects by Periconceptional Vitamin Supplementation

Abstract: Background. The risk of recurrent neural-tube defects is decreased in women who take folic acid or multivitamins containing folic acid during the periconceptional period. The extent to which such supplementation can reduce the first occurrence of defects is not known. Methods. We conducted a randomized, controlled trial of periconceptional multivitamin supplementation to test the efficacy of this treatment in reducing the incidence of a first occurrence of neural-tube defects. Women planning a pregnancy (in most cases their first) were randomly assigned to receive a single tablet of a vitamin supplement (containing 12 vitamins, including 0.8 mg of folic acid; 4 minerals; and 3 trace elements) or a trace-element supplement (containing copper, manganese, zinc, and a very low dose of vitamin C) daily for at least one month before conception and until the date of the second missed menstrual period or later. Results. Pregnancy was confirmed in 4753 women. The outcome of the pregnancy (whether the fetu...

Melanin Pigmentation in Mammalian Skin and Its Hormonal Regulation

Abstract: Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents interacting via pathways activated by receptor-dependent and -independent mechanisms, in hormonal, auto-, para-, or intracrine fashion. Because of the multidirectional nature and heterogeneous character of the melanogenesis modifying agents, its controlling factors are not organized into simple linear sequences, but they interphase instead in a multidimensional network, with extensive functional overlapping with connections arranged both in series and in parallel. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortins and ACTH, whereas among the negative regulators agouti protein stands out, determining intensity of melanogenesis and also the type of melanin synthesized. Within the context of the skin as a stress organ, melanogenic activity serves as a unique molecular sensor and transducer of noxious signals and as regulator of local homeostasis. In keeping with these multiple roles, melanogenesis is controlled by a highly structured system, active since early embryogenesis and capable of superselective functional regulation that may reach down to the cellular level represented by single melanocytes. Indeed, the significance of melanogenesis extends beyond the mere assignment of a color trait.

The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.

Abstract: Steroidogenesis entails processes by which cholesterol is converted to biologically active steroid hormones. Whereas most endocrine texts discuss adrenal, ovarian, testicular, placental, and other steroidogenic processes in a gland-specific fashion, steroidogenesis is better understood as a single process that is repeated in each gland with cell-type-specific variations on a single theme. Thus, understanding steroidogenesis is rooted in an understanding of the biochemistry of the various steroidogenic enzymes and cofactors and the genes that encode them. The first and rate-limiting step in steroidogenesis is the conversion of cholesterol to pregnenolone by a single enzyme, P450scc (CYP11A1), but this enzymatically complex step is subject to multiple regulatory mechanisms, yielding finely tuned quantitative regulation. Qualitative regulation determining the type of steroid to be produced is mediated by many enzymes and cofactors. Steroidogenic enzymes fall into two groups: cytochrome P450 enzymes and hydroxysteroid dehydrogenases. A cytochrome P450 may be either type 1 (in mitochondria) or type 2 (in endoplasmic reticulum), and a hydroxysteroid dehydrogenase may belong to either the aldo-keto reductase or short-chain dehydrogenase/reductase families. The activities of these enzymes are modulated by posttranslational modifications and by cofactors, especially electron-donating redox partners. The elucidation of the precise roles of these various enzymes and cofactors has been greatly facilitated by identifying the genetic bases of rare disorders of steroidogenesis. Some enzymes not principally involved in steroidogenesis may also catalyze extraglandular steroidogenesis, modulating the phenotype expected to result from some mutations. Understanding steroidogenesis is of fundamental importance to understanding disorders of sexual differentiation, reproduction, fertility, hypertension, obesity, and physiological homeostasis.