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P Nickson

Publications and source records attributed to P Nickson.

7 recordsLinked to original sources
PubMed2004

Expression of androgen receptors in upper human fetal reproductive tract.

BACKGROUND: Androgens play a key role in human fetal development. All androgens act through a single intracellular androgen receptor (AR), which is encoded by a single copy gene on the X chromosome. ARs are expressed as early as 9 weeks in the epithelium and mesenchyme of the urogenital sinus, paramesonephric (Müllerian) and mesonephric (Wolffian) ducts. METHODS: Using immunohistochemistry, we investigated the distribution of ARs in the gonads and lower genital tracts of 54 human fetuses at 8-11 weeks of gestation. Gender was determined by PCR. RESULTS: The AR was expressed in a similar pattern in both male and female fetuses. There appears to be no difference in expression in the mesonephros or the mesonephric ducts when male and female pelvises were compared. Expression in the female paramesonephric duct was within the epithelium, whereas, in the male pelvises, expression was in the mesenchyme of the paramesonephric duct. When AR expression was compared in the ovary and testes, both gonads seem to express AR at 9 weeks, but this expression was extended into the 10th week of gestation in the male. CONCLUSION: The specific pattern of AR expression implies a key role in gonadal development. However, the pattern of staining was similar in the gonads at 8 and 9 weeks in both sexes, although staining persisted longer in the testis until the 10th week. AR expression, therefore, is not a key determinant of human gonadal differentiation.

Embryo, Mammalian↗
PubMed2000

Joining together to combat poverty.

The International Poverty and Health Network (IPHN) was created in December 1997 following a series of conferences organized by the World Health Organization, with the aim of integrating health into plans to eradicate poverty. Around 1.3 billion people live on less than US$1 per day. Of the 4.4 billion people in developing countries nearly 60% lack access to sanitation, 30% do not have clean water, 20% have no health care, and 20% do not have enough dietary energy and protein. Even among rich nations there are gross socioeconomic inequalities. Many children are robbed of their physical and mental potential through poverty. Expressed in constant 1963 US dollars, an average Croatian family needed the annual income of US$894 to meet the poverty line in 1960 and US$9,027 in 1995. Accordingly, 9-25% of Croatian households were below the poverty line between 1960 and 1995. The increase in the poverty rate after 1991 was compounded by the war that destroyed almost a third of industrial capacity and infrastructure. Dissipation of the communist economy and inadequate privatization have contributed to the increase in unemployment rate, corruption, and other social ills. IPHN invited Croatian Medical Journal to publish this editorial to help push the issue of poverty up political and medical agendas on a global level. We argue that a factor contributing to the failure of most large-scale programs against poverty to date is the excessive emphasis on material and infrastructure assistance at the expense of spiritual, moral, and intellectual development.

Croatia↗
PubMed1998

Expression of type 2 11beta-hydroxysteroid dehydrogenase and corticosteroid hormone receptors in early human fetal life.

In adult life, the type 2 isozyme of 11beta-hydroxysteroid dehydrogenase (11betaHSD2) protects the mineralocorticoid receptor (MR) from glucocorticoid by inactivating cortisol to cortisone. 11betaHSD2 activity has been reported in human fetal tissues, where glucocorticoids may impair fetal growth yet are also required for normal fetal development. Using digoxigenin-labeled complementary ribonucleic acid (RNA) probes and an in-house 11betaHSD2 antiserum, we have analyzed the expression of 11betaHSD2, MR, and glucocorticoid receptor (GR) in human fetal tissues of gestational age 6-17 weeks (n=15). 11BetaHSD2 expression was absent at gestational age 6+ weeks, but was expressed in abundance in many fetal tissues between 8-12 weeks. At this time, 11betaHSD2 colocalized with GR messenger RNA (mRNA) expression in metanephros, gut, muscle, spinal cord and dorsal root ganglia, periderm, sex chords of testis, and adrenal. In particular within fetal kidney, intense expression of 11betaHSD2 and GR mRNA was observed over Bowman's capsule and the vascular tufts of developing glomeruli as they migrated from the surface of the kidney to the inner cortex. Only lung and adrenal medullary rests demonstrated high levels of GR mRNA but low levels of 11betaHSD2. 11BetaHSD2 mRNA and immunoreactivity staining patterns were similar, with the exception of the fetal adrenal, where mRNA was localized to the outer definitive zone but immunoreactivity was localized to the inner fetal zone. Colocalization of 11betaHSD2 (and GR mRNA) with MR mRNA was observed principally within epithelial cells of collecting ducts, particularly after 16 weeks gestation when the pattern of distribution of 11betaHSD2 became more adult in nature. High levels of MR mRNA were observed within developing bone. The data indicate that 11betaHSD2 in fetal life principally modulates ligand access to the GR in most fetal tissues, notably glomeruli and tubules in the developing kidney, testis, and periderm, and this may be have ramifications for fetal sodium homeostasis and differentiation. The development of tissues previously shown to have a critical requirement for glucocorticoids, such as lung and adrenal medulla, is facilitated by the expression of GR mRNA, but not 11betaHSD2. The expression of MR mRNA in high abundance in bone suggests a role for corticosteroids in human bone development, and the low/absent expression of 11betaHSD2 at this site suggests that it is functionally acting as a GR.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

The Knights of the Round Table hypothesis of tumour suppressor gene function--noble sacrifice or sexual dalliance: genes, including p53, BRCA1/2 and RB have evolved by horizontal and vertical transmission of mating factor genes and are involved in gametogenesis, implantation, development and tumourigenesis.

The genes involved in negative cell cycle regulation and familial tumour susceptibility including APC, BRCA, p53, RB, WT1 are unique and have no homologies with other genes. Our hypothesis suggests they originated from mating factor genes, which halted cell division in response to stress to generate genetic diversity by sexual mechanisms. Some have evolved principally by vertical transmission (mismatch repair), others by horizontal transmission via mobile elements, predominantly in oocytes. We demonstrate amplification in human extra-embryonic tissues in fetus and mother in implantation; in the developing fetus, differing tissue-specific patterns are seen, especially between testis and ovary. We suggest that the fetus is susceptible to maternal transmission of infections including CMV, malaria, trypanosomes, whose sequences occur within these genes. In head and neck cancers, we demonstrate specific patterns of loss or instability involving up to seven different TSG. We suggest mechanisms of tumourigenesis involve transposable elements and episome formation, leading to loss of negative cell cycle regulation and exit from G0.

Animals↗
PubMed1994

Obstetric uterine ruptures in a rural area in Zaïre.

Uterine ruptures with their deplorable sequelae constitute a major obstetrical problem in the rural areas of Africa. The maternal and perinatal mortality remain high as a result, mainly due to the lack of early and adequate care for these patients. Grande-multiparity is one of the major predisposing factors. Prevention must necessarily include the availability of family planning advice, improved organization of and access to maternal care, and good supervision during delivery and the post-partum period. The general improvement of the overall socio-economic condition is a pre-condition to the improvement of access to care.

Birth Weight↗
PubMed1992

Detrusor mast cells in refractory idiopathic instability.

The diagnosis of interstitial cystitis (IC) is not usually considered in patients with idiopathic instability. Because histamine provokes detrusor contractions in vitro, we assessed detrusor mast cell counts in 29 females with refractory instability. Raised mast cell counts (greater than 28/mm2 of detrusor muscle, consistent with a histological diagnosis of IC) were found in 29% of such cases. Thus cystoscopy and bladder biopsy should be considered in patients with idiopathic instability which fails to respond to anticholinergic drugs, as alternative therapy may be useful. Patients with refractory instability and normal detrusor mast cell counts often gave a history of prolonged childhood nocturnal enuresis (55% of cases); in contrast, patients with intractable instability and abnormally high mast cell counts seldom gave such a history (12%). These trends may give some insight into the aetiology of idiopathic instability--"congenital" or acquired?

Adult↗