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Biomedical subjects

T Stephenson

Publications and source records attributed to T Stephenson.

At least 55 records · Page 3Linked to original sources
PubMed2003

Endocrine and nutritional regulation of fetal adipose tissue development.

In the fetus, adipose tIssue comprises both brown and white adipocytes for which brown fat is characterised as possessing the unique uncoupling protein (UCP)1. The dual characteristics of fetal fat reflect its critical role at birth in providing lipid that is mobilised rapidly following activation of UCP1 upon cold exposure to the extra-uterine environment. A key stage in the maturation of fetal fat is the gradual rise in the abundance of UCP1. For species with a mature hypothalamic-pituitary axis at birth there is a gradual increase in the amount and activity of UCP1 during late gestation, in conjunction with an increase in the plasma concentrations of catecholamines, thyroid hormones, cortisol, leptin and prolactin. These may act individually, or in combination, to promote UCP1 expression and, following the post-partum surge in each hormone, UCP1 abundance attains maximal amounts. Adipose tIssue grows in the fetus at a much lower rate than in the postnatal period. However, its growth is under marked nutritional constraints and, in contrast to many other fetal organs that are unaffected by nutritional manipulation, fat mass can be significantly altered by changes in maternal and, therefore, fetal nutrition. Fat deposition in the fetus is enhanced during late gestation following a previous period of nutrient restriction up to mid gestation. This is accompanied by increased mRNA abundance for the receptors of IGF-I and IGF-II. In contrast, increasing maternal nutrition in late gestation results in less adipose tIssue deposition but enhanced UCP1 abundance. The pronounced nutritional sensitivity of fetal adipose tIssue to both increased and decreased maternal nutrition may explain why the consequences of an adverse nutritional environment persist into later life.

Adipose Tissue↗
PubMed2003

Cost-effective treatment solutions for rural areas: design and operation of a new package treatment plant for single households.

The design approach and operation of a newly developed package plant treating domestic sewage from single households were evaluated. Combining submerged aerated filter (SAF) technology with jet aeration and incorporating both into a compact and shallow tank resulted in a cost-effective treatment solution. A trial unit was permanently installed at a rural site, serving a single household. Jet aeration proved to be the best aeration method for the shallow bioreactor design. Further trials revealed a 50% reduction in suspended solids (SS) through the use of a static effluent filter and found that annual plant maintenance was vital to sustain stable operating conditions. Despite high variations in influent conditions, the trial unit produced good effluent quality during steady-state operation. Average effluent BOD5, COD and SS values were 19.6 mg l(-1), 98 mg l(-1) and 32 mg l(-1) achieving overall removal efficiencies of 94.2%, 85.9% and 87.6% respectively. However, effluent ammonia nitrogen (NH4-N) levels were found to be inconsistent varying from 9 mg l(-1) to over 60 mg l(-1).

Air↗
PubMed2003

Moving bed biofilm reactors: a small-scale treatment solution.

The design and operational suitability of the moving bed process for small-scale sewage treatment systems were evaluated. A prototype plant was installed at a new housing development near Winchester, UK, and operated under different conditions over an eight-month period. During normal operation, the MBBR plant produced a good quality effluent with average values for BOD5, COD, SS and NH4-N of 15.6 mg l(-1), 65.9 mg l(-1), 21 mg l(-1) and 4.7 mg l(-1), respectively. The plant was further subjected to organic and hydraulic shock loads. The treatment performance remained high over the organic shock period, however, hydraulic surges of up to 10 times the design flow caused a loss of solids from the final settlement stage. While organic carbon removal resumed to over 80% within a single week after a prolonged power failure, effluent NH4-N values remained high for a period of three weeks. Besides producing a good quality effluent, the MBBR plant proved to be simple and reliable to operate, thus providing a viable treatment solution for small-scale applications.

Biofilms↗
PubMed2002

Inhibins/activins as diagnostic markers for ovarian cancer.

It is widely recognised that the early detection and subsequent assessment of recurrence of ovarian cancers are key steps for successful treatment. Available serum markers (e.g. CA125) are sensitive for some epithelial carcinomas (e.g. serous, endometrioid, clear cell), however, these markers are less sensitive for granulosa cell tumours and mucinous carcinomas. Serum inhibin is an ovarian product which decreases to non detectable levels after menopause, however, certain ovarian cancers (mucinous carcinomas and sex cord stromal tumours such as granulosa cell tumours) continue to produce inhibin which provides a basis for a serum diagnostic test. Studies from this and other laboratories have investigated the suitability of inhibin as a diagnostic marker by identifying which inhibin (inhibin A (alphabetaA), inhibin B (alphabetaB), free alpha subunit) or activin (betaAbetaA) form is associated with these cancers. Available data show that inhibin assays which detect all inhibin forms, i.e. assays which detect the alpha subunit both as the free form and as an alphabeta subunit dimer provide the highest sensitivity/specificity characteristics as an ovarian cancer diagnostic test. This review will discuss the data supporting these observations and show recent studies in which a new alpha subunit monoclonal antibody-based ELISA is used as a potential diagnostic test. Furthermore, based on the high sensitivity/specificity characteristics of the respective assays for the various types of ovarian cancer, the combination of the inhibin assay with CA125 detects the majority of all ovarian cancers.

Activins↗
PubMed2002

Dinitrogen oxide production by a mixed culture of nitrifying bacteria during ammonia shock loading and aeration failure.

A number of experiments was conducted in order to establish if N(2)O in the exhaust gas from an aerobic consortium of nitrifiers could be used as an indicator for monitoring the nitrification process. Laboratory-scale experiments with an activated sludge system showed a strong correlation between ammonia shock loads and both the concentration of N(2)O and the rate of increase of N(2)O in the exhaust gas for shock loads less than 1.60 mg ammonical nitrogen (NH(3)-N) per g total suspended solids (TSS). For greater ammonia shock loads, correlation was found between build-up of nitrite in the aeration tank and the concentration of N(2)O in the exhaust gas from the tank. When subjecting the system to aeration failure, a similar pattern was seen, with a correlation between nitrite build-up in the aeration tank and increases in the concentration of N(2)O in the exhaust gas. The results from this work suggest that the changes in N(2)O concentration in the exhaust gas from a nitrifying process may be a useful parameter for monitoring such processes.

Aerobiosis↗
PubMed2002

The effects of pregnancy and maternal nutrition on the maternal renin-angiotensin system in sheep.

Physiological changes occurring in the mother during pregnancy can determine the outcome of pregnancy in terms of birthweight and neonatal viability. Maternal adaptations include plasma volume expansion linked to enhanced activity of the renin-angiotensin system (RAS). The present study was designed to determine whether these changes occur very early in gestation, and the extent to which maternal nutrient restriction may compromise the maternal RAS. Using sheep, we have investigated the effects of pregnancy per se, maternal nutrient restriction and later restoration of maternal diet on maternal body weight, plasma volume and plasma renin concentration (PRC), and angiotensinogen (Aogen) and arginine vasopressin (AVP) concentration. During the period of placental growth (i.e. 28-80 days gestation) ewes were fed either a nutrient-restricted (NR) diet or were well fed (WF). NR ewes consumed between 3.2 and 3.8 MJ day(-1) of metabolisable energy (ME) which is close to 60 % of requirements taking into account the ME required for both ewe maintenance and growth of the conceptus in order to produce a 4.5 kg lamb at term. WF ewes consumed 150 % of ME requirements. Restoration of maternal diet between 80 and 140 days gestation (i.e. fed to satiety and consuming between 8 and 10.9 MJ day(-1), which is close to 150 % of ME requirements) followed previous nutrient restriction. Between pre-conception and 28 days gestation, plasma volume increased in conjunction with a decline in PRC and Aogen concentration. During the period of nutrient restriction ewe body weight did not increase and plasma volume was lower in NR than WF ewes. During this time there was no effect of maternal nutrition on PRC; however, Aogen concentration was lower in the NR group. From 80 days gestation following the rise in food intake for previously NR ewes, greater increases in ewe body weight, plasma volume and PRC occurred up to term compared with ewes that were well fed throughout gestation. Plasma AVP concentration was not significantly affected by either maternal nutrition or gestational age. In conclusion, the stimulus of moderately severe maternal nutrient restriction evoked smaller rises in maternal weight, plasma volume and Aogen concentration than occurred in ewes that were well fed throughout gestation. Following the restoration of maternal diet after 80 days gestation, PRC gradually rose to peak at term. These adaptations in the maternal RAS during the critical period of placental growth may have long-term effects on fetal development.

Angiotensinogen↗
PubMed2002

Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy.

Generalised lipodystrophy of the Berardinelli-Seip type (BSCL) is a rare autosomal recessive human disorder with severe adverse metabolic consequences. A gene on chromosome 9 (BSCL1) has recently been identified, predominantly in African-American families. More recently, mutations in a previously undescribed gene of unknown function (BSCL2) on chromosome 11, termed seipin, have been found to be responsible for this disorder in a number of European and Middle Eastern families. We have studied the genotype/phenotype relationships in 70 affected subjects from 44 apparently unrelated pedigrees of diverse ethnic origin. In all subjects, hepatic dysfunction, hyperlipidaemia, diabetes mellitus, and hypertrophic cardiomyopathy were significant contributors to morbidity with no clear differences in their prevalence between subjects with BSCL1 or BSCL2 and those with evidence against cosegregation with either chromosome 9 or 11 (designated BSCLX). BSCL2 appears to be a more severe disorder than BSCL1 with a higher incidence of premature death and a lower prevalence of partial and/or delayed onset of lipodystrophy. Notably, subjects with BSCL2 had a significantly higher prevalence of intellectual impairment than those with BSCL1 or BSCLX (p<0.0001, OR 17.0, CI 3.6 to 79.0). The higher prevalence of intellectual impairment and the increased risk of premature death in BSCL2 compared to BSCL1 emphasise the importance of molecular diagnosis of this syndrome and have clear implications for genetic counselling.

Adolescent↗
PubMed2002

Characterization of inhibin forms and their measurement by an inhibin alpha-subunit ELISA in serum from postmenopausal women with ovarian cancer.

The aim of this study was to characterize the molecular wt forms of inhibins A and B and its free alpha-subunit present in serum from women with ovarian cancer as a basis for developing improved monoclonal antibody-based inhibin assays for monitoring ovarian cancer. Three new inhibin alpha-subunit (alphaC) ELISAs were developed using monoclonal antibodies directed to three nonoverlapping peptide regions of the alphaC region of the inhibin alpha-subunit. To characterize serum inhibin molecular wt forms present in women with ovarian cancer, existing inhibin immunoassays (inhibin A, inhibin B, and pro-alphaC) and the new alphaC ELISAs were applied to sera from women with granulosa cell tumors and mucinous carcinomas previously fractionated using a combined immunoaffinity chromatography, preparative SDS-PAGE, and electroelution procedure. The distribution and molecular size of dimeric inhibins and alpha-subunit detected were consistent with known mol wt forms of inhibins A and B and inhibin alpha-subunit and their precursor forms present in serum and follicular fluid from healthy women. The alphaC ELISAs recognized all known forms of inhibin and the free inhibin alpha-subunit, although differences between alphaC ELISAs were observed in their ability to detect high mol wt forms. To assess which of the alphaC ELISAs was preferred in application to ovarian cancer, the alphaC ELISAs were applied to serum from a range of normal postmenopausal women (n = 61) and postmenopausal women (n = 152) with ovarian (serous, mucinous, endometrioid, clear cell carcinomas, and granulosa cell tumors) and nonovarian (breast and colon) cancers. Despite differences in their ability to detect high mol wt forms of inhibin, the alphaC ELISAs showed similar sensitivity (i.e. proportion of cancer patients correctly detected) and specificity (proportion of controls correctly detected) indexes in the detection of mucinous carcinomas (84% and 95%) and granulosa cell tumors (100% and 95%) compared with earlier inhibin RIA or polyclonal antibody-based immunofluorometric assays. A combination of the alphaC ELISAs with the CA125 assay, an ovarian tumor marker that has a high sensitivity and specificity for other ovarian cancers (serous, clear cell, and endometrioid), resulted in an increase in sensitivity/specificity indexes (95% and 95%) for the all ovarian cancer group. These new monoclonal antibody-based inhibin alphaC ELISAs now provide practical and sensitive assays suitable for evaluation as diagnostic tests for monitoring ovarian cancers.

Adenocarcinoma, Mucinous↗
PubMed2002

The effect of maternal prolactin infusion during pregnancy on fetal adipose tissue development.

The present study determines whether maternal administration of prolactin (PRL) to dams promotes the abundance of the brown adipose tissue-specific uncoupling protein-1 (UCP1) in fetal and neonatal rat pups. Recombinant PRL (24 micro g/kg per day), or an equivalent volume of saline, were infused into dams (n=19 per group) throughout pregnancy from 12 h after mating. Interscapular brown adipose tissue was sampled either from fetuses at 19.5 days of gestation (term=21.5 days) or from neonatal rat pups at approximately 18 h after birth. The abundance of UCP1 was determined by immunoblotting on adipose tissue samples from individual pups and pooled from groups of pups. This analysis was complemented by immunocytochemistry on representative adipose tissue samples. Maternal PRL infusion resulted in a greater abundance of UCP1 in fetal rats at 19.5 days of gestation (control: 97.2+/-8.4% reference; PRL: 525.6+/-74.4% reference; P<0.001) and in neonates 18 h after birth. In contrast, the abundance of the outer mitochondrial membrane protein voltage-dependent anion channel was unaffected by PRL. Neonatal adipose tissue sampled from pups born to PRL-infused dams possessed fewer lipid droplets, but more UCP1, as determined by immunocytochemistry. Fetal, but not maternal, plasma leptin concentrations were also increased by maternal PRL administration. In conclusion, as rats are altricial, and the potential thermogenic activity of brown adipose tissue develops over the first few days of postnatal life, these changes prior to, and at the time of, birth implicate PRL in fetal and neonatal adipose tissue maturation.

Adipose Tissue, Brown↗
PubMed2002

Dinitrogen oxide detection for process failure early warning systems.

A number of experiments were conducted in order to establish whether the concentration of N2O in the off-gas from an activated sludge pilot plant could be used as a indicator for monitoring the nitrification process and as an early indication of ammonia appearing in the plant effluent. A strong correlation was found between ammonia shock loads and the concentration of N20 in the off-gas from the aeration tank for ammonia shock loads and dissolved oxygen depletion. When subjecting the experimental setup to doses of a nitrification inhibitor (allylthiourea) a similar pattern was seen with a correlation between nitrite build up in the aeration tank and concentration increase of N2O in the off-gas from the aeration tank. The results from this work suggest the concentration and the changes in the concentration of N2O in the exhaust gas from a nitrifying process may be a useful parameter for monitoring nitrifying activated sludge processes.

Ammonia↗
PubMed2001

Development of an inhibin alpha subunit ELISA with broad specificity.

Inhibin immunoassays with a sufficiently broad specificity to detect all alpha subunit-containing forms are of value in detecting and monitoring various ovarian cancers. Assays to date with this specificity are not readily amenable to wide diagnostic application. The objective of this study was to develop a sensitive two-site ELISA using alpha subunit-directed monoclonal antibodies (Mabs) able to detect all forms of inhibin to replace a previously described alpha subunit-directed immunofluorometric assay (IFMA). In this study, the major inhibin epitopes in the two polyclonal antisera used in the alphaC IFMA were initially identified and Mabs were raised to these regions. These Mabs in conjunction with the inhibin alpha subunit R1 Mab (Groome) were used to develop alpha subunit ELISAs with high sensitivity. Application of these assays to human serum and human follicular fluid following fractionation by an immunoaffinity/preparative PAGE/electroelution procedure which separated inhibins according to their molecular weights, indicated that the specificity of the various ELISAs differed between Mab combinations with preferences noted for either the alpha subunit or dimeric forms. A combination of Mabs in an ELISA was identified which provided data which matched that obtained with the alphaC IFMA and which may be useful as a replacement inhibin assay in clinical studies.

Animals↗
PubMed2001

The effects of media size on the performance of biological aerated filters.

Biological aerated filters (BAFs) are an attractive process option, particularly when low land usage is required. They can combine BOD, solids and ammoniacal nitrogen removal and can be utilised at both secondary and tertiary stages of wastewater treatment. Media selection is critical in the design and operation of BAFs to achieve effluent quality requirements. Two size ranges, 1.5-3.5 and 2.5-4.5 mm, of a foamed clay called StarLight C were used in pilot-scale reactors. Both performed well as BAF media, with reactor loads up to 12 kg COD m(-3) d and 4 kg suspended solids m(-3) d (based on working volumes). The most consistent effluent was obtained using the smaller medium since, at flow rates above 0.41 min(-1), the BAF using the larger medium produced an effluent containing more than 20 mg l(-1) of suspended solids for over 30 min after backwashing. Up to 70% longer run times, as determined by reaching a set head loss, were recorded for the BAF containing the larger rather than the smaller medium. Additionally, the development of pressure above the smaller medium filter bed tended to be logarithmic rather than linear. Reactor profiles indicated that suspended solids removal did not occur over the full 2.3 m depth of the columns. The BAF containing the smaller medium utilised a mean depth of 1.7 +/- 0.3 m, whereas a mean depth of 2.1 +/- 0.3 m was used by the larger medium BAF. Both the head loss development data and the suspended solids removal profiles indicated that the smaller medium BAF was underperforming as a filter.

Aerobiosis↗
PubMed2001

Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13.

Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.

Acanthosis Nigricans↗
PubMed2001

Fetal and neonatal adipose maturation: a primary site of cytokine and cytokine-receptor action.

During late gestation, the maturation of fetal adipose tissue is geared towards the synthesis of high levels of uncoupling protein 1 (UCP1), which is unique to brown adipose tissue. At birth, rapid activation of UCP1 ensures a large increase in heat production. These adaptations are nutritionally sensitive, and may be mediated in part by rapid changes in prolactin and leptin secretion after birth. Restriction of maternal nutrition reduces adipose tissue deposition, with no effect on UCP1. Increased maternal food intake results in increases in levels of UCP1 and the short form of the prolactin receptor, but in a decrease in adipose tissue content per kg of fetus. The ontogeny of the long and short forms of the prolactin receptor follows that of UCP1, to peak at birth. Then, during postnatal life, UCP1 disappears in parallel with the loss of prolactin receptors. Treatment of neonatal lambs with prolactin increases body temperature and the thermogenic potential of brown adipose tissue. In contrast, acute leptin treatment results in maintenance of colonic temperature, but chronic leptin treatment accelerates UCP1 loss. Increasing our understanding of the interaction between prolactin and leptin during perinatal development may enable the establishment of strategies aimed at maximizing adipose tissue development in order to promote metabolic adaptation to the extra-uterine environment.

Adipose Tissue↗
PubMed2001

Cytokines and cytokine receptors in fetal growth and development.

The cytokine receptors for growth hormone (GH), prolactin and leptin have a critical role in regulating embryo, placental and/or fetal development, which is dependent on stage of gestation and species. GH and prolactin receptors are detectable from conception, and alterations in the maternal hormonal environment may impact on placental growth from this early stage of gestation. Leptin is critical for conception, but its role in fetal growth remains elusive. During late gestation, when fetal growth accelerates and organ maturation occurs, prolactin and insulin-like growth factor-I may have interactive roles in regulating the growth of specific tissues, including adipose tissue. Prolactin, leptin and GH all have specific effects on fetal and neonatal energy balance, which are mediated in part through promoting lipolysis and/or enhancing the expression of uncoupling proteins. An increased understanding of these interactions is likely to have important implications for a number of potentially pathological conditions, including infection, obesity and hypertension.

Animals↗