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Biomedical subjects

R Wiggins

Publications and source records attributed to R Wiggins.

At least 19 recordsLinked to original sources
PubMed2005

Person, place or time? The effect of individual circumstances, area and changes over time on mortality in men, 1995-2001.

This article uses the ONS Longitudinal Study to explore, for a cohort of adult males who were aged 26 or over in 1971, the relative influence on mortality in 1995-2001 of their place of residence and individual socioeconomic circumstances, at three censuses over a 20-year period. Factors examined in this analysis include social class, neighbourhoo deprivation (at ward level), unemployment, residence in the South East region in 1971 or 1981 housing tenure, and change in social class and housing tenure between 1971 and 1991. The variation in mortality attributable to the local authority district of residence in 1991 was also investigated.

Adult↗
PubMed2003

Social inequalities in health by individual and household measures of social position in a cohort of healthy people.

STUDY OBJECTIVE: It is increasingly recognised that different dimensions of social inequality may be linked to health by different pathways. Furthermore, factors operating at the individual level such as employment conditions may affect health in a different way from household level factors. The paper examines the associations between self rated health and four measures of social position- occupational class, household social advantage, personal and household income. DESIGN: Multilevel logistic regression models were used to predict self rated health using longitudinal data from the British Household panel survey (BHPS) with respondents nested within households. Separate analyses were carried out for economically active and inactive respondents. SETTING: Interview based surveys of adults living within households that are representative of British households. PARTICIPANTS: Adult respondents from the BHPS. MAIN RESULTS: Occupational class has relatively strong effects on the self rated health of the economically active, although household level factors also seem to influence their health. Household social advantage has relatively strong effects on the self rated health of the economically inactive. CONCLUSIONS: The paper found evidence in support of the view that different dimensions of social inequality have different pathways to self rated health. There are unexplained similarities in health between household members, which require further investigation.

Adolescent↗
PubMed2002

Application of a novel human cervical mucin-based assay demonstrates the absence of increased mucinase activity in bacterial vaginosis.

Enzymes produced in bacterial vaginosis (BV) have been proposed as possible mediators of pre-term birth. Most studies have concentrated on mid-trimester measurements of enzyme activity, and utilize synthetic substrates to measure enzyme activity, which may not accurately represent mucinase activity in vivo. We have developed a novel ELISA mucinase assay using biotinylated human cervical mucin as a substrate. The assay is rapid, sensitive and can be used to screen large numbers of samples. The new assay has been used to assess vaginal mucinase activities in 92 women <14 weeks gestational age with and without BV. No differences in mucinase activity were detected between normal and BV groups while significant elevation of sialidase and other glycosidases was confirmed as reported before. This study shows that significant mucinase activity is a normal event in the mucus barrier, but does not reflect changes identified for individual enzyme activities associated with BV.

Adolescent↗
PubMed2001

Study status consistency and duplicate-read protection in a distributed architecture.

UNLABELLED: This presentation will discuss the benefits and pitfalls of implementing a study status and duplicate-read protection mechanism within a distributed picture archiving and communication system (PACS) architecture. There are many advantages to a distributed PACS network in which image studies are proactively pushed to reading stations before they are required by a radiologist. The absence of a central server, which serves on demand, makes managing study status and protecting against duplicate reads challenging. The system to manage study status and read access must be efficient, robust, and easy to administer. A system is presented that accomplishes these goals while maintaining the advantages of a distributed architecture. METHODS: The basic workflow of the system is that image studies acquired at a modality device are automatically sent to an archive server. Using a set of advanced routing rules, the archive automatically routes studies to diagnostic workstations where studies are candidates for diagnostic read. The workstations display a list of all local studies available for reading. A monitor application running on the workstations coordinates access to studies for diagnostic read. Once the status of a study has been changed, the workstations on the networks and the archive are notified, which causes the study to be automatically removed from any list on a workstation where it might be a read candidate. RESULTS: Implementation of this system provides a balanced workflow throughout the system while minimizing the need for costly high-speed network hardware. Additionally studies are read as soon as they are available by the next available radiologist. This workflow is enabled without the need for specific interaction by any of the radiologists on the network. By having the images available at the workstation in an organized worklist, this methodology increases the efficiency of the radiologist. CONCLUSION: The implementation of this system enables a radiology department, or even a specialty group within a department, to gain the benefit of a distributed system as well as the benefits provided by a central-server architecture. This can be done very cost effectively with minimal configuration overhead and hardware requirements.

Computer Systems↗
PubMed2001

Podocyte depletion and glomerulosclerosis have a direct relationship in the PAN-treated rat.

BACKGROUND: Podocytes are highly differentiated glomerular epithelial cells with limited potential to divide. They are responsible for maintaining and supporting the glomerular basement membrane so as to facilitate efficient filtration. The hypothesis tested was whether the development of glomerulosclerosis in the puromycin aminonucleoside (PAN)-treated rat could be attributed to podocyte depletion. METHODS: PAN was injected in Sprague-Dawley rats once, twice, or three times at 30-day intervals. Podocytes were counted in glomeruli using immunoperoxidase histochemistry and antibodies to both GLEPP1 (PTPRO) and WT-1. Podocytes were assayed in urine using reverse transcription-quantitative polymerase chain reaction (RT-QPCR). Glomerular areas were measured by computerized morphometry. RESULTS: In a preliminary experiment, a single injection of PAN caused a reduction in the glomerular podocyte count by 25%. Additional independent confirmation that podocytes were lost from glomeruli after PAN injection was obtained identifying detached podocytes in Bowman's space, measurement of nephrin and GLEPP1 mRNAs in urine, ultrastructural analysis of glomeruli, and identification of TUNEL-positive apoptotic podocytes in glomeruli. In a second experiment, sequential podocyte depletion by 15, 31, and 53% was achieved by the administration of one, two, or three injections of PAN at 30-day intervals. The region of the glomerulus devoid of podocytes developed glomerulosclerosis, and this area progressively increased as podocytes were progressively depleted. The correlation coefficient (r(2)) value for the relationship between percent podocyte depletion and glomerulosclerotic area was 0.99. The Y intercept of this plot showed that glomerulosclerosis was initiated when only 10 to 20% of podocytes were lost. CONCLUSION: This report supports the growing body of data linking glomerulosclerosis directly to a reduction in relative podocyte number [increased glomerular area per podocyte (GAPP)]. It raises important questions related to the mechanisms of podocyte loss, strategies for prevention of podocyte depletion, and the prevention of progression of glomerular diseases.

Animals↗
PubMed2001

Cryptosporidium meleagridis from humans: molecular analysis and description of affected patients.

OBJECTIVES: To genetically characterize an unusual genotype of Cryptosporidium from the stools of humans with diarrhoea and to identify risk factors in the affected patients. METHODS: DNA was extracted from human faeces where Cryptosporidium oocysts were detected by light microscopy. Cryptosporidial gene fragments from six different loci were analysed by PCR alone, PCR/RFLP and by DNA sequencing. Oocysts were characterized by light and immunofluorescence microscopy and epidemiological data was collected from the affected patients. RESULTS: Analysis of the Cryptosporidium oocyst wall protein (COWP) gene amplified from > 2000 human faecal samples identified 19 patients all of which produced an unusual RFLP profile. Subsequent DNA sequence analysis of this and an additional four genetic loci (including 18S rRNA sequences) confirmed these as a homogeneous group which was genetically distinct from Cryptosporidium parvum. The isolates were identified as Cryptosporidium meleagridis since the gene sequences were identical to those from this species recovered from birds. Conventional microscopy showed oocysts indistinguishable from C. parvum and reacted strongly with two different commercially available anti-oocyst monoclonal antibodies. None of the patients showed risk factors unusual for cryptosporidiosis; however, ten of the cases occurred during the summer/autumn, six had a history of foreign travel, four were co-infected with Giardia, two were HIV positive, and six were without identifiable immunocompromising factors. CONCLUSIONS: This study further confirms that C. meleagridis, in addition to C. parvum, is involved in human disease. The study also highlights the lack of basic information on the host range of this genus of parasites, the complexity of the transmission routes involved in human cryptosporidiosis, and the value of molecular techniques in identify hitherto unrecognised differences in Cryptosporidium from human faeces.

Adolescent↗
PubMed2001

Mucinases and sialidases: their role in the pathogenesis of sexually transmitted infections in the female genital tract.

BACKGROUND: Mucinases and sialidases contribute to the process of invasion and colonisation in many conditions and infections of the female reproductive tract by degrading the protective cervical mucus. The role of hydrolytic enzymes in the pathogenesis of sexually transmitted diseases and their effect on cervical mucus are discussed in this review. METHODS: Articles were searched for using the keywords "sialidase," "mucinase," "protease," and "sexually transmitted infections." As well as review and other articles held by our group, searches were conducted using PubMed, Grateful Med, and the University of Bath search engine, BIDS. RESULTS: Numerous publications were found describing the production of hydrolytic enzymes in sexually transmitted diseases. Because the number of publications exceeded the restrictions imposed on the size of the review, the authors selected and discussed those which they considered of the most relevance to sexually transmitted infections.

Cervix Mucus↗
PubMed2000

Use of 5-bromo-4-chloro-3-indolyl-alpha-D-N-acetylneuraminic acid in a novel spot test To identify sialidase activity in vaginal swabs from women with bacterial vaginosis.

The validity of measuring vaginal sialidase activity to identify bacterial vaginosis (BV) was determined by using 5-bromo-4-chloro-3-indolyl-alpha-D-N-acetylneuraminic acid in a near-patient test. The sensitivity and specificity of the test for prediction of BV were 95.6 and 96.3%, respectively. Positive and negative predictive values were 95.6 and 96.3%, respectively. This test may be an alternative to Gram staining.

Adolescent↗
PubMed1999

Mucinase and sialidase activity of the vaginal microflora: implications for the pathogenesis of preterm labour.

Evidence linking bacterial vaginosis (BV) to chorioamnionitis and spontaneous preterm birth is mounting. Successful treatment of BV could reduce the rate of late miscarriage and preterm birth. Mucinase and sialidase activity have been implicated in the pathogenesis of BV. This study extends the work of previous studies to investigate sialidase, other known mucin degrading enzymes and overall mucin degrading activity in samples of vaginal fluid from women with and without BV. Samples from 31 women were diagnosed for BV, and tested for enzyme activity using established assays. Activity was recorded in all samples. Significant increases in activity were detected in BV samples for sialidase using a mucin (BSM P<0.005) and serum type glycoprotein (AGP P<0.005) substrates, beta-galactosidase (P<0.001), and beta-N-acetylhexosaminidase (P<0.01). No significant increases in BV patients were detected in O-glycanase, proteinase, arylesterase, sulphatase or whole mucinase activities. These results support the hypothesis that certain BV-associated enzymes may detrimentally affect the mucosal barrier, permitting bacteria access to the uterus.

Bacterial Proteins↗
PubMed1998

A large outbreak of cryptosporidiosis associated with a public water supply from a deep chalk borehole. Outbreak Investigation Team.

Three hundred and forty-five confirmed cases were reported in a large waterborne outbreak of cryptosporidiosis in North Thames in the spring of 1997. The descriptive epidemiology, attack rates, a case control study, and the detection of oocysts in the water suggested strongly that the outbreak was associated with drinking unboiled tap water that originated from one deep chalk borehole. The 746,000 people living in the water distribution area were advised to boil their drinking water. Investigations did not reveal how oocysts entered the borehole. This is the first published report of a cryptosporidium outbreak caused by filtered borehole water and we believe it to be the largest outbreak due to groundwater to have been reported. Borehole supplies are regarded as relatively pure sources of water and this outbreak has implications for the future monitoring and treatment of drinking water extracted from boreholes.

Adolescent↗
PubMed1996

Glomerular epithelial protein 1 and podocalyxin-like protein 1 in inflammatory glomerular disease (crescentic nephritis) in rabbit and man.

The podocyte is the cell responsible in large part for maintaining the glomerular filtration barrier. Glomerular epithelial protein 1 (GLEPP1) is a novel receptor-like transmembrane protein tyrosine phosphatase present on the apical surface of podocyte foot processes. Podocalyxin-like protein 1 (PCLP1) is a transmembrane sialoglycoprotein which is also present on the foot process apical surface as well as on the surface of endothelial cells. GLEPP1 and PCLP1 are thought to play a role in regulating the structure and function of podocyte foot processes. Glomerular injury affecting the podocyte is likely to be reflected by changes in these proteins. GLEPP1 distribution in human renal biopsy with inflammatory glomerular disease and crescent formation was examined by immunocytochemistry. A model of inflammatory glomerular injury induced by guinea pig anti-rabbit basement membrane (anti-GBM) antibody was used to examine the distribution and amount of GLEPP1 and PCLP1 mRNA and protein. A biopsy study was done to determine whether the extent of GLEPP1 depletion from glomeruli at early time points (Day 7) would predict the severity of crescent formation at Day 30. Glomeruli from human renal biopsies with crescentic nephritis showed focal to diffuse disappearance of GLEPP1 protein. No GLEPP1 was present within the cellular crescent. By Day 4 of the rabbit anti-GBM model, before cellular crescents had formed, GLEPP1 protein was reduced from 127 +/- 28 X 10(7) to 30 +/- 5 X 10(7) molecules per glomerulus (p < 0.001), and GLEPP1 mRNA was reduced by 62% (p < 0.05). In contrast, at this time there was no significant reduction of PCLP1 protein from the normal number of 309 X 10(9) molecules per glomerulus and the PCLP1 mRNA level had not decreased. At Day 4, podocyte foot processes were effaced and proteinuria was present. Glomerular culture supernatants from Day 4 rabbits caused a reduction in GLEPP1 but not PCLP1 protein expression by cultured normal glomeruli, showing that a soluble factor was produced at Day 4 which reduced the number of GLEPP1 molecules in glomeruli. There was no detectable proteolysis of GLEPP1 or PCLP1 in glomeruli and no increase in GLEPP1 or PCLP1 excretion in urine. Therefore, the reduction in glomerular GLEPP1 was associated with reduced synthetic capacity. The proportion of glomeruli with reduced GLEPP1 at Day 7 of the model was significantly associated with the percent of glomeruli which had formed crescents at Day 30 (r = 0.86, p < 0.0001). GLEPP1 appears to be a sensitive indicator of glomerular injury during inflammation in man and in the rabbit model. A reduction in amount of GLEPP1 is associated with worse outcome for the glomerulus.

Animals↗
PubMed1996

Fibronectin is the major fibroblast chemoattractant in rabbit anti-glomerular basement membrane disease.

The mechanism for fibroblast recruitment in renal fibrosis due to anti-glomerular basement membrane (anti-GBM) disease is unknown. Since fibroblast recruitment can occur via chemotaxis, assessment of the possible production of fibroblast chemotactic activity by affected renal tissue and its identification could provide important clues. Anti-GBM disease was induced by injection of guinea pig anti-rabbit GBM immunoglobulin G into rabbits previously sensitized to guinea pig immunoglobulin G. On days 4, 7, and 14 after induction, renal tissue was harvested and glomeruli isolated. Overnight serum-free conditioned media from whole cortex and glomeruli were prepared and assayed for fibroblast chemotactic activity. The results show low level activity in both conditioned media from control animals. In contrast, conditioned media from anti-GBM-treated animals at all time points showed significantly elevated fibroblast chemotactic activity peaking on day 4 with subsequent reduction thereafter. The magnitude of increase in cortical conditioned media was significantly higher than that for glomerular conditioned media, suggesting that most of the activity was derived from extraglomerular sources. Gel filtration analysis revealed the activity to be heterogeneous, consisting of at least four major species with estimated molecular weights ranging from 10 to > 100 kd. Acidification of conditioned media failed to increase chemotactic activity significantly, whereas protease digestion abolished it. Treatment of conditioned media with antifibronectin inhibited > 85% of the chemotactic activity, whereas antibodies to platelet-derived growth factor and transforming growth factor-beta did not have a significant effect. These findings taken together suggest that fibronectin-derived peptides represent the predominant fibroblast chemoattractant produced by renal cortex in anti-GBM disease.

Animals↗
PubMed1993

Urine transforming growth factor-beta activity is related to the degree of scarring in crescentic nephritis in the rabbit.

Crescentic nephritis was induced in rabbits by injection of antirabbit glomerular basement membrane (GBM) antibodies. Urine samples were obtained by catheterization and assayed for transforming growth factor-beta (TGF-beta) activity. On day 31, all animals were sacrificed for evaluation of renal cortical histopathology and collagen content. The results show that control rabbit urine contains measurable amounts of TGF-beta. Urine TGF-beta activity was expressed in relation to urine creatinine concentration to correct for variation in urine concentration. When expressed in this manner, urine TGF-beta activity increased from day 2 onwards, peaked on day 7 and returned to normal levels after day 14. This time course is identical to that previously seen for the cortical and glomerular production of TGF-beta in the same model. Furthermore, when the normalized TGF-beta values for each animal were compared to their respective fibrosis parameters on day 31, significant correlations were observed for the values of urine TGF-beta activities on day 7 and all indices of fibrosis. These results suggest that measurements of urine TGF-beta activity at certain critical stages of disease could be useful in predicting the progression to end-stage renal disease with fibrosis and might serve as a helpful noninvasive adjunct in monitoring response to therapy.

Animals↗
PubMed1993

Vascular adventitial cell expression of collagen I messenger ribonucleic acid in anti-glomerular basement membrane antibody-induced crescentic nephritis in the rabbit. A cellular source for interstitial collagen synthesis in inflammatory renal disease.

BACKGROUND: Scarring in the interstitial compartment of the renal cortex heralds a poor prognosis in many forms of renal injury, however, the mechanism through which glomerular inflammation leads to interstitial scarring is not understood. In a model of anti-GBM disease in the rabbit, development of crescentic glomerulonephritis is associated with marked interstitial fibrosis and decreased renal function. We previously demonstrated that collagen accumulation in the model was preceded by increases in collagen I and IV mRNA and that these changes were primarily extraglomerular at early time points when inflammation was predominantly intraglomerular. In order to identify the cellular origins of extraglomerular collagen synthesis in this model, in situ hybridization using an alpha 2(I) procollagen probe was performed. EXPERIMENTAL DESIGN: A 602 bp rabbit alpha 2(I) procollagen cDNA was cloned using a PCR strategy and sequenced. The nucleotide sequence of the coding region was 94% identical with the human alpha 2(I) procollagen sequence. Northern blots were performed to define conditions of specific hybridization of the anti-sense riboprobe. Tissue sections from normal rabbit kidneys and from kidneys 4, 5, 7, 10 and 14 days after injection of anti-GBM antibody were hybridized with 35S-labeled sense and anti-sense riboprobes. Cells containing alpha 2(I) mRNA were identified by autoradiography and mRNA abundance was quantitated by grain density. RESULTS: No specific hybridization was detected with the sense probe at any time. alpha 2(I) mRNA was undetectable with the anti-sense probe in normal kidney sections. In contrast, the anti-sense probe hybridized specifically at all time points after induction of anti-GBM disease. In agreement with previous filter hybridization studies, on day 4, when inflammation was predominantly intraglomerular, cells in the periarterial adventitial compartment of renal cortex hybridized strongly. At later time points, labeling was also present in the interstitial spaces, the periglomerular region, in Bowman's space and in the glomerular tuft itself. CONCLUSIONS: We conclude that perivascular adventitial cells are among the first to respond to glomerular inflammation and represent a pool of cells that subsequently contribute to interstitial and glomerular scarring.

Amino Acid Sequence↗
PubMed1991

Fibronectin mRNA and protein accumulation, distribution, and breakdown in rabbit anti-glomerular basement membrane disease.

Fibronectin is a multifunctional matrix protein which by immunofluorescence appears to be present in increased amounts during glomerular injury. To examine fibronectin metabolism in glomerular injury, an anti-glomerular basement membrane model that progresses to severe glomerular crescent formation, glomerulosclerosis, and interstitial fibrosis was used. Fibronectin was purified from rabbit plasma, and a monoclonal antibody raised against rabbit fibronectin was used for immunolocalization and quantitation of fibronectin protein. RNA and protein were extracted from isolated glomeruli and whole renal cortex at various times during progression of disease. At day 4, there was a 2.5-fold increase in fibronectin protein which by immunofluorescence appeared to be in the glomerular mesangial area. There was no increase in glomerular fibronectin mRNA at this time. This discrepancy is consistent with the conclusion that, at this early time point, the increased glomerular fibronectin comes predominantly from plasma. By day 7, glomerular fibronectin mRNA and extractable fibronectin protein were increased in association with bright immunofluorescence along the inner aspect of Bowman's capsule where early crescents were forming. Similarly, at day 14, crescents stained very brightly for fibronectin. These results are consistent with the conclusion that, at later time points, fibronectin is synthesized in glomeruli in association with cell division and crescent formation. Degradation of fibronectin in glomerular and cortical extracts was demonstrated under normal and nephritic conditions by finding fibronectin proteolytic fragmentation by Western blot.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Analysis of T cells and major histocompatibility complex class I and class II mRNA and protein content and distribution in antiglomerular basement membrane disease in the rabbit.

The major interacting components of the immune system, major histocompatibility complex (MHC) class I and class II proteins and T cells were analyzed in a model of anti-GBM (glomerular basement membrane) disease in the rabbit that progresses to develop cellular crescents and glomerular and interstitial fibrosis. Class I and II mRNA and protein were measured in isolated glomeruli and whole renal cortex using cDNA probes and monoclonal antibodies. The distribution of T cells and class I and II proteins was assessed by immunofluorescence. Normal glomeruli contained no T cells and were class II negative. By day 4, glomeruli contained MHC class I and II mRNA and protein and class II positive T cells. Although some animals had T cells in the periglomerular area, these cells were class II negative. By day 7 periglomerular T cells were largely class II positive (activated) and there was increased MHC class I and II mRNA and protein in whole renal cortex. Later T cells accumulated in the tubulo-interstitial compartment, which became diffusely positive for MHC classes I and II, but to a variable extent in different animals. Those with high class II mRNA expression also had detectable T cell antigen receptor mRNA by Northern analysis. The authors conclude 1) in this model there was a close association between mRNA abundance and protein expression for both MHC classes I and II in glomeruli and renal cortex as a whole; 2) in this model of glomerular injury there are three phases of activation. The first phase takes place in the glomerulus and is associated with accumulation of activated T cells and MHC class I and II protein in the glomerulus. Phase 2 is associated with the accumulation of periglomerular T cells and their becoming class II positive. There is subsequent dissemination (phase 3) of activated T cells and accumulation of class I and II mRNA and protein throughout the interstitial compartment. This spacial progression of glomerulocentric inflammation is likely associated with degree of injury and permanent loss of renal function.

Animals↗