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Biomedical subjects

J E Scott

Publications and source records attributed to J E Scott.

At least 37 records · Page 2Linked to original sources
PubMed1999

Severe polyethylene wear in uncemented acetabular cup system components: a report of 5 cases.

We report 5 cases of severe failure of the polyethylene liner at 4 to 7.4 years after uncemented anatomic medullary locking (AML) total hip arthroplasty, using the acetabular cup system (ACS). The mode of failure was by a combination of wear-through to the metal backing and liner fracture. Four of the 5 cases were associated with a 32-mm head. The ACS design is flawed because of a lack of hemispherical geometry resulting in rim loading on a region of the liner that has the thinnest polyethylene. All patients with this type of implant should be monitored for evidence of excessive polyethylene wear.

Acetabulum↗
PubMed1999

Screening for fetal urological abnormalities: how effective?

OBJECTIVE: To analyse urological cases registered with the Northern Congenital Abnormality Survey (NorCAS) and thus assess antenatal diagnostic sensitivity, measure regional interhospital variation and determine whether antenatal ultrasonography has contributed to the prevention of urinary tract disease in childhood. METHODS: All notification documents forwarded to NorCAS from its inception in 1984 until 31 December 1996 were inspected and those relating to urological abnormalities were abstracted. Information about postnatal progress was often missing. Twenty-three hospitals delivering maternity services were identified and randomly allocated a code letter a-w. Data were analysed in two periods, 1984-90 and 1991-96. To quantify hospital performance an 'expected number' for each hospital was calculated from the overall incidence per 1000 births and the number of births in each hospital. RESULTS: There was a clear improvement in antenatal diagnostic sensitivity for the major urological abnormalities in the second period, but there was considerable variation among hospitals in the number of cases notified; this applied particularly to antenatal renal dilatation. Two hospitals notified significantly more cases in this category than all the others. The difference in notification rates among hospitals was caused by diagnoses such as vesico-ureteric reflux (VUR), pelvi-ureteric junction obstruction and megaureter, which often produce antenatal renal dilatation. Hospitals which notified more of these cases performed more micturating cystograms and identified more children with VUR. Measurements of the fetal renal pelvis were regularly made by only seven hospitals; one of these had difficulties with postnatal follow-up. There was evidence that moderate degrees of antenatal renal dilatation (4-10 mm) were associated with VUR; 8.5% of the children in whom VUR was diagnosed had fetal renal dilatation of this order. CONCLUSION: Antenatal renal dilatation and its significance are either not being recognized or not appreciated in some hospitals. The high incidence of VUR in cases with moderate antenatal renal dilatation indicates that children with this condition may be escaping diagnosis.

Dilatation, Pathologic↗
PubMed1998

Human cells unable to express decoron produced disorganized extracellular matrix lacking "shape modules" (interfibrillar proteoglycan bridges).

The shapes of extracellular matrices are determined by positioning collagen fibrils in the right places, oriented and maintained viv-à-vis each other. The fibrils are linked orthogonally by dermatan/chondroitin sulfates or keratan sulfate (in small proteoglycans) attached every approximately 65 nm via their protein moieties to collagen fibrils at specific binding sites. These regular repeating structures are the "shape modules." The characteristic arrays of orthogonal interfibrillar bridges were missing and the extracellular matrix was totally disorganized in matrices produced by fibroblasts taken postmortem from skin of an electively aborted fetus which did not express decoron in culture, thus supporting the shape module hypothesis. Biglycon, dermatan sulfate, heparan sulfate, collagen, and hyaluronan were produced by these cells but did not contribute to a normal extracellular matrix. A similar electron histochemical and biochemical survey of extracellular matrices produced by seven normal and eight osteogenesis imperfecta cell lines from donors of different ages and both sexes showed no comparable disruptions of their matrices. This investigation appears to be the first to demonstrate systematically proteoglycan:collagen interactions in matrices produced by cultured human cells.

Adult↗
PubMed1998

Risk of congenital anomalies near hazardous-waste landfill sites in Europe: the EUROHAZCON study.

BACKGROUND: Waste-disposal sites are a potential hazard to health. This study is a multicentre case-control study of the risk of congenital anomalies associated with residence near hazardous-waste landfill sites in Europe. METHODS: We used data from seven regional registers of congenital anomalies in five countries. We studied 1089 livebirths, stillbirths, and terminations of pregnancy with non-chromosomal congenital anomalies and 2366 control births without malformation, whose mothers resided within 7 km of a landfill site; 21 sites were included. A zone within 3 km radius of each site was defined as the "proximate zone" of most likely exposure to teratogens. FINDINGS: Residence within 3 km of a landfill site was associated with a significantly raised risk of congenital anomaly (295 cases/511 controls living 0-3 km from sites, 794/1855 living 3-7 km from sites; combined odds ratio 1.33 [95% CI 1.11-1.59], adjusted for maternal age and socioeconomic status). There was a fairly consistent decrease in risk with distance away from the sites. A significantly raised odds ratio for residence within 3 km of a landfill site was found for neural-tube defects (odds ratio 1.86 [1.24-2.79]), malformations of the cardiac septa (1.49 [1.09-2.04]), and anomalies of great arteries and veins (1.81 [1.02-3.20]). Odds ratios of borderline significance were found for tracheo-oesophageal anomalies (2.25 [0.96-5.26]), hypospadias (1.96 [0.98-3.92]), and gastroschisis (3.19 [0.95-10.77]). There was little evidence of differences in risk between landfill sites but power to detect such differences was low. INTERPRETATION: This study shows a raised risk of congenital anomaly in babies whose mothers live close to landfill sites that handle hazardous chemical wastes, although there is a need for further investigation of whether the association of raised risk of congenital anomaly and residence near landfill sites is a causal one. Apparent differences between malformation subgroups should be interpreted cautiously.

Case-Control Studies↗
PubMed1998

The blistering diseases.

The intent and purpose of the authors is to familiarize the reader with the principles that govern the diagnosis and management of autoimmune mucocutaneous blistering diseases. The purpose was not to be all-inclusive but illustrative. There are several other blistering diseases that have not been discussed because of the limited scope of this article. Of these, toxic epidermal necrolysis, erythema multiforme, and the like warrant the same attention and early recognition. These are covered in different articles. For the same reasons, certain genetically linked blistering diseases have not been discussed.

Autoimmune Diseases↗
PubMed1998

The role of calnexin in NK-target cell interaction.

In this study, a relationship between target cell sensitivity to natural killing and target cell expression of the molecular chaperone++ calnexin was assessed. The NK-resistant cell line NKR was originally derived from the NK-sensitive, human T-cell line CEM and does not synthesize calnexin protein or mRNA. The cell lines CEM, NKR and 1B9 (NKR transfected with a calnexin cDNA) were compared in a number of assays. All the lines but CEM were resistant to NK in conventional 4 h cytotoxicity assay, but were highly sensitive to IL-2 activated NK. Incubation of NK cells with CEM but not with the other two lines led to increased expression of the NK cell activation marker CD69. Treatment of effector cells with PGE2 and TGF-beta resulted in an inhibition of NK activity and CD69 expression. The calnexin transfected clone 1B9 clone had intermediate ability to block cytotoxicity in cold target inhibition assay compared to CEM and NKR. Expression of the adhesion molecules CD44 and LFA-1alpha was significantly higher on both calnexin positive cell lines compared to NKR. These data suggest that calnexin controls the expression of some, but not all, target structures that are necessary for binding and activation of NK cells.

CD11 Antigens↗
PubMed1998

The structure of interfibrillar proteoglycan bridges (shape modules') in extracellular matrix of fibrous connective tissues and their stability in various chemical environments.

Collagen fibrils in extracellular matrices of connective tissues (tendon, cornea, etc.) are bridged and linked by the anionic glycosaminoglycans (AGAGs) of the small proteoglycans (decoron, etc.). It was proposed that these bridges and ties maintain the collagen fibril dispositions in relation to each other, helping to define tissue shape, and hence called shape modules. This investigation describes chemical and physicochemical conditions in which these structures are stable and what treatments cause their disruption. The effects on fixed and unfixed sections of tendon, cornea, lung and ear from rat, mouse and rabbit of pH, electrolyte concentration, EDTA, mercaptoethanol, hydrogen peroxide, free radicals, periodate, acetylation, urea, nonionic detergent and organic solvents were assessed by staining with Cupromeronic blue or Alcec blue in CEC techniques to localise AGAG bridges or their disintegration products. Ca2+ was not involved in the structures, oxidation/reduction had no effect and Triton X100, a nonionic detergent did not damage them. They were stable between pH 4.5 and 9.5. Periodate as a glycol-cleaving reagent did not affect them. High concentrations of urea (> 2.0 M) and MgCl2 (0.5 M) disrupted the tissues. The combination of Triton and urea at concentrations too low to cause damage separately was disruptive. Free radicals in periodate solutions were damaging. Organic solvents caused collapse and rearrangements of the AGAG filaments. Acetylation caused considerable disruption of shape modules. Dermochondan but not keratan sulphate AGAGs were removed by treatment with NaOH. After fixing with glutaraldehyde only free radical and NaOH treatments were severely disruptive of shape modules. The results are compatible with a previously proposed structure for the shape modules, stabilised by hydrophobic and hydrogen bonding.

Acetylation↗
PubMed1998

How rational histochemistry produced order out of chaos in the "amorphous ground substance" (with a little help from biochemistry, biophysics etc.).

From an amorphous ground substance containing polymers of unknown composition arranged in no particular pattern we have in about 50 years arrived at a proposal where the very shape of the tissue and hence of the organism is determined by newly discovered structures, the shape modules, in the ground substance, which were demonstrated by histochemical techniques interpreted on rational biophysical and chemical principles.

Histocytochemistry↗
PubMed1998

Effects of Stachybotrys chartarum (atra) conidia and isolated toxin on lung surfactant production and homeostasis.

This study evaluated the effects of Stachybotrys chartarum conidia and a trichothecene, isosatratoxin-F, on choline incorporation into DSPC by fetal rabbit alveolar type II cells and on alveolar surfactant subtypes in mice. Exposure of fetal rabbit type II cells to S. chartarum conidia at concentrations of 10(3) to 10(6) conidia ml(-1) significantly depressed [3H] choline incorporation after 24 h of exposure. Exposure of the rabbit cells to 10(5) to 10(6) conidia ml(-1) also resulted in significantly depressed [3H] choline uptake after 48 h. Additionally, fetal rabbit alveolar type II cells exposed to isosatratoxin-F in concentrations ranging from 10(-9) to 10(-4) M showed a significant reduction in [3H] choline incorporation into DSPC. Alveolar surfactant phospholipid concentrations in the different metabolic subfractions of lung lavage fluid of mice intratracheally exposed to either 50 microl of 10(7) ml(-1) S. chartarum conidia or 50 microl 10(-7) M isosatratoxin-F showed some significant changes at 12, 24, 48, and 72 h post-exposure, compared to the surfactant subfractions of control mice which were either untreated, exposed to saline or to 50 microl of 10(-7) ml(-1) Cladosporium cladosporioides conidia. In both the S. chartarum- and the isosatratoxin-F-treated mice, exposure significantly increased P10, P100, and S100 phospholipid concentrations, while the P60 phospholipid concentrations were depressed. In contrast, C. cladosporioides-treated mice showed only one significant change in subfraction phospholipid concentration: P60 was depressed at 48 h post-exposure. These results reveal that alveolar type II cells are sensitive to exposure to S. chartarum conidia and to isosatratoxin F. Sensitivity is manifest by alterations in the normal metabolic processing of alveolar surfactant. In exposed mice, this effect appears to involve a significant increase in newly secreted surfactant and an accumulation of the used surfactant forms.

Analysis of Variance↗
PubMed1997

Methylmercury-induced alterations in lung and pulmonary surfactant properties of adult mice.

Exposure to methylmercuric chloride (MMC) has been shown to significantly affect development of the lung and pulmonary surfactant system of the fetus. Preliminary results suggest it may also affect adult lung and associated bronchoalveolar lavage (BAL), which represents the extracellular surfactant pool. To determine if mercury exposure has the potential to alter surfactant function, adult mice were treated with MMC, 15 mg/kg by intragastric intubation on 4 successive days. BAL was collected by repeated intratracheal lavage 24 h after the last treatment. Nucleated cell numbers in lavage were determined. Tissue was prepared for scanning electron microscopy (SEM). Lavage fluid was extracted into chloroform:methanol and phospholipid concentration determined. A sample of the extract was used at a constant phospholipid concentration to measure surface activity on a bubble surfactometer. Lung weight to body weight ratio increased whereas total numbers of nucleated cells in BAL were not altered by MMC. SEM of samples from lungs of animals exposed to MMC showed normal architecture. Surface tension measurements suggest that the mean time to minimum surface tension and the minimum surface tension were greater in BAL from mice exposed to MMC for 4 days. In addition samples of BAL were prepared for Fourier-transform infrared spectrophotometry (FT-IR). Spectra showed changes in both lipid and protein components of BAL. Morphometric analyses of micrographs showed that mean alveolar diameter was reduced and wall thickness increased after mercury exposure. These results suggest that methylmercury exposure may significantly affect surface tension characteristics and composition of BAL, possibly through leakage of edematous interstitial tissue.

Animals↗
PubMed1997

Screening of newborn babies for familial ureteric reflux.

BACKGROUND: Vesicoureteric reflux (VUR) is not usually diagnosed until it is complicated by urinary infection. Prevention probably requires diagnosis in a newborn baby before urinary infection occurs because the peak incidence for infection is in early infancy. VUR is a familial disorder. We sought to find out whether an at-risk group of newborn babies could be identified on the basis of the parents' family history. METHODS: Over a 3-year period, pregnant women attending the antenatal clinics of three hospitals in the northeast of England were screened for evidence of urinary-tract disease in themselves or their families with a view to eliciting a history of VUR. When a woman, her partner, or a member of either family had a definite (by cystography records) or probable positive history, we recruited the mother to our study. Renal ultrasonography and cystography were done on the newborn babies soon after delivery, and a dimercaptosuccinic acid (DMSA) radioisotope scan at 3 months was done on those with VUR. FINDINGS: The estimated number of deliveries during the study period was 34,555; 20,891 women were screened; and 211 were recruited and delivered. The index cases were identified from a wide range of family relationships, though over half consisted of mothers and siblings, 19 babies had more than one index case and in 21 families there was one index for more than one baby or a link between families. Cystography was carried out on 186 newborn babies; 38 (20.4%) had VUR. The proportion of newborn babies with VUR among linked index families was 31%. Mothers and siblings amounted to 71% of the index cases for newborn babies with VUR. The difference between confirmed and assumed index cases in VUR prediction was not significant. The female/male sex ratio among index cases was more than 4, but among newborn babies with VUR it was 1.5. Renal ultrasound showed no correlation with VUR, and all DMSA scans but one were normal. No newborn baby developed complications resulting from cystography. INTERPRETATION: The screening of pregnant women for familial VUR is worthwhile because the frequency of VUR among the newborn babies of those with such a history is significantly higher than in the general population (frequency of VUR 1-2%), particularly if the family history involves more than one member, or more than one generation.

Female↗
PubMed1997

Dynamic equilibrium between calcineurin and kinase activities regulates the phosphorylation state and localization of the nuclear factor of activated T-cells.

The nuclear factor of activated T-cells (NFATp) is a phosphorylated transcription factor that resides in the cytoplasm of unactivated T-cells. T-cell activation results in the activation of the phosphatase calcineurin (CaN), which leads to the dephosphorylation and subsequent nuclear localization of NFATp. We have investigated the role of kinases in the phosphorylation state and subcellular localization of NFATp. The phosphorylation state and nuclear/cytoplasmic location of NFATp were determined in unstimulated murine HT-2 cells treated with a panel of kinase inhibitors. Two of the seven kinase inhibitors, staurosporine (St) and bisindolylmaleimide I (BI), resulted in the dephosphorylation and nuclear localization of NFATp. These St-induced effects were inhibited by pretreatment with FK506, indicating that CaN activity was required for the observed effects on NFATp. Treatment of cells with ionomycin resulted in NFATp dephosphorylation and nuclear localization. Removal of ionomycin from the cells resulted in the reappearance of phosphorylated NFATp in the cytosol. St and BI also inhibited the re-accumulation of NFATp in the cytoplasm and its re-phosphorylation after ionomycin removal. The re-accumulation of NFATp in the cytosol after ionomycin withdrawal was shown to be energy- and temperature-dependent. Taken together, these results suggest that in unstimulated cells NFATp is actively maintained in the cytoplasm by kinases acting in opposition to basal CaN activity.

Animals↗
PubMed1997

Osteogenesis imperfecta mutations may probe vital functional domains (e.g. proteoglycan binding sites) of type 1 collagen fibrils.

Osteogenesis imperfecta (OI) is a disease characterized by bone malformations caused by mutations in type 1 collagen. Since many of the 338 possible glycine mutations have not been observed in clinical practice, is this due to chance alone? Because only 83 mutations have been reported in 126 patients, we conclude that many mutations are absent from clinical data for non-random causes. Mutations affecting vital intermolecular interactions in the extracellular matrix (e.g. potential collagen binding sites for proteoglycans) may result in non-viable fetuses that do not progress to clinical status. Some mutations may be silent because they do not significantly affect normal function. The total number of clinically active mutations that will be observed may be far fewer than the potential 338 maximum.

Binding Sites↗
PubMed1997

Modification of the Staphylococcus aureus fibronectin binding phenotype by V8 protease.

The amount of cell surface fibronectin (Fn)-binding protein (FnBP) adhesin expressed by Staphylococcus aureus is maximal during exponential growth but disappears rapidly as the culture progresses into stationary phase. To identify factors responsible for the loss of cell surface FnBP, a culture of S. aureus L170, which shows high levels of Fn binding, was supplemented at the time of inoculation with concentrated stationary-phase supernatant from S. aureus L530, a strain which binds Fn poorly. The resulting exponential-phase cells were devoid of FnBP. The factor responsible for this activity was purified from the culture supernatant and identified as V8 protease. When cultured with 375 ng of exogenous V8 protease ml(-1), exponential-phase cells of S. aureus L170 were devoid of cell surface FnBP, and concentrations as low as 23 ng x ml(-1) resulted in reduced amounts of FnBP. Addition of the protease inhibitor alpha2-macroglobulin to the culture medium prevented the growth-phase-dependent loss of cell surface FnBP, whereas growth with exogenous V8 protease resulted in reduced adherence to the solid-phase N-terminal fragment of Fn and to the extracellular matrix synthesized by fetal rabbit lung fibroblasts. Although FnBP was extremely sensitive to V8 protease, exogenous protease did not exert a significant influence on the amount of cell surface protein A. However, a limited number of other high-molecular-weight cell surface proteins were also sensitive to V8 protease. Therefore, both the adhesive phenotype and cell surface protein profile of S. aureus can be modified by V8 protease activity.

Adhesins, Bacterial↗
PubMed1996

Proteodermatan and proteokeratan sulfate (decorin, lumican/fibromodulin) proteins are horseshoe shaped. Implications for their interactions with collagen.

The small proteoglycans proteodermatan and proteokeratan sulfates organize collagen fibrils in extracellular matrix [Scott, J. E. (1992) FASEB J. 6, 2639-2645], thus helping to maintain tissue shape. Their interaction with fibrils is probably via the protein. They have been examined by rotary shadowing-electron microscopy, which showed that these leucine-rich-repeat proteins are horseshoe shaped. Morphometry and comparison with polypeptide sequences suggest ways in which decorin could interact with tissue collagen fibrils. It is proposed that decorin is a bidentate ligand attached to two parallel neighboring collagen molecules in the fibril, helping to stabilize fibrils and orient fibrillogenesis.

Amino Acid Sequence↗