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Biomedical subjects

S Clark

Publications and source records attributed to S Clark.

At least 37 records · Page 2Linked to original sources
PubMed2002

Occurrence and distribution of infection-specific PrP in tissues of clinical scrapie cases and cull sheep from scrapie-affected farms in Shetland.

The prion protein (PrP) genotypes of all cull sheep originating from four scrapie-affected farms in Shetland in 1998-1999 were determined and a representative sample of the different genotypes was selected for necropsy. Samples of brain and selected viscera were removed from 159 such sheep aged 2-11 years. These samples were examined immunohistochemically and by Western blotting for infection-specific forms of PrP. None of the sheep bearing the following genotypes showed any evidence of PrP accumulation in brain, intestine, selected lymph nodes or the cranial mesenteric ganglia: ARQ/ARQ (n = 41), ARQ/ARH (n = 12), ARH/ARH (n = 2), ARQ/ARR (n = 24), ARR/ARR (n= 2). In five of 71 sheep bearing a single VRQ allele, PrP accumulation was detected immunohistochemically in viscera or brain, or both. These results suggested that only a small proportion of susceptible sheep showed evidence of infection (accumulation of PrP) on the farms studied, and that even sheep of the most susceptible genotype (VRQ/VRQ) did not invariably develop disease in an infected environment. Furthermore, there was no evidence that, in sheep of semi-resistant or fully resistant genotypes, infection could be sequestered within the lymphoreticular system or peripheral nervous system and thereby provide a possible "carrier" source of infection. Rather, the data suggested that some sheep, possibly because they had been exposed to a relatively low infective dose, became infected and accumulated the infective agent over a protracted pre-clinical phase of the disease. Such sheep might be potentially infective for many years. In two VRQ/ARR genotype sheep, PrP was confined to the brain. Infection-specific PrP was also confined to the brain in two of 24 clinical cases of VRQ/ARQ scrapie. Thus, direct neuroinvasion, apparently without a prior phase of replication in the lymphoreticular system, occurred in a proportion of VRQ/ARQ sheep. Possibly it may occur in all sheep of the VRQ/ARR genotype. The factors responsible for direct neuroinvasion are not understood. However, it cannot be attributed to genotype alone.

Animals↗
PubMed2002

Tumorigenicity of cellulose fibers injected into the rat peritoneal cavity.

Cellulose fibers, along with many other organic fibers, are durable. Therefore, if inhaled, they have the potential to persist within the lung, and may then cause disease. Here we report the effects of injecting high-purity cellulose fibers into the abdominal cavity of rats. A respirable fraction of cellulose fiber was collected from an aerosol of a thermo-mechanically-processed wood pulp. A sample of respirable crocidolite asbestos, known to produce mesotheliomas in rats, was used as a positive control. Total doses of 10(6), 10(7), 10(8), or 10(9) WHO fibers were injected intraperitoneally as 3 weekly aliquots. A negative control was provided by phosphate-buffered saline used to suspend the fibers for injection. There were 50 rats per treatment group except for the 10(8) and 10(9) fibers crocidolite groups which were reduced to 26 rats because of the expectation of high tumor incidence in these groups. The two higher doses of crocidolite asbestos caused greatly reduced survival compared to the saline controls. With cellulose there was a much less marked effect on survival. In the highest dose cellulose group, multiple large nodules (granulomas) and widespread adhesions (bands of new tissue connecting organs to each other and to the abdominal wall) were present in all animals. Granulomas were not observed in the 10(9) fibers crocidolite group. More than 80% of animals in the 10(8) and 10(9) crocidolite asbestos groups had mesotheliomas, a type of tumor sometimes observed in people exposed to asbestos. In contrast, there were only 2 animals in the cellulose groups with mesothelioma tumors, 1 in the 10(7) and 1 in the 10(8) groups. However, 9 (18%) of the 10(9) cellulose group had malignant tumors that, in contrast to the usual pattern of mesothelioma development following treatment with mineral fibers in rats, showed no obvious involvement of mesothelial tissues, were not associated with blood-stained ascites fluid, and were thus classified as sarcomas. This study has demonstrated that a high dose of cellulose fibers is capable of producing tumors when injected into the abdominal cavity of rats.

Air Pollutants, Occupational↗
PubMed2002

Can transcutaneous bilirubinometry reduce the need for blood tests in jaundiced full term babies?

BACKGROUND: Previous studies have suggested that transcutaneous bilirubinometry (TcB) may provide a useful method for screening for significant jaundice, thereby reducing unnecessary blood tests. These studies have not allowed an estimation of the magnitude of such a benefit. OBJECTIVES: To evaluate the accuracy of TcB as a method of determining the need for serum bilirubin (SBR) measurements in full term babies and to quantify the magnitude of any benefit. SUBJECTS: Babies born at more than 34 weeks gestation who had not previously been exposed to phototherapy and were requiring blood sampling in the first week of life. METHOD: TcB measurements were made at the same time as blood sampling. SBR was measured in all blood samples. For jaundiced babies, the ability of TcB to detect significant jaundice (SBR > 249 micromol/l) was evaluated. RESULTS: There was a correlation between SBR and TcB measurements (n = 303, r = 0.76, p < 0.0001), but the 95% prediction interval for SBR from TcB was wide (+/- 88.3 micromol/l). For the 285 jaundiced babies, the area under the receiver operator characteristic curve was 0.89. A TcB value of 18 detected significant jaundice with a sensitivity of 100% and a specificity (95% confidence interval) of 45% (39% to 51%). If blood samples had only been taken from babies with a TcB value greater than 18, the number of samples taken would have been reduced by 34%. CONCLUSIONS: SBR cannot be measured accurately by TcB. However, TcB measurements can be used to determine the need for blood sampling in jaundiced babies and will reduce the number of blood samples taken. Recent improvements in TcB may improve the performance of this method.

Bilirubin↗
PubMed2001

Crossover phase behavior (discotic to calamitic) in liquid-crystalline copper complexes. Dependence on the length and position of alkoxy chains in new polycatenar bis[5-(dialkoxybenzylidine)aminotropololonato]copper(II) complexes.

New polycatenar metallomesogens have been synthesized containing a tropolone core joined to benzylidine terminal rings. Variation of the position, number, and nature of alkoxy substituents on the terminal rings allows for the control of the phase behavior of the compounds. In particular, for copper complexes with 3,4-dialkoxy substitution, a change from calamitic to discotic (columnar) behavior is seen as the chain lengths are increased.

Journal Article↗
PubMed2001

The role of Ca2+ in insulin-stimulated glucose transport in 3T3-L1 cells.

We have examined the requirement for Ca2+ in the signaling and trafficking pathways involved in insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Chelation of intracellular Ca2+, using 1,2-bis (o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra (acetoxy- methyl) ester (BAPTA-AM), resulted in >95% inhibition of insulin-stimulated glucose uptake. The calmodulin antagonist, W13, inhibited insulin-stimulated glucose uptake by 60%. Both BAPTA-AM and W13 inhibited Akt phosphorylation by 70-75%. However, analysis of insulin-dose response curves indicated that this inhibition was not sufficient to explain the effects of BAPTA-AM and W13 on glucose uptake. BAPTA-AM inhibited insulin-stimulated translocation of GLUT4 by 50%, as determined by plasma membrane lawn assay and subcellular fractionation. In contrast, the insulin-stimulated appearance of HA-tagged GLUT4 at the cell surface, as measured by surface binding, was blocked by BAPTA-AM. While the ionophores or ionomycin prevented the inhibition of Akt phosphorylation and GLUT4 translocation by BAPTA-AM, they did not overcome the inhibition of glucose transport. Moreover, glucose uptake of cells pretreated with insulin followed by rapid cooling to 4 degrees C, to promote cell surface expression of GLUT4 and prevent subsequent endocytosis, was inhibited specifically by BAPTA-AM. This indicates that inhibition of glucose uptake by BAPTA-AM is independent of both trafficking and signal transduction. These data indicate that Ca2+ is involved in at least two different steps of the insulin-dependent recruitment of GLUT4 to the plasma membrane. One involves the translocation step. The second involves the fusion of GLUT4 vesicles with the plasma membrane. These data are consistent with the hypothesis that Ca2+/calmodulin plays a fundamental role in eukaryotic vesicle docking and fusion. Finally, BAPTA-AM may inhibit the activity of the facilitative transporters by binding directly to the transporter itself.

3T3 Cells↗
PubMed2001

Limited phase I study of morphine-3-glucuronide.

The toxicity of morphine-3-glucuronide (M3G) has been investigated in an open, uncontrolled, single-blinded, single dose study over a limited range of doses. Three cohorts each of three healthy volunteers received 7.5, 15, and 30 mg/70 kg intravenous (IV) M3G. Blood sampling was undertaken for the following 24 h. Subjective toxicity was recorded on visual analogue scales and plasma M3G concentrations measured by a specific HPLC assay. Virtually no effects and no change in cardiovascular or respiratory parameters were seen. The pharmacokinetics fitted a two-compartment model. The mean elimination half-life (+/- S.D.) of M3G was 1.66 (+/- 0.47) h. Mean AUC standardized to a dose of 1 mg/70 kg was 228 (+/- 62) etamolL(-1) x h. Mean M3G clearance was 169 (+/- 48) mLmin(-1) and the mean volume of distribution was 23.1 (+/- 4.8) liters. At the doses investigated there were no clear neuroexcitatory effects, no opioid effects, and the pharmacokinetics were very similar to those of morphine-6-glucuronide (M6G).

Adult↗
PubMed2001

Evaluation of the HUD lead hazard control grant program: early overall findings.

This study evaluates the effectiveness of lead hazard control methods used in the Lead Hazard Control (LHC) grant program of U.S. Department of Housing and Urban Development. The LHC Program awards funds to local jurisdictions to address lead hazards in privately owned, low-income dwellings. Grantees in 14 cities, states, or counties collected environmental data in over 2600-treated dwellings making this the largest study of residential lead hazard control ever undertaken. Grantees employed a range of treatments, the most common being replacement of windows and repair of deteriorated lead-based paint. In this paper, dust lead loading levels and blood lead levels of children (6 months-6 years, if present) were observed at four periods of time (preintervention, immediate, and 6- and 12-months postintervention) in 1212 dwellings. Dust lead loading levels were also observed in a subset of these dwellings at 24- and 36-months postintervention. The geometric mean floor and window dust lead loadings declined at least 50 and 88% (P<0.0001), respectively, immediately postintervention. Three years later, floor dust lead loadings remained at or below the immediate postintervention levels. Window dust lead loadings had moderate increases, but remained substantially reduced from preintervention levels and below clearance standards. At 1 year after intervention, geometric mean age-adjusted blood lead levels had declined from 11.0 to 8.2 microg/dL, a 26% decline (P<0.0001). The LHC Program interventions produced blood lead declines similar to or greater than the percentage changes reported in earlier 1-year lead intervention studies.

Child↗
PubMed2001

Long-term stability of nutrients in a frozen mixed food control material.

A mixed food homogenate was prepared as a quality control material for two multi-center clinical feeding trials. Approximately 100 kg of homogenized human diet material was prepared under controlled conditions to maintain the stability of lipid components. More than 4,800 20-25 g aliquots were prepared and stored at -60 degrees C in glass jars with Teflon-lined lids. The homogeneity of the composite was validated by analysis of moisture and total fat in aliquots taken throughout the dispensing sequence. A portion of the material was reserved at the National Institute of Standards and Technology and further characterized as SRM 1544-Fatty Acids in Diet Composite. Moisture, protein, ash, total lipid, fatty acids, cholesterol, sodium, potassium, calcium, and magnesium were assayed as part of routine quality-control analyses. Components were analyzed over a total time period ranging from 29 months (minerals) to 60 months (moisture), and up to 319 values per nutrient were generated. Results for all components assayed were stable over the time period studied. For example, moisture (n = 319; 60 months) ranged from 70.66 to 72.58 g/100 g with a mean, standard deviation (SD), and relative standard deviation (RSD) of 71.90, 0.27, and 0.4%, respectively. The range, mean, SD, and RSD for cholesterol (mg/100 g; n = 98; 49 months) were 13.54-17.96, 15.14, 0.64, and 4%.

Diet↗
PubMed2001

Coral bleaching and mortality on artificial and natural reefs in Maldives in 1998, sea surface temperature anomalies and initial recovery.

The bleaching and subsequent mortality of branching and massive corals on artificial and natural reefs in the central atolls of Maldives in 1998 are examined with respect to sea surface temperature (SST) anomalies. SST normally peaks in April-May in Maldives. The UK Meteorological Office's Global sea-Ice and SST data set version 2.3 b shows that in 1998 monthly mean SST was 1.2-4 S.D. above the 1950-1999 average during the warmest months (March-June), with the greatest anomaly in May of +2.1 degrees C. Bleaching was first reported in mid-April and was severe from late April to mid-May with some recovery evident by late-May. At least 98% of branching corals (Acroporidae, Pocilloporidae) on artificial structures deployed on a reef flat in 1990 died whereas the majority of massive corals (Poritidae, Faviidae, Agariciidae) survived the bleaching. The pre-bleaching coral community on the artificial reefs in 1994 was 95% branching corals and 5% massives (n = 1589); the post-bleaching community was 3% branching corals and 97% massives (n = 248). Significant reductions in live coral cover were seen at all natural reefs surveyed in the central atolls, with average live coral cover decreasing from about 42% to 2%, a 20-fold reduction from pre-bleaching levels. A survey of recruitment of juvenile corals to the artificial structures 10 months after the bleaching event showed that 67% of recruits (> or = 0.5 cm diameter) were acroporids and pocilloporids and 33% were from massive families (n = 202) compared to 94% and 6%, respectively, in 1990-1994 (n = 3136). Similar post-bleaching dominance of recruitment by branching corals was seen on nearby natural reef (78% acroporids and pocilloporids; 22% massives). A linear regression of April mean monthly SST against year was highly significant (p < 0.001) and suggests a rise of 0.16 degree C per decade. If this trend continues, by 2030 mean April SST in the central atolls will normally exceed the anomaly level at which corals appear there are susceptible to mass bleaching.

Animals↗
PubMed2001

Circular polarisation in star-forming regions: possible implications for homochirality.

Our discovery of high degrees of circular polarisation in some star-forming regions provides an attractive mechanism for the origin of homochirality. The largest degrees of circular polarisation, so far observed at near-infrared wavelengths, are thought to arise from the scattering of stellar radiation from aligned dust grains and are calculated to extend down to UV wavelengths. The extent of the region where circularly polarised light (CPL) of a single handedness originates is very large, and it is likely that the whole of a planetary system would see a single handedness of CPL also. We present the observational data, models of the scattering that leads to the production of CPL, and a model for the origin of homochirality. We also discuss briefly future laboratory and space-based experiments.

Astronomical Phenomena↗
PubMed2001

Beta-lactoglobulin molten globule induced by high pressure.

Beta-lactoglobulin (beta-LG) was treated with high hydrostatic pressure (HHP) at 600 MPa and 50 degrees C for selected times as long as 64 min. The intrinsic tryptophan fluorescence of beta-LG indicated that HHP treatment conditions induced a conformational change. HHP treatment conditions also promote a 3-fold increase in the extrinsic fluorescence of 1-anilinonaphthalene-8-sulfonate and a 2.6-fold decrease for cis-paraneric acid, suggesting an increase in accessible aromatic hydrophobicity and a decrease in aliphatic hydrophobicity. Far-ultraviolet circular dichroism (CD) spectra reveal that the secondary structure of beta-LG converts from native beta-sheets to non-native alpha-helices following HHP treatment, whereas near-ultraviolet CD spectra reveal that the native tertiary structure of beta-LG essentially disappears. Urea titrations reveal that native beta-LG unfolds cooperatively, but the pressure-treated molecule unfolds noncooperatively. The noncooperative state is stable for 3 months at 5 degrees C. The nonaccessible free thiol group of cysteine121 in native beta-LG became reactive to Ellman's reagent after adequate HHP treatment. Gel electrophoresis with and without beta-mercaptoethanol provided evidence that the exposed thiol group was lost concomitant with the formation of S-S-linked beta-LG dimers. Overall, these results suggest that HHP treatments induce beta-LG into hydrophobic molten globule structures that remain stable for at least 3 months.

Electrophoresis, Agar Gel↗
PubMed2001

Features of carnitine palmitoyltransferase type I deficiency.

Carnitine palmitoyltransferase type I (CPT I) is unique among long-chain fatty acid oxidation enzymes in that there are two tissue-specific isoforms, 'hepatic' and 'muscle', which are encoded by two separate genes. The 'hepatic' isoform is expressed in liver, kidney and fibroblasts and at low levels in the heart, while the other isoform occurs in skeletal muscle and is the predominant form in heart. Reported patients with CPT I deficiency lack activity of the hepatic isoform and present before 30 months of age with hypoketotic hypoglycaemia, hepatomegaly with raised transaminases, seizures and coma. We discuss four new cases in three families showing, variously, renal tubular acidosis, transient hyperlipidaemia and, paradoxically, myopathy with elevated creatinine kinase or cardiac involvement in the neonatal period as additional features that deserve wider recognition.

Acidosis, Renal Tubular↗
PubMed2001

Expression and function of the Drosophila ACT88F actin isoform is not restricted to the indirect flight muscles.

Most higher eukaryotic genomes contain multiple actin genes, yet the sequence differences between isoforms are few. In Drosophila melanogaster it was previously established that one of the six actin genes, Act88F, is expressed only in the indirect flight muscles (IFMs). These muscles are highly specialised for oscillatory contractions to power flight. The implication was that this isoform had tissue-specific properties. In this paper we show using two reporter constructs expressing either beta-galactosidase, Act88F-lacZ, or the green fluorescent protein, Act88F-GFP, that the Act88F promoter is active in a small number of other muscles, including leg (femoral) and uterine muscles. However, the levels of Act88F driven non-IFM expression are much less than in the IFMs. We have confirmed endogenous Act88F gene expression in these other muscles by in situ hybridisation studies. Using null and antimorphic mutants to show decreased walking ability and delayed/reduced oviposition we demonstrated that Act88F expression is functionally important in multiple muscle groups. Since the mutant effects are mild, this supports the expectation that other actin genes are also expressed in these muscles. The Act88F-GFP promoter-reporter also detects Act88F-driven expression in the bristle-forming cells in the pupal wings. The implications of these results for the functions and developmental expression of the Drosophila ACT88F isoform are discussed.

Actins↗
PubMed2001

Bereavement after suicide--how far have we come and where do we go from here?

This paper identifies major issues faced by the bereaved, the community, and the helping professions after a suicide. Some significant milestones in knowledge and service provision that have been achieved so far are discussed. It considers how past research in the fields of suicide postvention and general bereavement have developed new variables and frameworks with which to find a way forward in understanding this neglected field. The new standards of care and public policy are described that are anticipated in the light of these insights.

Adaptation, Psychological↗
PubMed2001

A prospective study of the workload of a newly formed PEG advice team.

BACKGROUND: A multidisciplinary advice team may be the optimal way of providing the long-term nutritional and percutaneous endoscopic gastrostomy (PEG)-related care for patients dependent on PEG feeding but the workload involved is unknown. AIM: To study prospectively the workload of a proactive, multidisciplinary PEG advice team over a 2-year period. METHODS: Separate documentation from main case notes of each episode of the team's contact with PEG or potential PEG patients, including assessment, advice and therapy given, from the time of its establishment, for four consecutive 6-monthly periods. RESULTS: During the audit, 89 patients were referred to the team for consideration of PEG insertion and PEGs were placed in 74. Eighty-nine additional patients were referred for follow up having had a PEG placed elsewhere. During the four audit periods the rate of new PEG insertions increased by 53%, the rate of PEG replacements by 315%, and the number of patients under the team increased from 16 to 70, an increase of 337%. Numbers of inpatient and outpatient consultations, and visits to other institutions by members of the team increased commensurately. CONCLUSIONS: The rapidly increasing workload of the team suggests it is playing a valued role but there are significant resource implications.

Enteral Nutrition↗