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D Smith

Publications and source records attributed to D Smith.

At least 145 records · Page 8Linked to original sources
PubMed2001

Ubiquitin-activating enzyme (E1) isoforms in lens epithelial cells: origin of translation, E2 specificity and cellular localization determined with novel site-specific antibodies.

Lens development and response to peroxide stress are associated with dramatic changes in protein ubiquitination, reflecting dynamic changes in activity of the ubiquitin-activating enzyme (E1). Two isoforms of E1 (E1A and E1B) have been identified in lens cells although only one E1 mRNA, containing three potential translational start sites, has been detected. Novel, site-specific antibodies to E1 were generated and the hypothesis that the two isoforms of E1 are translated from alternative initiation codons of a single mRNA was tested. Antibodies raised against E1A-N peptide (Met(1)to Cys(23)of E1A) reacted only with E1A by immunoblot and immunoprecipitation. Antibodies raised against E1B-N peptide (Met(1)to Glu(25)of E1B or Met(41)to Glu(65)of E1A) and E1AB-C peptide (His(1030)to Arg(1058)of E1A or His(990)to Arg(1018)of E1B) reacted with both E1A and E1B. These results indicate that (1) E1A and E1B contain the same C-terminal residues; (2) E1A contains the N terminal sequence of E1B; and (3) E1B does not contain the N terminal sequence of E1A. The two isoforms of lens E1 are therefore translated from a single mRNA. Specifically, E1A is translated from the first initiation codon, and E1B translated from the second initiation codon. E1A and E1B were affinity-purified, and their ability to 'charge' ubiquitin carrier proteins (E2s) with activated ubiquitin was compared in a cell-free system. E1A and E1B were indistinguishable with respect to charging different E2s. However, E1 immunolocalization studies with human lens epithelial cells indicate that E1A and E1B are preferentially localized to the nucleus and cytosol, respectively. This observation suggests that E1A and E1B ubiquitinate different proteins and serve different functions in intact cells.

Animals↗
PubMed2001

Intra-amygdala injection of the substance P [NK(1) receptor] antagonist L-760735 inhibits neonatal vocalisations in guinea-pigs.

The involvement of the basolateral amygdala in mediating the inhibition of neonatal vocalisation by substance P (NK(1) receptor) antagonists was examined. These studies determined whether the time course for separation-induced vocalisations in guinea-pig pups coincided with NK(1) receptor internalisation (a marker of substance P release) in the amygdala, and whether vocalisations could be blocked by focal injection of the NK(1) receptor antagonist L-760735 into this brain region. The peak period for neonatal vocalisations occurred 5-10 min following maternal separation. This coincided with the peak increase in the number of cells in the basolateral amygdala exhibiting NK(1) receptor endocytosis, consistent with the proposal that substance P is released in the amygdala as a result of isolation stress. Focal injection of L-760735 (15 nmol per side) but not L-770765 (an analogue of L-760735 which has low NK(1) receptor affinity) into the basolateral amygdala attenuated separation-induced vocalisations. In contrast, injection of L-760735 (15 nmol per side) into the dorsal ventricular nucleus of the thalamus, a region with relatively low density of NK(1) receptors, had no effect on neonatal vocalisations. These findings are consistent with other evidence that the amygdala is one possible site of action for the inhibition of neonatal vocalisations by substance P antagonists.

Amygdala↗
PubMed2001

Identifying and separating the effects of practice and of cognitive ageing during a large longitudinal study of elderly community residents.

In protracted longitudinal studies of cognitive changes in old age volunteers must be repeatedly tested. Even with intervals of several years between assessment, this raises the possibility that improvements due to practice mask other changes. This problem is much more acute in brief studies of cognitive changes associated with progressive pathologies such as Alzheimer's disease or the effects of clinical interventions. Both types of study also encounter problems of selective dropout of frail and less able individuals leaving relatively 'elite' survivors. An analysis of data from repeated testing at 2-3 years intervals on the AH4 (1) intelligence test is presented to illustrate how a random effects model can be used to identify and disassociate age-related changes and practice effects at the population level, after effects of selective dropout and of background demographical variables have been taken into consideration. This analysis also provides some new, substantive empirical findings. Age-related changes are relatively slight between 49 and 70 years but much more marked between 70 and 80 years. Even with assessment points, several years apart the population average effect of practice is large relative to that of age-related change. Variation between individuals increases as samples age, providing the first clear evidence from a longitudinal study for marked individual differences in trajectories of cognitive ageing.

Age Factors↗
PubMed2001

Biliary dysplasia as a marker of cholangiocarcinoma in primary sclerosing cholangitis.

BACKGROUND/AIMS: Indentification of biliary dysplasia in a primary sclerosing cholangitis (PSC) liver biopsy may indicate developing cholangiocarcinoma. The objectives were to determine whether biliary dysplasia can be recognised reproducibly in PSC and to compare the frequency in cases with and without cholangiocarcinoma. METHODS: Liver biopsies from 26 PSC cases with concurrent or subsequent cholangiocarcinoma (within 2 years) were assessed for biliary dysplasia independently by three liver pathologists. This was done in two stages: initially, without agreement on criteria, and subsequently after such agreement. Liver biopsies from 60 PSC cases without cholangio-carcinoma were also assessed. RESULTS: Reproducibility for biliary dysplasia without prior agreement on criteria was only marginally better than random (kappa=0.129). In contrast, after prior agreement on criteria, reproducibility was moderate (kappa=0.44). Biliary dysplasia was agreed to be present by all three pathologists in 23% and 19% of biopsies in the first and second round, respectively, from patients with cholangiocarcinoma, but in none of the patients without cholangiocarcinoma. CONCLUSION: Criteria for biliary dysplasia can be agreed and the entity recognised in liver biopsies. The strong association of biliary dysplasia with cholangiocarcinoma in PSC suggests use of dysplasia as a marker for current or developing malignancy.

Adult↗
PubMed2001

Quantitative selected ion flow tube mass spectrometry: the influence of ionic diffusion and mass discrimination.

Selected ion flow tube mass spectrometry, (SIFT-MS), involves the partial conversion of mass-selected precursor ions to product ions in their reactions with the trace gases in an air sample that is introduced into helium carrier gas in a flow tube. The precursor and product ions are then detected and counted by a downstream quadrupole mass spectrometer. Quantification of particular trace gases is thus achieved from the ratio of the total count rate of the product ions to that for the precursor ions. However, it is important to appreciate that in this ion chemistry the light precursor ions (usually H3O+ ions) are invariably converted to heavier product ions. Hence, the product ions diffuse to the flow tube walls more slowly and thus they are more efficiently transported to the downstream mass spectrometer sampling orifice. This phenomenon we refer to as diffusion enhancement. Further, it is a well-known fact that discrimination can occur against ions of large mass-to-charge ratio, (m/z), in quadrupole mass spectrometers. If not accounted for, diffusion enhancement usually results in erroneously high trace gas concentrations and mass discrimination results in erroneously low concentrations. In this experimental investigation, we show how both these counteracting effects can be accounted for to increase the accuracy of SIFT-MS quantification. This is achieved by relating the currents of ions of various m/z that arrive at the downstream mass spectrometer sampling orifice disc to their count rates at the ion detector after mass analysis. Thus, both diffusion enhancement and mass discrimination are parameterized as a function of m/z and these are combined to provide an overall discrimination factor for the particular analytical instrument.

Journal Article↗
PubMed2001

Outcome of women admitted to hospital for depressive illness: factors in the prognosis of severe depression.

BACKGROUND: A previous study of women 9 months after discharge from in-patient treatment for depression found that low self-esteem as measured by a self-report questionnaire at admission was associated with a worse prognosis. This study investigates the womens' outcome more than 4 years after discharge and the continued prognostic relevance of self-esteem and other variables. METHOD: Fifty-six women who had been admitted to hospital with major depression and studied in detail during their admission and 9 months following discharge were traced 4-5 years later. Possible prognostic factors were investigated in relation to time to recovery and recurrence, and to a global outcome measure. RESULTS: In keeping with other published work only 16 out of 52 (31%) women had recovered and remained well. Fifteen out of 52 (29%) subjects had experienced depressive symptoms for more than 70% of the follow-up time or died from unnatural causes. Low self-esteem scores recorded at the initial admission correlated with slow recovery but not subsequent recurrence of depression. The occurrence of one or more life events in the year preceding admission was associated with a better prognosis. CONCLUSIONS: The poor long-term prognosis of many women with severe depression was confirmed. Social factors, such as social support and marital relationships were less important for prognosis than in previous studies of less severely ill subjects. The prognostic value of self-esteem warrants further investigation and appears to have therapeutic implications.

Adult↗
PubMed2001

Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts.

As part of the DaNeX study, the uptake and binding of several positron emitting tracers was recorded in brain of healthy Göttingen minipigs, in minipigs with a syndrome of parkinsonism due to MPTP intoxication, and in parkinsonian minipigs which had received intrastriatal grafts of mesencephalic neurons from fetal pigs. The specific binding of [11C]NS 2214 to catecholamine uptake sites was reduced by two thirds in striatum of the intoxicated animals, while the rate constant for the decarboxylation of [18F]fluorodopa was reduced by 50% in the intoxicated animals. Several months after grafting, both pre-synaptic markers of dopamine fibres were normal in striatum. Dopamine depletion or grafting were without effect on the cerebral perfusion rate, measured with [15O]-water, did not alter the rate of oxygen metabolism (CMRO2) in brain, and did not alter the binding potential of tracers for dopamine D1 or D2 receptors in pig striatum. However, the grafting was associated with a local increase in the binding of [11C]PK 11195, a tracer for reactive gliosis, suggesting that an immunological reaction occurs at the site of graft, which might potentially have reduced the graft patency. However, this apparent immunological response did not preclude the re-establishment of normal [18F]fluorodopa and [11C]NS 2214 uptake in the allografted striatum.

Animals↗
PubMed2001

Brain natriuretic peptide increases urinary albumin and alpha-1 microglobulin excretion in Type 1 diabetes mellitus.

UNLABELLED: Atrial natriuretic peptide (ANP) increases urinary albumin excretion in Type 1 diabetes mellitus (DM). Brain natriuretic peptide (BNP) is structurally and functionally related to ANP, but its effect on urine albumin excretion rate (UAER) is unknown. AIMS: To compare the albuminuric effects of intravenous infusion of ANP and BNP, and to assess the effect of both peptides on tubular protein excretion. METHODS: Eight subjects with Type 1 DM were randomised to a three leg, double blind, and placebo controlled study. On each study day, subjects were euglycaemic clamped and subsequently water loaded (20 mL/kg orally, plus urine losses) to steady state diuresis. When in steady state, creatinine clearance was estimated in three separate 1 hour periods. At the end of the first period, a 1 hour intravenous infusion of either placebo, ANP 0.025 microg/kg/min, or BNP 0.025 microg/kg/min was administered. There followed a 1 hour recovery period. Urine was collected at 15 min intervals for estimation of urine albumin (ACR) and alpha1 microglobulin creatinine ratio (MCR). Results were analysed by anova. RESULTS: Creatinine clearance was similar on the three study days, and was unaltered by any infusion. ACR was unaltered by placebo (1.3 +/- 0.5-1.2 +/- 0.4 mg/mmol, mean +/- SD, p = 0.81), but increased compared to placebo with infusion of both ANP (1.2 +/- 0.4-9.8 +/- 8.4 mg/mmol, P = 0.0004), and BNP (1.1 +/- 0.4-13.4 +/- 8.6 mg/mmol, P = 0.0001). The MCR was unaltered by placebo infusion (P = 0.89), but increased compared with placebo after infusion of ANP (5.4 +/- 0.9-12.3 +/- 4.2 mg/mmol, P < 0.0001), and BNP (5.4 +/- 0.8-12.1 +/- 2.5 mg/mmol, P < 0.0001). CONCLUSIONS: Intravenous infusion of BNP and ANP both increase the urine excretion of albumin and the tubular protein alpha1 microglobulin, independent of creatinine clearance.

Adult↗
PubMed2001

A randomized trial comparing the effectiveness and preference of a touch-screen computer system with a leaflet for providing women with information on urinary symptoms suggestive of detrusor instability.

OBJECTIVES: To evaluate how well women learned and retained information given to them by either a leaflet or a computer-generated information system, and which system they preferred to use for obtaining information about urinary symptoms. SUBJECTS AND METHODS: Forty women answered 11 questions on the aetiology, investigation and treatment of lower urinary tract symptoms. They were then randomized to use one of the information systems for 20 min, after which they answered the same urological questions. The women then crossed over to use the other information system for 20 min and afterwards completed a preference questionnaire. RESULTS: The mean baseline scores from a possible total of 11 were 3.9 and 4.3 for the computer and leaflet groups, respectively. The mean improvements in scores were 3.6 (P < 0.001) and 2.8 (P < 0.001) for the computer and leaflet groups, respectively. Both information systems were well liked by all of the women and 26 (65%) said they would prefer to use a computer-generated system in the future if given a choice. CONCLUSIONS: Women significantly increased their knowledge of urinary problems after using a computer-generated information system or a leaflet. Although there were few subjects, there appeared to be a trend for the computer system to be both better liked and slightly more effective.

Adult↗
PubMed2001

Therapeutic vaccination (p24-VLP) of patients with advanced HIV-1 infection in the pre-HAART era does not alter CD4 cell decline.

In a randomized placebo controlled trial 304 HIV infected patients with CD4 cell counts below 350 cells/microL received therapeutic vaccination with: alum placebo (Group I, n = 102), p24-VLP 500 microg (Group II, n = 101) or p24-VLP 1000 microg (Group III, n = 101) p24-VLP monthly for six months. Over one year the average change in CD4 cell count did not differ significantly between groups (-32, -40 and -52 cells per microL respectively). There was also no difference between groups in progression to CDC category B or C events, or in adverse events. Therapeutic vaccination with p24-VLP does not affect CD4 cell decline in patients with advanced HIV infection.

AIDS Vaccines↗
PubMed2001

Problems with phenytoin administration in neurology/neurosurgery ITU patients receiving enteral feeding.

Our objective was to investigate the relationship between phenytoin bioavailability, enteral feeding and serum albumin levels in patients admitted to neurology/neurosurgery ITU, via case studies of three patients. The research was performed at the Walton centre for Neurology and Neurosurgery NHS Trust, Liverpool, England, and our subjects consisted of three cases admitted to ITU (1 status epilepticus, 1 post-trauma and 1 post-subarachnoid haemorrhage (SAH)). Phenytoin levels were assessed in relation to the type of feeding and serum albumin levels. We found evidence of a complex relationship between phenytoin levels, enteral feeding and serum albumin in patients in the neuro ITU setting. We conclude that, in this setting the patient's phenytoin needs to be closely monitored and treated aggressively to maintain therapeutic levels. They should also be followed up during rehabilitation to avoid toxicity.

Adult↗
PubMed2001

Survival after first esophageal variceal hemorrhage in patients with biliary atresia.

OBJECTIVE: To determine the influence of the new onset of esophageal variceal hemorrhage (EVH) on transplant-free survival in children with biliary atresia and to examine variables that predicted survival after the onset of EVH. METHODS: Retrospective chart review of 134 patients with biliary atresia who underwent portoenterostomy between 1973 and 1992 at a single institution; 29% had EVH. RESULTS: The risk of death or need for liver transplantation was 50% at 6 years after the initial episode of EVH. Patients with a serum bilirubin concentration < or =4 mg/dL at the first episode of EVH had transplant-free survival of >80% for 4 years after this episode, those with bilirubin levels >4 to 10 mg/dL had 50% survival at 1 year, and those with bilirubin levels >10 mg/dL had 50% survival at 4 months. The risk of death or transplant for a child with EVH and total serum bilirubin levels >10 mg/dL was 12.0 (95% CI: 6.0, 24.1), 4 to 10 mg/dL was 7.2 (3.1, 16.7), and < or =4 mg/dL was 0.6 (0.1, 3.1) times the risk of a same-aged child who did not have EVH. CONCLUSIONS: Children with biliary atresia and first EVH episode have a variable prognosis related to total serum bilirubin concentration at the time of the episode.

Biliary Atresia↗
PubMed2001

Preliminary estimates of performance and cost of mercury control technology applications on electric utility boilers.

Under the Clean Air Act Amendments of 1990, the U.S. Environmental Protection Agency (EPA) determined that regulation of mercury emissions from coal-fired power plants is appropriate and necessary. To aid in this determination, preliminary estimates of the performance and cost of powdered activated carbon (PAC) injection-based mercury control technologies were developed. This paper presents these estimates and develops projections of costs for future applications. Cost estimates were developed using PAC to achieve a minimum of 80% mercury removal at plants using electrostatic precipitators and a minimum of 90% removal at plants using fabric filters. These estimates ranged from 0.305 to 3.783 mills/kWh. However, the higher costs were associated with a minority of plants using hot-side electrostatic precipitators (HESPs). If these costs are excluded, the estimates range from 0.305 to 1.915 mills/kWh. Cost projections developed using a composite lime-PAC sorbent for mercury removal ranged from 0.183 to 2.270 mills/kWh, with the higher costs being associated with a minority of plants that used HESPs.

Air Pollution↗
PubMed2001

An automated dosimetry system for testing whole-body ultraviolet phototherapy cabinets.

A new technique is described for automated ultraviolet dosimetry within whole-body phototherapy cabinets. A dual-head detector system has been designed, permitting simultaneous assessment of irradiance levels and radiant intensities from individual lamps. One detector is used in combination with a diffuser/filter system for the measurement of irradiance and the other is mounted at the end of a slit collimator to provide a measurement which can be related to the radiant intensities of the individual lamps. These quantities are derived from 800 separate measurements made during rotation of the detector head around a 360 degrees circle at a fixed height and position within the cabinet under remote computer software control. The device has advantages compared with standard techniques, enabling measurements to be made without the need for a person to be present in the cabinet. A full set of measurements is made with minimal switching of the power supply to the lamps. This simplifies the assessment and reduces the uncertainty from variation in output after the lamps are switched on. Variations in irradiance with orientation for the smaller phototherapy cabinets are clearly demonstrated. Plots of data from the collimated detector show peaks corresponding to the lamps and the surrounding reflectors. The plots enable failed lamps to be detected and peak values can be related to radiant intensities of individual lamps.

Biophysical Phenomena↗
PubMed2001

Rapid measurement of deuterium content of breath following oral ingestion to determine body water.

The ability to measure total body water accurately, non-invasively and rapidly with results that are immediately available would represent an important advance in body composition research. Flowing afterglow mass spectrometry (FA-MS) has been developed to enable immediate measurement of deuterium content in breath water from single exhalations, which when combined with oral D2O loading enables measurement of total body water. We report here its first use in normal subjects, demonstrating the dispersal kinetics of deuterium in the body by monitoring deuterium in breath water following ingestion. Ten studies were performed in six normal subjects. After obtaining baseline samples, each subject ingested 0.3 g x kg(-1) of 99.9% pure D2O. Subsequently, breath samples were obtained every 3-5 minutes until equilibration had occurred. Three distinct phases in breath deuterium content were observed: an initial immediate peak due to HDO remaining in the oral cavity, a secondary peak reflecting gastrointestinal absorption and finally equilibration with the body water. The incremental increase in breath deuterium abundance between baseline and equilibration was used to calculate the total body water. Mathematical fitting of this final equilibration phase demonstrated that the measured deuterium abundance was within 0.2% of the ideal (asymptotic) value within 2 hours in all cases. We conclude that FA-MS is a powerful new method that, when combined with oral D2O loading, enables measurement of the dispersal kinetics of HDO and the calculation of total body water within 2 hours.

Adult↗
PubMed2001

The Edinburgh Mouse Atlas: using the CD.

This paper provides a simple introduction to the reconstructions and data-handling tools stored on the Edinburgh Mouse Atlas CD, together with some of the ways in which the viewers and software can be used to understand mouse development and analyse data. The key aspect of the Mouse Atlas is that the underlying models are a complete representation of the histology, which has not been constrained to a particular interpretation. This means, for example, that the current anatomy domains can be further subdivided as required to any resolution up to the resolution of the models (2-7 microm). In the CD of the early embryos described here, virtually all tissues that can be usefully distinguished either by the histology or morphologically have been delineated.

Animals↗
PubMed2001

Retinoic acid synthesis for the developing telencephalon.

The small lipid retinoic acid is known to promote neuronal differentiation in vitro and to act as a teratogen in the embryonic brain, but very little is known about the natural role of endogenously synthesized retinoic acid in forebrain development. Retinoic acid is synthesized mainly by three retinaldehyde dehydrogenases. We show here where the retinaldehyde dehydrogenases for the developing telencephalon are expressed and how their expression patterns change over developmental time. Retinoic acid diffusing from the retinaldehyde dehydrogenase sites is likely to influence the early telencephalon before the beginning of neurogenesis, as well as differentiation and radial migration of neurons into the cerebral cortex. Because of its diffusible character, retinoic acid represents a unique tool for the coordination of growth processes over an intermediate distance range in the developing telencephalon.

Aldehyde Oxidoreductases↗