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S Moore

Publications and source records attributed to S Moore.

At least 73 records · Page 4Linked to original sources
PubMed2000

dCtBP-dependent and -independent repression activities of the Drosophila Knirps protein.

Transcriptional repressor proteins play essential roles in controlling the correct temporal and spatial patterns of gene expression in Drosophila melanogaster embryogenesis. Repressors such as Knirps, Krüppel, and Snail mediate short-range repression and interact with the dCtBP corepressor. The mechanism by which short-range repressors block transcription is not well understood; therefore, we have undertaken a detailed structure-function analysis of the Knirps protein. To provide a physiological setting for measurement of repression, the activities of endogenous or chimeric Knirps repressor proteins were assayed on integrated reporter genes in transgenic embryos. Two distinct repression functions were identified in Knirps. One repression activity depends on dCtBP binding, and this function maps to a C-terminal region of Knirps that contains a dCtBP binding motif. In addition, an N-terminal region was identified that represses in a CtBP mutant background and does not bind to the dCtBP protein in vitro. Although the dCtBP protein is important for Knirps activity on some genes, one endogenous target of the Knirps protein, the even-skipped stripe 3 enhancer, is not derepressed in a CtBP mutant. These results indicate that Knirps can utilize two different pathways to mediate transcriptional repression and suggest that the phenomenon of short-range repression may be a combination of independent activities.

Alcohol Oxidoreductases↗
PubMed2000

Biological tissue adhesive for multiple use in the accident and emergency department.

OBJECTIVE: To assess the strength of the glue and microbial contamination over 28 days from opening a vial of tissue adhesive in the accident and emergency setting, and to quantify cost savings of repeated use of the vials. METHOD: (1) Strips of reinforced nylon and a specially constructed piece of apparatus designed to measure the force at which the glue gave way were used to measure the strength of the tissue adhesive at various times after the glue was opened to assess if the glue strength deteriorated over time. (2) Microbial contamination of the glue was assessed. RESULTS: There was no deterioration in the glue strength over time. There was no evidence of microbial contamination of the glue. CONCLUSION: Cyanoacrylate tissue adhesive can safely be reused for a period of 28 days after opening with no risk of degradation of glue strength or contamination with micro-organisms. In our department this represents a potential saving of ł5400 per year.

Cost Savings↗
PubMed2000

Five cases of isolated glycerol kinase deficiency, including two families: failure to find genotype:phenotype correlation.

Little is understood of the genotype/phenotype correlations in X linked glycerol kinase deficiency (GKD) where most cases are caused by extensive deletions of Xp21, which often include genes flanking the GK locus. Few cases of isolated GKD have been investigated where the phenotype is not influenced by neighbouring genes. In this paper, we present the mutation data from four confirmed and one suspected case of non-deletion, isolated, X linked GKD and therefore extend the base of patients that can allow an assessment of genotype/phenotype correlations for this disease. The mutations found were two terminations leading to premature truncation of the GK polypeptide chain, one insertion, and an amino acid substitution. Phenotypic variation was observed in two families, where there was more than one affected subject carrying the same mutation, confirming previous studies that suggest there is no correlation between disease severity and genotype. Furthermore, the nature of the mutation in different families does not appear to influence the spectrum of phenotypic variation. In addition, one coding polymorphism in exon 3 has been found. The characterisation of the gene structure has been completed and shows that instead of 19 there are 21 exons.

Amino Acid Sequence↗
PubMed2000

Variability in the location of the retinal ganglion cell area centralis is correlated with ontogenetic changes in feeding behavior in the black bream, Acanthopagrus butcheri (Sparidae, teleostei).

The development of neural cell topography in the retinal ganglion cell layer was examined in a teleost, the black bream (Acanthopagrus butcheri). From Nissl-stained wholemounts, it was established that fish between 10 and 15 mm standard body length (SL) possess high cell densities throughout the dorso-temporal retinal quadrant, with peak cell densities located in temporal regions of the retina. However, in fish between 15 and 80 mm SL, a wide variation in the position of the peak cell density is revealed with the locations of the areae centrales (AC) ranging from exclusively temporal to periphero-dorsal retina. Fish larger than 80 mm SL always possess an AC located in the dorsal region of the dorso-temporal retinal quadrant. The topography of ganglion cells within the ganglion cell layer was determined by comparing the numbers of ganglion cells retrogradely-labeled from the optic nerve with the total population of Nissl-stained neurons (ganglion plus displaced amacrine cells) in a range of different-sized individuals. Ganglion cell topography was the same as that recorded for all Nissl-stained neurons. The feeding behavior of juveniles from metamorphosis to 80 mm SL was observed, where fish were given the choice of feeding on live food in mid-water (until 15 mm SL) or obtaining pellets from the surface or the bottom. A range of feeding patterns was recorded, with the smallest fish taking food from mid-water but individuals between 15 and 80 mm SL taking food either from the surface or the bottom or both. A correlation between the preferred mode of feeding and the position of the AC was found, such that those individuals feeding in mid-water or at the surface possess a temporal or intermediate (dorso- temporal) AC, whereas those predominantly feeding from the bottom possess a dorsal AC.

Animals↗
PubMed2000

Stem cell factor and chronic myeloid leukemia CD34+ cells.

Normal hematopoiesis is a tightly regulated process involving a balance between signals that stimulate and those that inhibit the proliferation and differentiation of hematopoietic progenitors. In chronic myeloid leukemia (CML) there is a perturbation of these controlling elements, resulting in overgrowth of leukemic cells in the bone marrow and spleen. In part, the proliferation of CML CD34+ cells may result from an abnormal response to the cytokine Stem Cell Factor (SCF). SCF induced proliferation and adhesion to the extracellular matrix via fibronectin are not coupled in CML as they are in normal cells and this may contribute to the accumulation of leukemic progenitors. We have previously shown that CD34+ CML cells and the more primitive CD34+ CD38- CML cells do not require the addition of synergistic cytokines to cultures, but are capable of proliferation in SCF alone, and that leukemic CFU-GM are selectively supported in these cultures. In the presence of other cytokines the response of CML cells to SCF is no greater than that of cells from normal donors, suggesting that the leukemic cells are not more sensitive to SCF, but that accessory pathways are already activated in these cells. Cells from patients with myeloproliferative disorders show variable proliferative response to SCF as the sole mitogenic stimulus, suggesting that expression of bcr-abl is essential for proliferation in this cytokine. Further studies to identify the key determinants of the abnormal response to SCF in CML may lead to a better understanding of the proliferative abnormality that underlies CML.

Apoptosis↗
PubMed1999

The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia.

We determined the breakpoint genes of the translocation t(4;11)(q21;p15) that occurred in a case of adult T-cell acute lymphocytic leukemia (T-ALL). The chromosome 11 breakpoint was mapped to the region between D11S470 and D11S860. The nucleoporin 98 gene (NUP98), which is rearranged in several acute myeloid leukemia translocations, is located within this region. Analysis of somatic cell hybrids segregating the translocation chromosomes showed that the chromosome 11 breakpoint occurs within NUP98. The fusion partner of NUP98 was identified as the RAP1GDS1 gene using 3' RACE. RAP1GDS1 codes for smgGDS, a ubiquitously expressed guanine nucleotide exchange factor that stimulates the conversion of the inactive GDP-bound form of several ras family small GTPases to the active GTP-bound form. In the NUP98-RAP1GDS1 fusion transcript (abbreviated as NRG), the 5' end of the NUP98 gene is joined in frame to the coding region of the RAP1GDS1 gene. This joins the FG repeat-rich region of NUP98 to RAP1GDS1, which largely consists of tandem armadillo repeats. NRG fusion transcripts were detected in the leukemic cells of 2 other adult T-ALL patients. One of these patients had a variant translocation with a more 5' breakpoint in NUP98. This is the first report of an NUP98 translocation in lymphocytic leukemia and the first time that RAP1GDS1 has been implicated in any human malignancy.

Adolescent↗
PubMed1999

Number of neurons in the retinal ganglion cell layer of the quokka wallaby do not change throughout life.

During adult life, the topography of the retinal pigment epithelium (RPE) of the quokka wallaby changes gradually. Cells in peripheral retina enlarge in surface area while those in mid-temporal retina, adjacent to the area centralis, a high density region in the ganglion cell layer, decrease in area, implying that the tissue in this area is drawing together. We speculated that high ganglion cell densities in temporal regions might be maintained, in the face of cell loss due to aging, by this apparent drawing together of the RPE sheet. Therefore, we examined the retinal ganglion cell layer of the quokka in cresyl violet stained wholemounts from animals aged from 0. 55 to 13.5 years. We found that total neuron number in the retinal ganglion cell layer of the quokka did not decrease significantly throughout life even though individuals in captivity live long lives (9-15 years). Ganglion and amacrine cells were counted separately and identified by strict morphological criteria. Nevertheless, the proportion of ganglion to amacrine cells appeared to decrease linearly throughout life, indicating that the morphology of a proportion of neurons became more amacrine-like during aging. Mean cell size did not change throughout life. In the quokka, retinal area increases slowly throughout life and may account for the small reduction in cell density seen in most retinal regions.

Aging↗
PubMed1999

Mechanisms and impact of enteric infections.

The increased recognition of both old and new enteric pathogens and their potential impact requires an improved understanding of pathogenesis and effective interventions. While the overwhelming mortality (> 3 million children per year) due to diarrheal diseases is well-recognized, the potential long-term impacts of enteric infections and early childhood diarrhea morbidity are just beginning to be appreciated. Furthermore, several enteric infections are now being recognized as causes of growth shortfalls with or without diarrhea; i.e., malnutrition may be one of the greatest yet of the "emerging infectious diseases." The increased appreciation of this extended impact calls for further quantification and improved understanding of the deranged physiology. In particular, persistent diarrheal illnesses exhibit common themes of blunted villi, disruption of intestinal barrier function and varying degrees of sub-mucosal inflammation for which lactulose/mannitol permeability and fecal lactoferrin provide respective quantification. Finally, such improved understanding will allow targeted interventions among those most vulnerable, which will enable further documentation of cost effectiveness and the potential for improved human development which is critical to reducing the widening disparity and population overgrowth which increasingly threaten our global security.

Animals↗
PubMed1999

Effect of gastric pH on the relative oral bioavailability and pharmacokinetics of temozolomide.

PURPOSE: Temozolomide is an imidazotetrazine alkylating agent which undergoes chemical conversion at physiological pH to the active species 5-(3-methyltriazene-1-yl)imidazole-4-carboxamide (MTIC) but is stable at acid pH. This study evaluated the effect of an increase in gastric pH, through the use of ranitidine, on the oral bioavailability and plasma pharmacokinetics of temozolomide and MTIC. METHODS: Fifteen patients with advanced cancer were enrolled of which 12 were evaluable, all of whom had pharmacokinetic blood sampling. Each patient received temozolomide 150 mg m(-2) day(-1) for 5 days in cycle 1 and also received ranitidine 150 mg every 12 h either on days 1 and 2 or days 4 and 5. Gastric pH was monitored by the use of the Heidelberg capsule system. RESULTS: Following the administration of ranitidine there was a rise in gastric pH by 1-2 pH units over the duration of the study period (pH range 2.2-5.2 without ranitidine and 3.5-6.0 with ranitidine). There was no difference in the pharmacokinetic parameters of temozolomide or MTIC with or without the concomitant administration of ranitidine. There was however, a lower C(max) for temozolomide and MTIC for patients receiving ranitidine on day 1 and 2 versus day 4 and 5. Temozolomide was rapidly absorbed [time to maximum plasma concentration (t(max)) 1.8 h] and eliminated [elimination half-life (t(1/2)) 1.8 h] and MTIC followed a similar pattern with a t(max) of 1.9 h and a t(1/2) of 1.9 h. Overall, the AUC of the MTIC represented about 2-4% of the AUC for temozolomide.

Administration, Oral↗
PubMed1999

Work stress and self-reported alcohol use: the moderating role of escapist reasons for drinking.

This study examines the moderating role of escapist reasons for drinking alcohol in the job stress/self-reported alcohol use and problems relationship. It was hypothesized that higher levels of job stress would be associated with higher levels of self-reported drinking (H1) and drinking problems (H2) only for those who endorsed escapist reasons for drinking. For those who did not hold such beliefs, higher levels of job stress were predicted to be associated with lower self-reported alcohol intake (H3) and problems (H4). Survey data from white- and blue-collar workers employed across all paycodes and positions were collected randomly at a large manufacturing organization (62% response rate). Participants responded to questions concerning work stress, reasons for drinking, alcohol intake, and alcohol problems. Using only nonabstainers with complete data (N = 1,645), results from regression analyses generally supported all hypotheses.

Adult↗
PubMed1999

Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies.

Temozolomide, an oral cytotoxic agent with approximately 100% bioavailability after one administration, has demonstrated schedule-dependent clinical activity against highly resistant cancers. Thirty patients with minimal prior chemotherapy were enrolled in this phase I trial to characterize the drug's safety, pharmacokinetics and anti-tumour activity, as well as to assess how food affects oral bioavailability. To determine dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD), temozolomide 100-250 mg m(-2) was administered once daily for 5 days every 28 days. The DLT was thrombocytopenia, and the MTD was 200 mg m(-2) day(-1). Subsequently, patients received the MTD to study how food affects the oral bioavailability of temozolomide. When given orally once daily for 5 days, temozolomide was well tolerated and produced a non-cumulative, transient myelosuppression. The most common non-haematological toxicities were mild to moderate nausea and vomiting. Clinical activity was observed against several advanced cancers, including malignant glioma and metastatic melanoma. Temozolomide demonstrated linear and reproducible pharmacokinetics and was rapidly absorbed (mean Tmax approximately 1 h) and eliminated (mean t1/2 = 1.8 h). Food produced a slight reduction (9%) in absorption of temozolomide. Temozolomide 200 mg m(-2) day(-1) for 5 days, every 28 days, is recommended for phase II studies.

Administration, Oral↗
PubMed1999

Identification and characterization of a tri-partite hydrophobin from Claviceps fusiformis. A novel type of class II hydrophobin.

A new type of hydrophobin is encoded by an abundant mRNA of Claviceps fusiformis. The predicted amino-acid sequence of the protein, dubbed CFTH1, shows a putative signal sequence for secretion, followed by three class II hydrophobin domains each preceded by glycine/asparagine rich regions. SDS/PAGE analysis of 60% ethanol extractions of C. fusiformis mycelia from shaken cultures showed CFTH1 at the 50-55-kDa position. N-terminal sequencing of both untreated mature CFTH1 and of a fragment obtained by trypsin digestion revealed that CFTH1 is not processed between the hydrophobin domains. Mass spectroscopy showed a mass of about 36 500 Da, which is about 1500 Da higher than the mass predicted from the constituent amino acids, indicating post-translational modification but not glycosylation. Purified CFTH1 self-assembled at hydrophilic/hydrophobic interfaces and, after assembly at a water/air interface, it was found to be highly surface active. Antibodies raised against CFTH1 localized the protein in a mucilageous coat surrounding submerged vegetative hyphae in liquid shaken culture and, as a discrete layer of about 10 nm thickness at the surface of aerial hyphae of standing cultures, suggesting a role in the formation of aerial hyphae.

Amino Acid Sequence↗
PubMed1999

Autogenous artery grafts in hypertensive (SHR) rats do not have increased smooth muscle cell hyperplasia in the graft neointima, compared with grafts in normotensive rats.

Vein-to-artery graft surgery is used widely to by-pass arterial stenoses, but such grafts can fail over a prolonged period as a result of excessive neointimal hyperplasia causing thrombosis and graft occlusion. It has been suggested that neointimal hyperplasia, in vein grafts, is a result of the vessel wall adapting to the higher intraluminal pressure of the arterial circulation, compared with the venous circulation. Autologous artery grafts have been used to bypass arterial stenoses. Initially it was assumed that donor artery segments would not develop neointimal hyperplasia as they are already adapted to the arterial circulation but this is not so. In this study we postulated that surgical or postsurgical trauma was the cause of neointimal hyperplasia in autologous artery-to-artery grafts. In addition, as artery grafts are pre-adapted to the arterial circulation, autologous artery-to-artery grafts in hypertensive rats should develop similar levels of neointimal hyperplasia as seen in normotensive rats. Artery-to-artery grafts were placed in a series of 20 spontaneously hypertensive rats (SHR). In a separate series of sham grafting experiments the effects of anoxia and clamp trauma were assessed in SHR and WKy normotensive control rats. Finally, clamping, anoxia and anastomosis trauma were assessed in a similar series of rats. In the artery-to-artery graft series there was no difference in neointimal thickness between the SHR and that previously reported for normotensive rats. Minimal neointimal hyperplasia was demonstrated in the sham grafted series of rats and only slightly more in the single anastomosis series. It was only in the full grafting procedure that considerable neointimal hyperplasia developed. These data demonstrate that neointimal hyperplasia in artery-to-artery grafts is not exacerbated by the hypertension. In addition, trauma appears to be the initiator of neointimal hyperplasia and the extent of trauma correlates with the degree of neointimal hyperplasia.

Animals↗
PubMed1999

Neuroblastoma in southern Africa: epidemiological features, prognostic factors and outcome.

We retrospectively analysed the epidemiological features and the importance of biochemical, histological and genetic parameters in predicting survival in 14 Namibian and 34 South African children treated for neuroblastoma (NB) from 1983 to 1997. Curative treatment consisted mainly of total (13%) or partial (44%) resection after chemotherapy (cyclophosphamide and doxorubicin x6 courses or carboplatin, etoposide, epirubicin and cyclophosphamide x6 courses). Localized radiotherapy with curative intent was given to 33% of patients. The male:female ratio was 0.9. The median age was 18 months (range 1-116) and was comparable in white, black and mixed ethnic patients. Primary disease was located in the abdomen (75%), thorax (15%), pelvis (5%) or elsewhere (5%). Evans stage distribution was: stage I, 2%; stage II, 19%; stage III, 21%; stage IV, 50%; and stage IVS, 8%. Stage III/IV disease was more common in black than in white children (p = 0.0001). Urinary vanillyl mandelic acid was elevated in 63% of those tested. Survival after 5-163 months' follow-up was 90% for stages I and II combined (median 2983, range 798-4661 days), 51% for stage III (median 367, range 61-5001 days), 6% for stage IV (median 227, range 20-4379 days) and 50% for stage IVS (median 532, range 54-1543 days). All seven children with para-spinal tumours survived. Individual factors associated with significantly poorer survival were elevated serum lactate dehydrogenase (p < 0.001), Joshi histological risk categorization adapted for age (p = 0.039), n-myc amplification (p = 0.006) and diploidy or tetraploidy (p = 0.006). All seven children with serum ferritin exceeding 149 ng/ml at the time of diagnosis died and survival was 33% in children with 1p deletion and 67% in those without, but the numbers were too small to achieve significance. These findings confirm the benefit of simple biochemical tests and histology in identifying those who are likely to respond favourably to conventional chemotherapy and surgery. Supportive genetic tests on formalin-fixed paraffin-embedded tumour tissue contributed to predicting outcome in 21 patients.

Abdominal Neoplasms↗
PubMed1999

Mannan binding lectin concentration and risk of miscarriage.

Recurrent miscarriage is associated with low concentrations of mannan-binding lectin (MBL), but it is not known below which value relative MBL deficiency becomes a significant risk factor. The sera of 397 patients (male and female) suffering from recurrent miscarriage and 376 controls were assayed for MBL and the data analysed. It was found that the lower the cut-off value, the greater the statistical strength of the association. It was concluded that only MBL concentrations </=0.1 microg/ml were clinically significant in this context. A corollary of this conclusion is that genotyping for point mutations in the structural gene for MBL would be a much less sensitive means of identifying couples at risk of experiencing recurrent miscarriage.

Abortion, Habitual↗
PubMed1999

The epidemiology of lip cancer: a review of global incidence and aetiology.

Lip cancer (140 ICD-9) is a form of oral cancer that has a distinctive global epidemiology. This review summarises global incidence rates for male and female lip cancer with the aid of cancer atlases. High male lip cancer rates are reported for regions of North America (12.7 per 100 000 per annum), Europe (12.0 per 100 000 per annum) and Oceania (13.5 per 100 000 per annum), while it is virtually unknown in parts of Asia. Factors commonly cited as important in the aetiology of lip cancer include solar radiation, tobacco smoking and viruses. An attempt is made to summarise the evidence for factors that may be important in lip carcinogenesis. While incidence rates are generally stable or falling among males worldwide, they are rising in many female populations. The aetiology of the disease is far from established and much information regarding its pathogenesis is based on anecdotal rather than case-controlled epidemiological evidence. The epidemiology of lip cancer supports the proposal that the lip should be considered as a distinct cancer site, rather than being included with other forms of intraoral cancer.

Asia↗
PubMed1999

Horse vision and an explanation for the visual behaviour originally explained by the 'ramp retina'.

Here we provide confirmation that the 'ramp retina' of the horse, once thought to result in head rotating visual behaviour, does not exist. We found a 9% variation in axial length of the eye between the streak region and the dorsal periphery. However, the difference was in the opposite direction to that proposed for the 'ramp retina'. Furthermore, acuity in the narrow, intense visual streak in the inferior retina is 16.5 cycles per degree compared with 2.7 cycles per degree in the periphery. Therefore, it is improbable that the horse rotates its head to focus onto the peripheral retina. Rather, the horse rotates the nose up high to observe distant objects because binocular overlap is oriented down the nose, with a blind area directly in front of the forehead.

Animals↗