PubMed Health⌕ Search

Biomedical subjects

S L Taylor

Publications and source records attributed to S L Taylor.

At least 55 records · Page 3Linked to original sources
PubMed1999

Prospective vancomycin audit in Auckland healthcare hospitals.

AIM: In response to emerging vancomycin resistance among gram-positive cocci, it is recommended that hospitals develop guidelines for the appropriate use of glycopeptides and identify situations where glycopeptide use should be discouraged. The aim of this study was to audit the use of vancomycin in Auckland Healthcare hospitals. METHOD: Patients prescribed vancomycin were recorded by pharmacy staff at Auckland, Starship, Green Lane and National Women's Hospitals. Clinical and laboratory information was collected for each course of vancomycin treatment. Standard definitions were used to classify prophylactic, empirical or specific directed therapy as appropriate or inappropriate. Continuing vancomycin when cultures were negative for beta-lactam-resistant, gram-positive organisms and/or initial choice of vancomycin when it was not necessary for the presumed source of infection were reasons for inappropriate empirical use. Reasons for inappropriate specific directed therapy included vancomycin prescribed for methicillin susceptible S. aureus and coagulase-negative staphylococci, or penicillin susceptible viridans streptococci when there was no history of beta-lactam allergy. RESULTS: One hundred and sixty-eight courses of vancomycin were prescribed for 146 patients; 42 in children (<16 years) and 126 in adults. Thirty-two per cent of all vancomycin courses were in renal patients, 26% in surgical specialities, 17% in haematology/oncology patients, 14% in medical specialities and 10% in intensive care unit patients. Eighty-six (51%) courses of vancomycin were considered inappropriate. The majority, 54/86 (63%) of inappropriate use, was for empirical therapy. It was an inappropriate initial choice in 25 instances, the duration of treatment was inappropriate, given no beta-lactam-resistant organisms were isolated in nine instances and both its initial choice and duration were inappropriate in 20 instances. Switching to other antimicrobial agents sooner when culture results and susceptibilities became available would have shortened the duration of 58/86 (67%) of the inappropriate courses. Of the inappropriate courses, 44/86 (51%) were prescribed for renal patients, 22 for empirical use, e.g. for peritoneal dialysis-related peritonitis, wound infections and presumed line infections and 22 for specific therapy of beta-lactam susceptible isolates because of dosing convenience in patients with renal failure. CONCLUSION: Half of the vancomycin use in Auckland Healthcare hospitals could potentially be modified. The majority of inappropriate use (63%) was for empirical therapy. The microbiology laboratory's ability to promptly and accurately report culture and susceptibility results and convey these to the prescribing clinician is important in reducing unnecessary doses. This study identified areas where interventions will be focused to reduce vancomycin use.

Adolescent↗
PubMed1999

Sequence variation in the human angiotensin converting enzyme.

Angiotensin converting enzyme (encoded by the gene DCP1, also known as ACE) catalyses the conversion of angiotensin I to the physiologically active peptide angiotensin II, which controls fluid-electrolyte balance and systemic blood pressure. Because of its key function in the renin-angiotensin system, many association studies have been performed with DCP1. Nearly all studies have associated the presence (insertion, I) or absence (deletion, D) of a 287-bp Alu repeat element in intron 16 with the levels of circulating enzyme or cardiovascular pathophysiologies. Many epidemiological studies suggest that the DCP1*D allele confers increased susceptibility to cardiovascular disease; however, other reports have found no such association or even a beneficial effect. We present here the complete genomic sequence of DCP1 from 11 individuals, representing the longest contiguous scan (24 kb) for sequence variation in human DNA. We identified 78 varying sites in 22 chromosomes that resolved into 13 distinct haplotypes. Of the variant sites, 17 were in absolute linkage disequilibrium with the commonly typed Alu insertion/deletion polymorphism, producing two distinct and distantly related clades. We also identified a major subdivision in the Alu deletion clade that enables further analysis of the traits associated with this gene. The diversity uncovered in DCP1 is comparable to that described for other regions in the human genome. The highly correlated structure in DCP1 raises important issues for the determination of functional DNA variants within genes and genetic studies in humans based on marker association.

Alu Elements↗
PubMed1999

Toxicology of protein allergenicity: prediction and characterization.

The ability of exogenous proteins to cause respiratory and gastrointestinal allergy, and sometimes systemic anaphylactic reactions, is well known. What is not clear however, are the properties that confer on proteins the ability to induce allergic sensitization. With an expansion in the use of enzymes for industrial applications and consumer products, and a substantial and growing investment in the development of transgenic crop plants that express novel proteins introduced from other sources, the issue of protein allergenicity has assumed considerable toxicological significance. There is a need now for methods that will allow the accurate identification and characterization of potential protein allergens and for estimation of relative potency as a first step towards risk assessment. To address some of these issues, and to review progress that has been made in the toxicological investigation of respiratory and gastrointestinal allergy induced by proteins, a workshop, entitled the Toxicology of Protein Allergenicity: Prediction and Characterization, was convened at the 37th Annual Conference of the Society of Toxicology in Seattle, Washington (1998). The subject of protein allergenicity is considered here in the context of presentations made at that workshop.

Allergens↗
PubMed1999

Mining SNPs from EST databases.

There is considerable interest in the discovery and characterization of single nucleotide polymorphisms (SNPs) to enable the analysis of the potential relationships between human genotype and phenotype. Here we present a strategy that permits the rapid discovery of SNPs from publicly available expressed sequence tag (EST) databases. From a set of ESTs derived from 19 different cDNA libraries, we assembled 300,000 distinct sequences and identified 850 mismatches from contiguous EST data sets (candidate SNP sites), without de novo sequencing. Through a polymerase-mediated, single-base, primer extension technique, Genetic Bit Analysis (GBA), we confirmed the presence of a subset of these candidate SNP sites and have estimated the allele frequencies in three human populations with different ethnic origins. Altogether, our approach provides a basis for rapid and efficient regional and genome-wide SNP discovery using data assembled from sequences from different libraries of cDNAs.

DNA, Complementary↗
PubMed1999

C-erbB-2 mRNA in breast cancer specimens that exhibit membrane or cytoplasmic immunoreactivity for c-erbB-2.

Immunocytochemically detected membrane staining for c-erbB-2 in 20-30% of breast cancers correlates with a poorer prognosis for the patients. However, cytoplasmic immunoreactivity for c-erbB-2 has also been found in some specimens using some particular antisera, and it has been suggested that this staining arises from a protein located in the mitochondrial membrane. It is possible that this protein is an alternative form of c-erhB-2. In the present article, adjacent histological sections have been stained for c-erbB-2 immunocytochemically, and for c-erbB-2 mRNA by in situ hybridization. The results show the absence of c-erbB-2 mRNA in regions of cancer specimens that exhibit cytoplasmic staining for c-erbB-2, strongly suggesting that cytoplasmic staining for c-erbB-2 is an immunocytochemical artefact.

Breast Neoplasms↗
PubMed1998

Cytoplasmic staining of c-erbB-2 is not associated with the presence of detectable c-erbB-2 mRNA in breast cancer specimens.

The cell-surface receptor tyrosine kinase protein c-erbB-2 is immunocytochemically detected as membrane staining on the surface of cancer cells in 20-30% of cases of breast cancer, and its presence has been associated with poor prognosis for the patient. However, there have been numerous reports of immunocytochemical staining for c-erbB-2 solely in the cytoplasm of some normal and tumour specimens with frequently used anti-sera, and the presence of such staining has been difficult to interpret. It is not known for certain that cytoplasmic c-erbB-2 staining is an artefact of the immunocytochemical procedures used. Thus, mRNA for c-erbB-2 has been quantified in tumours exhibiting only cytoplasmic staining or varying levels of membrane staining using a sensitive, competitive PCR method. Whereas abundant levels of c-erbB-2 mRNA are found in tumours exhibiting membrane staining for c-erbB-2 and these levels correlate with the percentage of tumour cells showing membranous staining for c-erbB-2, the level of c-erbB-2 mRNA in tumours displaying only cytoplasmic staining is no higher than in c-erbB-2-negative specimens.

Breast Neoplasms↗
PubMed1998

Automating the identification of DNA variations using quality-based fluorescence re-sequencing: analysis of the human mitochondrial genome.

Diagnostic re-sequencing plays a central role in medical and evolutionary genetics. In this report we describe a process that applies fluorescence-based re-sequencing and an integrated set of analysis tools to automate and simplify the identification of DNA variations using the human mitochondrial genome as a model system. Two programs used in genome sequence analysis (Phred, a base-caller, and Phrap, a sequence assembler) are applied to assess the quality of each base call across the sequence. Potential DNA variants are automatically identified and 'tagged' by comparing the assembled sequence with a reference sequence. We also show that employing the Consed program to display a set of highly annotated reference sequences greatly simplifies data analysis by providing a visual database containing information on the location of the PCR primers, coding and regulatory sequences and previously known DNA variants. Among the 12 genomes sequenced 378 variants including 29 new variants were identified along with two heteroplasmic sites, automatically detected by the PolyPhred program. Overall we document the ease and speed of performing high quality and accurate fluorescence-based re-sequencing on long tracts of DNA as well as the application of new approaches to automatically find and view DNA variants among these sequences.

Base Sequence↗
PubMed1998

Regulation of tenascin-C expression in bone cells by transforming growth factor-beta.

Transforming growth factor-beta (TGF-beta) stimulates new bone formation when administered locally in vivo. The extracellular matrix protein tenascin-C, which is secreted by osteoblasts but absent from mineralized bone matrix, supports differentiation of cultured osteoblast-like cells. The current study was undertaken to determine whether expression patterns of tenascin-C in TGF-beta-treated bone cells are in agreement with a role for this protein as a mediator of TGF-beta-stimulated new bone formation. Expression of tenascin-C was investigated by immunohistochemistry in calvarial bones of mice to which TGF-beta had been locally administered. Three days after initiation of daily TGF-beta treatment, strong staining for tenascin-C was seen in regions where periosteal osteoprogenitor cells were undergoing proliferation in response to TGF-beta; by comparison, staining of periosteal surfaces of control bones was weak and discontinuous. Seven days after initiation of a course of five daily injections of TGF-beta, tenascin-C staining was still enhanced in treated bones. The ability of TGF-beta to regulate expression of tenascin-C in osteoblast-like cells in vitro was investigated using an osteosarcoma-derived cell line (ROS 17/2.8). TGF-beta caused a small but significant increase in secretion of tenascin-C into the medium, as determined by a solid phase dot immunoassay quantitated by densitometry. Western and northern blot analysis indicated that TGF-beta did not influence the pattern of expression of tenascin-C splice variants. These results indicate that TGF-beta stimulates osteoblastic tenascin-C expression and suggest that tenascin-C may act as a mediator of TGF-beta-induced new bone formation.

Animals↗
PubMed1998

DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene.

Lipoprotein lipase plays a central role in lipid metabolism and the gene that encodes this enzyme (LPL) is a candidate susceptibility gene for cardiovascular disease. Here we report the complete sequence of a fraction of the LPL gene for 71 individuals (142 chromosomes) from three populations that may have different histories affecting the organization of the sequence variation. Eighty-eight sites in this 9.7 kb vary among individuals from these three populations. Of these, 79 were single nucleotide substitutions and 9 sites involved insertion-deletion variations. The average nucleotide diversity across the region was 0.2% (or on average 1 variable site every 500 bp). At 34 of these sites, the variation was found in only one of the populations, reflecting the differing population and mutational histories. If LPL is a typical human gene, the pattern of sequence variation that exists in introns as well as exons, even for the small number of samples considered here, will present challenges for the identification of sites, or combinations of sites, that influence variation in risk of disease in the population at large.

Base Sequence↗
PubMed1998

Haplotype structure and population genetic inferences from nucleotide-sequence variation in human lipoprotein lipase.

Allelic variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase gene (LPL) was scored in 71 healthy individuals (142 chromosomes) from three populations: African Americans (24) from Jackson, MS; Finns (24) from North Karelia, Finland; and non-Hispanic Whites (23) from Rochester, MN. The sequences had a total of 88 variable sites, with a nucleotide diversity (site-specific heterozygosity) of .002+/-.001 across this 9.7-kb region. The frequency spectrum of nucleotide variation exhibited a slight excess of heterozygosity, but, in general, the data fit expectations of the infinite-sites model of mutation and genetic drift. Allele-specific PCR helped resolve linkage phases, and a total of 88 distinct haplotypes were identified. For 1,410 (64%) of the 2,211 site pairs, all four possible gametes were present in these haplotypes, reflecting a rich history of past recombination. Despite the strong evidence for recombination, extensive linkage disequilibrium was observed. The number of haplotypes generally is much greater than the number expected under the infinite-sites model, but there was sufficient multisite linkage disequilibrium to reveal two major clades, which appear to be very old. Variation in this region of LPL may depart from the variation expected under a simple, neutral model, owing to complex historical patterns of population founding, drift, selection, and recombination. These data suggest that the design and interpretation of disease-association studies may not be as straightforward as often is assumed.

Animals↗
PubMed1998

Anaphylaxis in a milk-allergic child following ingestion of lemon sorbet containing trace quantities of milk.

Although allergic persons can react to foods containing trace quantities of unlabeled or unintended food allergens, there are few data available on the quantities of these allergens required to evoke allergic symptoms. We report a milk-allergic 3-year-old boy who experienced throat itching, facial angioedema, and vomiting within 20 min of ingesting 4 to 6 oz (ca. 113.4 to 170.1 g) of lemon sorbet. Subsequent analysis of two sorbet samples provided by the parents and a third sample purchased locally by the investigators revealed trace quantities of milk allergens, whey protein (8.8 micrograms/ml), or lactose (200 ppm). The quantity of whey protein ingested was estimated to be 120 to 180 micrograms (equivalent to 23 to 24 microliters of milk). All three sorbet samples had been manufactured in the same plant within a 4-month period; the equipment used to produce and package the sorbet was also used to produce and package ice cream. No milk allergen or whey protein was detected in 38 other marketplace sorbet samples submitted by the manufacturer for testing. We concluded that trace quantities of whey proteins (< 200 micrograms) can elicit systemic reactions in exquisitely milk-allergic individuals. Such individuals should avoid eating frozen desserts prepared using equipment also used for producing or packaging ice cream, unless manufacturers can demonstrate unequivocally that their cleaning practices are sufficient to prevent milk contamination. Adequate tests are not currently available to food manufacturers but are under development.

Allergens↗
PubMed1997

PolyPhred: automating the detection and genotyping of single nucleotide substitutions using fluorescence-based resequencing.

Fluorescence-based sequencing is playing an increasingly important role in efforts to identify DNA polymorphisms and mutations of biological and medical interest. The application of this technology in generating the reference sequence of simple and complex genomes is also driving the development of new computer programs to automate base calling (Phred), sequence assembly (Phrap) and sequence assembly editing (Consed) in high throughput settings. In this report we describe a new computer program known as PolyPhred that automatically detects the presence of heterozygous single nucleotide substitutions by fluorescencebased sequencing of PCR products. Its operations are integrated with the use of the Phred, Phrap and Consed programs and together these tools generate a high throughput system for detecting DNA polymorphisms and mutations by large scale fluorescence-based resequencing. Analysis of sequences containing known DNA variants demonstrates that the accuracy of PolyPhred with single pass data is >99% when the sequences are generated with fluorescent dye-labeled primers and approximately 90% for those prepared with dye-labeled terminators.

Animals↗
PubMed1997

Surveillance for antimicrobial resistance in enterococci.

AIM: To describe antimicrobial resistance patterns of Enterococcus species in Auckland. BACKGROUND: Antimicrobial resistant enterococci have emerged as major nosocomial pathogens in overseas hospitals. It is recommended that hospitals perform periodic surveys to determine local enterococcal resistance patterns. METHODS: Enterococcal isolates from four patient groups were tested: group I were recovered from routine clinical specimens; group II were stool isolates from patients at risk of having vancomycin resistant enterococci, eg, intensive care unit patients, patients receiving vancomycin, and immunocompromised patients receiving antibiotics; group III were enterococci from stool specimens sent for Clostridium difficile toxin testing; group IV were isolates from stool specimens submitted to a community laboratory for enteric pathogen testing. All enterococci isolated were tested for the presence of beta-lactamase, susceptibility to amoxycillin, teicoplanin, vancomycin, and for high level gentamicin and streptomycin resistance. RESULTS: There were 121 group I enterococcal isolates. 628 stool specimens were cultured. Enterococci were isolated from: 76/148 (51%) group II specimens; 166/279 (60%) group III specimens; and 70/201 (35%) of group IV specimens. Antimicrobial susceptibility testing was performed on 433 isolates; 74% were E faecalis, 12% E faecium, 6% E gallinarum/casseliflavus group and 8% other enterococcal species. No isolate produced beta-lactamase. All E faecalis were susceptible to amoxycillin. Two E faecium and one enterococcus species were resistant to amoxycillin (MICs all 16 mg/L). All isolates were susceptible to teicoplanin. Fourteen E gallinarum/casseliflavus group isolates had intermediate susceptibility to vancomycin (MICs of 8 mg/L). One E faecium had intermediate susceptibility to vancomycin (MIC 8 mg/L). High level gentamicin and streptomycin resistance occurred in 64 (15%) and 50 (12%) isolates respectively. CONCLUSION: Vancomycin resistance is rare and is essentially restricted to species that are rarely clinical pathogens, i.e., E casseliflavus and E gallinarum. Our results have established the local susceptibility profile for enterococcal isolates. This allows comparison with other locations and the detection of emerging trends of resistance.

Cross Infection↗
PubMed1997

An evaluation of the sensitivity of subjects with peanut allergy to very low doses of peanut protein: a randomized, double-blind, placebo-controlled food challenge study.

BACKGROUND: The minimum dose of food protein to which subjects with food allergy have reacted in double-blind, placebo-controlled food challenges is between 50 and 100 mg. However, subjects with peanut allergy often report severe reactions after minimal contact with peanuts, even through intact skin. OBJECTIVE: We sought to determine whether adults previously proven by challenge to be allergic to peanut react to very low doses of peanut protein. METHODS: We used a randomized, double-blind, placebo-controlled food challenge of 14 subjects allergic to peanuts with doses of peanut ranging from 10 microg to 50 mg, administered in the form of a commercially available peanut flour. RESULTS: One subject had a systemic reaction to 5 mg of peanut protein, and two subjects had mild objective reactions to 2 mg and 50 mg of peanut protein, respectively. Five subjects had mild subjective reactions (1 to 5 mg and 4 to 50 mg). All subjects with convincing objective reactions had short-lived subjective reactions to preceding doses, as low as 100 microg in two cases. Five subjects did not react to any dose up to 50 mg. CONCLUSION: Even in a group of well-characterized, highly sensitive subjects with peanut allergy, the threshold dose of peanut protein varies. As little as 100 microg of peanut protein provokes symptoms in some subjects with peanut allergy.

Adult↗