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Biomedical subjects

Ruth Taylor

Publications and source records attributed to Ruth Taylor.

8 recordsLinked to original sources

Cutaneous immune responses in the common carp detected using transcript analysis.

In order to detect new immune-related genes in common carp (Cyprinus carpio L.) challenged by an ectoparasitic infection, two cDNA libraries were constructed from carp skin sampled at 3 and 72h after infection with Ichthyophthirius multifiliis. In a total of 3500 expressed sequence tags (ESTs) we identified 82 orthologues of genes of immune relevance previously described in other organisms. Of these, 61 have never been described before in C. carpio, thus shedding light on some key components of the defence mechanisms of this species. Among the newly described genes, full-length molecules of prostaglandin D2 synthase (PGDS), the CC chemokine molecule SCYA103, and a second gene for the carp beta(2)-microglobulin (beta(2)m), beta(2)m-2, were described. Transcript amounts of the genes PGDS, interferon (IFN), SCYA103, complement factor 7 (C7), complement factor P (FP), complement factor D (FD) and beta(2)m-2 were evaluated by real-time quantitative PCR (RQ-PCR). Samples from skin, blood and liver from fish challenged with I. multifiliis were taken at 3, 12, 24, 36 and 48h post infection. Higher expression levels of most of these transcripts were observed in skin from uninfected fish, compared to the transcript levels detected in blood and liver from the same animals. Also, there was significant down-regulation of the genes PGDS and beta(2)m-2 in skin, whilst significant up-regulation was observed for the C7 and SCYA103 genes in liver of fish infected with the parasite. These results confirm the active role of fish skin in the immune response against infections, acting as an important site of expression of immune-related molecules.

Amino Acid Sequence↗

Genomic anatomy of the Tyrp1 (brown) deletion complex.

Chromosome deletions in the mouse have proven invaluable in the dissection of gene function. The brown deletion complex comprises >28 independent genome rearrangements, which have been used to identify several functional loci on chromosome 4 required for normal embryonic and postnatal development. We have constructed a 172-bacterial artificial chromosome contig that spans this 22-megabase (Mb) interval and have produced a contiguous, finished, and manually annotated sequence from these clones. The deletion complex is strikingly gene-poor, containing only 52 protein-coding genes (of which only 39 are supported by human homologues) and has several further notable genomic features, including several segments of >1 Mb, apparently devoid of a coding sequence. We have used sequence polymorphisms to finely map the deletion breakpoints and identify strong candidate genes for the known phenotypes that map to this region, including three lethal loci (l4Rn1, l4Rn2, and l4Rn3) and the fitness mutant brown-associated fitness (baf). We have also characterized misexpression of the basonuclin homologue, Bnc2, associated with the inversion-mediated coat color mutant white-based brown (B(w)). This study provides a molecular insight into the basis of several characterized mouse mutants, which will allow further dissection of this region by targeted or chemical mutagenesis.

Animals↗

Seasonally hibernating phenotype assessed through transcript screening.

Hibernation is a seasonally entrained and profound phenotypic transition to conserve energy in winter. It involves significant biochemical reprogramming, although our understanding of the underpinning molecular events is fragmentary and selective. We have conducted a large-scale gene expression screen of the golden-mantled ground squirrel, Spermophilus lateralis, to identify transcriptional responses associated specifically with the summer-winter transition and the torpid-arousal transition in winter. We used 112 cDNA microarrays comprising 12,288 probes that cover at least 5,109 genes. In liver, the profiles of torpid and active states in the winter were almost identical, although we identified 102 cDNAs that were differentially expressed between winter and summer, 90% of which were downregulated in the winter states. By contrast, in cardiac tissue, 59 and 115 cDNAs were elevated in interbout arousal and torpor, respectively, relative to the summer active condition, but only 7 were common to both winter states, and during arousal none was downregulated. In brain, 78 cDNAs were found to change in winter, 44 of which were upregulated. Thus transcriptional changes associated with hibernation are qualitatively modest and, since these changes are generally less than twofold, also quantitatively modest. Unbiased Gene Ontology profiling of the transcripts suggests a winter switch to beta-oxidation of lipids in liver and heart, a reduction in metabolism of toxic compounds and the urea cycle in liver, and downregulated electron transport in the brain. We identified just one strongly winter-induced transcript common to all tissues, namely an RNA-binding protein, RBM3. This analysis clearly differentiates responses of the principal tissues, identifies a large number of new genes undergoing regulation, and broadens our understanding of affected cellular processes that, in part, account for the winter-adaptive hibernating phenotype.

Animals↗

Mutagenic insertion and chromosome engineering resource (MICER).

Embryonic stem cell technology revolutionized biology by providing a means to assess mammalian gene function in vivo. Although it is now routine to generate mice from embryonic stem cells, one of the principal methods used to create mutations, gene targeting, is a cumbersome process. Here we describe the indexing of 93,960 ready-made insertional targeting vectors from two libraries. 5,925 of these vectors can be used directly to inactivate genes with an average targeting efficiency of 28%. Combinations of vectors from the two libraries can be used to disrupt both alleles of a gene or engineer larger genomic changes such as deletions, duplications, translocations or inversions. These indexed vectors constitute a public resource (Mutagenic Insertion and Chromosome Engineering Resource; MICER) for high-throughput, targeted manipulation of the mouse genome.

Animals↗

Postoperative analgesia in video-assisted thoracoscopy: the role of intercostal blockade.

OBJECTIVES: This study examined (1) the opioid and nonopioid requirement of patients undergoing video-assisted thoracoscopy (VATS) as a measure of postoperative pain and (2) whether percutaneous intercostal blockade might reduce morphine requirements and improve analgesia in VATS procedures. DESIGN: A combined retrospective and prospective study. SETTING: A university teaching hospital. PARTICIPANTS: Patients undergoing VATS procedures. INTERVENTIONS: A retrospective analysis of 26 sequential patients; perioperative intercostal blockade with bupivacaine, either with or without dextran 40, in 26 prospective patients. MEASUREMENTS AND MAIN RESULTS: Retrospective: opioid and nonopioid analgesic requirements of 26 sequential patients who had undergone VATS surgery without intercostal blockade were determined from a study of the case records. Twenty-six additional patients undergoing VATS surgery by the same surgeon were randomly divided to receive either percutaneous intercostal nerve block using plain bupivacaine 0.375% or bupivacaine 0.375% in dextran 40. The duration of local anesthesia was assessed. Postoperative opioid and nonopioid analgesic requirements were compared with the retrospective group. CONCLUSIONS: Postoperative morphine requirements after VATS surgery are considerable, with pleurectomy being the most painful procedure. Intercostal blockade with bupivacaine provided effective pain relief and a dramatic reduction in morphine requirements. This technique is recommended for VATS surgery, especially if day-case procedures are being contemplated.

Analgesics↗

Defined-contribution health insurance products: development and prospects.

Defined-contribution health insurance products have received considerable recent attention, stimulated by double-digit increases in health plan premiums and employers' desire to get their employees more involved in health care purchasing decisions. Existing products typically feature a consumer health spending account, a major medical or other insurance policy, and the use of the Internet to support consumer decision making. They vary in their use of provider networks, provider payment approaches, the specific design of spending accounts, marketing strategies, and infrastructure investment. The companies producing these products are now at a critical juncture. They could grow rapidly over the next few years, be acquired by existing health plans, or fail if they do not deliver on their promises.

Consumer Behavior↗

Health savings accounts: early estimates of national take-up.

The 2003 Medicare Prescription Drug, Improvement, and Modernization Act (MMA) approved tax-advantaged health savings accounts (HSAs) for certain high-deductible health insurance plans. We predict that MMA could lead to approximately 3.2 million HSA contracts among Americans ages 19-64 who are not students, not enrolled in public health insurance plans, and not eligible for group coverage as a dependent. We simulate the effect of several additional tax subsidies for HSAs. We predict that the Bush administration's refundable tax-credit proposal would double HSA take-up and reduce the number of uninsured people by 2.9 million, at an annual cost of $8.1 billion.

Adult↗