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K Taylor

Publications and source records attributed to K Taylor.

At least 73 records · Page 4Linked to original sources

Prevalence of small inversions in yeast gene order evolution.

Gene order evolution in two eukaryotes was studied by comparing the Saccharomyces cerevisiae genome sequence to extensive new data from whole-genome shotgun and cosmid sequencing of Candida albicans. Gene order is substantially different between these two yeasts, with only 9% of gene pairs that are adjacent in one species being conserved as adjacent in the other. Inversion of small segments of DNA, less than 10 genes long, has been a major cause of rearrangement, which means that even where a pair of genes has been conserved as adjacent, the transcriptional orientations of the two genes relative to one another are often different. We estimate that about 1,100 single-gene inversions have occurred since the divergence between these species. Other genes that are adjacent in one species are in the same neighborhood in the other, but their precise arrangement has been disrupted, probably by multiple successive multigene inversions. We estimate that gene adjacencies have been broken as frequently by local rearrangements as by chromosomal translocations or long-distance transpositions. A bias toward small inversions has been suggested by other studies on animals and plants and may be general among eukaryotes.

Candida albicans↗

Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS.

An expression cloning approach was employed to identify the receptor for B-lymphocyte stimulator (BLyS) and identified the tumor necrosis factor receptor superfamily member TACI as a BLyS-binding protein. Expression of TACI in HEK293T cells confers on the cells the ability to bind BLyS with subnanomolar affinity. Furthermore, a TACI-Fc fusion protein recognizes both the cleaved, soluble form of BLyS as well as the membrane BLyS present on the cell surface of a recombinant cell line. TACI mRNA is found predominantly in B-cells and correlates with BLyS binding in a panel of B-cell lines. We also demonstrate that TACI interacts with nanomolar affinity with the BLyS-related tumor necrosis factor homologue APRIL for which no clear in vivo role has been described. BLyS and APRIL are capable of signaling through TACI to mediate NF-kappaB responses in HEK293 cells. We conclude that TACI is a receptor for BLyS and APRIL and discuss the implications for B-cell biology.

B-Cell Activation Factor Receptor↗

Disparity between whites and african-americans in knowledge and treatment of cholesterol. Carolina heart survey.

PURPOSE: Elevated cholesterol is a known risk factor for coronary heart disease and studies have demonstrated a decrease in myocardial infarctions and strokes in those treated with cholesterol-lowering medications. A statewide survey was conducted to determine knowledge and treatment of cholesterol in South Carolina residents.METHODS: In 1998, a random digit telephone survey was conducted of 1200 adults in South Carolina, including 28.2% African Americans (AA), using a 46-item instrument developed to quantify awareness, knowledge and treatment of cholesterol.RESULTS: Nearly 90% of both AA and Whites (W) believe high cholesterol levels can cause a "heart attack." However, more AA (90.2%) than W (82.8%) believe that high cholesterol levels cause a "stroke" (p = 0.005). Though not statistically significant, 19.5% of W compared to 23.4% of AA reported not ever having their cholesterol checked (p = 0.066). Of those who had their cholesterol checked, less than half (47%) knew their most recent cholesterol or knew a "good" cholesterol level for an adult (41%). Fewer AA could recall their cholesterol level (p = 0.011), or knew a "good" cholesterol level for an adult (p < 0.001) as compared with W. Of the 24.2% who were told they had elevated cholesterol, 59% were under the care of a physician for cholesterol treatment, of which 56.6% reported taking cholesterol-lowering medications. There was a significant difference in the reported treatment with cholesterol-lowering medications between W and AA, 63% versus 33%, respectively (p = 0.006) and ranged from a high of 73.5% in W males to 29.4% in AA females (p = 0.005).CONCLUSIONS: The results of this population assessment suggest less knowledge about cholesterol among AA and racial disparity with regard to treatment with medications of elevated cholesterol levels.

Journal Article↗

Significant frequencies of T cells with indirect anti-donor specificity in heart graft recipients with chronic rejection.

BACKGROUND: The purpose of this study was to determine whether T cells with indirect allospecificity could be detected in heart transplant recipients with chronic rejection. METHOD AND RESULTS: Human T-cell clones were used to determine the most effective way to deliver major histocompatibility complex alloantigens for indirect presentation. Seven allograft recipients with evidence of progressive, chronic rejection were selected. Four heart graft recipients with no evidence of chronic rejection were used as controls. Peripheral blood T cells and antigen-presenting cells from the recipients were cultured with frozen/thawed stored donor cells or major histocompatibility complex class I-derived synthetic peptides in limiting dilution cultures and then compared with controls using tetanus toxoid and frozen/thawed third-party cells with no human leukocyte antigens in common with the donor. In 5 of 7 patients analyzed who had chronic rejection, elevated frequencies of T cells with indirect, anti-donor specificity (iHTLf) were detected. No such elevated iHTLf were detected in recipients without chronic rejection. DISCUSSION: iHTLf can be obtained from human transplant recipients, which supports the contention that the indirect pathway is involved in chronic transplant rejection.

Animals↗

Candidate locus for a nuclear modifier gene for maternally inherited deafness.

Maternally inherited deafness associated with the A1555G mutation in the mitochondrial 12S ribosomal RNA (rRNA) gene appears to require additional environmental or genetic changes for phenotypic expression. Aminoglycosides have been identified as one such environmental factor. In one large Arab-Israeli pedigree with congenital hearing loss in some of the family members with the A1555G mutation and with no exposure to aminoglycosides, biochemical evidence has suggested the role of nuclear modifier gene(s), but a genomewide search has indicated the absence of a single major locus having such an effect. Thus it has been concluded that the penetrance of the mitochondrial mutation appears to depend on additive effects of several nuclear genes. We have now investigated 10 multiplex Spanish and Italian families with 35 members with the A1555G mutation and sensorineural deafness. Parametric analysis of a genomewide screen again failed to identify significant evidence for linkage to a single autosomal locus. However, nonparametric analysis supported the role of the chromosomal region around marker D8S277. The combined maximized allele-sharing LOD score of 3.1 in Arab-Israeli/Spanish/Italian families represents a highly suggestive linkage result. We suggest that this region should be considered a candidate for containing the first human nuclear modifier gene for a mitochondrial DNA disorder. The locus operates in Arab-Israeli, Spanish, and Italian families, resulting in the deafness phenotype on a background of the mitochondrial A1555G mutation. No obvious candidate genes are located in this region.

Arabs↗

The protein core of the proteoglycan perlecan binds specifically to fibroblast growth factor-7.

Perlecan is a multifaceted heparan sulfate proteoglycan that is expressed not only as an intrinsic constituent of basement membranes but also as a cell-surface and pericellular proteoglycan. Perlecan functions as a ligand reservoir for various growth factors that become stabilized against misfolding or proteolysis and acts as a co-receptor for basic fibroblast growth factor by augmenting high affinity binding and receptor activation. These biological properties are mediated by the heparan sulfate moiety. Rather little is known about the protein core's mediation of functions. We have recently discovered that fibroblast growth factor-7 (FGF7) binds to perlecan protein core and that exogenous perlecan efficiently reconstitutes FGF7 mitogenic activity in perlecan-deficient cells. In this report we examined the specific binding of FGF7 to various domains and subdomains of perlecan protein core. Using several experimental approaches including overlay protein assays, radioligand binding experiments, and the yeast two-hybrid system, we demonstrate that FGF7 binds specifically to the N-terminal half of domain III and to a lesser extent to domain V, with affinity constants in the range of 60 nM. Thus, perlecan protein core should be considered a novel biological ligand for FGF7, an interaction that could influence cancer growth and tissue remodeling.

Cells, Cultured↗

Polar Plasmodium falciparum lipids induce lipogenesis in rat adipocytes in vitro.

Previous studies have shown that 'toxic malarial antigens' released by Plasmodium yoelii can induce hypoglycaemia in mice and act synergistically with insulin in stimulating lipogenesis in rat adipocytes in vitro. In this study, it was shown that similar bioactivity could be detected in Plasmodium falciparum culture supernatant, and the molecular basis of this activity was further investigated. Boiled spent culture medium from P. falciparum cultures ('BS-Pf') (exclusively released into the culture supernatant when schizonts rupture) acts in synergy with insulin to increase lipogenesis in a rat adipocyte assay by more than 250% (P < 0.001). Control preparations prepared from non-parasitized erythrocytes grown under similar conditions had no effect (P < 0.001). While contamination with mycoplasma has previously been shown to interfere with the interpretation of data obtained with other molecules thought to be released from P. falciparum in culture, including those inducing TNF-alpha and NO production by macrophages, such contamination was unequivocally ruled out here. BS-Pf alone did not stimulate the lipogenesis in short-term assays (less than 4 h), while long-term exposure of rat adipocytes to BS-Pf alone (12-24 h) caused a stimulation of lipogenesis at a level comparable to that observed with insulin. Furthermore, lipogenesis-inducing activity was also detected in the serum of squirrel monkeys infected with different species of malaria parasites (P. vivax, P. falciparum and P. brasilianum). Preliminary biochemical characterization showed that the biological activity was found in the solvent-extracted polar lipid fraction of boiled supernatant of P. falciparum cultures. All the different polar lipid fractions, collected from silica gel column chromatography, showed a comparable lipogenesis-inducing activity. Enzymatic treatment by phospholipase C of the lipid fraction, which co-migrated with the phosphatidylcholine standard, showed that the activity of the fraction was associated with the 1,2-diacylglycerol (1,2-DAG) moieties released from polar lipids. When this exogenous 1,2-DAG was added to the adipocyte cultures (short- and long-term cultures), it induced stimulation of lipogenesis in rat adipocytes, while no lipogenic activity was obtained from bacterial polar lipids and 1,2-DAG isolated from unparasitized erythrocytes. The importance of these findings is discussed with reference to other toxic malarial antigens and also to the potential role of these molecules in the induction of hypoglycaemia in the severe forms of malaria.

Adipocytes↗

DMBA-induced mammary pathologies are angiogenic in vivo and in vitro.

We have previously shown that human pre-invasive diseases of the breast are angiogenic. In addition, normal epithelium from women with coincident or subsequent invasive breast cancer is more vascular than normal epithelium from women with no breast cancer. To develop a model in which to study the regulation of angiogenesis in pre-invasive mammary pathologies, we examined 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tissues for the presence of neovascularization in pre-invasive histopathologies. These studies included morphometric analysis of tissue vascularity in pre-invasive lesions. In addition, we isolated fresh tumors and histologically normal epithelium (organoids) from DMBA or vehicle-treated control rats to test their ability to induce endothelial cell tubule formation in vitro. Finally, we examined tumors for their ability to produce vascular endothelial cell growth factor. The morphometric studies documented that with epithelial progression, the ability of individual cells to elicit angiogenesis increases. The in vitro studies showed that isolated tumors from these animals stimulate angiogenesis. Furthermore, normal epithelium from DMBA-treated rats is more angiogenic than epithelium from control animals. Finally, DMBA-induced tumors produce vascular endothelial growth factor (VEGF) mRNA, therefore, DMBA-induced mammary tumorigenesis is one model in which to test the dependency of progression on angiogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Diagnosis and management of subdural haematoma complicating bone marrow transplantation.

Subdural haematoma (SDH) is a known complication of bone marrow transplantation (BMT). A retrospective review of 657 consecutive patients undergoing allogeneic or autologous bone marrow/stem cell transplantation at the Royal Brisbane Hospital between January 1991 and December 1998 is reported. Seventeen cases of subdural haematoma/hygroma were identified (2.6%). Eleven of these (65%) were bilateral. Four required surgical drainage, with two developing re-accumulation of SDH. All cases presented with a headache and eight of these had associated neurological complications. Diagnosis was made predominately by CT scan: however in 25% of cases definitive diagnosis could only be made in MRI studies. An association with intrathecal methorexate-containing conditioning therapy, post lumbar puncture headache, prolonged thrombocytopenia and coagulopathy was noted. In our experience, conservative management with platelet support and correction of coagulopathy achieved resolution of subdural haematoma in most cases, with surgical intervention being reserved for neurological deterioration. Bone Marrow Transplantation (2000) 25, 549-552.

Adolescent↗

Is familial non-medullary thyroid carcinoma more aggressive than sporadic thyroid cancer? A multicenter series.

BACKGROUND: The aggressiveness of familial non-medullary thyroid cancer (FNMTC) has been a subject of debate. The purpose of the study was to determine whether FNMTC is more aggressive than sporadic thyroid cancer. METHODS: A multicenter retrospective matched-case control study of FNMTC versus sporadic non-medullary thyroid cancer was conducted. Disease-free survival (time to recurrence) for both groups was compared. RESULTS: Forty-eight familial cases were compared with 144 age-, gender-, and stage-matched controls. Patients with FNMTC had a significantly shorter disease-free survival compared with sporadic non medullary thyroid cancer. Patients with FNMTC who presented with evidence of distant metastasis, or who were from families with more than 2 thyroid cancer-affected members, had the worst prognosis. The available staging systems were less likely to predict the outcome in patients with FNMTC than in patients with sporadic non-medullary thyroid cancer unless one accounted for the strength of family history in the staging system. CONCLUSIONS: FNMTC is more aggressive than sporadic non-medullary thyroid cancer. The best predictors of a poor outcome in patients with FNMTC are the number of family members affected by thyroid cancer and evidence of distant metastasis.

Adult↗

A validation of the Mobil O Graph (version 12) ambulatory blood pressure monitor.

OBJECTIVE: To assess the clinical accuracy of the Mobil O Graph (version 12) ambulatory blood pressure monitor in an adult population. METHODS: The accuracy of the device was assessed by predefined criteria (British Hypertension Society, BHS) in 85 subjects recruited from the patients and staff in a teaching hospital. A series of same-arm sequential blood pressure measurements were taken: first two observers taking simultaneous mercury readings, followed by a reading with the Mobil O Graph ambulatory monitor. A total of seven readings were taken from each subject in the sitting position. The data were then analysed according to the BHS protocol and the criteria of the Association for the Advancement of Medical Instrumentation (AAMI). RESULTS: The Mobil O Graph ambulatory monitor fulfilled the criteria of the BHS protocol, achieving a grade B for systolic blood pressure (SBP) and a grade A for diastolic blood pressure (DBP). The mean differences were -2+/-8 mmHg for SBP and -2+/-7 mmHg for DBP. The device therefore also passed the AAMI standard (the mean to be within 5+/-8 mmHg). CONCLUSION: The Mobil O Graph ambulatory monitor performed in a satisfactory manner according to the BHS and the AAMI criteria and can therefore be recommended for clinical use in the general population.

Adolescent↗

Can diagnostic laparoscopy be avoided in routine investigation for infertility?

OBJECTIVE: To determine whether routine testing for serum Chlamydia trachomatis antibodies, considered in combination with a woman's clinical features, may avoid the need for diagnostic laparoscopy in routine investigation for infertility. DESIGN: Retrospective case notes analysis. SETTING: Secondary level care infertility clinic. POPULATION: Eighty women who had undergone both laparoscopy and serum Chlamydia trachomatis antibody testing. METHODS: Ascertainment of any history of suspected pelvic inflammatory disease, pelvic pain, cervical intraepithelial neoplasia, pelvic surgery or appendicectomy; any abnormality on clinical pelvic examination; the findings at laparoscopy; the result of serum Chlamydia trachomatis antibody testing by enzyme-linked immunosorbent assay (ELISA) screening with microimmunofluorescence (MIF) confirmatory diagnostic testing. The usefulness of clinical features, the serum Chlamydia trachomatis antibody test and these two variables combined in the detection of tubal disease and pelvic pathology of relevance to infertility were measured statistically. MAIN OUTCOME MEASURES: Specificity, sensitivity, positive predictive value, negative predictive value and likelihood ratio for each of the tests. RESULTS: The combination of any positive clinical feature with a positive test for serum Chlamydia trachomatis antibodies detects tubal disease with sensitivity 92%, specificity 70%, positive predictive value 72%, negative predictive value 91% and likelihood ratio 3 x 1; it detects bilateral tubal obstruction with sensitivity 84%, specificity 51%, positive predictive value 35%, negative predictive value 91% and likelihood ratio 1 x 7; it detects pelvic pathology relevant to infertility with sensitivity 76%, specificity 71%, positive predictive value 80%, negative predictive value 65% and likelihood ratio 2 x 6. The negative predictive value for pelvic pathology from the use of clinical features in addition to the chlamydia antibody test is not significantly higher than that from the chlamydia antibody test alone (53%). CONCLUSIONS: A policy of selective laparoscopy in routine investigation for infertility, based on the result of the test for serum Chlamydia trachomatis antibodies and a woman's clinical features, is not supported.

Adult↗