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Biomedical subjects

C T Taylor

Publications and source records attributed to C T Taylor.

At least 19 recordsLinked to original sources
PubMed2001

Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia.

Mucosal organs such as the intestine are supported by a rich and complex underlying vasculature. For this reason, the intestine, and particularly barrier-protective epithelial cells, are susceptible to damage related to diminished blood flow and concomitant tissue hypoxia. We sought to identify compensatory mechanisms that protect epithelial barrier during episodes of intestinal hypoxia. Initial studies examining T84 colonic epithelial cells revealed that barrier function is uniquely resistant to changes elicited by hypoxia. A search for intestinal-specific, barrier-protective factors revealed that the human intestinal trefoil factor (ITF) gene promoter bears a previously unappreciated binding site for hypoxia-inducible factor (HIF)-1. Hypoxia resulted in parallel induction of ITF mRNA and protein. Electrophoretic mobility shift assay analysis using ITF-specific, HIF-1 consensus motifs resulted in a hypoxia-inducible DNA binding activity, and loading cells with antisense oligonucleotides directed against the alpha chain of HIF-1 resulted in a loss of ITF hypoxia inducibility. Moreover, addition of anti-ITF antibody resulted in a loss of barrier function in epithelial cells exposed to hypoxia, and the addition of recombinant human ITF to vascular endothelial cells partially protected endothelial cells from hypoxia-elicited barrier disruption. Extensions of these studies in vivo revealed prominent hypoxia-elicited increases in intestinal permeability in ITF null mice. HIF-1-dependent induction of ITF may provide an adaptive link for maintenance of barrier function during hypoxia.

Animals↗
PubMed2001

Corticotropin for acute management of gout.

OBJECTIVE: To evaluate safety and efficacy of corticotropin for acute gout. DATA SOURCES: Clinical literature was accessed through MEDLINE (1966-August 2000). Key search terms included gout, ACTH, adrenocorticotropic hormone, and corticotropin. DATA SYNTHESIS: Joint pain and local signs of inflammation characterize gout. Acutely, colchicine and nonsteroidal antiinflammatory drugs (NSAIDs) are first-line therapy. Adverse effects or concomitant diseases limit therapy and necessitate alternative options. An evaluation of studies involving corticotropin was conducted. CONCLUSIONS: Corticotropin alone or in combination with colchicine was more rapidly effective and associated with fewer adverse effects than indomethacin. This regimen may be considered an alternative, especially for patients with medical problems in which other regimens are contraindicated.

Adrenocorticotropic Hormone↗
PubMed2001

Safety and effectiveness of ibutilide in a community hospital.

To determine the safety and effectiveness of ibutilide, we conducted a retrospective study of patients in a community hospital from December 1997-January 2000, reviewing hospital and pharmacy records for 12 inpatients (aged 68+/-13 yrs) receiving ibutilide for atrial fibrillation or flutter. The cumulative conversion rate with ibutilide 0.012+/-0.004 mg/kg was 58%. Serious cardiovascular adverse events were documented in six patients; of those patients, five had baseline QTc intervals above 440 msec, two experienced ventricular fibrillation, and four experienced symptomatic bradycardia (range 49-60 beats/minute) requiring medical intervention. The effectiveness of ibutilide was similar to that found in previous studies. However, more complications were seen in this setting where ibutilide was used infrequently and without stringent patient selection criteria or standardized administration protocols. To ensure optimal patient care, institutions should consider implementing guidelines or education strategies to reduce the potential for serious adverse effects associated with improper screening, dosing, and monitoring of patients receiving ibutilide.

Aged↗
PubMed2001

The appearance of a second genotype of Japanese encephalitis virus in the Australasian region.

In mid-January 2000, the reappearance of Japanese encephalitis (JE) virus activity in the Australasian region was first demonstrated by the isolation of JE virus from 3 sentinel pigs on Badu Island in the Torres Strait. Further evidence of JE virus activity was revealed through the isolation of JE virus from Culex gelidus mosquitoes collected on Badu Island and the detection of specific JE virus neutralizing antibodies in 3 pigs from Saint Pauls community on Moa Island. Nucleotide sequencing and phylogenetic analyses of the premembrane and envelope genes were performed which showed that both the pig and mosquito JE virus isolates (TS00 and TS4152, respectively) clustered in genotype I, along with northern Thai, Cambodian, and Korean isolates. All previous Australasian JE virus isolates belong to genotype II, along with Malaysian and Indonesian isolates. Therefore, for the first time, the appearance and transmission of a second genotype of JE virus in the Australasian region has been demonstrated.

Animals↗
PubMed2000

Phosphorylation-dependent targeting of cAMP response element binding protein to the ubiquitin/proteasome pathway in hypoxia.

Hypoxia activates a number of gene products through degradation of the transcriptional coactivator cAMP response element binding protein (CREB). Other transcriptional regulators (e.g., beta-catenin and NF-kappa B) are controlled through phosphorylation-targeted proteasomal degradation, and thus, we hypothesized a similar degradative pathway for CREB. Differential display analysis of mRNA derived from hypoxic epithelia revealed a specific and time-dependent repression of protein phosphatase 1 (PP1), a serine phosphatase important in CREB dephosphorylation. Subsequent studies identified a previously unappreciated proteasomal-targeting motif within the primary structure of CREB (DSVTDS), which functions as a substrate for PP1. Ambient hypoxia resulted in temporally sequential CREB serine phosphorylation, ubiquitination, and degradation (in vitro and in vivo). HIV-tat peptide-facilitated loading of intact epithelia with phosphopeptides corresponding to this proteasome targeting motif resulted in inhibition of CREB ubiquitination. Further studies revealed that PP1 inhibitors mimicked hypoxia-induced gene expression, whereas proteasome inhibitors reversed the hypoxic phenotype. Thus, hypoxia establishes conditions that target CREB to proteasomal degradation. These studies may provide unique insight into a general mechanism of transcriptional regulation by hypoxia.

Amino Acid Sequence↗
PubMed2000

Parallel induction of epithelial surface-associated chemokine and proteoglycan by cellular hypoxia: implications for neutrophil activation.

Neutrophil-induced damage to the protective epithelium has been implicated in mucosal disorders associated with hypoxia, and such damage may be initiated by epithelial-derived chemokines. Because chemokines can bind to membrane proteoglycans, we hypothesized that chemokines may associate with epithelial surfaces and activate polymorphonuclear neutrophils (PMN). Epithelial hypoxia (pO2 20 torr) resulted in a time-dependent induction of interleukin-8 (IL-8) mRNA, soluble protein, as well as surface protein. Such surface IL-8 expression was demonstrated to be dependent on heparinase III expression, and extensions of these experiments indicated that hypoxia induces epithelial perlecan expression in parallel with IL-8. Finally, co-incubation of post-hypoxic epithelia with human PMN induced IL-8-dependent expression of the PMN beta2-integrin CD11b/18. These data indicate that chemokines liberated from epithelia may exist in a surface-bound, bioactive form and that hypoxia may regulate proteoglycan expression.

CD18 Antigens↗
PubMed1999

Critical role of cAMP response element binding protein expression in hypoxia-elicited induction of epithelial tumor necrosis factor-alpha.

Tissue hypoxia is intimately associated with a number of chronic inflammatory conditions of the intestine. In this study, we investigated the impact of hypoxia on the expression of a panel of inflammatory mediators by intestinal epithelia. Initial experiments revealed that epithelial (T84 cell) exposure to ambient hypoxia evoked a time-dependent induction of the proinflammatory markers tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and major histocompatibility complex (MHC) class II (37 +/- 6.1-, 7 +/- 0.8-, and 9 +/- 0.9-fold increase over normoxia, respectively, each p < 0.01). Since the gene regulatory elements for each of these molecules contains an NF-kappaB binding domain, we investigated the influence of hypoxia on NF-kappaB activation. Cellular hypoxia induced a time-dependent increase in nuclear p65, suggesting a dominant role for NF-kappaB in hypoxia-elicited induction of proinflammatory gene products. Further work, however, revealed that hypoxia does not influence epithelial intercellular adhesion molecule 1 (ICAM-1) or MHC class I, the promoters of which also contain NF-kappaB binding domains, suggesting differential responses to hypoxia. Importantly, the genes for TNF-alpha, IL-8, and MHC class II, but not ICAM-1 or MHC class I, contain cyclic AMP response element (CRE) consensus motifs. Thus, we examined the role of cAMP in the hypoxia-elicited phenotype. Hypoxia diminished CRE binding protein (CREB) expression. In parallel, T84 cell cAMP was diminished by hypoxia (83 +/- 13.2% decrease, p < 0.001), and pharmacologic inhibition of protein kinase A induced TNF-alpha and protein release (9 +/- 3.9-fold increase). Addback of cAMP resulted in reversal of hypoxia-elicited TNF-alpha release (86 +/- 3.2% inhibition with 3 mM 8-bromo-cAMP). Furthermore, overexpression of CREB but not mutated CREB by retroviral-mediated gene transfer reversed hypoxia-elicited induction of TNF-alpha defining a causal relationship between hypoxia-elicited CREB reduction and TNF-alpha induction. Such data indicate a prominent role for CREB in the hypoxia-elicited epithelial phenotype and implicate intracellular cAMP as an important second messenger in differential induction of proinflammatory mediators.

Cell Hypoxia↗
PubMed1999

Scrub typhus in north Queensland.

Scrub typhus was once common in north Queensland, but no reports from this region have been published for nearly 30 years, and the focus has turned to cases from the Northern Territory and Western Australia. In 1996, diagnosis of scrub typhus in a Queensland soldier led to recognition of an earlier outbreak with up to 17 cases. Another outbreak occurred a year later with 11 confirmed cases. All cases were in soldiers who had visited a training area near Innisfail. Review of other laboratory diagnoses of scrub typhus shows it is still prevalent in north Queensland, with several "hot spots".

Adult↗
PubMed1999

Berberine inhibits ion transport in human colonic epithelia.

The effects of berberine on ion transport in both human colonic mucosal epithelia and an intestinal epithelial cell line (T84) were examined. Berberine (concentration range 0-500 microM) reduced both basal and stimulated ion transport responses in human colonic mucosae in a manner which was non-specific for Ca2+ -or cAMP-mediated signals. Similarly, in cultured intestinal epithelial monolayers, berberine inhibited Ca2+ -and cAMP-mediated responses indicating an inhibitory activity directly at the level of the epithelium rather than an indirect effect through other mucosal element(s). Berberine did not alter the rate of generation of cAMP by adenylyl cyclase or the activity of protein kinase A, the effector enzyme of the cAMP pathway. Berberine inhibited carbachol-stimulated 86Rb+ efflux from T84 monolayers. Berberine also inhibited K+ conductance in apically-permeabilised re-sected mucosae. These results indicate i) that berberine exerts an anti-secretory action directly upon epithelial cells and ii) the mechanism of action may be at the level of blockade of K+ channels.

Berberine↗
PubMed1999

Therapeutic targets for hypoxia-elicited pathways.

Diminished oxygen supply to tissues (hypoxia) can stem from many sources, and is a contributing factor to diverse disease processes. Cell and tissue responses to hypoxia are diverse and include dramatic changes in metabolic demand, regulation of cellular gene products, and release of lipid and protein mediators. Surprisingly little attention has been paid to targeted development of therapeutics for hypoxia-related disease processes. This review will focus on recent advances in cellular and molecular biology pertaining to the hypoxia response, and will discuss paradigms used to study hypoxia and the potential targets for therapeutic intervention.

Animals↗
PubMed1999

Quality of life and Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PD) have a progressive loss of function eventually leading to severe disability. Although PD would be expected to have a profound impact on an individual's psychosocial health, there is relatively limited research on its psychosocial effect. The purposes of this study were (a) to examine the relationships between physical disability, depression, and control beliefs and quality of life in people with PD and (b) to characterize how these psychosocial variables differ by stage of disease. METHODS: Eighty-six individuals from five stages based on clinical disability, ages 51-87, were interviewed. Established instruments were used to measure physical disability, depression, and control beliefs. Quality of life (QOL) was rated on a 5-point Likert scale. RESULTS: A multivariable regression model including physical disability, stage of disease, depression, mastery, and health locus of control predicted QOL (R2 = 0.48), with mastery as the only significant predictor (p = .0001). There were significant differences by PD stage for all variables (p < .05). CONCLUSIONS: Mastery predicted quality of life in individuals with PD even when depression and physical disability were included in the model. Differences in psychosocial variables by stage of PD suggest that the psychosocial profile of PD patients may change as the disease progresses.

Activities of Daily Living↗
PubMed1999

Omeprazole and vitamin B12 deficiency.

The mainstay for cobalamin deficiency is correction of the underlying disorder and replacement therapy. Because the defect is often one of absorption, parenteral or intranasal routes are recommended. In most cases, replacement therapy is all that is needed. The vitamin preparation most commonly used is cyanocobalamin (also called vitamin B12), which has no known physiologic role but instead is converted to a biologically active form before it can be used by tissues. The studies reviewed in this article clearly show that omeprazole therapy will decrease the absorption of vitamin B12 by preventing its cleavage from dietary proteins. However, these data are insufficient to infer that clinically significant deficiency will occur over time. In fact, some of the studies suggest that the simple addition of juices or other acidic drinks into the diet may dramatically increase cobalamin absorption. Clearly, well-designed clinical trials are needed to evaluate this theory over an extended follow-up period to determine the clinical significance of omeprazole-associated vitamin B12 deficiency and possibly identify patients at risk for deficiency. In conclusion, the possibility of dietary vitamin B12 malabsorption should be considered in patients receiving chronic omeprazole treatment and presenting with signs and symptoms of deficiency. All healthcare workers should be made aware of the potential clinical complications of omeprazole-associated vitamin B12 deficiency since it may go unrecognized and is easily corrected. This is particularly relevant for elderly patients with poor dietary intake of vitamin B12, impaired vitamin B12 stores, and certain gastrointestinal disorders.

Humans↗
PubMed1999

Treatment of Wegener's granulomatosis with immune globulin: CNS involvement in an adolescent female.

OBJECTIVE: To describe the use of intravenous immune globulin (IVIG) to treat Wegener's granulomatosis (WG) in an adolescent female with an abnormal magnetic resonance imaging (MRI) scan and electroencephalogram (EEG), as well as central nervous system involvement manifesting as generalized seizures. CASE SUMMARY: A 15-year-old white girl diagnosed with WG and receiving prednisone and cyclophosphamide was admitted with new-onset tonic-clonic seizures. The patient received phenobarbital and phenytoin to control seizures and was receiving cyclophosphamide and corticosteroids for WG. She developed cyclophosphamide-induced cystitis and was started on a four-day therapeutic course of IVIG following the discontinuation of cyclophosphamide. After 16 days of hospitalization, repeat EEG and MRI were within normal limits, and laboratory and clinical improvement was evident in at least nine of the affected organ systems including pulmonary, hematologic, renal, ocular, cutaneous, musculoskeletal, central nervous system, gastrointestinal, and genitourinary. The patient was discharged with clinical involvement of WG documented in two organ systems, hematologic and renal. DISCUSSION: WG is a form of vasculitis believed to develop due to an autoimmune disorder. The diagnosis is based on radiographic and histopathologic findings, as well as the presence of elevated antineutrophil cytoplasmic antibodies and a suggestive clinical presentation. The presentation is widely variable and is most commonly associated with upper-airway involvement such as sinusitis, cough, pulmonary infiltrates, and cavitary nodules. Renal involvement signifies generalized disease. Conventional treatment for WG includes cyclophosphamide and prednisone. Little information is available describing therapeutic alternatives. Cytotoxicity related to immunosuppressant regimens limits continuous treatment and may necessitate the use of alternative agents. CONCLUSIONS: This case describes the use of IVIG in an adolescent patient presenting with WG as a generalized, active disease with neurologic complications. IVIG may be useful in generalized, active WG complicated by intolerance to cyclophosphamide and seizures, but further study is necessary to define its role.

Adolescent↗
PubMed1999

Vitamin K to reverse excessive anticoagulation: a review of the literature.

We conducted an extensive literature review to evaluate the appropriate use, route, and dose of vitamin K to reverse excessive anticoagulation. Issues such as sample size, study design, different patient populations, and various study end points confounded results. Of 18 studies published, 8 enrolled 229 patients to evaluate parenteral vitamin K administration. Nine studies with 288 patients evaluated oral administration, and only 2 retrospective studies (280 patients) compared routes of administration. Reductions in international normalized ratios at 24 hours ranged from 21-42%, 47-86%, 25-67%, and 40-75% for temporary warfarin discontinuation alone, and intravenous, subcutaneous, and oral routes of vitamin K administration, respectively. Methodologically weak studies and indeterminate results plague interpretation of the literature on vitamin K. In general, results of this review support current guidelines for reversing excessive warfarin anticoagulation. However, it is important to realize that the quality of literature on which these recommendations are based is poor and that optimal dose and route of vitamin K administration remain unclear. Large, well-designed, randomized, controlled trials are necessary to define optimum management strategies for excessively anticoagulated patients.

Anticoagulants↗
PubMed1999

Vancomycin-induced neutropenia associated with fever: similarities between two immune-mediated drug reactions.

A 39-year-old woman being treated for osteomyelitis with vancomycin developed severe neutropenia and drug fever. After she discontinued therapy, both disorders quickly resolved. These adverse reactions have rarely been reported with vancomycin, and share many similarities with regard to clinical features and postulated mechanisms of induction. To our knowledge this is the first case documenting drug fever as a principal component of vancomycin-induced neutropenia, and provides further evidence in support of an immune-mediated mechanism.

Adult↗
PubMed1999

Two instruments to determine activated partial thromboplastin time: implications for heparin monitoring.

STUDY OBJECTIVE: To measure the difference in therapeutic ranges of activated partial thromboplastin time (APTT) between two laboratory devices. DESIGN: Prospective, controlled laboratory study. SETTING: University-affiliated hospital. PATIENTS: Thirty inpatients receiving intravenous unfractionated heparin for treatment of myocardial infarction, unstable angina, deep venous thrombosis, or pulmonary embolism. INTERVENTIONS: Therapeutic APTT ranges were determined by a portable (whole blood assay) and a central laboratory device (plasma assay) based on heparin serum concentrations. They were compared with APTT ranges equivalent to 1.5-2.5 times the mean normal determination. MEASUREMENTS AND MAIN RESULTS: The central laboratory and portable devices produced therapeutic ranges of 61-93 and 56-73 seconds, respectively. Both differed from conventional therapeutic ratios of 1.5-2.5 times the mean normal (41-68 sec). Mean absolute APTT differences between instruments were statistically significant (12 +/- 20 sec, p<0.006), and 58% of paired APTT values differed by more than 10 seconds. CONCLUSION: A fixed APTT ratio as a goal for monitoring unfractionated heparin may result in significant underanticoagulation. Individual therapeutic APTT ranges must be reported for each instrument if more than one is used for heparin monitoring.

Adult↗
PubMed1998

Neutrophil-derived 5'-adenosine monophosphate promotes endothelial barrier function via CD73-mediated conversion to adenosine and endothelial A2B receptor activation.

During episodes of inflammation, polymorphonuclear leukocyte (PMN) transendothelial migration has the potential to disturb vascular barrier function and give rise to intravascular fluid extravasation and edema. However, little is known regarding innate mechanisms that dampen fluid loss during PMN-endothelial interactions. Using an in vitro endothelial paracellular permeability model, we observed a PMN-mediated decrease in endothelial paracellular permeability. A similar decrease was elicited by cell-free supernatants from activated PMN (FMLP 10(-6) M), suggesting the presence of a PMN-derived soluble mediator(s). Biophysical and biochemical analysis of PMN supernatants revealed a role for PMN-derived 5'-adenosine monophosphate (AMP) and its metabolite, adenosine, in modulation of endothelial paracellular permeability. Supernatants from activated PMN contained micromolar concentrations of bioactive 5'-AMP and adenosine. Furthermore, exposure of endothelial monolayers to authentic 5'-AMP and adenosine increased endothelial barrier function more than twofold in both human umbilical vein endothelial cells and human microvascular endothelial cells. 5'-AMP bioactivity required endothelial CD73-mediated conversion of 5'-AMP to adenosine via its 5'-ectonucleotidase activity. Decreased endothelial paracellular permeability occurred through adenosine A2B receptor activation and was accompanied by a parallel increase in intracellular cAMP. We conclude that activated PMN release soluble mediators, such as 5'-AMP and adenosine, that promote endothelial barrier function. During inflammation, this pathway may limit potentially deleterious increases in endothelial paracellular permeability and could serve as a basic mechanism of endothelial resealing during PMN transendothelial migration.

5'-Nucleotidase↗