Ondansetron versus droperidol for postoperative nausea and vomiting.
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Administration, Oral↗
Biomedical subjects
J Phillips
Publications and source records attributed to J Phillips.
Evaluation of a novel, anti-herpes simplex virus compound, acyclovir elaidate (P-4010), in the female guinea pig model of genital herpes.
The antiviral effect of acyclovir elaidate in the female guinea pig model of genital herpes was investigated in a series of experiments. The antiherpesvirus effects of this novel compound, 9-(2'-[trans-9"-octadecenoyloxyl]ethoxymethyl)guanine (code no. P-4010), were studied in both primary and recurrent genital herpes in the female guinea pig, following oral gavage or intraperitoneal injection, with different formulations of the compound, and in comparison with acyclovir (ACV) or penciclovir (PCV). The results indicate that compound P-4010 has a greater capability than either ACV or PCV in reducing the clinical symptoms of primary genital herpes induced following the inoculation of herpes simplex virus type 2 (HSV-2) intravaginally into guinea pigs. In addition, the administration of P-4010 twice daily over a 10-day period by the intraperitoneal route (15 to 40 mg/kg of body weight/day) or by oral gavage (50 to 200 mg/kg/day), commencing 4 h subsequent to intravaginal HSV-2 infection, resulted in a degree of reduction in the incidence and severity of spontaneous, recurrent genital herpes in these animals. The findings are discussed in the light of the value and relevance of the female guinea pig model of genital herpes for the assessment of anti-herpes simplex virus compounds.
Acyclovir↗
Acid- and base-induced proteins during aerobic and anaerobic growth of Escherichia coli revealed by two-dimensional gel electrophoresis.
Proteins induced by acid or base, during long-term aerobic or anaerobic growth in complex medium, were identified in Escherichia coli. Two-dimensional gel electrophoresis revealed pH-dependent induction of 18 proteins, nine of which were identified by N-terminal sequencing. At pH 9, tryptophan deaminase (TnaA) was induced to a high level, becoming one of the most abundant proteins observed. TnaA may reverse alkalinization by metabolizing amino acids to produce acidic products. Also induced at high pH, but only in anaerobiosis, was glutamate decarboxylase (GadA). The gad system (GadA/GadBC) neutralizes acidity and enhances survival in extreme acid; its induction during anaerobic growth may help protect alkaline-grown cells from the acidification resulting from anaerobic fermentation. To investigate possible responses to internal acidification, cultures were grown in propionate, a membrane-permeant weak acid which acidifies the cytoplasm. YfiD, a homologue of pyruvate formate lyase, was induced to high levels at pH 4.4 and induced twofold more by propionate at pH 6; both of these conditions cause internal acidification. At neutral or alkaline pH, YfiD was virtually absent. YfiD is therefore a strong candidate for response to internal acidification. Acid or propionate also increased the expression of alkyl hydroperoxide reductase (AhpC) but only during aerobic growth. At neutral or high pH, AhpC showed no significant difference between aerobic and anaerobic growth. The increase of AhpC in acid may help protect the cell from the greater concentrations of oxidizing intermediates at low pH. Isocitrate lyase (AceA) was induced by oxygen across the pH range but showed substantially greater induction in acid or in base than at pH 7. Additional responses observed included the induction of MalE at high pH and induction of several enzymes of sugar metabolism at low pH: the phosphotransferase system components ManX and PtsH and the galactitol fermentation enzyme GatY. Overall, our results indicate complex relationships between pH and oxygen and a novel permeant acid-inducible gene, YfiD.
Acetyltransferases↗
Identification of a unique glomerular factor X activator in murine lupus nephritis.
The role of glomerular procoagulant activity (PCA) was studied in mice (MRL/lpr, NZBxWF,, and BXSB) that are known to develop lupus nephritis. In young mice (6 to 8 wk) without renal disease, there was no increase in spontaneous glomerular PCA. In contrast, older (5 to 8 mo) autoimmune mice had significant augmentation in glomerular PCA, coinciding with the histologic appearance of severe glomerulonephritis and renal fibrin deposition. The PCA was characterized as a serine protease that directly activated factor X. This factor X activator is not tissue factor because (1) expression of PCA was not dependent on factor VII; (2) a monoclonal antibody against the factor X activator inhibited glomerular PCA, but not tissue factor; (3) the molecular weight (66 kD) of the activator was different from that of tissue factor; and (4) concanavalin A inhibited tissue factor but not glomerular PCA. Immunohistochemical studies localized the factor X activator to the glomerular mesangium and capillary wall of 4- to 6-mo-old diseased MRL/lpr mice. Immunogold-labeled antibody bound to the dense deposits, macrophages, and endothelial cells of diseased glomeruli. These studies define the role of a unique glomerular factor X activator in murine lupus nephritis.
Animals↗
Interleukin-13 prevents autoimmune diabetes in NOD mice.
Interleukin (IL)-13 is a cytokine primarily produced by the T-helper (Th)-2 subset of lymphocytes that possesses powerful anti-inflammatory properties. Here, we have evaluated the impact of IL-13 treatment on development of type 1 diabetes in diabetes-prone nonobese diabetic (NOD) mice. Prolonged treatment with recombinant human IL-13 (hIL-13) markedly diminished the incidence of spontaneous type 1 diabetes in the mice. Female NOD mice treated from age 5-16 weeks with hIL-13 also showed significantly milder insulitis than control mice. The preventive action of hIL-13 was associated with a slight but significant change from a type 1 to a type 2 cytokine response. Accordingly, splenic lymphoid cells (SLC) from hIL-13-treated mice secreted less interferon (IFN)-gamma upon ex vivo stimulation with Concanavalin A than controls, and anti-CD3 monoclonal antibody-induced activation of T-cells in vivo resulted in lower blood levels of IFN-gamma and tumor necrosis factor-alpha and augmented blood levels of IL-4 in NOD mice pretreated with hIL-13. hIL-13 treatment also increased the blood levels of IgE and inhibited the transfer of type 1 diabetes by spleen cells from a diabetic donor to irradiated recipients. Taken together, these data add hIL-13 to the list of cytokines capable of downregulating immunoinflammatory diabetogenic pathways in NOD mice, and further support the concept that IL-4-related anti-inflammatory cytokines might have a role in the prevention of type 1 diabetes.
Animals↗
Comparison of arcuate-legged clipped versus sutured hepatic artery, portal vein, and bile duct anastomoses.
Attempts at improving anastomoses have included the development of stapling techniques. Our purpose was to evaluate arcuate-legged clipped versus standard sutured anastomoses of the hepatic artery (HA), portal vein (PV), and bile duct in a porcine liver transplantation model. Two groups of pigs were studied intraoperatively and 1 day after liver transplantation. A control group underwent sutured anastomosis of PV and HA with polypropylene and of bile duct with polydioxanone (n = 8). An experimental group underwent anastomoses with arcuate-legged clips (n = 8). We analyzed the time to perform anastomosis and flows before and at various time points after anastomosis. In addition, patency and histology of the anastomoses were evaluated 1 day after operation, including a fibrin-thrombosis score, medial injury, and inflammation score. Times to complete HA and PV anastomoses were not different between clipped and sutured groups. However, the time was shorter to complete bile duct anastomosis with clips than with sutures (6.3 +/- 1.1 minutes and 13.3 +/- 2.0 minutes, respectively). Flows through HA anastomoses were not different between groups, but flow through the PV was higher in clipped compared with sutured anastomosis (P = 0.06). Patency was 100 per cent with no leaks for all three anastomoses in both groups. Histologic data were similar between vascular anastomotic groups. Sutured bile duct anastomoses revealed mild smooth muscle injury in 75 per cent whereas clipped bile duct anastomoses displayed no smooth muscle injury. We conclude that arcuate-legged clipped anastomosis represents a viable option to sutured anastomoses of the PV, HA, and bile duct anastomoses. Bile duct anastomoses were completed in less than half the time and with less tissue damage documented histologically.
Anastomosis, Surgical↗
Comprehensive evaluation of isoprenoid biosynthesis regulation in Saccharomyces cerevisiae utilizing the Genome Reporter Matrix.
Gene expression profiling is rapidly becoming a mainstay of functional genomic studies. However, there have been relatively few studies of how the data from expression profiles integrate with more classic approaches to examine gene expression. This study used gene expression profiling of a portion of the genome of Saccharomyces cerevisiae to explore the impact of blocks in the isoprenoid biosynthetic pathway on the expression of genes and the regulation of this pathway. Approximately 50% of the genes whose expression was altered by blocks in isoprenoid biosynthesis were genes previously known to participate in the pathway. In contrast to this simple correspondence, the regulatory patterns revealed by different blocks, and in particular by antifungal azoles, was complex in a manner not anticipated by earlier studies.
Base Sequence↗
Ocular microtremor in brain stem death
OBJECTIVE: This study was undertaken to establish whether measurement of ocular microtremor (OMT) activity could be used as a method to establish brain stem death. Presently, the diagnosis of brain stem death can be made using clinical criteria alone. OMT is a high-frequency, low-amplitude physiological tremor of the eye caused by impulses emanating from the brain stem. There have been a number of reports indicating that the recording of OMT may be useful in the assessment of comatose states and in establishing brain stem viability or death. METHODS: We obtained the OMT recordings of 32 patients suspected of having brain stem death using the piezoelectric strain gauge technique. This method involves mounting the piezoelectric probe in a headset and lowering the rubber-tipped end piece onto the anesthetized scleral surface of the subject. The signal produced is recorded on audiomagnetic tape and later played back and analyzed on an electrocardiographic tape analyzer. RESULTS: In 28 patients, initial clinical assessment confirmed the diagnosis of brain stem death and no OMT activity was recorded from these subjects. In three patients in whom initial clinical assessment demonstrated brain stem function, OMT activity was present; when brain stem death was subsequently diagnosed in these three patients, no OMT activity could be demonstrated. In the remaining patient, two of three OMT recordings demonstrated activity in spite of the absence of clinical evidence of brain stem function. A post mortem revealed bacterial cerebritis in this subject. CONCLUSION: The results suggest that OMT is a sensitive method of detecting brain stem life and that it could play an important role in the assessment of brain stem death.
Journal Article↗
Use of glycoprotein IIb/IIIa inhibitors in patients with coronary artery disease.
GP IIb/IIIa inhibitors are one of the most exciting pharmacological advances in the treatment of coronary artery disease to be developed this decade. They have proven benefit in the treatment of patients undergoing high-risk percutaneous interventions and in patients with unstable angina or non-Q-wave myocardial infarction. In all of these patients, they should be used in conjunction with aspirin and heparin. Although bleeding complications are high in initial studies, they are much less common with increased clinical experience and careful attention to heparin dosing. Important questions that will be answered in the next several years include whether there are significant differences between the available agents and whether oral formulations will be safe and effective.
Abciximab↗
Revealing interactions among brain systems with nonlinear PCA.
In this work, we present a nonlinear principal component analysis (PCA) that identifies underlying sources causing the expression of spatial modes or patterns of activity in neuroimaging time series where these sources can interact to produce second-order modes. This nonlinear PCA uses a neural network architecture that embodies a specific form for the mixing of sources that is based on a second-order approximation to any general nonlinear mixing. The modes obtained have a unique rotation and scaling that does not depend on the biologically implausible constraints adopted by conventional PCA. Interactions among sources render the expression of any mode or brain system sensitive to the expression of others. The example considers interactions among functionally specialized brain systems (using a fMRI study of colour and motion processing).
Brain↗
FGFR2 mutation associated with clinical manifestations consistent with Antley-Bixler syndrome.
The Antley-Bixler syndrome (ABS) is a rare syndrome with synostosis of cranial sutures and elbow joints as minimal diagnostic criteria. The inheritance has been suggested to be autosomal recessive based on two families with sib recurrence with both sexes being affected, and two cases born to consanguineous parents. We report the first case of ABS associated with an apparent dominant de novo mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. The patient was found to be heterozygous for a C-->G transversion at nucleotide 1064, which predicts a Ser351Cys amino acid substitution in the IgIII domain of FGFR2. Apart from the craniosynostosis and elbow ankylosis, our patient also presented with severe spinal dysraphism, the first report of such a finding in association with ABS. This suggests that FGFR2 is expressed as early as the fourth week of embryogenesis when somite formation occurs. We propose that the Antley-Bixler syndrome is an autosomal dominant condition with possible gonadal mosaicism. Alternatively, there may be two types of ABS: an autosomal dominant form and an autosomal recessive form. In light of our findings, FGFR mutations should be looked for in other craniosynostosis patients with elbow synostosis.
Abnormalities, Multiple↗
Blood polymorphonuclear leukocytes from the majority of sickle cell patients in the crisis phase of the disease show enhanced adhesion to vascular endothelium and increased expression of CD64.
There is increasing interest in the role of blood polymorphonuclear leukocytes (PMNs) in the pathogenesis of sickle cell crisis. We studied the adherence of PMNs from 18 sickle cell patients in crisis, 25 out of crisis, and 43 healthy subjects (controls) to monolayers of human umbilical cord endothelium that were either untreated or pretreated with tumor necrosis factor alpha (TNFalpha). Overall, the PMNs from patients in crisis were more adherent than control PMNs to untreated endothelial monolayers (mean 53% increase; P < .001) and TNFalpha-treated monolayers (mean 41% increase; P < .002). Increased adhesiveness was not associated with an abnormal expression of CD11a, CD11b, CD11c, CD18, CD62L, or CD15. There was an increase in the number of PMNs expressing CD64 in patients in crisis (median value, 44%) compared with patients out of crisis (median, 21%; P = .025) and controls (median, 6.5%; P < .001). Sera from patients in crisis had normal levels of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon-gamma, TNFalpha, interleukin-1 (IL-1), IL-6, or IL-8 and did not modify the adherence of PMNs or their expression of CD64. Only IFN-gamma induced CD64 expression on PMNs, but this effect was not associated with enhanced binding to endothelium. Because PMNs bound to endothelial monolayers were CD64(+) and CD64-enriched PMNs were 7 times more adherent to endothelial monolayers than CD64-depleted PMNs, it is likely that CD64 is a marker of adherent PMNs. Two of the three anti-CD64 antibodies used in our antibody blocking studies (clones 32.2 and 197) partially inhibited the binding of sickle cell PMNs to untreated endothelium (mean inhibitions of 33% [P = .01] and 21% [P = .03], respectively), whereas only one (clone 197) inhibited binding to TNFalpha-treated endothelium (mean inhibition, 29%; P = . 004). In some patients with sickle cell disease, an enhanced PMN adhesion to vascular endothelium could contribute to the vascular occlusion that characterizes the acute crisis of the disease.
Acute Disease↗
Speed-dependent motion-sensitive responses in V5: an fMRI study.
This fMRI study examined motion-sensitive responses in human area V5 as a function of stimulus speed. Consistent with electrophysiological findings, we observed optimal responses at intermediate speeds of around 7 degrees/s to 30 degrees/s. The results are consistent with a nonlinear (inverted "U") dependency on speed that was also observed in V3a. V1 activation was observed to decrease linearly as speed increased. This is consistent with the fact that speed-sensitive cells in V1 have been shown to be tuned to much slower speeds than in V5.
Brain↗
Two dehydration-inducible transcripts from the resurrection plant Craterostigma plantagineum encode interacting homeodomain-leucine zipper proteins.
The molecular dissection of desiccation tolerance in the resurrection plant Craterostigma plantagineum led to the isolation of two dehydration-stress inducible homeo-domain-leucine zipper genes (CPHB-1 and -2). When the coding region of CPHB-1 was used as bait in the yeast two-hybrid system, the ability of CPHB-1 to form homodimers was demonstrated. The two-hybrid system was also used to isolate CPHB-2, which heterodimerises with CPHB-1. Both transcripts are inducible by dehydration in leaves and roots, but steady state levels vary in response to exogenously applied ABA. Although expression of CPHB-1 is not inducible by ABA, the transcript level of CPHB-2 increases during ABA-treatment. Both genes are expressed at very early stages of dehydration and thus may be involved in the regulation of gene expression during dehydration. CPHB-1 and -2 differential expression in response to ABA suggests that they act in different branches of the dehydration-induced signalling network. In vitro binding studies revealed that CPHB-1 specifically binds to the pseudopalindromic sequence CAAT(C/G)ATTG. Using this element for in vitro binding studies with nuclear proteins from dehydrated leaves, an inducible DNA-protein complex was identified.
Abscisic Acid↗
Worksite and family education for dietary change: the Treatwell 5-a-Day program.
The National Cancer Institute's '5-a-Day for Better Health Campaign is examining the efficacy of interventions in increasing the consumption of fruits and vegetables to five or more servings a day. This paper presents the study design, intervention and baseline survey results of the Treatwell 5-a-Day project, a randomized, controlled worksite-based intervention study. Twenty-two community health centers were randomly assigned to either a Minimal Intervention, Worksite Intervention or Worksite Plus Family Intervention. The Worksite Intervention included participation of employee advisory boards, programs aimed at individual behavior change and programs aimed at changes in the worksite environment. The Worksite Plus Family Intervention incorporated family-focused interventions into the worksite program, including a learn-at-home program, family newsletter, family festival and materials mailings. A self-administered survey was conducted prior to randomization (mean response rate: 87%, n = 1359). Twenty-three percent reported consuming five or more servings of fruits and vegetables a day. Consumption of fruits and vegetables was directly associated with level of household support for healthy eating. The Treatwell 5-a-Day intervention model has the potential to enhance existing worksite-based intervention through incorporation of its family focus, especially given the association of household support with individual eating habits.
Adult↗
Targeted recombination within the spike gene of murine coronavirus mouse hepatitis virus-A59: Q159 is a determinant of hepatotropism.
Previous studies of a group of mutants of the murine coronavirus mouse hepatitis virus (MHV)-A59, isolated from persistently infected glial cells, have shown a strong correlation between a Q159L amino acid substitution in the S1 subunit of the spike gene and a loss in the ability to induce hepatitis and demyelination. To determine if Q159L alone is sufficient to cause these altered pathogenic properties, targeted RNA recombination was used to introduce a Q159L amino acid substitution into the spike gene of MHV-A59. Recombination was carried out between the genome of a temperature-sensitive mutant of MHV-A59 (Alb4) and RNA transcribed from a plasmid (pFV1) containing the spike gene as well as downstream regions, through the 3' end, of the MHV-A59 genome. We have selected and characterized two recombinant viruses containing Q159L. These recombinant viruses (159R36 and 159R40) replicate in the brains of C57BL/6 mice and induce encephalitis to a similar extent as wild-type MHV-A59. However, they exhibit a markedly reduced ability to replicate in the liver or produce hepatitis compared to wild-type MHV-A59. These viruses also exhibit reduced virulence and reduced demyelination. A recombinant virus containing the wild-type MHV-A59 spike gene, wtR10, behaved essentially like wild-type MHV-A59. This is the first report of the isolation of recombinant viruses containing a site-directed mutation, encoding an amino acid substitution, within the spike gene of any coronavirus. This technology will allow us to begin to map the molecular determinants of pathogenesis within the spike glycoprotein.
Amino Acid Substitution↗
Requirement for cellular cyclin-dependent kinases in herpes simplex virus replication and transcription.
Several observations indicate that late-G1/S-phase-specific cellular functions may be required for herpes simplex virus (HSV) replication: (i) certain mutant HSV strains are replication impaired during infection of cells in the G0/G1 but not in the G1/S phase of the cell cycle, (ii) several late-G1/S-phase-specific cellular proteins and functions are induced during infection, and (iii) the activity of a cellular protein essential for expression of viral immediate-early (IE) genes, HCF, is normally required during the late G1/S phase of the cell cycle. To test the hypothesis that late-G1/S-phase-specific cellular functions are necessary for HSV replication, HEL or Vero cells were infected in the presence of the cell cycle inhibitors roscovitine (Rosco) and olomoucine (Olo). Both drugs inhibit cyclin-dependent kinase 1 (cdk-1) and cdk-2 (required for cell cycle progression into the late G1/S phase) and cdk-5 (inactive in cycling cells) but not cdk-4 or cdk-6 (active at early G1). We found that HSV replication was inhibited by Rosco and Olo but not by lovastatin (a cell cycle inhibitor that does not inhibit cdk activity), staurosporine (a broad-spectrum protein serine-threonine kinase inhibitor), PD98059 (an inhibitor specific for erk-1 and -2) or iso-Olo (a structural isomer of Olo that does not inhibit cdk activity). The concentrations of Rosco and Olo required to inhibit cell cycle progression and viral replication in both HEL and Vero cells were similar. Inhibition of viral replication was found not to be mediated by drug-induced cytotoxicity. Efforts to isolate Rosco- or Olo-resistant HSV mutants were unsuccessful, indicating that these drugs do not act by inhibiting a single viral target. Viral DNA replication and accumulation of IE and early viral RNAs were inhibited in the presence of cell cycle-inhibitory concentrations of Rosco or Olo. We therefore conclude that one or more cdks active from late G1 onward or inactive in nonneuronal cells are required for accumulation of HSV transcripts, viral DNA replication, and production of infectious virus.
Amino Acid Sequence↗
Coexistent hairy cell leukaemia and chronic lymphocytic leukaemia.
Chronic lymphocytic leukaemia (CLL) and hairy cell leukaemia (HCL) are chronic B-cell lymphoproliferative disorders (B-LPDs) with distinct clinical, morphological and immunocytochemical features. Transformation of CLL into other B-LPDs (prolymphocytic leukaemia (PLL) and large cell lymphoma) is a well recognised phenomenon. One previous report has suggested that HCL may also arise by clonal evolution from CLL. We report the case of a 75 year old man in whom a diagnosis of coexisting HCL was made seventeen years after an initial diagnosis of CLL. Immunoglobulin heavy chain rearrangement studies suggest that the two B-LPDs developed independently. A steady increase in the bone marrow HCL component at the expense of the CLL component was observed with time, suggesting that HCL may have a growth advantage over CLL.
Aged↗