In the present study, a collection of unmatched clinical isolates of C. albicans was analyzed for the known molecular mechanisms of resistance by standard methods. Chiller, T., Farrokhshad, K., Brummer, E., Stevens, D. A. Animal models are developed and used to study differences in virulence in fungal strains, their biochemical characterization and interaction with host defenses, particularly the role of therapy with recombinant cytokines and other immunomodulators, and preclinical studies of diagnosis. Beta-D-Glucan levels were similar in both groups for patients without an IFI [AUC(GLUCAN) of 362 and 683 (P=0.36) for groups A and B, respectively]. Truck Transportation. However, no single model can answer all questions and different animal species or different routes of infection can show somewhat different results. The Archaeologist Who Collected 4,500 Beer Cans David Maxwell's hobby has become essential to the field. Most of these clinical isolates are able to grow at 42 degrees, a temperature that completely inhibits the growth of most other S. cerevisiae strains. A., Leung, A. N., Robbins, R. C., Stevens, D. A. Perhaps the greatest contribution has been the development of well-tolerated oral drugs that make possible prolonged courses of a conveniently administered agent, and perhaps the most impressive advance has been the utility of the agents in coccidioidal meningitis, at least as an adjunct to the polyenes. Overall, clinical isolates of Saccharomyces were very heterogeneous and exhibited little clonality. David Stevens Family. MICA given at 1 mg/kg significantly prolonged survival over the saline controls (P = 0.008). Stevens, D. A., Moss, R. B., Kurup, V. P., Knutsen, A. P., Greenberger, P., Judson, M. A., Denning, D. W., Crameri, R., Brody, A. S., Light, M., Skov, M., Maish, W., Mastella, G. Management of varicella-vaccinated patients and employees exposed to varicella in the healthcare setting. Interleukin 18 (IL-18), transforming growth factor beta1, and IL-12p(40) mRNAs were constitutively expressed in the brains of infected and uninfected mice; IL-2 mRNA was not detected at any time. With the development of these models, studies of pathogenesis, host response, and therapy are possible. Hepatotoxicity may contribute to high-dose Abelcet and AmBisome failures. Alice Roberts was previously married to David Stevens (2000). Resistance to azole antifungals continues to be a significant problem in the common fungal pathogen Candida albicans. These studies have made it possible to consider using cytokines, now available in abundant quantities via recombinant DNA technologies, to treat fungal infections. ITZ-B suspension was prepared by dispersing the complex of the drug with hydroxypropyl-beta-cyclodextrin in water. They suggest that the resistance mechanisms identified in matched sets of susceptible and resistant isolates are not sufficient to explain resistance in a collection of unmatched clinical isolates and that additional mechanisms have yet to be discovered. Fungal burdens in brains and kidneys were reduced after > 0.3 mg of mannan-BSA (all P < 0.05). 1891. The importance of C5 was confirmed by studies using B10.D2/oSnJ (C5-) mice and their congenic C5+ counterparts. Thanks Alice. The overall success rate (i.e., the data review committee-assessed global response at the end of treatment) was 42% for posaconazole recipients and 26% for control subjects (odds ratio, 4.06; 95% confidence interval, 1.50-11.04; P=.006). More young children have wandered into the pop-up store. Genes potentially involved in signaling, such as palmitoyltransferase (erf2), small GTPase RhoA, phosphatidylinositol-4-kinase, and protein kinase (serine/threonine) showed low expression in the presence of E(2), whereas a gene encoding for an arrestin domain-containing protein showed high expression. Outbred mice are immunosuppressed using weekly doses of 5-fluorouracil to induce neutropenia and damage the mucosal epithelial layer, and are also maintained on a broad-spectrum antibiotic regimen to reduce secondary bacterial infection. Dose-finding studies in CD-1 mice showed that infection with 5 x 106 conidia/mouse consistently caused 100% mortality by day 5-8; no mice died before day 3. View details for DOI 10.1128/AAC.06015-11, View details for Web of Science ID 000306826300050. View details for Web of Science ID 000180334200005. View details for PubMedID 17071553, View details for DOI 10.1080/13693780600810040, View details for Web of Science ID 000242552000003. Res Publica: A journal of social and political philosophy. Growth occurs by hyphal tip extension, in which the hypha elongates and a septum is formed behind the tip to divide it in to a separate compartment. The definitions are intended for use in the context of clinical and/or epidemiological research, not for clinical decision making. Neither the optimal steroid dose nor the duration of therapy has been standardised but limited data suggest the starting dose should be prednisone (approximately 0.5 mg/kg/day). Choi, J., Kwon, E., Park, C., Choi, S., Lee, D., Yoo, J., Shin, W., Stevens, D. A. Moreover, such treatment of PMN also enhanced the collaboration of PMN with VCZ. Multiple asthmatic exacerbations in a patient with ABPA suggest that chronic steroid therapy should be used. Previously we reported that in vitro granulocyte-macrophage colony-stimulating factor (GM-CSF) blocks the immunosuppressive action of DEX on bronchoalveolar macrophages (BAMs). VCZ was ineffective and AMBd plus CAS showed a possible antagonism. David Stevens We found 100+ records for David Stevens in NY, FL and 48 other states. Male. In May 2007, 2 patients developed, days apart, bacteremia with an apparently identical nonfermentative Gram-negative rod. TNFalpha production by young macrophages (BAM or PM), when cocultured with Bd for 18 h, was half of TNFalpha secreted by adult macrophages. View details for Web of Science ID 000085132000001. Voriconazole (VCZ) was tested for antifungal activity against Aspergillus fumigatus hyphae alone or in combination with neutrophils or monocytes. View details for DOI 10.1128/IAI.01185-07, View details for Web of Science ID 000253563500016, View details for Web of Science ID 000252221200001. On the other hand, desired effects of DEX could be maintained in other compartments. The most common adverse events were dry mouth (in 5 patients [25%]) and headache (in 3 patients [15%]).Courses of posaconazole therapy that were up to 6 months in duration were well tolerated in patients with coccidioidomycosis. You took your baby daughter with you when filming Digging for Britain. > present (Member of the Longitude Prize Committee), [????] In an assessment of innate responses, we found spleen cells from young mice produced three-fold less IFN-gamma and three-fold less IL-2 than adult spleen cells in response to 1 microg/ml concanavalin A (Con A). Histopathologically, VCZ-treated birds did not have necrotic lesions and showed a trend toward fewer with acute inflammatory changes. (ODYSEA), Decadal variability of the extratropical response to the Madden-Julian Oscillation, North Atlantic Oscillation response to the MaddenJulian Oscillation in a coupled climate model, Reversal of ocean gyres near ice shelves in the Amundsen Sea caused by the interaction of sea ice and wind, Seasonal extrema of sea surface temperature in CMIP6 models. Frequency of paradoxical effect with caspofungin in Candida albicans, Comparative Efficacies of Lipid-Complexed Amphotericin B and Liposomal Amphotericin B against Coccidioidal Meningitis in Rabbits. View details for Web of Science ID 000177080400004. This facility allows three categories of dogs to interact with their patients: service dogs, therapy dogs, and pet visitation dogs by the "Furry Friends Foundation." Animal models of fungal infections are, and will remain, a key tool in the advancement of the medical mycology. With Aspergillus fumigatus synergy was noted for inhibition and killing, and synergistic activity was also noted for some isolates of other species presently regarded as difficult to treat. Caspofungin was co-cultured for 24h with either human monocytes (Monos), monocyte-derived macrophages (MDM), or polymorphonuclear neutrophils (PMN) against germlings of A. fumigatus and antifungal activity assessed using the XTT metabolic assay. View details for DOI 10.1196/annals.1406.029, View details for Web of Science ID 000250750700017. In contrast, four of seven controls showed mild to severe meningitis, with arteritis detected in three animals. MICA alone at 1 mg/kg approached significance in prolonging survival. The cumulative percent toxicity requiring discontinuation of drug was 6, 17, 23, and 56% at 400-, 800-, 1,200-, and 1,600-mg doses. View details for Web of Science ID 000242479500001. Most Aspergillus culture isolates from nonsterile body sites do not represent disease. Company. In addition, clearance of the infection from both tissues was achieved in none of the rabbits, and neither tissue was cleared of infection in AMB-treated animals. View details for DOI 10.1378/chest.07-0114, View details for Web of Science ID 000249742100036. Regulation of bronchoalveolar macrophage proinflammatory cytokine production by dexamethasone and granulocyte-macrophage colony-stimulating factor after stimulation by Aspergillus conidia or lipopolysaccharide, Resistance mechanisms in clinical isolates of Candida albicans. View details for DOI 10.1111/j.1574-695X.2010.00664.x, View details for Web of Science ID 000277321600009. Preassigned birds were euthanized on days 5 or 10 PI. Oral therapy with cyclodextrin (control) or itraconazole or fluconazole at 10, 25, or 50 mg/kg of body weight twice daily (BID) was given for 12 days, from day 3 of infection. And thank you to everyone who made motherhood month such a success! After pulmonary infection with conidia, normal males showed progressive infection, whereas normal females restricted proliferation and progressive disease. View details for Web of Science ID 000172929200007. Virulence factors in Aspergillus that could aggravate these diseases, and particularly immunogenetic factors that could predispose persons to ABPA, were identified. After administration of two ITZ controlled-release formulations, plasma and tissue concentrations of ITZ and OH-ITZ were either very low (< or = 52 ng/mL) or undetectable. Alice Roberts boyfriend, husband list. Albany. The decision to taper corticosteroids should be made on an individual basis, depending on the clinical course (BIII). The remaining 11 isolates were DNA group A; 2patients that shared a room had identical group A isolates, both converted to DNA group B type colonization within 2 months. At the highest inoculum, all WT and 90% of KO mice died on day 4 (P>0.05). View details for DOI 10.1016/j.diagmicrobio.2010.06.010, View details for Web of Science ID 000283833100005. Daniel's 5th outing as Bond gets bums back on seats in the cinema. View details for DOI 10.1128/AAC.47.4.1452-1455.2003, View details for Web of Science ID 000181842000049. Many of the molecular mechanisms of resistance have been defined with matched sets of susceptible and resistant clinical isolates from the same strain. A similar setup has existed in Denmark and Sweden for years. View details for Web of Science ID 000175084400015. What can we do to help women who dont fit that description, and why are they less likely to breastfeed to start with? Abelcet renal localization appears to be a precursor to late nephrotoxicity. The term "aspergillosis" comprises several categories of infection: invasive aspergillosis; chronic necrotizing aspergillosis; aspergilloma, or fungus ball; and allergic bronchopulmonary aspergillosis. The infiltrates were comprised primarily of cells expressing CD4, CD8, or CD11b; low numbers of cells expressing CD45R/B220 were also present. We postulate that high drug concentrations derepress or activate resistance mechanisms. Depressed IL-2 production by Con A stimulated CD-1 spleen cells correlated with depressed proliferative responses. Dose range, drug bioavailability, and single and multiple treatment pharmacokinetics studies were performed. Y-related genes, -1,3-glucan synthase, mannosyltransferase and Y20, demonstrated low or delayed expression in E(2)-treated cultures. In all studies, 90% of mice infected with 10(7) CFU of YJM128 died between days 2 and 7, whereas no mice infected with equivalent numbers of Y55 died. Recombinant human GM-CSF did not boost spleen cell proliferation to a mitogenic stimulus, and did not reverse dexamethasone suppression of proliferation. Monoclonal antibodies against the cryptococcal capsule have been shown to act as an adjunct in enhancing the outcome of cryptococcosis in animal models. Again, the C5- mice were most susceptible to infection with S. cerevisiae, with 63% infected with YJM128 dying by day 7; no C5+ mice died. The restoration of activity of caspofungin was seen at concentrations as low as 0.05% human serum. Liu, M., Clemons, K. V., Johansen, M. E., Martinez, M., Chen, V., Stevens, D. A. The bioassay had an overall positive bias (+23.5%) compared to the UPLC. She worked as Senior Teaching Fellow at the University of Bristol Centre for Comparative and Clinical Anatomy, where her main roles were teaching clinical anatomy, embryology, and physical anthropology, as well as researching osteoarchaeology and paleopathology. Abelcet at 8 mg/kg or AmB at 0.8 mg/kg were superior to all regimens of caspofungin in reducing cfu (P < or = 0.05-0.001). Although other studies have suggested an association between some azole resistance mechanisms and caspofungin resistance, our studies with isolates susceptible and resistant to azoles (the latter including groups with defined resistance mechanisms and derived mutants) suggest a weak association at most with a paradoxical effect. The patient was treated with intravenous amphotericin B followed by endoscopic laser surgery that relieved the obstruction. Animal models of infection are invaluable tools in studies of pathogenesis, immunological response, and for the testing of experimental therapeutics, which cannot be done in humans. In this study we have profiled transcript expression to understand the molecular mechanism of how E(2) inhibits M-to-Y transition.We assessed temporal gene expression in strain Pb01 in the presence or absence of E(2) at various time points through 9 days of the M-to-Y transition using an 11,000 element random-shear genomic DNA microarray and verified the results using quantitative real time-PCR. Cultured spleen or lymph node cells were stimulated with HKY. You may recognise Professor Alice Roberts - she's travelled the country, lime-green Volkswagen van in tow, to present Coast, as well as fronting numerous other science programmes. Alveolar surfactant modulates the antimicrobial function of bronchoalveolar macrophages (BAM). Director of Archaeology at Jamestown Rediscovery Williamsburg, Virginia, United States. Overall, petites were significantly less virulent than the parental strains. At 0.01 and 0.05 microg ml(-1) of VCZ, G-CSF or GM-CSF enhanced PMN killing to 92% and 93% or 87% and 94%, respectively. These types of infection may occur in laboratories outside the endemic areas, because the etiologic agent is unexpected in the submitted specimens and because personnel may be unfamiliar with the hazards of dealing with Coccidioides species in the laboratory. Clemons, K. V., Steinbach, W. J., Denning, D. W., Stevens, D. A. Efficacy of posaconazole in a murine model of central nervous system aspergillosis. Each remained at these levels thereafter. My husband [field archaeologist David Stevens] took on the role of primary carer when we were filming, and he came with me on all the shoots. Current pharmacotherapy of allergic bronchopulmonary aspergillosis. Who let the dogs out? Stevens, D. A., Kan, V. L., Judson, M. A., Morrison, V. A., Dummer, S., Denning, D. W., BENNETT, J. E., Walsh, T. J., Patterson, T. F., Pankey, G. A. Chiller, T. M., Sobel, R. A., Luque, J. C., Clemons, K. V., Stevens, D. A. Kramer, M. R., Marshall, S. E., Denning, D. W., Keogh, A. M., Tucker, R. M., Galgiani, J. N., LEWISTON, N. J., Stevens, D. A., Theodore, J. Coccidioidal meningitis (CM) is a devastating disease that requires long-term therapy and for which there is little hope of a cure. Industry. Winzeler, E. A., Richards, D. R., Conway, A. R., Goldstein, A. L., Kalman, S., McCullough, M. J., McCusker, J. H., Stevens, D. A., Wodicka, L., Lockhart, D. J., Davis, R. W. Stevens, D. A., Walsh, T. J., Bistoni, F., Cenci, E., Clemons, K. V., Del Sero, G., d'Ostiani, C. F., Kullberg, B. J., Mencacci, A., Roilides, E., Romani, L. Intergenic transcribed spacer PCR ribotyping for differentiation of Saccharomyces species and interspecific hybrids. Utah Department of Transportation. A satisfactory efficacy response was defined as a >or=50% reduction in the Mycoses Study Group score from baseline.Seventeen (85%) of 20 patients had a satisfactory response to treatment. Tortorano, A. M., Prigitano, A., Dho, G., Biraghi, E., Stevens, D. A., Ghannoum, M., Nolard, N., Viviani, M. A. MDMs and micafungin (0.01 or 0.10 microg/ml) caused an additive inhibition of growth, 85% and 95%, respectively. Join Facebook to connect with Dave Stevens and others you may know. Oral itraconazole is attractive for continuing therapy in the patient who responds to initial iv therapy (CIII). Infection is initiated by inhalation of conidia or mycelial fragments by the host, followed by further differentiation into the yeast form. The pharmacokinetics of voriconazole (VRC) administered intravenously (IV) or orally (PO; with and without liquid diet) to mallard ducks were studied. She is especially interested in how material culture and urban space can shed light on the lives of the non-elite in ancient Egypt. Alice Roberts is a 49 year old British TV Personality. The availability of genetically defined strains of mice, immunological reagents, cost and ease of handling are factors. On the other hand, in another compartment GM-CSF could not block the DEX reduction of spleen weight and spleen cellularity. Business Email. However, pioneering studies using Aspergillus particulate forms or homogenates, and recently, recombinant proteins, have demonstrated feasibility. Protein targets for broad-spectrum mycosis vaccines: quantitative proteomic analysis of Aspergillus and Coccidioides and comparisons with other fungal pathogens. He believes that we must harness the human mind, especially working in focused groups, as the . In susceptible BALB/c the response is Th-2, in immunized, resistance is associated with Th-1. Five patients received therapy for >or= 12 months. [1] Stevens died in St Mary Bourne, Hampshire, at the age of 81. The results indicated that the two mutations occur frequently in different isolates of C. albicans and are not reliably associated with resistance. However, death of some DBA/2N mice caused by YJM128 petite 1 showed that petites are not totally avirulent. Ulceration, necrosis, cartilage invasion, and formation of a pseudomembrane are the pathologic features. It describes a range of group problem solving methodologies and illustrates vividly how they can aid modern business. The inhibition of the combination was significantly greater than drug alone (P Login Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Biography. A model was used to compare the efficacies of itraconazole and fluconazole. Statistical analysis of the data demonstrates a strong correlation between homozygosity at the MTL locus and azole resistance (P<0 small middle dot003). The protective moiety(ies) appeared to reside in the cell wall and was resistant to 100 C, but not to protease or formalin. We have recently noted tracheobronchitis in six patients with heart-lung and lung transplants, three of whom had deep mucosal ulceration and histologic evidence of invasive aspergillosis. The group B isolates that formed viable spores were tetraploid and may also be interspecific hybrids. View details for Web of Science ID 000235777000016. Two cohorts were studied. B. dermatitidis incubated with BALF and washed, plus BAM, stimulated 63% less production of TNF-alpha than did unwashed B. dermatitidis (P < 0.05). Neither the optimal corticosteroid dose nor the duration of therapy has been standardized, but limited data suggest the starting dose should be approximately 0.5 mg/kg/d of prednisone. Overall, these models have been critical to the advancement of therapy, and our current understanding of pathogenesis and host-resistance. > present (Science columnist for The Observer newspaper), 2018 > present (president of Humanists UK), 2011 > present (patron of Humanists UK), 2012 > present (Chair of the Birmingham universitys Public Engagement with Science Committee), [????] Okay, so, here we go: Yesterday was my last day at Selbstregulierung Informationswirtschaft e.V. View details for DOI 10.3109/13693786.2011.577822, View details for Web of Science ID 000295893300006. I will move on to a. View details for DOI 10.1093/jac/dkm264 We tested the efficacy of micafungin (FK) alone or in combination with other antifungals against systemic murine aspergillosis. View details for Web of Science ID 000220735200015. View details for Web of Science ID 000267459900022 These species susceptibility differences could affect therapeutic choices. I think that its great to be informing parents about the health benefits of breastfeeding, but the emotional benefits may be underplayed. The most common presenting symptom was back pain. A. fumigatus DNA was detected in blood (88%), brain (96%), CSF (52%) and spinal cord (92%) samples. Here, we report on the construction of a genomic DNA microarray, covering approximately 25 % of the genome of the organism, and its utilization in identifying genes and gene expression patterns during growth in vitro. DEX (10(-7)M) significantly suppressed IL-1 and TNF production by BAM+conidia. The central nervous system (CNS) is the most common site of dissemination during Aspergillus infection. The efficacy of combination therapy for IA has not been established; sparse data on combination or sequential antifungal therapy depict interactions ranging from synergy to antagonism. > present (Patron of the Association of Science and Discovery Centres) and [????] The efficacy of MICA was difficult to assess because of an apparent toxicity at 10 mg kg(-1). Two of the most common point mutations in ERG11 associated with resistance, D116E and E266D, were tested by restriction fragment length polymorphism analysis of the isolates from this collection. Invasive aspergillosis is a devastating and increasingly common disease, seen almost exclusively in immunosuppressed patients. Liu, M., Machova, E., Nescakova, Z., Medovarska, I., Clemons, K. V., Martinez, M., Chen, V., Bystricky, S., Stevens, D. A. Topical administration of rhMBL in a cream appeared more effective than rhMBL in a gel and both were inferior to commercial clotrimazole cream. Denning, D. W., Stepan, D. E., Blume, K. G., Stevens, D. A. ULCERATIVE TRACHEOBRONCHITIS AFTER LUNG TRANSPLANTATION - A NEW FORM OF INVASIVE ASPERGILLOSIS. Self - Blacksmith 1 episode, 2005 Jon Adams . Login Safety, tolerance, and efficacy of posaconazole therapy in patients with nonmeningeal disseminated or chronic pulmonary coccidioidomycosis. Stevens, D. A., Schwartz, H. J., Lee, J. Y., Moskovitz, B. L., Jerome, D. C., Catanzaro, A., Bamberger, D. M., Weinmann, A. J., TUAZON, C. U., Judson, M. A., Platts-Mills, T. A., DeGraff, A. C., Grossman, J., Slavin, R. G., Reuman, P. Combined treatment: antifungal drugs with antibodies, cytokines or drugs. Competition studies for the binder in M. canis resulted in similar findings: DOC and DHT were effective competitors for [3H]progesterone binding. Dissemination to livers occurred and was 100% on days 5 to 15; fewer animals had kidney infection. If you made any changes in Pure these will be visible here soon. In experimental pulmonary blastomycosis, susceptibility varied in mouse strains. Click here to Start FameChaining. Capilla, J., Clemons, K. V., Liu, M., Levine, H. B., Stevens, D. A. To catch up with our other motherhood content, click here. See Stevens, Nathan E. 2009 Archaeology is for the Living. An outbreak of Candida parapsilosis fungemia involving 17 neonatal intensive care unit (NICU) patients was studied. Our Renal Care Center (RCC) is a separate building, performing almost 2500 outpatient dialysis runs per month. In a second, open-label part of the trial, all the patients received 200 mg of itraconazole per day for 16 weeks.There were responses in 13 of 28 patients in the itraconazole group (46 percent), as compared with 5 of 27 patients in the placebo group (19 percent, P=0.04). Steinbach, W. J., Stevens, D. A., Denning, D. W. Invasive aspergillosis in the setting of cardiac transplantation. 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