And we all need university research to be as relevant to wider society as possible". Although this study was limited by the number of patients enrolled, it clearly demonstrates that posaconazole shows promise in the treatment of patients with coccidioidomycosis and warrants additional investigation in a full-scale clinical trial. Consistent with the in vitro enhancement of effector cell function by IFN-gamma, in vivo therapy with IFN-gamma significantly (P<0.0001) improved survival of BALB/c mice with pulmonary blastomycosis. Law and Social Sciences buildingUniversity of NottinghamUniversity Park Nottingham, NG7 2RD. This review addresses a variety of uses for animal models in medical mycology. Last year, you joined our Twitter chat on breastfeeding bribes. Taken together, the results suggested that HKY vaccination induces significant and specific Th1 type cellular immune responses and antibodies to glucan and mannan. Infected animals were treated with CAS at various dosages (0.01 to 20 mg/kg) and CFU remaining in the kidneys determined. A., Leung, A. N., Robbins, R. C., Stevens, D. A. Analysis of the population genetic structure of microbial species is of fundamental importance to many scientific disciplines because it can identify cryptic species, reveal reproductive mode, and elucidate processes that contribute to pathogen evolution. In vitro and in vivo studies suggest that the female hormone (17-estradiol, E(2)) regulates or inhibits M-or-C-to-Y transition. In general, posaconazole therapy was well tolerated, with 12 of 20 patients reporting adverse events that were possibly or probably related to treatment. The species Candida orthopsilosis (eight isolates) and Candida metapsilosis (two isolates) consisted of five and one other RFLP types, respectively; none were VII-1. Mice are infected orally to allow for the colonization of Candida albicans on the mucosal surfaces of the tongue, esophagus, stomach, small intestine, and cecum. Epidemiological studies show a striking predominance of paracoccidioidomycosis in adult men compared to premenopausal women. View 4 David Stevens Age Guide: 40-44 Director London, London, SW16. View details for DOI 10.1099/mic.0.027441-0, View details for Web of Science ID 000269028900033. HK B. dermatitidis incubated with serum and then washed also failed to stimulate significant TNF-alpha production by PM. of California, Berkeley; Univ. In previous studies on the colony phenotype switching of Saccharomyces cerevisiae, we observed that the least virulent isolates formed greater numbers of petite colonies when grown at body temperature, 37 degrees C. To determine if there is a link between virulence and petite formation, we examined the frequency of spontaneous petite formation for virulent clinical isolates (YJM128, YJM309), an intermediate virulent segregant of YJM128 (YJM145) and avirulent clinical (YJM308) and nonclinical S. cerevisiae (Y55, YJM237) after growth at 37 degrees C. The rank order of increasing frequency of petite formation was YJM128 = YJM145 < YJM309 < Y 55 < YJM308 = YJM237, which is similar to the rank-order of virulence in CD-1 mice. Q U O T E ::: "I dont think learning stops when you finish school, or university. During the past several decades, there has been a steady increase in the frequency of opportunistic invasive fungal infections (IFIs) in immunocompromised patients. Hemoptysis is a dangerous sequela. Because it is highly lethal in the immunocompromised host, even in the face of therapy, work-up must be prompt and aggressive, and therapy may need to be initiated upon suspicion of the diagnosis, without definitive proof (BIII). No Y55-infected mice died, and mean burdens in the brain at day 14 were sevenfold lower in C5+ mice than in C5- mice. We have found that Saccharomyces species can act as a protective vaccine against a lethal systemic Aspergillus infection, and describe experiments optimizing a subcutaneous regimen with killed yeast. Alice Roberts and David Stevens have been mar See We noted paradoxical turbid growth of Candida albicans isolates in broth in some high (supra-MIC) concentrations. View David Stevens's Family Tree and History, Ancestry and Genealogy. However, the literature is growing that this mycosis, particularly pulmonary aspergillosis, can be seen in patients lacking these factors. The larger repertoire of cytokine production in the macrophages that had been cultured longer (20 h+20 h) in serum may be related to maturation of cell receptors. Cortisone acetate gave results similar to dexamethasone, but cortisone acetate suppression of BAM responses lasted 7 days, > or = 4 days longer than dexamethasone suppression. Of 35 speciated isolates, 22 were H. stevensii, 10 H. johnsoniae, and 3 H. hamiltonii. All it took was one encounter with an ancient Roman portrait bust. Genes upregulated in yeasts were found to encode proteins shown to be involved in methionine/cysteine metabolism, respiratory and metabolic processes (of sugars, amino acids, proteins and lipids), transporters (small peptides, sugars, ions and toxins), regulatory proteins and transcription factors. Only the 40-mg/kg dose of VCZ was effective. Greater numbers of chronic inflammatory foci did not correlate with higher CFU. Field of expertise. GM-CSF given 24 h before DEX resulted in blocking of DEX suppression of BAM conidiacidal activity. We show that the resistant phenotype is first detectable after 24 h of drug exposure. Chronic necrotizing aspergillosis, aspergilloma, and allergic bronchopulmonary aspergillosis have variable management strategies and better short-term outcomes. We used EcoRI digestion of cellular DNA to generate RFLP; RAPD analysis on genomic DNA. Oxford University Press and Hurst Publishers. Monocytes alone inhibited hyphal growth by only 5%. There were 351 registrants from 26 countries. MICA given at 1 mg/kg significantly prolonged survival over the saline controls (P = 0.008). Cell-mediated immunity (CMI) has been shown, over many decades of clinical observation and bench research, to be central to the outcome of invasive fungal infections. View details for DOI 10.1196/annals.1406.029, View details for Web of Science ID 000250750700017. Almost all models are murine, with 1 rabbit model; and 2 avian models (in collaboration with Veterinary School, Univ. Experimental vaccines in mouse models have demonstrated a promising avenue of approach for the prevention of aspergillosis, as well as infections caused by other fungal pathogens, such as Coccidioides, the etiological agent of valley fever (coccidioidomycosis). View details for Web of Science ID 000177080400004. Other combinations were not better than Abelcet alone. Did he struggle with this decision? Kamberi, P., Sobel, R. A., Clemons, K. V., Stevens, D. A., Pappagianis, D., Williams, P. L. Efficacy of amphotericin B or itraconazole in a murine model of central nervous system Aspergillus infection. Therapy is predominantly directed at preventing life-threatening hemoptysis. This diagnostic dilemma results in under- or over-treatment of patients, potentially contributing to poor outcomes and antifungal resistance. The therapy of coccidioidomycosis has been an early target, both experimentally and clinically, for study of new members of the azole class of drugs, because of the recognition that coccidioidomycosis is one of the most difficult mycoses to treat, and because our research group and our collaborators have been eager to pioneer new therapies for this problem pathogen. [1][6] The bust was intended to be placed at the entrance of the museum. However, cost and increased needs of animal care and husbandry are limitations that influence the use of the larger animal species. We have shown in a randomized, double-blind, placebo-controlled study that maintenance therapy can completely prevent thrush in AIDS patients with recurrent thrush and possibly prevent all deep and superficial mycoses. Sequential studies with peritoneal macrophages indicated that recombinant human GM-CSF pretreatment also blocked dexamethasone suppression, but the GM-CSF treatment given after dexamethasone did not block the suppressive effect. > present (Patron of the Association of Science and Discovery Centres) and [????] 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. Maffei, C. M., Mirels, L. F., Sobel, R. A., Clemons, K. V., Stevens, D. A. View details for DOI 10.3109/1040841X.2011.581223, View details for Web of Science ID 000295616800001. Assessment of the paradoxical effect of caspofungin in therapy of candidiasis. Because vasculitis is seen frequently in patients with coccidioidal meningitis (CM), this study evaluated the presence of MMP-9 within the cerebrospinal fluid (CSF) of rabbits infected intracisternally with Coccidioides immitis arthroconidia. This review summarizes basic science, clinical and experimental information about C. parapsilosis. New information has come from transgenic animals and recombinant fungal and host molecules. Abelcet and voriconazole showed significantly enhanced efficacy in reducing brain infection. Caspofungin, the first inhibitor of fungal beta-1,3 glucan synthesis to receive approval by the United States Food and Drug Administration, is effective for the treatment of mucosal and invasive candidiasis and invasive aspergillosis. Coccidioides, a fungus, is endemic to specific parts of the Western Hemisphere. The fungal genes responsive to estrogen action are under study. He has been involved in more than 1000 studies and projects with major government and multinational organisations in Australasia, the USA, the UK, Europe and the Asia-Pacific region. Here, we examined the population genetic structure and geographic differentiation of the sexual, dimorphic fungus Blastomyces dermatitidis, the causative agent of blastomycosis.Criteria for Genealogical Concordance Phylogenetic Species Recognition (GCPSR) applied to seven nuclear loci (arf6, chs2, drk1, fads, pyrF, tub1, and its-2) from 78 clinical and environmental isolates identified two previously unrecognized phylogenetic species. 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). A total cumulative dose of 1275 mg (group A) and 2800 mg (group B) was administered. An exposure-response relationship was suggested by pharmacokinetic analyses.Although the study predates extensive use of echinocandins and voriconazole, these findings demonstrate that posaconazole is an alternative to salvage therapy for patients with invasive aspergillosis who are refractory to or intolerant of previous antifungal therapy. View details for DOI 10.1007/s11046-017-0133-9, View details for DOI 10.1128/AAC.00316-13. Analysis of the turbid growth indicated slowing of growth in the presence of drug but with numbers of CFU up to 72% those of drug-free controls. Posaconazole, an oral extended-spectrum triazole agent, has been shown in vitro and in vivo to have potent activity against this fungus.An open-label multinational study of posaconazole, 800 mg/d, administered in divided doses for the treatment of invasive fungal infection that has been refractory to previous therapy was conducted. In addition, three other metabolites were isolated. What can we do to help women who dont fit that description, and why are they less likely to breastfeed to start with? View details for Web of Science ID 000177999000007. and more from FamousFix.com. Getty. Ravuconazole has good efficacy and the potential to cure mucosal candidosis in the absence of a functional immune response. In the second study, drug concentrations in plasma samples were also analyzed using a bioassay. Liu, M., Machova, E., Nescakova, Z., Medovarska, I., Clemons, K. V., Martinez, M., Chen, V., Bystricky, S., Stevens, D. A. dermatitidis (P < 0.01). Review of newer antifungal and immunomodulatory strategies for invasive aspergillosis. Monocytes inhibited hyphal growth. View details for DOI 10.1099/jmm.0.033290-0, View details for Web of Science ID 000295860400002. Alice Roberts was previously married to David Stevens (2000). Get David Stevens Contact Info. 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. Help us build our profile of Alice Roberts and David Stevens! Its virulence appears associated with a capacity to produce biofilm and production of phospholipase and aspartyl protease. Gender. Overall, these data indicate that rhMBL may have utility in the treatment of candidal vaginitis when used as an adjunctive therapy. It is also active in vitro and in animal models against a number of other filamentous and dimorphic endemic fungi and in animal models of Pneumocystis carinii infection. Unlike GM-CSF, granulocyte colony-stimulating factor did not block DEX suppression of BAMs. The fungus usually affects lung parenchyma and may disseminate from there. Luque, J. C., Clemons, K. V., Stevens, D. A. Chiller, T. M., Galgiani, J. N., Stevens, D. A. But Janet Stephens, a hair archeologist (yes, that's her job), made her greatest discovery by questioning a simple fact about ancient Roman hair that everyone had thought to be true. Here we investigated the possibility that GM-CSF could antagonize DEX down-regulation of interleukin (IL)-1alpha and tumour necrosis factor (TNF)-alpha production by stimulated BAM. Reduction of the inoculum to 5.5 x 10(6) conidia was lethal, but comparison showed KO mice less susceptible to lethal infection (P<0.015). Beta-1,6-glucan declined 73%. > present (Member of the Visitors Board of Oxford University Museum of Natural History) and [????] For the efficacy study, ten-day-old Japanese quail (n = 60) were infected intratracheally with A. fumigatus conidia. Here we report that BAMs freshly isolated from mice treated intraperitoneally with DEX for 24 h had significantly (P<0.01) reduced killing of conidia, i.e., 15 +/- 5% conidia killed by BAMs from DEX-treated mice versus 35 +/- 3% by BAMs from mice given saline, 38 +/- 5% by BAMs from mice given GM-CSF, and 39 +/- 1% by BAMs from mice given both DEX and GM-CSF. To assess the virulence of petites in vivo, two mouse models, CD-1 and DBA/ 2N, were infected i.v. Differences among mouse strains in susceptibility to C. albicans, as seen in previous studies involving nonvaginal challenge routes, are not reflected in this vaginal candidiasis model; in general, such resistance patterns appear specific to the route of challenge administration. 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. Increased understanding of these relationships in future will help understand fungal pathogenesis and host defenses against mycoses. Invasive aspergillosis. HUSARI, A. W., Jensen, W. A., Kirsch, C. M., Campagna, A. C., Kagawa, F. T., Hamed, K. A., AZZI, R. L., Stevens, D. A. GENETIC-CHARACTERIZATION OF PATHOGENIC SACCHAROMYCES-CEREVISIAE ISOLATES, CONTROL OF INVASIVE PULMONARY ASPERGILLOSIS WITH ORAL ITRACONAZOLE IN A BONE-MARROW TRANSPLANT PATIENT. Levels of matrix metalloproteinase-9 within cerebrospinal fluid in a rabbit model of coccidioidal meningitis and vasculitis. We postulated that DEX inhibition of NF-kappaB was opposed by induction of IkappaB kinases (IKK) by GM-CSF + conidia stimulation, degradation of IkappaB, and release of nuclear factor kappa B (NF-kappaB). Six isolates failed to amplify MTLa1 and six failed to amplify MTLalpha1. trivia, Help keep Alice Roberts and David Stevens profile up to date. 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. The mean histological scores for AmBi-treated rabbits were lower than those for FLC-treated and control rabbits (P < 0.016 and 0.0005, respectively); the scores for AMB-treated animals were lower than those for the controls (P < 0.0005) but were similar to those for FLC-treated rabbits. View details for Web of Science ID 000286214200026. Treatment of aspergillosis: Clinical practice guidelines of the infectious diseases society of America. CD-1 outbred mice were markedly resistant, with day 6 cfu levels showing a 74- to 87-fold decrease with respect to day 1 levels, whereas other outbred strains (CF-1, SW, ICR) were susceptible. View details for Web of Science ID 000175665800009. The distributions among ethnic groups were not different, however they differed (p = 0.002) from global populations. Stevens was a significant contributor to the archaeological field and is noted for being the first curator of Reading Museum. Moreover, such treatment of PMN also enhanced the collaboration of PMN with VCZ. In these studies we assessed the utility of recombinant human MBL (rhMBL) as a therapeutic against experimental C. albicans vaginitis. The results showed that although vaginal isolates did not cluster in any particular genetic subtype, multiple patients were infected with indistinguishable strains (there were nine distinct strains among 23 isolates). Other groups included conventional amphotericin B (1 mg/kg), Abelcet at 10 or 12 mg/kg or 5% dextrose water (diluent control).All controls died and all treatment regimens significantly prolonged survival. There were no differences in distribution of types comparing babies versus adults, or bloodstream isolates versus colonizing or environmental isolates. In candidosis, the number of sites of colonization correlates with invasion. 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. No toxicity was noted. Hope, W. W., Goodwin, J., Felton, T. W., Ellis, M., Stevens, D. A. Fiberoptic bronchoscopy revealed an endobronchial mass obstructing the left mainstem bronchus. Weger, S. D., Ganji, A., Clemons, K. V., Byron, J. K., Minn, Y., Stevens, D. A. Homozygosity at the Candida albicans MTL locus associated with azole resistance. Prof. Alice May Roberts. But at home, in her secret . In a pilot reconstitution experiment in pulmonary blastomycosis, treatment of infected young mice with IFN-gamma (18.5 x 10(3) U, s.c.) on days 0, 1, and 2 significantly increased survival. CLINICAL AND MICROBIOLOGICAL FEATURES OF INFECTION WITH MALASSEZIA-PACHYDERMATIS IN HIGH-RISK INFANTS. There were 54 recognized species of this genus, associated with marine or saline sites. Because no animal models are available for studying this infection, we sought to develop a murine model of CNS aspergillosis. View details for Web of Science ID 000085846900002. Like a superhero of the coiffe, she spends her days as a regular hair dresser, giving people layers and funky bobs. The increasing incidence of invasive fungal infections is the result of many factors, including an increasing number of patients with severe immunosuppression. [2] His body was moved to St Mary Borne where he was buried next to his wife Mary who had died in 1874. An outbreak of Candida parapsilosis fungemia involving 17 neonatal intensive care unit (NICU) patients was studied. 01). View details for DOI 10.1016/j.ccr.2010.02.027. Monte Carlo simulations demonstrated considerable variability in drug exposure. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses study group and European Organization for Research and Treatment of Cancer consensus criteria. In one patient, fungemia was accompanied by clinical and laboratory evidence of Broviac catheter infection. The ability to control numerous variables in performing the model allows us to mimic human disease states and quantitatively monitor the course of the disease. Concentrations above the MIC of caspofungin allow growth of some Candida isolates. Fifty-eight patients received > or = 300 mg/day, and 7 received > or = 600 mg/day. (Medical school lecturer of Anatomy) and [????] Expertise Summary I am interested in a variety of questions within the broad field of normative political philosophy/theory. Clemons, K. V., Gonzalez, G. M., Singh, G., Imai, J., Espiritu, M., Parmar, R., Stevens, D. A. Efficacy of Abelcet alone, or in combination therapy, against experimental central nervous system aspergillosis. Clemons, K. V., Martinez, M., Calderon, L., Stevens, D. A. View details for DOI 10.1128/AAC.00332-06, View details for Web of Science ID 000244665500028, View details for PubMedCentralID PMC1803148. University Museum of Natural History ) and CFU remaining in the treatment of PMN enhanced... To produce biofilm and production of phospholipase and aspartyl protease colony-stimulating factor did not correlate with higher CFU 10.1196/annals.1406.029. Specific parts of the coiffe, she spends her days as a therapeutic against experimental C. albicans vaginitis not. 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And more from FamousFix.com given at 1 mg/kg significantly prolonged survival over the saline controls ( P = ). We assessed the utility of recombinant human MBL ( rhMBL ) as regular!
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