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1.  Distribution and prevalence of vector-borne diseases in California chipmunks (Tamias spp.) 
PLoS ONE  2017;12(12):e0189352.
California, with 13 chipmunk (Tamias) species, has more than any other state or country, occupying habitats ranging from chaparral to the high peaks of the Sierra Nevada. Chipmunks host zoonotic pathogens including Yersinia pestis, Anaplasma phagocytophilum, relapsing fever (RF) Borrelia spp., Borrelia burgdorferi, and spotted fever group (SFG) Rickettsia species. Chipmunk species are often not differentiated by public health workers, yet different species utilize different ecological niches and may have intrinsically different capacities for maintaining vector-borne pathogens and infecting vectors. We surveyed over 700 individuals from nine species of chipmunks throughout California for exposure to and infection by Y. pestis, A. phagocytophilum, RF Borrelia spp., Borrelia burgdorferi, and SFG Rickettsia species. DNA of all five pathogens was found and all chipmunks except Merriam’s chipmunk (T. merriami) were PCR-positive for at least one of the pathogens. Anaplasma phagocytophilum was most common (40.0%, 2/5) in Sonoma chipmunks (T. sonomae) from Marin county and B. burgdorferi most common (37.5%, 27/72) in redwood chipmunks (T. ochrogenys) from Mendocino county. RF Borrelia spp. was detected in 2% (6/297) of redwood chipmunks in Mendocino county and 10% (1/10) of both least (T. minimus) and lodgepole (T. speciosus) chipmunks in the western Sierra. Exposure to SFG Rickettsia spp. was found in the Northern Coastal region (Del Norte, Humboldt and Mendocino counties) and in the northern and western Sierra in several species of chipmunks. Y. pestis infection was found only in the western Sierra—in a yellow-pine (T. amoenus) and a long-eared (T. quadrimaculatus) chipmunk. Though more data are needed to thoroughly understand the roles that different chipmunk species play in disease transmission, our findings suggest that some chipmunk species may be more important to the maintenance of vector-borne diseases than others within each geographic area.
PMCID: PMC5726628  PMID: 29232397
2.  PIM Kinase Inhibitor AZD1208 for Treatment of MYC-Driven Prostate Cancer 
PIM1 kinase is coexpressed with c-MYC in human prostate cancers (PCs) and dramatically enhances c-MYC-induced tumorigenicity. Here we examine the effects of a novel oral PIM inhibitor, AZD1208, on prostate tumorigenesis and recurrence.
A mouse c-MYC/Pim1-transduced tissue recombination PC model, Myc-CaP allografts, and human PC xenografts were treated with AZD1208 (n = 5–11 per group). Androgen-sensitive and castrate-resistant prostate cancer (CRPC) models were studied as well as the effects of hypoxia and radiation. RNA sequencing was used to analyze drug-induced gene expression changes. Results were analyzed with χ2 test. Student’s t test and nonparametric Mann-Whitney rank sum U Test. All statistical tests were two-sided.
AZD1208 inhibited tumorigenesis in tissue recombinants, Myc-CaP, and human PC xenograft models. PIM inhibition decreased c-MYC/Pim1 graft growth by 54.3±39% (P < .001), decreased cellular proliferation by 46±14% (P = .016), and increased apoptosis by 326±170% (P = .039). AZD1208 suppressed multiple protumorigenic pathways, including the MYC gene program. However, it also downregulated the p53 pathway. Hypoxia and radiation induced PIM1 in prostate cancer cells, and AZD1208 functioned as a radiation sensitizer. Recurrent tumors postcastration responded transiently to either AZD1208 or radiation treatment, and combination treatment resulted in more sustained inhibition of tumor growth. Cell lines established from recurrent, AZD1208-resistant tumors again revealed downregulation of the p53 pathway. Irradiated AZD1208-treated tumors robustly upregulated p53, providing a possible mechanistic explanation for the effectiveness of combination therapy. Finally, an AZD1208-resistant gene signature was found to be associated with biochemical recurrence in PC patients.
PIM inhibition is a potential treatment for MYC-driven prostate cancers including CRPC, and its effectiveness may be enhanced by activators of the p53 pathway, such as radiation.
PMCID: PMC4326311  PMID: 25505253
3.  Visualization of arrestin recruitment by a G Protein-Coupled Receptor 
Nature  2014;512(7513):218-222.
G Protein Coupled Receptors (GPCRs) are critically regulated by β-arrestins (βarrs), which not only desensitize G protein signaling but also initiate a G protein independent wave of signaling1-5. A recent surge of structural data on a number of GPCRs, including the β2 adrenergic receptor (β2AR)-G protein complex, has provided novel insights into the structural basis of receptor activation6-11. Lacking however has been complementary information on recruitment of βarrs to activated GPCRs primarily due to challenges in obtaining stable receptor-βarr complexes for structural studies. Here, we devised a strategy for forming and purifying a functional β2AR-βarr1 complex that allowed us to visualize its architecture by single particle negative stain electron microscopy (EM) and to characterize the interactions between β2AR and βarr1 using hydrogen-deuterium exchange mass spectrometry (HDXMS) and chemical cross-linking. EM 2D averages and 3D reconstructions reveal bimodal binding of βarr1 to the β2AR, involving two separate sets of interactions, one with the phosphorylated carboxy-terminus of the receptor and the other with its seven-transmembrane core. Areas of reduced HDX together with identification of cross-linked residues suggest engagement of the finger loop of βarr1 with the seven-transmembrane core of the receptor. In contrast, focal areas of increased HDX indicate regions of increased dynamics in both N and C domains of βarr1 when coupled to the β2AR. A molecular model of the β2AR-βarr signaling complex was made by docking activated βarr1 and β2AR crystal structures into the EM map densities with constraints provided by HDXMS and cross-linking, allowing us to obtain valuable insights into the overall architecture of a receptor-arrestin complex. The dynamic and structural information presented herein provides a framework for better understanding the basis of GPCR regulation by arrestins.
PMCID: PMC4134437  PMID: 25043026
4.  Multisector dosimetry in the immediate post-implant period: significant under dosage of the prostate base 
While there are several reports of prostate multisector dosimetry data obtained from CT or MRI scans performed at intervals ranging from 14-70 days after prostate brachytherapy (PB), there are no reports on multisector dosimetry performed in the immediate post-implant period. This study was undertaken to determine the results of prostate multisector dosimetry performed in the immediate post-implant period on day 1 post-implant dosimetry after 125I PB.
Material and methods
The day 1 post-implant CT-based V100 and D90 were determined for the prostate base (PGB) and compared to doses to the entire gland (PG), mid-gland (PMG), and apex (PA) in 75 patients who underwent 125I PB to a dose of 144 Gy. Similar multisector dosimetry was also performed on the pre-implant ultrasound volume study scans of these patients.
All patients had good quality implants. On day 1 post-implant multisector dosimetry there was significant under dosage of the PGB for both V100 and D90. The average magnitude of under dosage of PGB compared to PMG and PA was 17.2% and 22.7% for V100 and 44.6 Gy and 31.7 Gy for D90, respectively. On pre-implant multisector dosimetry there was no statistically significant under dosage of the PGB for V100, but the PGB D90 was significantly lower compared to PMG and PA, however, the average magnitude of under dosage was small at 12.6 Gy and 4.2 Gy, respectively.
This report demonstrates that similar to other reports on more delayed post-implant multisector dosimetry data, there is significant under dosage of the prostate base in the immediate post-implant period based on day 1 post-implant dosimetry. The clinical significance of this under dosage remains to be defined and further studies are warranted.
PMCID: PMC4003430  PMID: 24790620
brachytherapy; CT-based dosimetry; multisector; prostate cancer
5.  Ligand-Induced Architecture of the Leptin Receptor Signaling Complex 
Molecular cell  2012;48(4):655-661.
Despite the crucial impact of leptin signaling on metabolism and body weight, little is known about the structure of the liganded leptin receptor (LEP-R) complex. Here we applied single-particle electron microscopy (EM) to characterize the architecture of the extracellular region of LEP-R alone and in complex with leptin. We show that unliganded LEP-R displays significant flexibility in a hinge region within the cytokine homology region 2 (CHR2) that is connected to rigid membrane-proximal FnIII domains. Leptin binds to CHR2 in order to restrict the flexible hinge and the disposition of the FnIII ‘legs’. Through a separate interaction, leptin engages the Ig-like domain of a second liganded LEP-R, resulting in the formation of a quaternary signaling complex. We propose that the membrane proximal domain rigidification in the context of a liganded cytokine receptor dimer is a key mechanism for the transactivation of Janus kinases (Jaks) bound at the intracellular receptor region.
PMCID: PMC3513567  PMID: 23063524
Leptin Receptor; Cytokine Receptor; Electron Microscopy; Structure
6.  Unsaturated fatty acids induce mesenchymal stem cells to increase secretion of angiogenic mediators 
Journal of Cellular Physiology  2012;227(9):3225-3233.
PMCID: PMC3305849  PMID: 22105830
Unsaturated fatty acids; Mesenchymal stem cells; Bone marrow; Linoleic acid; Oleic acid; Cell proliferation; Gene expression; Angiogenesis
7.  Search for lepton flavour violation in the eμ continuum with the ATLAS detector in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\sqrt{s} = 7~\mbox{TeV}$\end{document}pp collisions at the LHC 
Aad, G. | Abbott, B. | Abdallah, J. | Abdelalim, A. A. | Abdesselam, A. | Abdinov, O. | Abi, B. | Abolins, M. | Abramowicz, H. | Abreu, H. | Acerbi, E. | Acharya, B. S. | Adams, D. L. | Addy, T. N. | Adelman, J. | Adomeit, S. | Adragna, P. | Adye, T. | Aefsky, S. | Aguilar-Saavedra, J. A. | Aharrouche, M. | Ahlen, S. P. | Ahles, F. | Ahmad, A. | Ahsan, M. | Aielli, G. | Akdogan, T. | Åkesson, T. P. A. | Akimoto, G. | Akimov, A. V. | Akiyama, A. | Aktas, A. | Alam, M. S. | Alam, M. A. | Albrand, S. | Aleksa, M. | Aleksandrov, I. N. | Aleppo, M. | Alessandria, F. | Alexa, C. | Alexander, G. | Alexandre, G. | Alexopoulos, T. | Alhroob, M. | Aliev, M. | Alimonti, G. | Alison, J. | Aliyev, M. | Allport, P. P. | Allwood-Spiers, S. E. | Almond, J. | Aloisio, A. | Alon, R. | Alonso, A. | Alviggi, M. G. | Amako, K. | Amelung, C. | Ammosov, V. V. | Amorim, A. | Amorós, G. | Amram, N. | Anastopoulos, C. | Andeen, T. | Anders, C. F. | Anderson, K. J. | Andreazza, A. | Andrei, V. | Anduaga, X. S. | Angerami, A. | Anghinolfi, F. | Anjos, N. | Annovi, A. | Antonaki, A. | Antonelli, M. | Antonelli, S. | Antonov, A. | Antos, J. | Anulli, F. | Aoun, S. | Aperio Bella, L. | Apolle, R. | Arabidze, G. | Aracena, I. | Arai, Y. | Arce, A. T. H. | Archambault, J. P. | Arfaoui, S. | Arguin, J-F. | Arik, E. | Arik, M. | Armbruster, A. J. | Arnaez, O. | Arnault, C. | Artamonov, A. | Artoni, G. | Arutinov, D. | Asai, M. | Asai, S. | Asfandiyarov, R. | Ask, S. | Åsman, B. | Asner, D. | Asquith, L. | Assamagan, K. | Astbury, A. | Astvatsatourov, A. | Atoian, G. | Aubert, B. | Auge, E. | Augsten, K. | Aurousseau, M. | Austin, N. | Avolio, G. | Avramidou, R. | Axen, D. | Azuelos, G. | Azuma, Y. | Baak, M. A. | Baccaglioni, G. | Bacci, C. | Bach, A. M. | Bachacou, H. | Bachas, K. | Bachy, G. | Backes, M. | Backhaus, M. | Badescu, E. | Bagnaia, P. | Bahinipati, S. | Bai, Y. | Bailey, D. C. | Bain, T. | Baines, J. T. | Baker, O. K. | Baker, M. D. | Baker, S. | Baltasar Dos Santos Pedrosa, F. | Banas, E. | Banerjee, P. | Banerjee, Sw. | Banfi, D. | Bangert, A. | Bansal, V. | Bansil, H. S. | Barak, L. | Baranov, S. P. | Barbaro Galtieri, A. | Barber, T. | Barberio, E. L. | Barberis, D. | Barbero, M. | Bardin, D. Y. | Barillari, T. | Barisonzi, M. | Barklow, T. | Barlow, N. | Barnett, B. M. | Barnett, R. M. | Baroncelli, A. | Barr, A. J. | Barreiro, F. | Barreiro Guimarães da Costa, J. | Barrillon, P. | Bartoldus, R. | Barton, A. E. | Bartsch, D. | Bartsch, V. | Bates, R. L. | Batkova, L. | Batley, J. R. | Battaglia, A. | Battistin, M. | Battistoni, G. | Bauer, F. | Bawa, H. S. | Beare, B. | Beau, T. | Beauchemin, P. H. | Beccherle, R. | Bechtle, P. | Beck, G. A. | Beck, H. P. | Beckingham, M. | Becks, K. H. | Beddall, A. J. | Beddall, A. | Bedikian, S. | Bednyakov, V. A. | Bee, C. P. | Begel, M. | Behar Harpaz, S. | Behera, P. K. | Beimforde, M. | Belanger-Champagne, C. | Bell, P. J. | Bell, W. H. | Bella, G. | Bellagamba, L. | Bellina, F. | Bellomo, G. | Bellomo, M. | Belloni, A. | Beloborodova, O. | Belotskiy, K. | Beltramello, O. | Ben Ami, S. | Benary, O. | Benchekroun, D. | Benchouk, C. | Bendel, M. | Benedict, B. H. | Benekos, N. | Benhammou, Y. | Benjamin, D. P. | Benoit, M. | Bensinger, J. R. | Benslama, K. | Bentvelsen, S. | Beretta, M. | Berge, D. | Bergeaas Kuutmann, E. | Berger, N. | Berghaus, F. | Berglund, E. | Beringer, J. | Bernardet, K. | Bernat, P. | Bernhard, R. | Bernius, C. | Berry, T. | Bertin, A. | Bertolucci, F. | Besana, M. I. | Besson, N. | Bethke, S. | Bhimji, W. | Bianchi, R. M. | Bianco, M. | Biebel, O. | Bieniek, S. P. | Biesiada, J. | Biglietti, M. | Bilokon, H. | Bindi, M. | Binet, S. | Bingul, A. | Bini, C. | Biscarat, C. | Bitenc, U. | Black, K. M. | Blair, R. E. | Blanchard, J.-B. | Blanchot, G. | Blocker, C. | Blocki, J. | Blondel, A. | Blum, W. | Blumenschein, U. | Bobbink, G. J. | Bobrovnikov, V. B. | Bocchetta, S. S. | Bocci, A. | Boddy, C. R. | Boehler, M. | Boek, J. | Boelaert, N. | Böser, S. | Bogaerts, J. A. | Bogdanchikov, A. | Bogouch, A. | Bohm, C. | Boisvert, V. | Bold, T. | Boldea, V. | Bona, M. | Bondioli, M. | Boonekamp, M. | Boorman, G. | Booth, C. N. | Booth, P. | Bordoni, S. | Borer, C. | Borisov, A. | Borissov, G. | Borjanovic, I. | Borroni, S. | Bos, K. | Boscherini, D. | Bosman, M. | Boterenbrood, H. | Botterill, D. | Bouchami, J. | Boudreau, J. | Bouhova-Thacker, E. V. | Boulahouache, C. | Bourdarios, C. | Bousson, N. | Boveia, A. | Boyd, J. | Boyko, I. R. | Bozhko, N. I. | Bozovic-Jelisavcic, I. | Bracinik, J. | Braem, A. | Brambilla, E. | Branchini, P. | Brandt, A. | Brandt, G. | Brandt, O. | Bratzler, U. | Brau, B. | Brau, J. E. | Braun, H. M. | Brelier, B. | Bremer, J. | Brenner, R. | Bressler, S. | Breton, D. | Brett, N. D. | Bright-Thomas, P. G. | Britton, D. | Brochu, F. M. | Brock, I. | Brock, R. | Brodet, E. | Broggi, F. | Bromberg, C. | Brooijmans, G. | Brooks, W. K. | Brown, G. | Brubaker, E. | Bruckman de Renstrom, P. A. | Bruncko, D. | Bruneliere, R. | Brunet, S. | Bruni, A. | Bruni, G. | Bruschi, M. | Buanes, T. | Bucci, F. | Buchanan, J. | Buchanan, N. J. | Buchholz, P. | Buckingham, R. M. | Buckley, A. G. | Buda, S. I. | Budagov, I. A. | Budick, B. | Büscher, V. | Bugge, L. | Buira-Clark, D. | Buis, E. J. | Bulekov, O. | Bunse, M. | Buran, T. | Burckhart, H. | Burdin, S. | Burgess, T. | Burke, S. | Busato, E. | Bussey, P. | Buszello, C. P. | Butler, B. | Butler, J. M. | Buttar, C. M. | Butterworth, J. M. | Buttinger, W. | Byatt, T. | Caballero, J. | Cabrera Urbán, S. | Caccia, M. | Caforio, D. | Cakir, O. | Calafiura, P. | Calderini, G. | Calfayan, P. | Calkins, R. | Caloba, L. P. | Caloi, R. | Calvet, D. | Calvet, S. | Camacho Toro, R. | Camard, A. | Camarri, P. | Cameron, D. | Cammin, J. | Campana, S. | Campanelli, M. | Canale, V. | Canelli, F. | Canepa, A. | Cantero, J. | Capasso, L. | Capeans Garrido, M. D. M. | Caprini, I. | Caprini, M. | Capriotti, D. | Capua, M. | Caputo, R. | Caramarcu, C. | Cardarelli, R. | Carli, T. | Carlino, G. | Carminati, L. | Caron, B. | Caron, S. | Carpentieri, C. | Carrillo Montoya, G. D. | Carter, A. A. | Carter, J. R. | Carvalho, J. | Casadei, D. | Casado, M. P. | Cascella, M. | Caso, C. | Castaneda Hernandez, A. M. | Castaneda-Miranda, E. | Castillo Gimenez, V. | Castro, N. F. | Cataldi, G. | Cataneo, F. | Catinaccio, A. | Catmore, J. R. | Cattai, A. | Cattani, G. | Caughron, S. | Cavallari, A. | Cavalleri, P. | Cavalli, D. | Cavalli-Sforza, M. | Cavasinni, V. | Cazzato, A. | Ceradini, F. | Cerqueira, A. S. | Cerri, A. | Cerrito, L. | Cerutti, F. | Cetin, S. A. | Chafaq, A. | Chakraborty, D. | Chan, K. | Chapleau, B. | Chapman, J. D. | Chapman, J. W. | Chareyre, E. | Charlton, D. G. | Chavda, V. | Cheatham, S. | Chekanov, S. | Chekulaev, S. V. | Chelkov, G. A. | Chelstowska, M. A. | Chen, C. | Chen, H. | Chen, L. | Chen, S. | Chen, X. | Cheplakov, A. | Cherkaoui El Moursli, R. | Chernyatin, V. | Cheu, E. | Cheung, S. L. | Chevalier, L. | Chiefari, G. | Chikovani, L. | Childers, J. T. | Chilingarov, A. | Chiodini, G. | Chizhov, M. V. | Choudalakis, G. | Chouridou, S. | Christidi, I. A. | Christov, A. | Chromek-Burckhart, D. | Chu, M. L. | Chudoba, J. | Ciapetti, G. | Ciba, K. | Ciftci, A. K. | Ciftci, R. | Cinca, D. | Cindro, V. | Ciobotaru, M. D. | Ciocca, C. | Ciocio, A. | Cirilli, M. | Citterio, M. | Ciubancan, M. | Clark, A. | Clark, P. J. | Cleland, W. | Clemens, J. C. | Clement, B. | Clement, C. | Clifft, R. W. | Coadou, Y. | Cobal, M. | Coccaro, A. | Cochran, J. | Coe, P. | Coelli, S. | Cogan, J. G. | Coggeshall, J. | Cogneras, E. | Cojocaru, C. D. | Colas, J. | Colijn, A. P. | Collard, C. | Collins, N. J. | Collins-Tooth, C. | Collot, J. | Colon, G. | Coluccia, R. | Comune, G. | Conde Muiño, P. | Coniavitis, E. | Conidi, M. C. | Consonni, M. | Constantinescu, S. | Conta, C. | Conventi, F. | Cooke, M. | Cooper, B. D. | Cooper-Sarkar, A. M. | Copic, K. | Cornelissen, T. | Corradi, M. | Corriveau, F. | Corso-Radu, A. | Cortes-Gonzalez, A. | Cortiana, G. | Costa, G. | Costa, M. J. | Costanzo, D. | Costin, T. | Côté, D. | Coura Torres, R. | Courneyea, L. | Cowan, G. | Cowden, C. | Cox, B. E. | Cranmer, K. | Cranshaw, J. | Crescioli, F. | Cristinziani, M. | Crosetti, G. | Crupi, R. | Crépé-Renaudin, S. | Cuenca Almenar, C. | Cuhadar Donszelmann, T. | Cuneo, S. | Curatolo, M. | Curtis, C. J. | Cwetanski, P. | Czirr, H. | Czyczula, Z. | D’Auria, S. | D’Onofrio, M. | D’Orazio, A. | Da Rocha Gesualdi Mello, A. | Da Via, C. | Dabrowski, W. | Dahlhoff, A. | Dai, T. | Dallapiccola, C. | Daly, C. H. | Dam, M. | Dameri, M. | Damiani, D. S. | Danielsson, H. O. | Dankers, R. | Dannheim, D. | Dao, V. | Darbo, G. | Darlea, G. L. | Daum, C. | Dauvergne, J. P. | Davey, W. | Davidek, T. | Davidson, N. | Davidson, R. | Davies, M. | Davison, A. R. | Dawe, E. | Dawson, I. | Daya-Ishmukhametova, R. K. | De, K. | de Asmundis, R. | De Castro, S. | De Castro Faria Salgado, P. E. | De Cecco, S. | de Graat, J. | De Groot, N. | de Jong, P. | De La Taille, C. | De la Torre, H. | de Mora, L. | De Nooij, L. | De Oliveira Branco, M. | De Pedis, D. | de Saintignon, P. | De Salvo, A. | De Sanctis, U. | De Santo, A. | De Vivie De Regie, J. B. | Dean, S. | Dedovich, D. V. | Degenhardt, J. | Dehchar, M. | Deile, M. | Del Papa, C. | Del Peso, J. | Del Prete, T. | Dell’Acqua, A. | Dell’Asta, L. | Della Pietra, M. | della Volpe, D. | Delmastro, M. | Delpierre, P. | Delsart, P. A. | Deluca, C. | Demers, S. | Demichev, M. | Demirkoz, B. | Deng, J. | Deng, W. | Denisov, S. P. | Derendarz, D. | Derkaoui, J. E. | Derue, F. | Dervan, P. | Desch, K. | Devetak, E. | Deviveiros, P. O. | Dewhurst, A. | DeWilde, B. | Dhaliwal, S. | Dhullipudi, R. | Di Ciaccio, A. | Di Ciaccio, L. | Di Girolamo, A. | Di Girolamo, B. | Di Luise, S. | Di Mattia, A. | Di Micco, B. | Di Nardo, R. | Di Simone, A. | Di Sipio, R. | Diaz, M. A. | Diblen, F. | Diehl, E. B. | Dietl, H. | Dietrich, J. | Dietzsch, T. A. | Diglio, S. | Dindar Yagci, K. | Dingfelder, J. | Dionisi, C. | Dita, P. | Dita, S. | Dittus, F. | Djama, F. | Djilkibaev, R. | Djobava, T. | do Vale, M. A. B. | Do Valle Wemans, A. | Doan, T. K. O. | Dobbs, M. | Dobinson, R. | Dobos, D. | Dobson, E. | Dobson, M. | Dodd, J. | Dogan, O. B. | Doglioni, C. | Doherty, T. | Doi, Y. | Dolejsi, J. | Dolenc, I. | Dolezal, Z. | Dolgoshein, B. A. | Dohmae, T. | Donadelli, M. | Donega, M. | Donini, J. | Dopke, J. | Doria, A. | Dos Anjos, A. | Dotti, A. | Dova, M. T. | Dowell, J. D. | Doxiadis, A. D. | Doyle, A. T. | Drasal, Z. | Drees, J. | Drevermann, H. | Dris, M. | Drohan, J. G. | Dubbert, J. | Dubbs, T. | Dube, S. | Duchovni, E. | Duckeck, G. | Dudarev, A. | Dudziak, F. | Dührssen, M. | Duerdoth, I. P. | Duflot, L. | Dufour, M-A. | Dunford, M. | Duran Yildiz, H. | Duxfield, R. | Dwuznik, M. | Dydak, F. | Dzahini, D. | Düren, M. | Ebke, J. | Eckert, S. | Eckweiler, S. | Edmonds, K. | Edwards, C. A. | Efthymiopoulos, I. | Egorov, K. | Ehrenfeld, W. | Ehrich, T. | Eifert, T. | Eigen, G. | Einsweiler, K. | Eisenhandler, E. | Ekelof, T. | El Kacimi, M. | Ellert, M. | Elles, S. | Ellinghaus, F. | Ellis, K. | Ellis, N. | Elmsheuser, J. | Elsing, M. | Ely, R. | Emeliyanov, D. | Engelmann, R. | Engl, A. | Epp, B. | Eppig, A. | Erdmann, J. | Ereditato, A. | Eriksson, D. | Ernst, J. | Ernst, M. | Ernwein, J. | Errede, D. | Errede, S. | Ertel, E. | Escalier, M. | Escobar, C. | Espinal Curull, X. | Esposito, B. | Etienne, F. | Etienvre, A. I. | Etzion, E. | Evangelakou, D. | Evans, H. | Fabbri, L. | Fabre, C. | Facius, K. | Fakhrutdinov, R. M. | Falciano, S. | Falou, A. C. | Fang, Y. | Fanti, M. | Farbin, A. | Farilla, A. | Farley, J. | Farooque, T. | Farrington, S. M. | Farthouat, P. | Fasching, D. | Fassnacht, P. | Fassouliotis, D. | Fatholahzadeh, B. | Favareto, A. | Fayard, L. | Fazio, S. | Febbraro, R. | Federic, P. | Fedin, O. L. | Fedorko, I. | Fedorko, W. | Fehling-Kaschek, M. | Feligioni, L. | Fellmann, D. | Felzmann, C. U. | Feng, C. | Feng, E. J. | Fenyuk, A. B. | Ferencei, J. | Fernandes, B. | Fernando, W. | Ferrag, S. | Ferrando, J. | Ferrara, V. | Ferrari, A. | Ferrari, P. | Ferrari, R. | Ferrer, A. | Ferrer, M. L. | Ferrere, D. | Ferretti, C. | Ferretto Parodi, A. | Fiascaris, M. | Fiedler, F. | Filipčič, A. | Filippas, A. | Filthaut, F. | Fincke-Keeler, M. | Fiolhais, M. C. N. | Fiorini, L. | Firan, A. | Fischer, G. | Fischer, P. | Fisher, M. J. | Fisher, S. M. | Flammer, J. | Flechl, M. | Fleck, I. | Fleckner, J. | Fleischmann, P. | Fleischmann, S. | Flick, T. | Flores Castillo, L. R. | Flowerdew, M. J. | Föhlisch, F. | Fonseca Martin, T. | Fopma, J. | Formica, A. | Forti, A. | Fortin, D. | Fournier, D. | Fowler, A. J. | Fowler, K. | Fox, H. | Francavilla, P. | Franchino, S. | Francis, D. | Frank, T. | Franklin, M. | Franz, S. | Fraternali, M. | Fratina, S. | Freestone, J. | French, S. T. | Froeschl, R. | Froidevaux, D. | Frost, J. A. | Fukunaga, C. | Fullana Torregrosa, E. | Fuster, J. | Gabaldon, C. | Gabizon, O. | Gadfort, T. | Gadomski, S. | Gagliardi, G. | Gagnon, P. | Galea, C. | Gallas, E. J. | Gallas, M. V. | Gallo, V. | Gallop, B. J. | Gallus, P. | Galyaev, E. | Gan, K. K. | Gao, Y. S. | Gaponenko, A. | Garberson, F. | Garcia-Sciveres, M. | García, C. | García Navarro, J. E. | Gardner, R. W. | Garelli, N. | Garitaonandia, H. | Garonne, V. | Garvey, J. | Gatti, C. | Gaudio, G. | Gaumer, O. | Gaur, B. | Gauthier, L. | Gauzzi, P. | Gavrilenko, I. L. | Gay, C. | Gaycken, G. | Gazis, E. N. | Ge, P. | Gee, C. N. P. | Geerts, D. A. A. | Geich-Gimbel, Ch. | Gellerstedt, K. | Gemme, C. | Gemmell, A. | Genest, M. H. | Gentile, S. | George, M. | George, S. | Gerlach, P. | Gershon, A. | Geweniger, C. | Ghazlane, H. | Ghodbane, N. | Giacobbe, B. | Giagu, S. | Giakoumopoulou, V. | Giangiobbe, V. | Gianotti, F. | Gibbard, B. | Gibson, A. | Gibson, S. M. | Gieraltowski, G. F. | Gilchriese, M. | Gillberg, D. | Gillman, A. R. | Gingrich, D. M. | Ginzburg, J. | Giokaris, N. | Giordani, M. P. | Giordano, R. | Giorgi, F. M. | Giovannini, P. | Giraud, P. F. | Giugni, D. | Giusti, P. | Gjelsten, B. K. | Gladilin, L. K. | Glasman, C. | Glatzer, J. | Glazov, A. | Glitza, K. W. | Glonti, G. L. | Godfrey, J. | Godlewski, J. | Goebel, M. | Göpfert, T. | Goeringer, C. | Gössling, C. | Göttfert, T. | Goldfarb, S. | Goldin, D. | Golling, T. | Golovnia, S. N. | Gomes, A. | Gomez Fajardo, L. S. | Gonçalo, R. | Goncalves Pinto Firmino Da Costa, J. | Gonella, L. | Gonzalez, S. | González de la Hoz, S. | Gonzalez Silva, M. L. | Gonzalez-Sevilla, S. | Goodson, J. J. | Goossens, L. | Gorbounov, P. A. | Gordon, H. A. | Gorelov, I. | Gorfine, G. | Gorini, B. | Gorini, E. | Gorišek, A. | Gornicki, E. | Gorokhov, S. A. | Gosdzik, B. | Gosselink, M. | Gostkin, M. I. | Gouanère, M. | Gough Eschrich, I. | Gouighri, M. | Goujdami, D. | Goulette, M. P. | Goussiou, A. G. | Goy, C. | Grabowska-Bold, I. | Grabski, V. | Grafström, P. | Grah, C. | Grahn, K-J. | Grancagnolo, F. | Grancagnolo, S. | Grassi, V. | Gratchev, V. | Grau, N. | Gray, H. M. | Gray, J. A. | Graziani, E. | Grebenyuk, O. G. | Green, B. | Greenfield, D. | Greenshaw, T. | Greenwood, Z. D. | Gregor, I. M. | Grenier, P. | Griesmayer, E. | Griffiths, J.
This paper presents a search for the t-channel exchange of an R-parity violating scalar top quark (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\tilde{t}$\end{document}) in the e±μ∓ continuum using 2.1 fb−1 of data collected by the ATLAS detector in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\sqrt{s}=7~\mbox{TeV}$\end{document}pp collisions at the Large Hadron Collider. Data are found to be consistent with the expectation from the Standard Model backgrounds. Limits on R-parity-violating couplings at 95 % C.L. are calculated as a function of the scalar top mass (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$m_{\tilde{t}}$\end{document}). The upper limits on the production cross section for pp→eμX, through the t-channel exchange of a scalar top quark, ranges from 170 fb for \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$m_{\tilde{t}}=95~\mbox{GeV}$\end{document} to 30 fb for \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$m_{\tilde{t}}=1000~\mbox{GeV}$\end{document}.
PMCID: PMC4370899  PMID: 25814838
8.  Characteristics of Epstein-Barr Virus Envelope Protein gp42 
Virus genes  2010;40(3):307-319.
Epstein-Barr virus (EBV) glycoprotein 42 (gp42) is a membrane protein essential for fusion and entry of EBV into host B-lymphocytes. Gp42 is a member of the protein fold family C-type lectin or lectin-like domains (CLECT or CTLD) and specifically is classified as a natural-killer receptor (NKR)- like CLECT. Literature review and phylogenetic comparison show that EBV gp42 shares a common structure with other NKR-like CLECTs and possibly with many viral CTLDs, but does not appear to exhibit some common binding characteristics of many CTLDs, such as features required for calcium binding. The flexible N-terminal region adjacent to the CTLD fold is important for binding to other EBV glycoproteins and for a cleavage site that is necessary for infection of host cells. From structural studies of gp42 unbound and bound to receptor and extensive mutational analysis, a general model of how gp42 triggers membrane fusion utilizing both the flexible N-terminal region and the CTLD domain has emerged.
PMCID: PMC2854865  PMID: 20162447
Epstein-Barr virus; glycoprotein; herpesvirus; EBV; gp42; viral entry
9.  Structure of Epstein-Barr Virus glycoprotein 42 suggests a mechanism for triggering receptor-activated virus entry 
Epstein-Barr virus requires glycoproteins gH/gL, gB, and gp42 to fuse its lipid envelope with B cells. Gp42 is a type II membrane protein consisting of a flexible N-terminal region, which binds gH/gL, and a C-terminal lectin-like domain that binds to the B cell entry receptor human leukocyte antigen (HLA) class II. Gp42 triggers membrane fusion after HLA binding, a process that requires simultaneous binding to gH/gL and a functional hydrophobic pocket in the lectin domain adjacent to the HLA binding site. Here we present the structure of gp42 in its unbound form. Comparisons to the previously determined structure of a gp42:HLA complex reveals additional N-terminal residues forming part of the gH/gL binding site and structural changes in the receptor-binding domain. While the core of the lectin domain remains similar, significant shifts in two loops and a α-helix bordering the essential hydrophobic pocket suggest a structural mechanism for triggering fusion.
PMCID: PMC3085316  PMID: 19217393
Epstein-Barr virus; fusion mechanism; glycoprotein structure; membrane fusion; viral entry
10.  Mapping the N-Terminal Residues of Epstein-Barr Virus gp42 That Bind gH/gL by Using Fluorescence Polarization and Cell-Based Fusion Assays ▿  
Journal of Virology  2010;84(19):10375-10385.
Epstein-Barr virus (EBV) requires at a minimum membrane-associated glycoproteins gB, gH, and gL for entry into host cells. B-cell entry additionally requires gp42, which binds to gH/gL and triggers viral entry into B cells. The presence of soluble gp42 inhibits membrane fusion with epithelial cells by forming a stable heterotrimer of gH/gL/gp42. The interaction of gp42 with gH/gL has been previously mapped to residues 36 to 81 at the N-terminal region of gp42. In this study, we further mapped this region to identify essential features for binding to gH/gL by use of synthetic peptides. Data from fluorescence polarization, cell-cell fusion, and viral infection assays demonstrated that 33 residues corresponding to 44 to 61 and 67 to 81 of gp42 were indispensable for maintaining low-nanomolar-concentration gH/gL binding affinity and inhibiting B-cell fusion and epithelial cell fusion as well as viral infection. Overall, specific, large hydrophobic side chain residues of gp42 appeared to provide critical interactions, determining the binding strength. Mutations of these residues also diminished the inhibition of B-cell and epithelial cell fusions as well as EBV infection. A linker region (residues 62 to 66) between two gH/gL binding regions served as an important spacer, but individual amino acids were not critical for gH/gL binding. Probing the binding site of gH/gL and gp42 with gp42 peptides is critical for a better understanding of the interaction of gH/gL with gp42 as well as for the design of novel entry inhibitors of EBV and related human herpesviruses.
PMCID: PMC2937788  PMID: 20668073
11.  Characterization of a CNS penetrant, selective M1 muscarinic receptor agonist, 77-LH-28-1 
British Journal of Pharmacology  2008;154(5):1104-1115.
Background and purpose:
M1 muscarinic ACh receptors (mAChRs) represent an attractive drug target for the treatment of cognitive deficits associated with diseases such as Alzheimer's disease and schizophrenia. However, the discovery of subtype-selective mAChR agonists has been hampered by the high degree of conservation of the orthosteric ACh-binding site among mAChR subtypes. The advent of functional screening assays has enabled the identification of agonists such as AC-42 (4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl]-piperidine), which bind to an allosteric site and selectively activate the M1 mAChR subtype. However, studies with this compound have been limited to recombinantly expressed mAChRs.
Experimental approach:
In this study, we have compared the pharmacological profile of AC-42 and a close structural analogue, 77-LH-28-1 (1-[3-(4-butyl-1-piperidinyl)propyl]-3,4-dihydro-2(1H)-quinolinone) at human recombinant, and rat native, mAChRs by calcium mobilization, inositol phosphate accumulation and both in vitro and in vivo electrophysiology.
Key results:
Calcium mobilization and inositol phosphate accumulation assays revealed that both AC-42 and 77-LH-28-1 display high selectivity to activate the M1 mAChR over other mAChR subtypes. Furthermore, 77-LH-28-1, but not AC-42, acted as an agonist at rat hippocampal M1 receptors, as demonstrated by its ability to increase cell firing and initiate gamma frequency network oscillations. Finally, 77-LH-28-1 stimulated cell firing in the rat hippocampus in vivo following subcutaneous administration.
Conclusions and implications:
These data suggest that 77-LH-28-1 is a potent, selective, bioavailable and brain-penetrant agonist at the M1 mAChR and therefore that it represents a better tool than AC-42, with which to study the pharmacology of the M1 mAChR.
PMCID: PMC2451039  PMID: 18454168
muscarinic receptors; selective agonist; allosteric; AC-42; 77-LH-28-1; calcium mobilization; inositol phosphate; cell firing; network oscillations
12.  Inter‐ and intra‐rater reliability for classification of medication related events in paediatric inpatients 
Quality & Safety in Health Care  2006;15(3):196-201.
In medication safety research studies medication related events are often classified by type, seriousness, and degree of preventability, but there is currently no universally reliable “gold standard” approach. The reliability (reproducibility) of this process is important as the targeting of prevention strategies is often based on specific categories of event. The aim of this study was to determine the reliability of reviewer judgements regarding classification of paediatric inpatient medication related events.
Three health professionals independently reviewed suspected medication related events and classified them by type (adverse drug event (ADE), potential ADE, medication error, rule violation, or other event). ADEs and potential ADEs were then rated according to seriousness of patient injury using a seven point scale and preventability using a decision algorithm and a six point scale. Inter‐ and intra‐rater reliabilities were calculated using the kappa (κ) statistic.
Agreement between all three reviewers regarding event type ranged from “slight” for potential ADEs (κ = 0.20, 95% CI 0.00 to 0.40) to “substantial” agreement for the presence of an ADE (κ = 0.73, 95% CI 0.69 to 0.77). Agreement ranged from “slight” (κ = 0.06, 95% CI 0.02 to 0.10) to “fair” (κ = 0.34, 95% CI 0.30 to 0.38) for seriousness classifications but, by collapsing the seven categories into serious versus not serious, “moderate” agreement was found (κ = 0.50, 95% CI 0.46 to 0.54). For preventability decision, overall agreement was “fair” (κ = 0.37, 95% CI 0.33 to 0.41) but “moderate” for not preventable events (κ = 0.47, 95% CI 0.43 to 0.51).
Trained reviewers can reliably assess paediatric inpatient medication related events for the presence of an ADE and for its seriousness. Assessments of preventability appeared to be a more difficult judgement in children and approaches that improve reliability would be useful.
PMCID: PMC2464860  PMID: 16751470
medication error; children; classification; inter‐rater reliability; intra‐rater reliability
13.  Binding-Site Interactions between Epstein-Barr Virus Fusion Proteins gp42 and gH/gL Reveal a Peptide That Inhibits both Epithelial and B-Cell Membrane Fusion▿  
Journal of Virology  2007;81(17):9216-9229.
Herpesviruses require membrane-associated glycoproteins gB, gH, and gL for entry into host cells. Epstein-Barr virus (EBV) gp42 is a unique protein also required for viral entry into B cells. Key interactions between EBV gp42 and the EBV gH/gL complex were investigated to further elucidate their roles in membrane fusion. Deletion and point mutants within the N-terminal region of gp42 revealed residues important for gH/gL binding and membrane fusion. Many five-residue deletion mutants in the N-terminal region of gp42 that exhibit reduced membrane fusion activity retain binding with gH/gL but map out two functional stretches between residues 36 and 96. Synthetic peptides derived from the gp42 N-terminal region were studied in in vitro binding experiments with purified gH/gL and in cell-cell fusion assays. A peptide spanning gp42 residues 36 to 81 (peptide 36-81) binds gH/gL with nanomolar affinity, comparable to full-length gp42. Peptide 36-81 efficiently inhibits epithelial cell membrane fusion and competes with soluble gp42 to inhibit B-cell fusion. Additionally, this peptide at low nanomolar concentrations inhibits epithelial cell infection by intact virus. Shorter gp42 peptides spanning the two functional regions identified by deletion mutagenesis had little or no binding to soluble gH/gL and were also unable to inhibit epithelial cell fusion, nor could they complement gp42 deletion mutants in B-cell fusion. These studies identify key residues of gp42 that are essential for gH/gL binding and membrane fusion activation, providing a nanomolar inhibitor of EBV-mediated membrane fusion.
PMCID: PMC1951443  PMID: 17581996
14.  Soluble Epstein-Barr Virus Glycoproteins gH, gL, and gp42 Form a 1:1:1 Stable Complex That Acts Like Soluble gp42 in B-Cell Fusion but Not in Epithelial Cell Fusion 
Journal of Virology  2006;80(19):9444-9454.
Epstein-Barr virus (EBV) is a herpesvirus that infects cells by fusing its lipid envelope with the target cell membrane. The fusion process requires the actions of viral glycoproteins gH, gL, and gB for entry into epithelial cells and additionally requires gp42 for entry into B cells. To further study the roles of these membrane-associated glycoproteins, purified soluble forms of gp42, gH, and gL were expressed that lack the membrane-spanning regions. The soluble gH/gL protein complex binds to soluble gp42 with high affinity, forming a stable heterotrimer with 1:1:1 stoichiometry, and this complex is not formed by an N-terminally truncated variant of gp42. The effects of adding soluble gp42, gH/gL, and gH/gL/gp42 were examined with a virus-free cell-cell fusion assay. The results demonstrate that, in contrast to gp42, membrane fusion does not proceed with secreted gH/gL. The addition of soluble gH/gL does not inhibit or enhance B-cell or epithelial cell fusion when membrane-bound gH/gL, gB, and gp42 are present. However, the soluble gH/gL/gp42 complex does activate membrane fusion with B cells, similarly to soluble gp42, but it does not inhibit fusion with epithelial cells, as observed for gp42 alone. A gp42 peptide, derived from an N-terminal segment involved in gH/gL interactions, binds to soluble gH/gL and inhibits EBV-mediated epithelial cell fusion, mimicking gp42. These observations reveal distinct functional requirements for gH/gL and gp42 complexes in EBV-mediated membrane fusion.
PMCID: PMC1617263  PMID: 16973550
15.  Excessive exposure of sick neonates to sound during transport 
Objective: To determine the levels of sound to which infants are exposed during routine transport by ambulance, aircraft, and helicopter.
Design: Sound levels during 38 consecutive journeys from a regional level III neonatal intensive care unit were recorded using a calibrated data logging sound meter (Quest 2900). The meter was set to record "A" weighted slow response integrated sound levels, which emulates the response of the human ear, and "C" weighted response sound levels as a measure of total sound level exposure for all frequencies. The information was downloaded to a computer using MS HyperTerminal. The resulting data were stored, and a graphical profile was generated for each journey using SigmaPlot software.
Setting: Eight journeys involved ambulance transport on country roads, 24 involved fixed wing aircraft, and four were by helicopter.
Main outcome measures: Relations between decibel levels and events or changes in transport mode were established by correlating the time logged on the sound meter with the standard transport documentation sheet.
Results: The highest sound levels were recorded during air transport. However, mean sound levels for all modes of transport exceeded the recommended levels for neonatal intensive care. The maximum sound levels recorded were extremely high at greater than 80 dB in the "A" weighted hearing range and greater than 120 dB in the total frequency range.
Conclusions: This study raises major concerns about the excessive exposure of the sick newborn to sound during transportation.
PMCID: PMC1763236  PMID: 14602701
16.  Regional cerebral blood flow velocity changes after indomethacin infusion in preterm infants. 
Archives of Disease in Childhood  1992;67(7 Spec No):851-854.
Cerebral blood flow velocity was assessed during infusion of indomethacin over 30 minutes. Eleven preterm infants with symptomatic patent ductus arteriosus were studied on 12 occasions. Indomethacin infusion was associated with a significant reduction in time averaged mean velocity (TAMV), peak systolic velocity (PSV), and end diastolic velocity in both the anterior cerebral artery and middle cerebral artery. The fall in the TAMV and PSV was gradual with maximal change 30-40 minutes after the start of the infusion. It was concluded that administration of indomethacin by slow infusion produces haemodynamic alterations to the cerebral circulation comparable in magnitude with changes described with bolus administration. Indomethacin remains a useful and effective treatment for patent ductus arteriosus in preterm infants, but should continue to be used with caution.
PMCID: PMC1590416  PMID: 1519988
17.  Turnover of exogenous artificial surfactant. 
Archives of Disease in Childhood  1992;67(4 Spec No):383-387.
The turnover of the artificial surfactant Exosurf after its administration to infants with respiratory distress syndrome was studied. High performance liquid chromatography was used to compare the phosphatidylcholine (PC) composition of serial endotracheal tube secretions from three groups of infants. There were 22 infants who received two doses of Exosurf in 24 hours (group 1), 10 infants who received four doses in 36 hours (group 2), and 41 control infants who did not receive Exosurf. Two parameters were studied: (i) dipalmitoylphosphatidylcholine (DPPC), which is present in both Exosurf and endogenous surfactant, expressed as a percentage of total PC (% DPPC) and (ii) the ratio of DPPC to the entirely endogenous palmitoyloleoylphosphatidylcholine (DPPC:POPC ratio). The administration of Exosurf produced changes in endotracheal tube aspirate PC composition that were detectable for over one week. Four doses of Exosurf in 36 hours prolonged the persistence of these changes compared with two doses in 24 hours, but the numbers of infants were small, and should not be over-interpreted. We conclude that after giving two doses of Exosurf, further doses might best be delayed until after two days, and that further clinical evaluation of dosage regimens is required.
PMCID: PMC1590490  PMID: 1586175
18.  Mold Sensitivity in the Allergic Respiratory Diseases 
Canadian Medical Association Journal  1962;87(25):1310-1313.
A study to determine the role of mold allergens in the allergic respiratory diseases was made by reviewing the skin sensitivity reactions to molds of 257 consecutive cases of asthma and/or rhinitis in southwestern British Columbia. Failure to adequately seek out and to treat even minor mold allergy was noted to be a frequent cause of therapeutic failure or of only limited success. Apparently bearing a consistent relation to age and being most prevalent in the mature adult, allergy to fungi appeared to develop slowly and insidiously. The incidence of mold sensitivity was 78.5% and exceeded that of house dust sensitivity by 3.1%. Evidence of clinical sensitivity was present in excess of 52.4% of mold-sensitive patients. Asthmatic patients showed a greater incidence of sensitivity to molds and to multiplicity of species than did patients with rhinitis only. The hypothesized evolution of rhinitis to asthma appeared to be paralleled by the acquisition of sensitivity to increasing numbers of species of fungi. This suggests that the development of sensitivity to multiple mold species may be an etiologic factor in the production of the asthmatic state.
PMCID: PMC1920858  PMID: 14028235

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