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CONTRIBUTORS M. Arango Corporacion para Investigaciones Biologicas Hospital Pablo Tobon Uribe Medellin Colombia I.D. Arteaga Corporacion para Investigaciones Biologicas Hospital Pablo Tobon Uribe Medellin Colombia H. Beguin Institute of Hygiene and Epidemiology Section Mycology 14, rue Juliette Wytsman B-1050 Brussels Belgium J.E. Bennett Clinical Mycology Section Laboratory of Clinical Investigation National Institute of Allergy and Infectious Disease Bethesda, Md. 20854 U.S.A. M. Borgers Janssen Research Foundation Turnhoutseweg 30 B-2340 Beerse Belgium Geert Cauwenbergh Janssen Research Foundation Turnhoutseweg 30 B-2340 Beerse Belgium S.D. Chaparas Office of Biologics Research and Review Food and Drug Administration Bethesda Maryland 20892 u.s.A. K. Chikakane Dept. Dermatology Teikyo University School of Medicine ll-1, Kaya-2 Itabashi-ku Tokyo-173 Japan A. De Coster Departement des voies respiratoires Hopital Universitaire Saint-Pierre 322, rue Haute B-1000 Brussels Belgium L. Desplenter Janssen Research Foundation Turnhoutseweg 30 B-2340 Beerse Belgium M. Detandt Institute of Hygiene and Epidemiology Section Mycology 14, rue Juliette Wytsman B-1050 Brussels Belgium P. Dierckx Departement des voies respiratoires Hopital Universitaire Saint-Pierre 322, rue Haute B-1000 Brussels Belgium 303

u.s.A. - link.springer.com978-1-4899-3505-2/1.pdf · B-2340 Beerse Belgium S.D. Chaparas Office of Biologics Research and Review ... Arginine-nch protem, 127 Aromatase, effects of

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CONTRIBUTORS

M. Arango Corporacion para Investigaciones Biologicas Hospital Pablo Tobon Uribe Medellin Colombia

I.D. Arteaga Corporacion para Investigaciones Biologicas Hospital Pablo Tobon Uribe Medellin Colombia

H. Beguin Institute of Hygiene and Epidemiology Section Mycology 14, rue Juliette Wytsman B-1050 Brussels Belgium

J.E. Bennett Clinical Mycology Section Laboratory of Clinical Investigation National Institute of Allergy and Infectious Disease Bethesda, Md. 20854 U.S.A.

M. Borgers Janssen Research Foundation Turnhoutseweg 30 B-2340 Beerse Belgium

Geert Cauwenbergh Janssen Research Foundation Turnhoutseweg 30 B-2340 Beerse Belgium

S.D. Chaparas Office of Biologics Research and Review Food and Drug Administration Bethesda Maryland 20892 u.s.A.

K. Chikakane Dept. Dermatology Teikyo University School of Medicine ll-1, Kaya-2 Itabashi-ku Tokyo-173 Japan

A. De Coster Departement des voies respiratoires Hopital Universitaire Saint-Pierre 322, rue Haute B-1000 Brussels Belgium

L. Desplenter Janssen Research Foundation Turnhoutseweg 30 B-2340 Beerse Belgium

M. Detandt Institute of Hygiene and Epidemiology Section Mycology 14, rue Juliette Wytsman B-1050 Brussels Belgium

P. Dierckx Departement des voies respiratoires Hopital Universitaire Saint-Pierre 322, rue Haute B-1000 Brussels Belgium

303

E. Drouhet Institut Pasteur Unite de MYcologie 28, rue du Dr. Roux F-75724 Paris France

B. Dupont Hopital Institut Pasteur 211, rue Vaugirard F-75015 Paris France

J.L. Evans Dept. of Medicine Dartmouth University School of Medicine Hanover, NH 03756 u.s.A.

M.A. Gealt Department of Bioscience and Biotechnology Drexel University 32nd and Chestnut Streets Philadelphia PA 19104 U.S.A.

H. Geerts Janssen Research Foundation Turnhoutseweg 30 B-2340 Beerse Belgium

I. Gomez Corporacion para Investigaciones Biologicas Hospital Pablo Tobon Uribe Medellin Colombia

304

J .R. Graybill Medical Service Audie Murphy Memorial Veterans Hospital University of Texas Health Sciences Center San Antonio TX 78284 U.S.A.

A. Grivegnee Departement de radiologie Hopital Universitaire Saint-Pierre 322, rue Haute B-1000 Brussels Belgium

S. Hanawa Dept. Dermatology Teikyo University School of Medicine 11-1, Kaya-2 Itabashi-ku Tokyo-173 Japan

M. Hatano Dept. Dermatology Teikyo University School of Medicine 11-1, Kaya-2 Itabashi-ku Tokyo-173 Japan

A. Hasegawa Dept. Veterinary Medicine University of Tokyo Tokyo Japan

R.J. Hay Medical Mycology and Tropical Dermatology Unit London School of Hygiene and Tropical Medicine Keppel Street London we IE 7HT United Kingdom

V.M. Hearn Mycological Reference Laboratory Central Public Health Laboratory 61 Colindale Avenue London NW9 SliT United Kingdom

P.A.J. Janssen Janssen Research Foundation Turnhoutseweg 30 B-2340 Beerse Belgium

Y. Kawa Dept. Dermatology Teikyo University School of Medicine 11-1, Kaya-2 Itabashi-ku Tokyo-173 Japan

D. Kerridge Department of Biochemistry University of Cambridge Tennis Court Road Cambridge CBl 4XD United Kingdom

K. Kikuchi Dept. Dermatology Teikyo University School of Medicine 11-1, Kaya-2 Itabashi-ku Tokyo-173 Japan

S.J. Kim Korean National Tuberculosis Association 121-150 Dangsan-dong Seoul 150 Korea

G.S. Kobayashi Divisions of Laboratory Medicine Dermatology and Infectious Diseases Departments of Internal Medicine and Pathology Washington University School of Medicine St. Louis, MO 63110 U.S.A.

K.J. Kwon-Chung Clinical Mycology Section Laboratory of Clinical Investigation National Institute of Allergy and Infectious Diseases National Institute of Health Bethesda, MD 20892 U.S.A.

T.A. Lindley Dept. of Microbiology Medical College of Pennsylvania Philadelphia PA 19129 U.S.A.

D.W.R. Mackenzie Mycological Reference Laboratory Central Public Health Laboratory 61 Colindale Avenue London, NW9 SliT United Kingdom

P. Marichal Janssen Research Foundation Turnhoutseweg 30 B-2340 Beerse Belgium

G. Medoff Washington School of Medicine Infectious Diseases St. Louis, MO 63110 U.S.A.

305

M.I. Munera Corporacion para Investigaciones Biologicas Hospital Pablo Tobon Uribe Medellin Colombia

N. Nolard Institute of Hygiene and Epidemiology Section Mycology 14, rue Juliette Wytsman B-1050 Brussels Belgium

M. Okuda Dept. Dermatology Teikyo University School of Medicine 11-1, Kaya-2 Itabashi-ku Tokyo-173 Japan

M.M. Patino Corporacion para Investigacion Biologicas Hospital Pablo Toben Uribe Medellin Colombia

A. Polak Pharmaceutical Research F. Hoffman- La Roche & Co. Ltd. 4002 Basel Switzerland

J. Rajasekaran Dept. of Microbiology and Ophthalmology Institute of Ophtalmology Joseph Eye Hospital Tiruchirapalli 620001 South India

306

A. Restrepo Corporacion para Investigaciones Biologicas Hospital Pablo Tobon Uribe Medellin Colombia

H.P.R. Seeliger Institut flir Hygiene und Mikrobiologie der Universitat Wlirzburg 8700 Wlirzburg - FRG

B.E. Shapiro Dept. of Anesthesiology Hanemann University Hospital Philadelphia, PA 19102 - 1192 U.S.A.

E.D. Spitzer Divisions of Laboratory Medicine Dermatology and Infectious Diseases Dept. of Internal Medicine and Pathology Washington University School of Medicine St. Louis, MO 63110 U.S.A.

W.J. Stevens Immunology University of Antwerp (U.I.A.) B-2610 Antwerp Belgium

A.M. Tabares Corporacion para Investigaciones Biologicas Hospital Pablo Toben Uribe Medellin Colombia

H. Takahashi Dept. Dermatology Teikyo University School of Medicine 11-1, Kaya-2 Itabashi-ku Tokyo-173 Japan

Ph.A. Thomas Departments of Microbiology and Ophtalmology Institute of Ophtalmology Joseph Eye Hospital Tiruchirapalli 620 001 South India

K. Tintelnot Institut ftir Hygiene und Mikrobiologie der Universitat Wtirzburg 8700 Wtirzburg - FRG

J. Van Cutsem Janssen Research Foundation Turnhoutseweg 30 B-2340 Beerse Belgium

H. Vanden Bossche Janssen Research Foundation Turnhoutseweg 30 B-2340 Beerse Belgium

M.-A. Van de Ven Janssen Research Foundation Turnhoutseweg 30 B-2340 Beerse Belgium

307

INDEX

ABPA, see Allergic bronchopulmonary asperg1llos1s Acelyi-CoA. 136 Achlya bisexualis. amino ac1dlproton symporters, 190 Intracellular pH, 190

Acholeplasmas. effects of polyenes. 150 plasma membrane. 150 sterols (exogenous). 150

Acid proteases, produced by Aspergillus, 129

Adenine, antagonist of 5-FC, 165

Adrenals, steroid synthesis, 177-178

Affinity chromatography, 44 AflatoxlcOSIS, 6 Aflatoxin B1. 87 Aflatox1n, 5. 6, 38, 137. 289 Agar gel immunodlfUSIOn,

d1agnos1s of aspergillOSIS and asperg1lloma, 254, 257, 258

Agan·cus campestns, 24-methylatlon of sterols, 136

AIDS, 26, 88, 115-118 and Aspergillus fum1gatus. 26 and Cryptococcus neoformans, 26 and Histoplasma capsulatum. 26

Air cond1t10mng, 28, 30, 39. 88 Air pollut1on, 29-31 Air sampl1ng, 31 Alerg1c aspergillosis, 87-93 pathology, 92 prognOSIS, 92 saprophytic growth, 87 symptoms, 87 therapy, 93

Algae, cycloartenol, 136 ergosterol. 136

Alkaline phosphatase, and ilraconazole, 257-258

Alkaline proteases. produced by Asperg11/us, 130

Allergens. 43, 88, 99-100 Allergic alveoli tiS, 92 Allerg1c bronchopulmonary

aspergillOSIS, 43, 50-52, 87-93, 98, 100-103, 229, 233-234

amphotenc1n B. 233 corticosterone, 233-234

prednisolone. 233 Allerg1c rhm1t1s, 89 Allergy, 35, 87-93. 97 Allylam1nes, 147 Alternaria. 1 00 Alveolar macro phages. 1 15-1 18 Alveol1t1s, 97-98 Am1no acid ox1dase, 1 27 Aminoglucos1dase, 4 AMP-cyclase, 169 Amphotencm B IV+ flucytosme,

treatment of aspergillOSIS, 247 Amphotenc1n B + itraconazole, effects on Aspergillus spec1es. 217, 220. 223, 226

Amphotenc1n B + ketoconazote, effects on Aspergillus species, 217, 220. 223, 226

Amphotenc1n B, 25, 54, 103, 110-111 and ac1dlf1cat1on of the cytoplasm. 152 treatment of aspergillosis, 253 and Aspergillus keratitiS, 265, 268-270, 272-275 and cholesterol-binding, 147-156 circular d1chr01sm. 1 52 effects on art1f1ciat membranes,148, 150-152 effecls on Asperg1llus spec1es, 215-226 effects on Cand1da albicans, 149, 1 53-154 effects on C. alb1cans, mycelium form, 154 effects on erythrocytes, 153, 155 effects on plat1ng eff1c1ency of C. albicans, 153 effects on the uptake of daunorub1cin, 155 effects on the uptake of ant1fungals, 154 and ergosterol-bmd1ng. 149, 151 fung1c1dal elfects,153

309

310

Amphotericin B (continued) fungistatic effects, 152·153

hyperpolarisabon of membranes, 155 immunoadjuvant acbvity, 14 7, 155, 163 and invasive aspergillOSIS, 235·237 in hposomes,155-156, 238,282 management of allerg1c bronchopulmonal}'

aspergillosis, 233·234 MtC-value, 244 mode of action, 147-157, 161-164 NMR, 152 potassium leakage, 148, 150, 152·153, 156 and prophylaxis of asperg111os1s, 282, 284 proton movement, 148, 152·154, 156 resistance to, 110, 162 selectivity of, 149 treatment of aspergitloma, 231 treatment of aspergillosis, 229·231, 233·238, 243,

247, 250 Amphotencin B-Ftuorocytos1ne combmat1on, 154, 247 Amphotenc1n IV, 110 a-Amylase,

produced by Aspergillus, 4, 129 Arnynns, 138·139

mass spectrometry, 137-138 Ankyfosmg spondylitis, 98, 107 Anomorph, 17 AntibiOtiCS, 6, 25 Ant1bod1es, 43-45, 99 Ant1gens, 43·45 Arginine-nch protem, 127 Aromatase,

effects of itraconazole,178 effects of ketoconazole, 177 effects of micmazole, 177

Arthus skin reaction, 89·90 Artificial membranes,

effects of amphotheric1n 8 on, 148, 150-151 effects of polyenes on, 148, 150-151

Asclad1ol, 5 Asoocarps, 12, 16 Ascomycobna, 17 Asoospores, 12 Ascus, 16 Aspergilhc ac1d, 6 Aspergitloma,43, 51, 53, 58, 87, 90,.97·99,103, 107·

112,130 and Aspergillus ffavus, 98 and A. fum,gatus, 98 and A. mger, 98 and Cocadio1des tmmtbs, 98 comp1tcat1ons, 1 09·11 0 CT-scan,107, 112 development of, 108 d1agnos1s of, 109 localtreatment of. 111 medical treatment of, 231 natural h1Sl01}' of,108·109 Pseudatleschena boyd11, 98 rad1olog1cal p1cture, 107-108 surgicaltreatment,111-112, 231 Syncephalastrum 98 treatment With 1traconazo1e. 249, 252-262 treatment of, 110. 230-232, 249, 252·262

Aspergillosis, 2, 23· 31, 76, 84, 87· 93,97-104, 115, 129·131

and amphotericin B, 229-231, 233· 238, 243, 247, 250

and ammal health care, 287-295 in compromised pat1ents, 281-284 histol}' of treatment, 229·238 hostdefence,115-118 in immunocompromised patients, 281-284 in av1an spec1es, 288·289 in gumea-fowl, 287, 289 1n honey bees, 288 1n horses, 288 in insects, 288 in japanese quails, 287, 289 in pet ammals, 288 in pheasants, 289 in poultry, 287-295 in rodents, 288 1n turkeys, 287, 289 in wtld an1mals, 288 in w1ld btrds, 288 1n zoo anmals, 288 itraconazole, 243-251, 252·262 prophylaxis, 281·284, 287·295 and proteases. 129-131 serodtagnos1s of, 43·58 treatment 1'11th azole ant1fungals, 243·251 treatment, 229-238, 243-251

Aspergtllusamstelodamt, 16, 19,26 37, 219 ascocarps, 16 effects of itraconazote, 219

Aspergtllus aureolus, 13 Aspergtl/us avenaceus, aspergilloSts,19

Aspergtllus btsporus, 12, 13 cornd1phores, 12 ph1at1des, 12

Aspergillus caesteUus, aspergillOSIS, 19

A. candidus, 13, 15, 19, 36,38 aspergillOSIS, 19 candidultn, 6 effects of itraconazole, 219, koJic acid,6 metulae,15 B-mtro prop1omc ac1d produced by, 6 sclerotia, 15

A. capttatus captulo glauca, 11 A. capt/a/us capttulo puJJo, 11 A. carneus. 19 A cervmus, 15, 18·19 ves~le, 15

A chevaliera, 36, 38 glyotox1n, 6 xanthocill1n, 6

A clava/us, 15, 18-19,39,88,97,99 and allergiC alveoltbs, 5 asclad1ol, 5 mitochondna, 15 morphology, 15 nucleus, 15 patulin, 5 ph1al1des, 15

A clavatus (continued) sterigmata, 15 tremorgens, 5

A cremeus, 17-18 A ctystalinus, 13 A deflectus, 19 Aspergillus endocarditis, 30 A tischen, 18 A flavipes, 16-17 ascocarps, 16 HOlle cells, 16

A navus var colunaris, 36 A flavus, 3,13, 15,18-19,25,28-30,36,38,43, 52, 55,

75, 77, 79, 98, 109,129, 137 aftatox1n, 5, 6, 129-t31, 137 aspergillic acid, 6 conid1ophores, 15 effects of itraconazole, 219, 269-270 ergosterol t36 granuloma,6 in honey bees, 288 in VItro sensitivity to amphotenc1n 8, 269-270 1n vitro sensitivity to itraconazole, 269-270 10 vitro sensitivity to ketoconazole, 269-270 mycot1c keratitis, 265, 266 B-mtro propionic acid, 6 production of kaflir beer, 3 sclerotia, 15 stone brood, 288 tremorgens,5 virus-like part1ctes 1n, 6-7

Aspergillus fumigatus, 2-3, 6-7, 13-14, 17-19,25-26, 28-31, 36-39,43-55,75-84,87-92, 98-tOO,

102, 108-t09, 115, t2t, 123-124,130-131,136, 217, 220, 223, 226, 257-258, 269-270

14a-methyl,24-methylene-ergosterol, t79, 18t

14a -methyl-ergosta-8, 24(28 )-dlen-3 B, 6a -d1ol, t79, t81

24-methylenedihydrolanosterol, t73-t74, t79-t8t an1mal models for, 216-2t7, 220-226 antigens, 7 calCIUm, 208 carbohydrate content, 166 cell wall of, 203-204 chitin in, t91-193 conid1a, 3 conidial head, 14 comd1ophores, 14 DNA, 166-t67 effects of 5-FC on DNA syntheSIS, 166-169 effects of 5-FC on protein syntheSIS, t66-169 effects of 5-FC on RNA syntheSIS, 166-t69 effects of 5-fluorocytoslne, 165-t69 effects of 5-fluorodeoxycytldme, t65 effects of 5-fluorodeoxyundine, t65 effects of azote ant1fungals, 17t-t93, t99-2t0, 2t5-

226, 243-262, 265-275 effects of econazole, 206, 208 effects of 5-fluorocytosiOe, 206, 208 effects of 1traconazole, t71-193, t99-

2t0, 2t5-226, 243-262, 265-275 effects of ketoconazole, t80-t89,206-208, 2t8-22t,

223-226, 232, 243-245, 265-266, 269-275

Aspergiftus fumigatus, (continued) effects of pH on growth, 182-183 endoplasmic retiCulum, 240 ergosterol, t36, 179-18t fumigatin, 6 fungiStatiC effect ol 5-fluorocytosine, t65 gliotoxiO, 6 growth inhibition by itraconazole, t82-183 hyphae, 183, t88, t99-2t0 m vitro sensitivity to amphotericin 8, 244,269-270 in vitro sensitivity to itraconazole, t82-183, 244-

245, 269-270 in vitro sensitiVIty to ketoconazole, 182-t83, 244-

245, 265, 266 production of insulin,6 Interference contrast microscopy, t82-t83, 200-20t mtracellutar pH of, 187-t90 1traconazote metabolism by, t85-186 ketoconazole metabolism by, t85-t86 lipid globules 10, 208 m1tochondna, 208 morphology, 75-84, 199-201 morphology- effects of itraconazole, t82-t86 nucleus, 208 ObtUSifOiiol, t79, t8t osmoph111ic ves1cles, 203-206 pathogenicity of,6 phlalides, 14 plasmalemma, 203·206 prote1ns, t66, 168-t69 proton distnbution, t86-t89 RNA, 166-t68 stengmata,205, 209-2t0 sterols, 179-t8t tremorgens, 5 ultrastructure of, t99-2t0 uptake of itraconazote by,t84-t85 uptake of ketoconazole by, t84-t85 vacuoles 10, 204-205, 208 ves1cle, t4, 208-2t0 MIC of amphotenc1n 8, 218, 244 MIC of itraconazote, 2t8-2t9, 244-245 MIC of ketoconazole, 218-2t9, 244-245 MIC ol miconazole, 2t8-219, 244

A g1ganteus, patulin, 5

A glaucus, t4, 37 med1a, t4

Aspergillus granuloma, ( A ffavus), 6 Aspergillus kerat1t1s 1n rabbits,

effects of ketoconazole,266 effects of ptmancm -chloramphentcol, 266 mycotic kerattlls,266

Aspergillus kerattlts, amphotenctn B, 265, 267-270, 272-275 clotnmazole, 274 1traconazote, 265-275 ketoconazole, 265-27t, 273-275 mteonazole, 266, 274 ptmancin, 265-275 p1mancin-chloramphemcol, 266 sod1um sulphacetamide, 266 thiabendazole, 266

311

A. melleus, 36 A nidufans var echmulatus, 19 A mdulans, 15-19,29,36,43, 109, 130 amyrins, 137-138 ascocarps, 16 conid1ophores, 14 DNA,S effects of itraconazole, 219 effects of miconazole, 140 ergosterol in, 137-139 latty acids 1n , 136-140 fructose uptake by, 140 gene expression, 4 glucose uptake by, 140 heterokaryon, 4 HMG-CoA-reductase, 140-141 Hulle cells, 16 1nlung, 16 iron uptake by, 140 lanosterol, 138-139 mycetoma,6 nasal sinus, 16 nitrate reductase, 140 parasexuallity of, 4 protease 1nduct1on, 140 proteases I, 130 proteases II, 130 squalene, 137 sterigmatocystin, 5 sterols of, 137-139

A. mger, 11, t3-14, 18-19, 28, 31' 36, 39, 43, 52, 55

a-amylase, 4 amytoglucosidase, 4 catalase, 4 citric ac1d product1on by, 3, 137 conidial head, 14 effects of S-fluorocytos1ne, 165 effects of griseofulvin, 206, 208-209 effects of itraconazole, 219 effects of rad1C1col1n, 206, 208-209

A nidufans (continued) 8-galactos1dase, 4 8-glucanase, 4 glucose ox1dase, 4 hem1cellulase, 4 and hypopyon kerat1t1s, 266 lactase, 4 lipase, 4 metulae, 15 andmycotic keratitiS, 265, 266 naring1nase, 4 and oxaloSis, 99 pectinase, 4 sclerotia, 15 sterigmata, 15 tannase,4 xytanase. 4

A roveus citrinin, 5

A ochraceus, conidial head, 14 contdtophores, 13 metulae, 15

312

A ochraceus, (continued) ochratoxin, 5-6 pathogenictly of, 18 pemllic acid,5 sclerotia, 15-16 secalomc actd, 5 septation, 15

A ornatus, 16-18 palhogemcily of, 18 sclerotia, 16

A. oryzae, aspergillosis, 19 brassicasterol, 136 eptsterol, 136 ketJap, 3 kOtl, 3 ma1toryz1ne, 6 248-methylcholesta-5,trans 22-dien- 38-ol, 136

mlso,3 rice wtne, 3 sake, 3 shogu, 3 taka d1astase, 4 tamari, 3

A. asuanus, 36 A paras1ticus, allatox1n, 5 aspertoxln, 6 ergosterol, 136 flavotox1n, 6 host ltssue responces, 121. 123-124 8-nitro prop1onic ac1d 6

A pemcifloiaes, 19,37-38 effects of itraconazole, 219

A pseudagfaucus, 36 A repens, 36-37 A restnctus, 14, 18-19

med1a, 14 vestcle, 14 effects of itraconazole, 219

A ruber, 36 A sparsus, 12 Aspergillus spec1es, 1 ,2, 12, 129-130

11-hydroxylation, 129-130 and alf condltloning,38, 40 amylases production by, 129 anttbod1es, 75-76, 79, 83 ant1gens, 75-84 in cellars, 38 citnc actd productton by, 129 conid1a, 156 in decorations, 37 in dust, 37 effects of amphotencin B, 147, 154-155,215- 226 effects of econazole, 216, 218 effects of entlconazote, 215-219, 289-295 elfects of itraconazole,171-193, 199-210, 215-226,

243-262, 265-275 effects of ketoconazole, 180-189,

206-208,215-221, 223-226,232, 243-245, 265-266, 269-275

effects of m1conazote, 215-219, 244 effects of nystatin, 216, 218 effects of p1maric1n, 216, 218 lumanc acid 4

Aspergillus species (continued) in furniture, 37 gluconic acid, 4 gluconic ac1d, 129 glutaric ac1d, 4 glycoliC acid, 4 in v1tro models for, 215-226 1n vivo models for, 215-226 incidence of,35-40 indoor, presence of, 37 itaconic acid, 4, 129 itatartaric ac1d, 4 in kitchens, 38 kojic acid, 4 malic acid,4 and malt workers, 5 mycelial extracts of, 75-84 nucleases, 129 organic acids produc\Jon of, 4 pect1nases, 130 pepbdases, 129 polansat1on of hypha! tip, 154 in potted plants, 38 progesterone metabolism, 130 proteases, 129 resistance to amphotenc1n B, 155 steroids production of, 4 SUCCiniC acid, 4 type 1 hypersensitiVIty, 5 vitamins, 4 1n workplaces, 38

Aspergillus spinufosus, (Raperia), 12 A. stromatoides, 19 A. sydowi, and aspergillosis, 19

A. tamam, koJiC acid, 6

A. terreus, 14, 19, 38 citnnin, 5 conidial head, 14 gliotoxin, 6 vesicle, 14

A. unguis, 36 A. ustus, 36 A. versicolor, 12, 19, 36-38 and aspergillosis, 19 effects of 1traconazote, 219 sterigmatocystin, 5

A. wentii, 18 Aspertox1n, 6 Asthma, 87, 89-90, 97, 100, 103, 108 and aspergillOSIS, 255 and Aspergillus, 229

ATP, 136 ATPase, plasma membrane, 153, 156

Avid1n-b1obn assay, 51, 54 Azote antifungals, hypothesis on the mode of action, 171-193 treatment of aspergillOSIS, 238, 243-251, 254-257

Basic protem, 127 Beer, and Aspergillus, 3

Bile acids, 177 Blindness, 266 Bone marrow transplants, 30 Botrytts, 1 Brassicasterol,

1n A. oryzae 136 Bronchial provoca\Jon, 92 Bronchiectasis, 89, 91, 108 Broncho-alveolar lavage, 92 Bronchocentnc granulomatosis, 100-101 Bronchopleural f1stuta, 102 Buthiobate, chemical stnucture,172 mode of action, 173

C-react1ve protem, 45, 90 C5a,115 Calcium, in A. fumtgatus, 208 effects of econazole, 208 effects of fluorocytosine, 208 effects of ketoconazole, 208 leakage induced by amphoterian B, 162

Candida afbJcans, 26, 131 catalase,162 ch1t1n, 192 elects of itraconazole, 178, 180, 200 pH-dependency, 186

eHects of 5-FC on DNA synthesis, 166 effects of 5-FC on RNA synthesis, 166 effects of amphotericin B, 161-162 effects of ketoconazole, 178, 180 pH-dependency, 186

effects of m1conazole, 173-174 effects of polyenes, 149, 153-155 electron microscopy, 123-124 ergosterol biosynthesis, 177, 180 mycel1um form, 166-167, 180 N-phenylim1dazole, 178 osmoph1111c granules, 203, 205 potass1um leakage,149, 153, 162 protoplasts, 162 res1stance to amphotenc1n B, 149, 153, 162 yeast form, 178, 180

Candtda fusitaniae effects of 1traconazote, 180 pH-dependency, 186-187

effects of ketoconazole, 180 pH-dependency, 186-187

ergosterol synthes1s, 180 intracellular pH, 189 1traconazote metabolism, 185-186 ketoconazole metabolism, 185-186 uptake of 1traconazole by, 185 uptake of ketoconazole by, t85

Candtda parapstlosis, 127 Candtda spp, effects of ketoconazole, 281 cross react1v1ty with Aspergtllus, 52

CandidOSIS, 52, 115-117 Candidulin, 6 Carbon monoxide.

compet1\Jon w1th 1traconazole, 178 Carcinogens, 6

313

Catalase, 4, 44-45, 51, 55, 58, 117 effects on lhe amphotericin 1nduced Jys1s, 153 protection aga1nst effects of polyenes. 162

Cattle, aspergillosis, 288

Cell wall, 149, 155 barner to amphotericin B, 155 of C. alticans, 155 effects of 5-fluorocytosme, 168 effects of itraconazole, 203-205, 209 glucan, 155

Cellulase,4 Cephlosporium, 39 Cereals,

and kallir beer, 3 andkojl,3

Chaetosartorya, 17 Charcot-Layden crystals, In aspergiJIOSIS,229

Chemoattractant, production 1nduced by swollen con1d1a, 115

Chcken eggs, Aspergillus, 287-291

Chitin synthase, effects of amphotenc1n 8, 154

Chitin, 154, 191, 193 in A. fumigatus, 191, 193 In c. albicans, 191 effects of itraconazole on synlhesis, 191, 193

Chitosomes, effects of amphotericin 8, 154

ChlorampheniCOl, and Aspergillus keratitis, 266

Cholesterol, 135,148-149,152,161,176, ChroniC bronchiectasis, 91 Chror11c granulomatous disease, 102, 115 and aspergilloSIS, 250

Chronic necrobsing pulmonary aspergillOSIS, 98, 102-103

treatment w1th itraconazole, 246-247 Chronic obstructive pulmonary d1sease,

and aspergillOSIS, 247-248 Chronic pulmonary aspergillosis,

1traconazole, 252-262 ketoconazole,252-262

Chymotrypsin, 56 CIE, see Counterimmunoelectrophores1s Circular dichroism, conformational states of amphotencin 8, 152

C1tric aCid, 3 ,4, 31, 137 Citrinin, 5 CJass1f1cation, of Aspergillus, 17-19

C/eistothecia, 16 Cbnafarrn see enftconazole, Clinical trials,

Asperg1lloma, 252-262 Aspergillosis, 243-251 Aspergillus keratitis,270-275 Fusarium kerat1t1s, 270- 273

Clotr1mazole,

314

aspergillOSIS, 253 Aspergillus kerat1t1s, 27 4 chem1cal structure, 174

Clotnmazole {continued) effects on ergosterol biosyntheSis, 172 effects on Us&lago a venae, 17 4

CNPA,see Chronic necrotising pulmonary asperg1ll0s1s Coccidiodomycosls, 48, 52 Coccidioides imm1tis, 98 Complement fixation, 47 Complement, 115-118 Concanavalin A, 44-45, 51, 55, 75, 81-84 Conidia, 11, 13, 15-16, 26- 27, 31, 97, 99, 115, 116, 142 swelling,166

Conidial head, 14 Conidiophore, 12, 14, 18 Corneal ulceration,

mycot1c kerabtis, 265 CortiCOsteroid-dependent asthma

and A8PA, 234 Corticosteroids, 25, 90, 93, 99, 102 and aspergillosis, 117. 230

Counter immunoelectrophoresis, d1agnos1s of aspergillosis and aspergilloma,

46, 48, 52,254, 257, 258 Cryptococcos1s, 52, 115 Cryptococcus neoformans, 26, 52, 115, 163, 186 amphotericin 8-fluorocytos1ne

combinabon,163 effects of pH on growlh 1nhiblt1on by

ketoconazole, 186 Cycloartenol, 136 Cyclophosphamide, leukopenia, 216

Cystic f1bros1s, 91 Cytochrome P-450,171, 174-178, 184, 187-188, 192-

193 1n cholesterol biosynthesiS, 175-176 effects of ketoconazole, 176-177, 184 effects of m1conazole, 177-178, 184 14a-demelhylation, 174-178, 192-193 in adrenals, 177-178 apoprotein, 178 bmd1ng of1m1dazoles, 176,178, 184,187-188 bind1ng of pyndmes, 176 bind1ng of pynm1dines, 173 effects of 1traconazole, 178, 187-188 effects of N-phenylimldazole, 178 effects of triadimefon, 178

1n human placenta, 177-178 hydroxylation oflanosterol, 174-175 hydroxylation of the C-32 methyl, 174·175 Intracellular pH effects of, 187-188 in leukotnene synlheSis, 177 in liver m1crosomes, 176-178 in prostaglandin syntheSIS, 177 in SaccharomycescereVIsiae,178, 188 1n steroid synlhes1s, 177-178 in testes, 177-178 1n lhromboxane synlhesis, 177 type II spectra, 176 in vitamin 03 act1vanon, 177-178

Cytomegalovirus, d1hydrophosphoguanid1ne, 250

Cytoplasm, calcium after treatment w1th azoles, 208

Cytos1ne dearninase, 165

Cytosme permease, 154 and uptake of 5-FC, 165

Cytosine, antagonist of 5-FC, 165

Czapek's solubon agar, 14

Dandruff, 37 Daunorubicin, effects of amphotericin 8 on the uptake of, 155

Dermatophagoides pteronyssmus, 37, 88

14a-Demethylase, effects of azole antifungals, 171-181

14a-Demethylation, cytochrome P-450 dependency, 174-175

14a-Demethylatlon, effects of itraconazole, 171-181 effects of ketoconazole, 177- 181

4-Desmethylsterols, 135-138 Diagnosis, 11-19,89,99-102,109

of mycotic keratitis, 266 Diastase, 4 0/CIJ/aena, 17 D1doconosanoyt phosphatidylcholine ves1cles,

effects of amphotericin 8,148 Differential scannmg calonmetry, 191 24-Dihydrolanosterol, 137, 139 D1hydrophosphoguan1d1ne, cytomegalovirus, 250

D1hydroxyprogesterone, 129 4,4-Dimethylsterols, 135-138 DNA syntheSIS,

effects of 5-FC, 165-169 DNA, 154 Dot-ELISA, 48 Double diffus1on, 45-46, 57

E.8.1., see ergosterolbiosynthesis 1nh1b1tors, Ecology, 35-40 Eoonazole, effects on AspergJ!Ius spec1es, 216, 218 effects on calc1um precipitates, 208 effects on mitochondria, 208 effects on ultrastructure, 208

Edywi/Ja, 17-18 Eggs,

AspergJIIus, 287-294 Elastase, 131 ELIFA, see Enzyme-linked immunohtrabon assay ELISA, 48-53, 76 Emericella, 17 EndoplasmiC reticulum,

A. fumigatus, 204 Enilconazole smoke,

prophylaxis of aspergillosis, 287, 289-294 Enilconazole spray,

prophylaxis of aspergillOSIS, 287, 289-294 Enilconazole,

clinical results, 291-295 effects on Aspergillus species, 215-219 effects on AspergJI/us spores in the air, 282 and Japanese quails, 293 prophylaxis of aspergillOSIS, 287-295

Enzyme· linked immunofiltration assay, 48, 51 Enzyme-linked immunosorbent assay, 48-53 Eosinophilia, 88-90, 100- 101, 103 in aspergillosis, 229

Eosinophilic pneumonibs, 98, 100·101 Epidemiology, 23·31 Episterol, 136 2,3-Epoxlde, 136 Ergosterol biosynthesis inhibitors, 171, 173-193

effects on ultrastructure, 199- 210 Ergosterol biosynthesis,

effects of itraconazole, 177-181 effectsofketoconazole, 171,174,176-178,180-181

Ergosterol depletion, effects on cell proliferation, 190-191, 193 effects on chitin synthesis, 191, 193 effects on membrane-bound enzymes, 191

Ergosterol, 135-139, 148-149,152 161-162, 171, 173-182, 190-193

biosynthesis, 135-142, 171,173-182, 190-193 cell function, 138 d1fferenllal scanning calonmetry, 191 effects on cell proliferation, 190· 191, 193 effects on membrane fiU1d1ty, 190-191, 193 effects on prOtein kinase, 136 membrane-bound enzymes, 191 and membranes, 135, 140

Ergosteryllinoleate, 138 Ergosteryl oleate, 138 Erythrocytes, effects of amphotericin 8, 153, 155 potaSSIUm leakage, 153

Estradiol syntheSIS, 177- 178 Etaconazole,

accumulation of 14a-methyl-ergosta-8,24(28)-dlen-3B,6a-diOI, 181

chem1cal structure, 172 effects on Us/J/ago maydJs, 181

Eurohales, 17 Eurotium, 17-18 Extrinsic alveol1tis, 98·99 Extrinsic asthma, 98, 100

Farmer's lung, 99 Farnesyl pyrophosphate, 136 Fatty acids, 137, 141-142, 177 Fenneffa, 17 Fibrinogen, 131 Ravotoxin, 6 Ruconazole, effects on A. fumigatus,221, 224 effects on testosterone metabolism, 177

Fluorocytosme, 25,110, 147,154 blebbmg ,208 combinaiiOn with amphotericin 8,147, 154 effects on A. fumJgatus, 165-169 effects on A . niger, 165 effects on calcium content, 168-169 effects on carbohydrate content,166-168 effects on cell wall, 168 effects on DNA content, 166-169 effects on hyphallenght, 166-168 effects on lipid metabolism, 169

315

Ruorocytosine (continued) effects on mitochondria, 168 effects on nuclei, 168, 208 effects on protein content, 166-168 effects on RNA content, 168-169 effects on ultrastructure, 208

MIC, 165 and prophylaxis of aspergillosis, 282 treatment of aspergilloma, 253 uptake, 165-166

Fluorodeoxycytidine, 165 Ruorodeoxyuridine, 166 Ruorodeoxyuridine-monophosphate, 166 Fluorouracil, 165-166 Fluorouridylic acid, 166 Foot cell, 11-14 Formaldehyde, use in hatcheries, 289

FRIE, see Fused-rocket-immunoelectrophoresis Fructose, uptake by A mdulans, 140

Fumaric acid, 4 Fumigati, 18 Fungal cell wall, 149, 155 Fungizone, see amphotericin 8 Fungus ball, 98, 107-109, 130, 246 Fusarium keratitis,

antifungal therapy, 270-273 Fusarium spp., amphotericin B, 269, 270 imidazoles, 269, 270 1traconazole, 269, 270 ketoconazole, 269, 270

Fused-rocket-immunoelectrophoresis, 46, 75, 77, 78

Galactomannans, 45. 53, 55·56 Galactose, 137 a-Galactosidase, 4 Gas liquid chromatography, 137·138 Gel diffusion, 45 Gel flltrat1on, 44, 75 Geranyl pyrophosphate, 136 G1ant cells, 1 02 Gliotoxin, 6, 84 B-Giucanase, 4 Glucoamylase, 4 Glucon1c aad, 4 Glucose ox1dase, 4 Glucose, 137, 140 Glycogen,

effects of azoles, 208 Glycolic acid , 4 Glycolys.s, 152 Glycoprote1ns, 44, 50, 53, 56-57 Glycosylated sterols, 137, 140 Granulocytopema, 115

1nc1dence of Asperg1flus, 282 incidence of Cand1da spp, 282

Granulocytopema (continued) mvasive asperg1llo~s. 281

Grass pollen, 88 Griseofulvin,

effects on ultrastructure, 206, 208·209

316

G.Janine, antagonist of 5-FC, 165

Guinea-fowl, aspergillosis, 287, 289

Guttural pouch, topical enilconazole, 289

Gymnoasrus, ascocarp wall, 12

Haemoptysis,87,99, 102,109,111-112 and aspergillosis, 232, 237

Haemorrhage, 99 Hatcheries,

A. fumigatus, 287·294 Hemicarpenteles, 17 Hemicellulase, 4 Hemisartorya, 17 Heterochromatin,

in nuclei after 5-FC treatment, 168, 208 Histidine nch protein, 127 H1stones, 127 Histoplasma capsula tum, 26 Histoplasmosis, 52, 108 HMG-CoA, see 3-hydroxy-3-methylglularyi·CoA, Honeybees,

A. flavus, 288 Horses,

aspergillosis, 288-289 en11conazole, 289

Host defence, 115 Host tissue responces,

to fungi, 121 127 House dust m1te, 37, 88, 92 HPLC,

sterols,137·138, 179 Hulle cells, 16-18 Humoral responses, 84 Hydrocortisone, 216 Hydrogen peroxide, 117·118, 127 1 a-Hydroxylation, effects of ilraconazole, 178 effects of ketoconazole, 177

6B-Hydroxyla!lon of testosterone, effects of ketoconazole, 177

3-Hydroxy-3-methylglutaryi-CoA, 136, 140·141 3-Hydroxy-3-methylglutaryi·CoA-reductase, 136,

140·141 Hydroxyl groups, 151 11 a-Hydroxyprogesterone, 129 Hypersens1t1v1ty pneomonitis, 88, 98-99 Hypersens1t1v1ty, 99 Hyphae, 12, 116·118 Hyphae (cont1nued)

effects of 1traconazole, 199-210 growth of, 166-169

Hypoxanthine, antagonist of 5-FC, 165

lgA, 51 lgD, 51 lgE, 48, 50-52, 87-93,100·101, 229, 234

and ABPA, 229, 234

lgG, 48, 50-52, 92 lgM, 51-52 lmmunoadjuvant activity, of amphotericin B, 163

lmmunoblots, 52 lmmunocompromised host, 88,101, 130

aspergtllosis, 281-284 Immunodiffusion, 79 tmmunoelectroosmophoresis, 46 ImmunoelectrophoreSIS, 44, 46, 77 lmmunoflucrescence, 43,47 In vitro models, Aspergillus species,215-226

In vivo models, Aspergillus species. 215-226

lnd1rect immunofluorescence, 47 Influenza A, 25 Insects. aspergillosis, 288

Insulin, 6 Interference contrast mtcroscopy,

A. fumigatus, 183, 200-201 Intracellular pH, 187-190

A. fumrgatus, 188-190 C. lusitaniae,189

Intrinsic asthma, 100 lnvastve aspergillosis, 88, 91, 235-238 amphotenctn B, 235 granulocytopemc pabents, 251 treatment wtth 1traconazole, 245, 249 cort1costero1d therapy,230

Invasive pulmonary aspergillosis, 28,97-98,101-103 IPP, 136 lsoelectnfocussing, 44 3-lsopentenyl pyrophosphate, 136 ltacomc acid, 4 ltatartaric actd, 4 ltraconazole, 111 alkaline phosphatase, 257-258 and aspergtlloma, 249-262, Aspergrllus keratitis, 265-275 chem teal structure, 172 chrome necrottsong pulmonary

aspergillosis, 246-249 effects on A. amstefodamrr, 219 effects on A. candtdus. 219 effects on A. 1/avus, 219 effects on A tumrgatus, 217-220, 224, 226 elfects on A. nrdufans, 219 effects on A niger, 219 effects on A penrcrllotdes. 219 effects on A restrrcticus. 219 effects on Aspergrffus spectes, 215-226 effects on A versrcofor, 219 effects on the growth of A tumrgatus, 182-183 effects on ultrastructure of Aspergrflus, 199-210 m tnvasive aspergillosis, 245, 249 and leucocytes, 257-258 logP,185 mean energy of mteraction, 185 metabolism, 185-186 MIG-value, 244-245 modeofaction,171-193 mode of msert1on tnto the liptd matnx, 185

ltraconazole (continued) molecular area occupied per molecule, 185 pKa, 187 prophylaxis of aspergillosis, 282-284 protonatton proftle, 188 pulmonary aspergilloma, 252-262 spacefillmg model, 179 tolerance. 250, 257-258 treatment of aspergillosis, 243-251 treatment of chronic pulmonary

aspergillOSIS, 252-262 uptake by A lumrgatus, 184-185

Japanese quails, aspergillOSIS, 287, 293

Kaff11 beer, 3 Keratttts, and Aspergillus. 265-275

KetJap, 3 Ketoccnazole, 110-111 and aspergtllosis, 253 Aspergrllus kerattlis in rabbtts,266 Aspergrllus keratttts,265-271, 273-275 chemtcal structure,171-172 chrontc pulmonary aspergtllosis,255-262 effects on A fumtgatus, 217-225 effects on Aspergillus spectes, 215-226 effects on calctum prectpttates, 208 effects on cholesterol btosynthesl6,176 effects on mttochondna, 208 effects on testosterone metabol1sm. 177 effects on the 1 a-hydroxylase, 177 effects on the 11 B-hydroxylase, 177 effects on the 17,20-lyase,177 effects on the aromatase, 177 effects on the cholesterol desmolase

(cholesterol stde-chatn cleavage), 177 effects on the growth of A fumrgatus, 182-183 effects on ultrastructure, 206, 208 effects on vttamtn 03 acttvatton, 177 effets on testosterone btosynthests,177 log P, 185 metaboltsm of, 185-186 MIG-value, 244- 245 mode ot actton, 173-174, 176-177, 180 molecular area occupted per molecule, 185 pKa, 186 prophylaxts of asperglllosts,282, 284 protonatton proftle, 188 pulmonary aspergtlloma, 243-262 treatment ot aspergtlloma, 232 treatment of aspergillosis, 245 uptake by A fumrgatus, 184-185

Kidney transplant, 25, 28, 30 Ktdney, mttochondna, 177-178 vttamtn 0 activabon, 177-178

KoJi,3 KOJIC actd, 4, 6

Lactase, 4 Lactobacillus, 3 Lactofernn, 127

317

lanosterol, 136-139, 174-176, dtlferenhal scanning calonmetry, 191 effects on membranes, 191

laser microprobe mass analySis, A fumigatus, 208

lectin, 116 Leucor:ema, in gutnea-pigs, 216

leukemia, 115 leukotrienes, 177 linoleate, 137, 142 linolenic add, A nidulans, 142

lipase, 4 liptd globules,

effeciS or fluorocytosine, 208 Upopolysacchande, 81-82 Uposomes,

earners for amphotericin B, 156, 238 Listena,

res1stance to amphothenctn B, 163 liver, 6, 176-178 ltver m~erosomes,

cytochrome P-450, 176-178 liver transplants, 28 lung, 16, 25-26, 97-104 lung adenocarcinoma, 247 lung function studtes, 91, 99 lymphocyte transformation, 77, 80 lymphocytes, 75-76, 80, 82-83, 115 17,20-lyase, effects of ketoconazole, 177

lysosomes, 127 lysozyme, 127

Macts,38 Macrophages,84, 116-117,129,131

rungtctdaf actiVIty, 116-117 Malic acid, 4 Malt extract, 14 Malt workers lung, 88 Malt workers, 99 Maf!oryzme, 6 Maltose fermentation, 152 Mannose, 116,118,137 receptor, 116, 118

Mechlorethamine hydrochlonde, leukopema and neutror;ema,216-217

Membranes, 135 aqueous pores, 148-152 effects of polyenes, 14 7-156 permeability, 148-156 proton movement, 148, 152-154, 156

Metulae, 13, 15,18 24-Methylenedthydrolanosterol,

ergosterol precursor 1n fungi, 173-174

in Aspergillus, 173-174, 179-181 14a-Methyl-ergosta-8,24(28)-dten-3B,6a-dtol,

1n Aspergtllus, 179-181 1n C. albicans, 181 1n Usttlago, 181

14-Methylfecosterol, 1n Aspergtllus, 179-181

318

14-Methyl-24-methylene-ergosterol, in Aspergillus, 177-181

14-Methylsterols, dtfferenbal scanning calorimetry, 191 effects on chitin synthesis, 191-193 effects on membranes, 191-193

Mevalonic add, 136, 176-177 MIC-values,

amphotericin B, 244, 269 itraconazole, 186, 244-245, 269 ketoconazole, 186, 244-245, 269 miconazole, 244 pH-der;endency, 186

M100nazole IV, aspergillOSIS, 253

Miconazole, 111 Aspergrllus keratitis, 266 chemtcal structure, 171-172 effects on cholesterol biosynthesis, 176 effects on 3-hydroxy-3-methyl-

glutaryl CoA reductase, 140 effecls on aromalase, 177 effects on A. tumigatus, 218-219 effects on ergosterol brosynthesis, 140, 173-174 effects on membrane permeability, 173 MIC-value, 244 mode of acbon, 173-174 prophylaxis of aspergillOSIS, 282 treatment of aspergillOSIS, 245

Mtcrosomes cytochrome P-450, 176-178

Microsporum cants, effeciS of pH on growth 1nhib1t1on by ketoconazole,

186 Microsporum gypseum, macrocontdta,121, 123

Mrso,3 Mitochondria, 15 Mitochondria,

cytochrome P-450, 177-178 effects ol 5-FC, 168

Mrtogens, 76 Mode of act1on, of azole antrfungals, 171-193 of 5-FC, 165-169 polyenes, 147-157

Monilinia tructtgena, effects of buthrobate, 173 ergosterol btosynthesls, 173

Monocyte-macrophage, 117 Monocytes, 117-118 Mononuclear cells, 26, 92 Morphological descripbon, 13-17 Morphology, 11-19 MUCOid plugs, 100-101 Mucor, 1

kafftr beer, 3 Mucorales, 17

raJt,3 suftn,3

Mushroom worke~s lung, 99 Mycetoma, a

treatment, 230

Mycobacterium tuberculosis, 54, 258, 260 Mycopesma, incorporation of exogenous sterols, 150 polyenes, 150 potass1um efllux, 150

Mycotic kerat1tis, Aspergillus, 265- 275

Mycotoxicosis, 87 and Aspergillus, 289

Mycotoxins, 5, 6, 35, 87 and Asperg111us, 289

Myctoma, 107, 109 Myeloperoxidase, 117, 127

Nannginase, 4 Nasal s1nuses, 16, 87, 229 Natamy<in, 110

aspergiiiOSIS,253 Neosartorya, 17 Nephropathy, 6 Neurospora crassa, 140 Neutral proteases, produced by Aspergillus, 130

Neutropenia, 97 in guinea-piQS, 216

Neulrophils, 115,116,118,127,130 Neutrophlls (continued)

fungiCidal actiVIty, 118 Nitrate reductase, A nidulans, 140

B-N1tro propionic acid, 6 NMR, polyene-induced perturbations, 152

Nocardiosis, 52 Nutnu mice, 117 Nudeases, 130 Nudeus,t5

effects of 5-FC, 168-169 effects of fluorocytos1ne, 208

Nutmeg, and Aspergillus. 38

Nuls, and Aspergillus, 28

Nystabn, 110, 147, 152 aspergiiiOSIS,253 effects on Aspergillus spooes, 218 prophylaxiS of aspergillosis, 282 treatment of asperg1lloma. 229, 232

Obtusifoliol, 173, 179, 181 Ochratoxins, 5, 6 and Aspergillus, 289

Ocular toxicity, and anbfungal therapy, 266

Oleate, 137-138, 142 Opsomns, 116-117 Opsomzabon,117-118 Orgamc ac1ds,

production by Aspergillus, 4 Osmoph111ic vesicles, A fumigatus, 203-206 C. alb/Cans, 203, 205 Tnchphyton rubrum. 203, 205

OsteomyelitiS, 102

Otitis, 31 Otomycosis, Aspergillus, 229, 299

Oxalic acid crystals, 99 Oxalosis,99 Oxidase,

candidaC1dal acbvity, 127

PAGE, 77,79 ParacoCCidiodes brasiliensis, 46 ParacocC1dioidomycoses, 52 Paranasal siruses, Aspergillus, 229

Passive haemagglutination, 47, 57 Palhoge111c spooes, Aspergillus spp., 18-19

Palhology, 6, 92, 97-104, 107-112 Patulin, 5 Pectinase, 4, 129 Penic111ic acid, 5 Penicillium atrovenetum, 139 P. urt1cae, 140 P. urt1cae (conbnued)

steryl esters, 140 PeniCillium, 2, 12, 27, 35,38 Pepper, and Aspergillus, 38

Pept1dases, 130 Perid1um, 17 Peroxidase, 117 Pet animals,

aspergillOSIS, 287-288 Petromyces, 16-17 pH, cell, 171,187-190,192-193 med1Um,166

PHA, see Passive haemaglubnation Phagocytes, 84,108,116-118 PhagocyiOSIS, 84,116-118 Phenobarbital,

and cytochrome P-450, 178 Phialides, 11-15,18 Phialophora, 39 Phoma,39 Phosphatases, 130, 257 Phosphate, leakage Induced by amphotericin B, 162

PhosphOlipidS, 135, 148, 150-151 accumulallon 1n the cell wall, 203

Phycomyces blakes/eeanus, 136-140 sleryl esters,140

Phytohaemagglutunin, 75, 82 P1geon droppings, 28-29 P1geons, 28-29,31 P1manc1n, Aspergillus keratitiS, 266 effects on Aspergillus spec1es. 218

Plmaricln-chloramphenicol, Aspergillus keratll1S,266

l'ltyrosporum ovale, effects of 1traconazole, 180-181 effects of ketoconazole, 180-181 ergosterol synthesis, 180-181

319

320

Placenta, aromatase. 117-178

Plants, sitosterol, 135

Plasmalemma, 15,148-156 ATPase. 153, 156 effects of ilraconazole. 203, 205

Plasmin, 127 PMN, see Polymorphonuclear leucccytes Pneumon1a, 26, 28,31 Pokeweed m1togen, 75,81-82 Polansat1on of hypha! t1p growth. Aspergillus, I 56

Pollen, 88, 92 Polyenes,

mode of action, 147-157, 161-164 potass1um efflux, 148, 150, 152-153, 156 resistance, 149, 153

Polymorphonuclear leucocytes, 97, 102 Polymorphonuclear phagocytes. 26 Polyporus, 1 Post-irradiation llbros1s, 98 Potassium-efflux. Induced by polyenes. 148,150.152-153,156,162

Potassium permanganate, use 1n hatchenes, 289

Potted plants, and Aspergillus. 28-29.31,38

Poultry, aspergillOSIS, 287-295 A tumigatus, 287-295

Prec1p1!1ns, 45-46, 87 Prednisolone, effects on Aspergillus spec1es, 21 8

Presqualene, 136 Preven!lon.

of aspergillosis, 27-28, 281-295 Progesterone, 1 29 ProphylaxiS of aspergillosis, 281-284, 289-295

amphotencm B. 282, 284 en1lconazole, 287-295 flucytosme, 282,284 1traconazole, 282-284 keloconazole. 282, 284

Prostaglandms, 1 77 Protease I, 130-1 31 Protease II, 130-131 Proteases, 56, 129-131 Proteases. A.mdulans. 1 40

ProteJn k1nase. effects of ergosterol, 136

Protein synthesis, 152 Proton d1stnbut10n, 188-189 Proton gradient, 153 Proton magnet1c resonance spectroscopy,

sterols, 137-138 Protons, 148, 152-154, 156 Protoplasts.

C. alblcans, 162 Protoplasts. effects of polyenes, 153

Protoporphynn IX, 174 Pseudalleschena boydu, 98

Puccinia, 1 Pullulana pullulans, 39 Pulmonary aspergtlloma, 87

ttraconazole, 252-262 ketoconazole,255

Pulmonary aspergillosis, 97-104 classiflca!lon, 98

Pulmonary eos1nophiha, 88 Pulmonary tuberculosis, 98, 102 Pyrazinamide, 254 Pynmidmes, A. fumigatus, 173

Pythiaceae, absence of sterol synthes1s, 139

RabbitS, Aspergillus keratitiS, 265-275

RadiCICOhn, elects on ultrastructure, 206, 208-

209 Rad1o Immunoassay,

47-48, 53, 55, 57 Radtoallergosorbent test, 48, 51 Rad101mmunodtffusion. 45-46 Ragi, 3 Rape ria spinulosa. 12 RAST, see Rad1oallergosorbent test Reductase, membrane-bound, 136, 140-141 soluble. 140

Res1stance. 149. 153 Resp~ratory allergy, 88 Rettno1c ac1d metabolism,

effects of ltraconazole,178 Rhodamine. 83-84 RIA, see.Radlo 1mmuncassay Ribosomes, 168 RICe, produc!lon of mtso, 3 prodoct1on of rag1, 3

productton of sake,3 R1fampm, 254 RNA.

effects of 5-FC. 166-168 Rodents,

asperg111os1s, 288 Roentgenographic f1nd1ngs, 89, 91

Saccharomyces, productton of m1so, 3

Saccharomyces carlbergenSis, sterols, 139

S. cerevisiae. 14a-demelhylase, 174, 176, 178 3-hydroxy-3-methylglutaryl GoA reductase. 140 cholesterolln,135 cytochrome P-450. 174, 176, 178, 187-188 effects of amphotericin 8, 162 effects of 1traconazole, 178, 187-188 effects of keloconazole. 178, 187-188 effects of tnad1mefon. 178 ergosterol biosynthesis. 174, 176,178 ergosterol, 1 35 lanosterol, 136

Saccharomyces, (conbnued) N-phenyl1mmidazole, effects on cyt.P-450, 178 protein kinase,136 purified cyt. P-450, 178

Sa1toa, 17 Sake, and Aspergillus,3, 129

Saprophytic colomsation, 98 Sarcoidosis, 98, 102-103, 108 Scales, and Aspergillus, 37

Scanmng electron m1croscopy, A tum1gatus, 202, 206

Scleroclelsla, 17 SDS-PAGE, 52-53 Secalonic ac1d, 5 SerodiagnoSis, 43-58 sroyu, production by Aspergillus, 3

SiliCOSIS, and aspergillosis, 98

Sinusibs, 26 Sitosterol,

1n plants, 135 Skm test reaction, 76, 78, 80 Sk1n test, 89- 90 Sk1n, 122-127 epidermal microsomes, 178 extract, 125-127 hydroxylation of re11no1c ac1d , 178

Sod1um 1od1de, treabnent of aspergilloma, 110-111

Sodium sulphacelam1de, Aspergillus kerat1t1s, 266

Soybeans, fermentabon products, 3

Squalene, 136-137 Stalk, 15 Stearate, 142 Sterigmata, 11-12, 15,210 Sterigmatocystm, 5 Stero1ds, 4, 135

effects of 1traconazole, 177 Sterol esters, 137 Sterols, 135-141, 148-149, 152 biosynthesis, 135-141 hplc, 179

Stipe, 12-14 Stone brood, A. flavus, 288

Stregmatocyst1s antacustica, see A mger, 18 Streptomyces, 147 Stroma, 17 Succinic acid, 4 Suf1n, 3 Superoxlde d1smutase, elfects on lhe amphotericin mduced lysis, 153 protection aga1nst effects of polyenes,153, 162

Surgery,111-112 Symptoms, 107 Syncephelastum, 98

T -cells, 26, 84, 92, 117 Taka d1astase,

produced by A. niger, 4 Tamari, 3 Tandem-crossed-

immunoelectrophoresiS, 46 Tannase,produced by A. niger, 4 Teleomorph, 17 Tempeh,3 Testes,

effects of itraconazole, 178 elfecls of keloconazole, 177

Testosterone metabolism, effects of 1traconazole, 178 elfects of ketoconazole, 177

Tetraethyl ammonium, effects on 10n movement, 151

Thermoph1lhc act1nomycetes, 99 Thiabendazole, Aspergillus keratitis, 266 in hatchenes, 289

Th1n layer chromatography, sterols, 137-139

Thloglycolale, 116 Thrombocytopema, 102 Thromboxane synthesiS,

and cyt P-450, 177 Thymid1late synlhetase,

mh1b1bon by 5-fluorodeoxyundlne monophosphate, 166 TLC,

sterols, 180-181 TOXInS, 87 T racheobronchitls, 31 Transm1ss10n electron m1croscopy, A tum1gatus, 202-205, 207-210

Tremorgens, 5 Tnad1melon, chem1cal structure, 172 effects on cyt. P-450, 178 mode of acbon, 173

Tnanmol, chem1cal structure. 172 effects on ergosterol biosyntheSis, 173

Trichocomaceae, 16-17 Trichophyton mentagrophytes, elfects of pH on growth inhll>1t1on by

ketooonazole, 186 osmoph1fl1c ves1cles, 203, 205

T. rubrum, osmoph1lhc ves1cles, 203, 205 effects of pH on growth 1nhibit1on by

ketooonazole, 186 T ubercuhn, 75 TuberculOSIS, 98-99, 108-109, 111,

254-255 and aspergillosis, 229, 247-249

Turl<ey-X-disease, 129 Turkeys,

aspergillOSIS, 287 Two-dimensional-electrophoresiS, 44 Type I hypersens1tiv1ty, 100

321

322

Ultrastructure, A. fumigatus, 199-210 effects of azote ant1fungals, 199-210

Uracil uptake by fung1, 166 Ustilago avenae,

effects of clotrimazole, 17 4 Ustilago maydis, effects of etaconazole, 181 14a-methyl-ergosta-8,24(28)-dien-3 B,6a-d1ol, 181

Vacuoles, A. fumigatus, 204-205

Vesicles, 13-14 V1rus-like part1cles,

in A. flavus, 6, 7 Vitamin D3-activatlon, effects of 1traconazole, 178 effects of ketoconazole, 177

Warcupiella spinulosa, 12 Wheat,

production of ketjap, 3 of shoyu, 3 of taman, 3

Wild birds, aspergillosiS, 288

Xanthoc1111n X, 6 XRIE, 46,51 Xylanase. 4

lJXJ an~mals, asperg1llos1s, 288