SUBJECT INDEX A64077 422 pharmacokinetics and action 316 AA861 421 resistance 318 Acyclovir 318 toxicity 317 Adenosine-3’, 5’-monophosphate Azone, skin penetration enhancer 222, 225, mediated secretions, cystic fibrosis 42, 43 226, 230 role in inflammation 434 second messenger 31, 434 Adenosine triphosphatases, ion-transporting 51 BB16 427 Adenosine triphosphate-driven transport B cells, rheumatoid arthritis 418 protein 49 Becker muscular dystrophy 181, 183 Adenosine triphosphate, oxidant effects on molecular diagnostics 185 cellular levels 139 Bicarbonate secretion by epithelial cells 24 Adenylate cyclase, signal transduction 33 p-Bromophenacylbromide 431 Adhesion molecules, rheumatoid arthritis 354, Buprenorphine hydrochloride, iontophoresis 357, 413 through skin 220 Adjuvant arthritis 417 8-Adrenergic agonists, epithelial cell secretion 36 Calcitonin gene-related peptide, in synovial 8-Adrenergic sensitivity, cystic fibrosis 41, 42, joints 360, 361 56 Calcium AHP, cpd4 408, 409 epithelial cell secretion 36 AIDS 245 oxidant effects on cellular homeostasis 138 AZT 316 second messenger 34 CD4 in pathogenesis 273 Cartilage degradation 423 chemotherapy 313-328 CD4 255 endothelial cell involvement 305 endocytosis 269 immunomodulation 322 epitopes 257 Kaposi’s sarcoma 297, 303 function and signalling 272 passive immunisation 322 gp120 interaction 270, 315, 320 soluble CD4 320 HIV infection 268, 304 Airways, cystic fibrosis 18 H,O,-induced alterations 155 AL721 323 pathogenesis of AIDS 273 Amiloride, cystic fibrosis treatment 63 rheumatoid arthritis 417, 419 Ampligen 322 soluble 271, 320 Angiogenesis, mechanisms and regulation 300 structure and function 256 Antigen-presenting cell CD7 419 AIDS 273, 284 CD25, effect of U75412E on expression T cell interaction 412, 413 of 163, 165 Anti-inflammatory drugs 397 CD28, rheumatoid arthritis 415 Antioxidant drugs, effect on lymphocyte Cell culture, free radical-induced DNA function 161 damage 97 AP-1 441 Cell surface receptors, viruses 268 induction by interleukin-1 442 Cerulenin, inhibition of HIV proteinase 331 Arachidonic acid CGP 28238 408 activation of lymphocyte NADPH Chemotherapy, HIV infection 313-328 oxidase 89 Chloride control of 433 permeability in cystic fibrosis 40, 42, 44 metabolism and inflammatory mediators 420 reabsorption 26 Arthritis secretion by epithelial cells 19, 30 generation of free radicals 93 Chloride channel, fluid secretion 22, 30 molecular basis of therapy 395-473 Cholera 30 Aspartic proteinases, HIV 329 Chondriotin sulphate, rheumatoid arthritis 365 Aspirin 397 Collagen arthritis 417 Atherosclerosis, free radicals and protein Collagenase damage 124, 126 gene expression 440 Autoimmune disease 400 inhibitors 426 3'-Azido,3’-deoxythymidine 313, 315 rheumatoid arthritis 370, 423, 425 Viii Subject Index Collagens, rheumatoid arthritis 363 E-5090 406 Computer graphics molecular modelling 285 E-5110 406 Corticosteroids, arthritis 347, 445 Effector cells, rheumatoid arthritis 418 CP-66,248 406 Electrolytes Cyclic nucleotide phosphodiesterases, role in abnormalities in cystic fibrosis epithelial inflammation 434 cells 40 Cyclophilin 416 reabsorption 25 Cyclosporin A 415 secretion 19, 30 Cysteamine, protector of free radical ELISA damage 133 free radical-induced DNA damage 95 Cystic fibrosis 1-81 reactivity of IgG with protein A 111 CFTR 48 Endocytosis, HIV 268 clinical features 5 Endothelial cell adhesion molecule-1 171, 172, epithelia affected 17 357 epithelial cell regulation 30, 40 Endothelial cells gene identification 8 angiogenesis 300 gene therapy 62 HIV interactions 304, 305 genetic screening 15 neutrophil induced injury 171 history 5 role in Kaposi’s sarcoma 299, 302 management of 61 Energy system, oxidant effects 139 models 56 Epidermal growth factor, rheumatoid Cystic fibrosis gene arthritis 439 cystic fibrosis models 56 Epidermis 197 protein structure 47 drug transport 201 treatment of cystic fibrosis 62 permeation pharmacokinetics 212 Cystic fibrosis transmembrane conductance Epithelia affected in cystic fibrosis 17 regulator protein 47, 57 Epithelial cells Cytokines cultured, cystic fibrosis models 58 endothelial cell activation 172, 299, 301 regulation 30 immunomodulation 322 regulation in cystic fibrosis 40 rheumatoid arthritis 348, 401 relation of cystic fibrosis gene to dysfunction stimulation of superoxide production by 47 lymphocytes 88 Exocrine glands Cytolysis, free radical generation 125 cystic fibrosis 17 Cytoskeleton, effect of oxidants 139 regulation 30 Cytotoxic T cells, rheumatoid arthritis 418 Exocytosis, secretory proteins 26, 28, 30 Deoxyribonucleic acid FVIIIRAg 302 diagnosis of muscular dystrophies 185 Fibroblast growth factors free radical-induced damage 95, 129, 376 angiogenesis 300° oxidant-induced damage 141 rheumatoid arthritis 348, 352 rheumatoid arthritis 376 Fibronectin, rheumatoid arthritis 356, 357, 366 Dermis 198 Flow cytometry, free radical damage within drug delivery 212 ; single cells 129° Dextran sulphate, antiviral activity 321 Fluid secretion by epithelial cells 19, 30 Diacylglycerol kinase 434 a-Fluoroketones 336 ' 2',3'-Dideoxycytidine 319 5-Fluorouracil, terpene penetration enhancers 2’ 3’-Dideoxyinosine 315, 318, 320 223, 225, 229, 232 Dimethylsulphoxide, skin penetration Foscarnet 320 enhancer 222, 227 Free radicals Diphenylene iodium, effect on lymphocyte induced DNA damage 95, 129 function 162 in inflammation 94,101 Disease modifying anti-rheumatic agents 398 protein damage and role in immune Duchenne muscular dystrophy 175-194 response 121 — dystrophin-deficiency 179 rheumatoid arthritis 372 . dystrophin gene abnormalities 179 Free radical scavengers, effect on nucleoid molecular diagnostics 185 forward scatter response 133 Dystrophin gene 177 abnormalities 179 Dystrophin protein 177 Gelatinase 370, 423, 425 abnormalities 181 Gender, dystrophin abnormalities 183 Subject Index Gene expression, therapeutic intervention in Hydroxyl radical, DNA damage 143 rheumatoid arthritis 444 Hypochlorous acid, injury to cells 144 Gene sequence identification, cystic fibrosis 12 Hypothalamic-pituitary-adrenal axis, Gene therapy, cystic fibrosis 62 arthritis 347 Genetic counseling, muscular dystrophies 185 Hypoxic-reperfusion injury, rheumatoid Genetic screening, cystic fibrosis 15 joints 374 Glucocorticoid receptor 445 Glutathione-redox system, effect of oxidants 137 Glycolysis, effects of oxidants 139 Glycoproteins, rheumatoid arthritis 365 Immune complex vasculitis 169 Glycoprotein gp41 255 Immune response, role of free radical damage Glycoprotein gp120 257 to proteins 121 carboxy terminus 283-296 Immunodeficiency viruses 247-252 CD4 interaction 270, 320 Immunoglobulin G Glycosaminoglycans, rheumatoid arthritis 365 effect of antioxidants on synthesis of 163, G-proteins 32 164 role in rheumatoid arthritis 428 effect of reactive oxygen species on Graft versus host disease 274, 305 function 107 Granulocyte-monocyte stimulating factor 301 synovial fluid 376 Granulocytic leukemia, Immunomodulation 322 8-hydroxydeoxyguanosine in urine 98 Immunophilins 415 Growth factors, rheumatoid arthritis 348, 352, Immunoregulation, hydrogen peroxide and 439 lymphocyte function 149 Guanosine-3’ ,5’-monophosphate, second Indomethacin 397 messenger 32 Inflammation, role of free radicals 94, 101 Guanylate cyclase, signal transduction 33 Inflammatory mediators 420 Inflammatory synovitis 344, 397 Inositol phosphates, intracellular Ca2+ 34 H7 437 Integrins 355 H261 333 rheumatoid arthritis 357 Hair follicles 198 Intercellular adhesion molecule-1 299, 356 Haloperidol, antiviral action 332 rheumatoid arthritis 357 Heat aggregated immunoglobulin, stimulation of Interferona, immunomodulation, AIDS 322 superoxide generation by lymphocytes 89 Interferony Heparan sulphate proteoglycans, rheumatoid AIDS 306 arthritis 365 rheumatoid arthritis 403, 413 Heparin, angiogenic effect 300 Interleukin-1 HIV 245 AP-1 induction 442 CD4-gp120 interaction 271, 315, 320 effect on endothelial cells 172 CD4 receptor 256 inhibitors of function 408, 409 chemotherapy 313-328 metalloproteinase expression 370 endothelial cell interactions 304 production in HIV-infected patients 306 gp120 carboxyterminus 283-296 rheumatoid arthritis 348, 401-411 proteinase inhibitors 329-340 Interleukin-1B, stimulation of superoxide relationship to SIVs_ 247 production by lymphocytes 89 therapeutic inhibition of cell entry 271 Interleukin-1 inhibitors 350 tropism 267-282 Interleukin-1 receptor, antagonists 406 vascular endothelium 305 Interleukin-2, production by T cells in HPLC, free radical-induced DNA damage 98 rheumatoid arthritis 150 HTLV-I 268 Interleukin-2 gene expression 443 Hyaluronate, rheumatoid arthritis 365 Interleukin-2 receptor, effect of U75412E on Hydrogen peroxide expression 163, 165 endothelial cell killing by neutrophils 171 Interleukin-6 effect on lymphocyte receptor function 149 angiogenesis 301 mechanisms of cell injury 137 rheumatoid arthritis 350, 402 Hydroperoxides, protein damage 126 Interleukin-6 gene expression 440, 442 Hydroxamic acid derivatives, lipoxygenase Interleukin-8, rheumatoid arthritis 351 inhibitors 422 Intestinal tract, cystic fibrosis 18 8—Hydroxydeoxyguanosine, HPLC, free ion transport 43 radical-induced DNA damage 98 Iontophoresis 218 Hydroxyethylene isosteres, antiviral Iron, free radical damage to proteins 122 activity 333 1X207887 406 x Subject Index K252a 438 Multidrug resistance genes 49 Kaposi’s sarcoma Muscular dystrophies 175 AIDS 303 Myoblast therapy, Duchenne muscular clinical features 297 dystrophy 179 histogenesis 302 NADPH oxidase role of endothelial cells 299 in lymphocytes 87 Keratan sulphate, rheumatoid arthritis 365 rheumatoid arthritis 422 Keratin 206 Natural killer cells, rheumatoid arthritis 418 Keratosis 199 Natural moisturizing factor 217 Neuropeptides, synovitis 359 Neuropeptide Y, in synovial joints 360, 361 Laminin, rheumatoid arthritis 367 Neurotransmitters, synovial 360 Lazaroid U75412E, effect on lymphocyte Neutrophils, role of toxic oxygen products function 162 from 171 Leucocyte adhesion molecule-1 357 NF-kB 442, 443 Leucocyte adhesion receptor 269 Nucleoid, free radical damage within single Leukotriene B4, rheumatoid arthritis 421 cells 129 Limb-girdle dystrophy 183 Lipid, interacting skin-penetration enhancers 227 OKT9 151 Lipid bilayers, skin 201 Oleic acid, skin penetration enhancer 222, 230 Lipid hydroperoxides, DNA damage 144 Oligonucleotides, antiviral activity 323 Lipid peroxidation, rheumatoid arthritis 375 Oncogenes Lipocortin 430 angiogenesis 301 Lipofuschin 126 Kaposi’s sarcoma 300, 301 Lipopolysaccharide, stimulation of superoxide Osteoarthritis 423 generation by lymphocytes 89 Osteocalcin 445 Lipoxygenase 420 Oxidants, mechanisms of cell injury 137 inhibitors 421 Oxidative phosphorylation, oxidant effects 141 Lung Oxygen radical cystic fibrosis 5, 18 production by lymphocytes 87 immune complex induced vasculitis 170 protein damage 124 Lymphocyte function associated rheumatoid arthritis 372 molecule-3 355 systemic lupus erythematosus 93 rheumatoid arthritis 358 Lymphocytes effect of antioxidant drugs on function 161 P388D1 cells, effect of oxidants 137 DNA damage in single cells 129 p56lck 438 endothelial cell adhesion 299 Pancreas, cystic fibrosis 5, 17 effect of hydrogen peroxide on receptor Pansorbin function 149 IgG reactivity 111 oxygen radical production 87 stimulation of superoxide generation by lymphocytes 89 Paraoxonase, cystic fibrosis 9 a2 Macroglobulin 370 Passive immunization 322 Macrophages, derived cytokine synthesis 403 D-Penicillamine 398 Manoalide 432 Pentoxifylline 408 Metalloprotease gene expression 441 Peptide T 323 Metalloproteases Peptidyl-prolyl-cis-trans-isomerase 416 rheumatoid arthritis 368, 423 P-glycoproteins, CFTR 49 tissue inhibitor 370 Phonophoresis 217 MHC class I, role in viral infection 270, 306 Phorbol myristate acetate, stimulation of MK-886 422 superoxide generation by lymphocytes 88 Molecular diagnostics, Duchenne/Becker Phosphinic acids, antiviral activity 335 dystrophies 185 Phospholipase A2 Molecular modelling 285 inflammatory role 430 Monoclonal antibodies inhibitors 431 arthritis treatment 419 Phospholipase C, phosphoinositide-specific 429 CD4 257 Plasmin, metalloprotease activation 424 free radical-induced DNA damage 98 Plasminogen activator, rheumatoid joints 372, H,O, effect on binding to T cell surface 424 antigens 152 ' Platelet activating factor receptors, immune Mucin secretion, cystic fibrosis 41, 45 complex and vasculitis 169 Subject Index Platelet-activation-dependent granule-external NADPH oxidase 422 membrane protein 357 neuroendocrine mechanisms 359 Platelet-derived growth factor pathogenesis 344 Kaposi’s sarcoma 301 protein kinases 435 rheumatoid arthritis 353, 439 proteolytic enzymes 368 Platelet glycoprotein IIb/IIIa 357 signal transduction 428 Prednisolone 348 T-helper targets 413 Prodrug absorption through skin 214 transcriptional control 440 Programmed cell death, rheumatoid Rheumatoid factors 108, 418 arthritis 376 effect of ROS on IgG binding 113 Propylene glycol, skin penetration Ribavarin 321 enhancer 232 Ro 20-1724 434 Protein Rolipram 434 free radical damage, role in immune Romazarit 408, 409 response 121 interacting skin penetration enhancers 229 secretion 26, 30 Salivary glands Proteinase inhibitors, HIV 329-340 cystic fibrosis 17 Protein kinase A, epithelial cell secretion 37 regulation 31, 41 Protein kinase C Sebaceous glands 198 epithelial cell secretion 38 Second messenger, cell activation 31, 32 inhibitors 437 Secretory proteins 26, 30 role in inflammation 436 Selectins 357 Protein kinases, role in inflammation 435 Signal transduction Protein phosphorylation, cystic fibrosis cells 45 arachidonate levels 433 Protein replacement therapy, cystic fibrosis 63 CD4 256 Proteoglycans, rheumatoid arthritis 365 effector enzymes 429 Proteolytic enzymes, rheumatoid arthritis 368 G proteins 428 phospholipase A2 430 protein kinases 435 Rapamycin 416 Simian immunodeficiency viruses Reactive oxygen species pathogenesis 250 effect on IgG function 107 relationship to HIVs 247 induced DNA damage 94 vaccine trials in macaques 251 Respiratory epithelia, ion transport, cystic Single cell, free radical damage 129 fibrosis 42 SKF 86002 406 Reticulum fibres 367 Skin Retinoic acid receptor 445 aqueous pores 206 Reverse transcriptase drug delivery 209 inhibitors 316 drug penetration 200, 201 virus concentration 314, 315 enhancement of drug absorption 214, 220 RG5901 422 hydration 217 RG59022 434 immune complex induced vasculitis 170 Rheumatoid arthritis iontophoresis 218 adhesion molecules 354, 413 permeation, diffusion 207 antigen presentation 411 structure 196 arachidonic acid metabolites 420 topical treatments 198 CD4+ cells 417 transdermal route for systemic therapy 213 cell-cell interactions 347, 400 Sodium, absorption 25 cytokines 348, 401 Sodium chloride effector cells 418 secretion by epithelial cells 21 effector enzymes 429 in sweat, cystic fibrosis 40 extracellular matrix 362 Soluble CD4 271, 320 free radicals and programmed cell death 372 Spindle cells, Kaposi’s sarcoma 302 glycoproteins 365 Statine, anti-HIV activity 332 glycosaminoglycans 364 Staurosporine G proteins 428 inhibition of protein kinase C 438 growth factors 348, 439 effect on superoxide generation by IgG dysfunction 107 lymphocytes 90 lymphocyte function 149 Steroids metalloproteases 368, 423 absorption through skin 214 molecular basis of therapy 395-473 anti-inflammatory activity 444 monoclonal antibodies 419 Stromelysin 370, 423, 425 Xil Subject Index Submandibular acinar cells, secretion, cystic Tumour necrosis factora fibrosis 41 AIDS 306 Substance P, synovitis 359, 361 angiogenic factor 301 Sulphated polysaccharides, antiviral effect on endothelial cells 172 activity 321 metalloproteinase expression 370 Superoxide, production by lymphocytes 87 participation in immune complex induced Surface antigens, hydrogen peroxide and injury 170 lymphocyte function 150, 152 rheumatoid arthritis 350, 351, 402, 405 Sweat, electrolyte abnormalities in cystic stimulation of superoxide production by fibrosis 40 lymphocytes 89 Sweat glands 198 Tyrosine-specific protein kinases, growth factor cystic fibrosis 17, 31, 42 receptor 439 Syncytia 257 Tyrphostins 439 Synovitis 344, 397 Systemic lupus erythematosus, reactive oxygen species damage to DNA 93 U75412E 162 U-75875 334 Ultrasound, drug absorption through skin 217 T-cells Urea derivatives, skin penetration antigen-presenting cell interactions 412 enhancers 222 antioxidant effects 161 CD4 272 cytokine activation 301 Vascular endothelium role in HIV infection and hydrogen peroxide and function 150 Kaposi’s sarcoma 297-312 immunomodulation 414 Vasculitis, PAF receptors in immune complex T-cell receptor 169 AIDS pathogenesis 304, 305 VCAM-1 299 ps6ik 438 Virus rheumatoid arthritis 412, 414 cellentry 267 T-cell receptor/CD3 355, 438 chemotherapy 313 Terpene, skin penetration enhancers 223, 229, Vitamin D3 receptor 445 232 Vitronectin 367 Tissue inhibitor of metalloproteinase 370 Vitronectin receptor 356 Transdermal drug delivery 209 systemic therapy 213 Transferrin/transferrin receptor interaction, WR 1065 = 133 effect of hydrogen peroxide 151 WY-48,989 408, 409 Transforming growth factor-B angiogenesis 300 rheumatoid arthritis 353, 403 Xanthine, endothelial cell killing by neutrophils Transgenics 417 172 cystic fibrosis 57 Transition metals, radical reactions 122 Tropism, HIV 267-282 Zidovudine 313, 316