1,779
Views
12
CrossRef citations to date
0
Altmetric
Review Article

Elimination of endoplasmic reticulum stress and cardiovascular, type 2 diabetic, and other metabolic diseases

Pages 194-202 | Received 29 Feb 2012, Accepted 11 May 2012, Published online: 28 Aug 2012

References

  • Wu J, Kaufman RJ. From acute ER stress to physiological roles of the unfolded protein response. Cell Death Differ. 2006;13:374–84.
  • Boyce M, Yuan J. Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ. 2006;13:363–73.
  • Mandl J, Mèszàros T, Bànhegyi G, Hunguady L, Csala M. Endoplasmic reticulum: nutrient sensor in physiology and pathology. Trends Endocrinol Metab. 2009;20:194–201.
  • Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007;8:519–29.
  • Kim I, Xu W, Reed JC. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Discov. 2008;7:1013–30.
  • Sriburi R, Jackowski S, Mori K, Brewer JW. XBP1: a link between the unfolded protein response, lipid biosynthesis, and biogenesis of the endoplasmic reticulum. J Cell Biol. 2004;167:35–41.
  • Shaffer AL, Shapiro-Shelef M, Iwakoshi N, Lee AH, Qian SB, Zhao Hong, . XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Immunity. 2004;21:81–93.
  • Luoma PV. Gene activation, apolipoprotein A-I/high density lipoprotein, atherosclerosis prevention and longevity. Pharmacol Toxicol. 1997;81:57–64.
  • Luoma PV, Sotaniemi EA, Pelkonen RO, Ehnholm C. Plasma high density lipoprotein and liver microsomal enzyme activity in man. In: Pilli-Sihvola AS, Laaksovirta T, editors The Medical Research Council 1977–1979. Helsinki: The Academy of Finland; 1980. p. 71.
  • Sotaniemi EA, Arranto AJ, Sutinen S, Stengård J, Sutinen S. Treatment of noninsulin dependent diabetes mellitus with enzyme inducers. Clin Pharmacol Ther. 1983;33:826–35.
  • Lahtela JT, Arranto AJ, Sotaniemi EA. Enzyme inducers improve insulin sensitivity in non-insulin dependent diabetic subjects. Diabetes. 1985;34:911–6.
  • Hetz C, Martinon F, Rodriquez D, Glimcher LH. The unfolded protein response: integrating stress signals through the stress sensor IRE1. Physiol Rev. 2011;91:1219–43.
  • Engin F, Hotamisligil GS. Restoring endoplasmic reticulum function by chemical chaperones: an emerging therapeutic approach for metabolic disease. Diabetes Obes Metab. 2010;12(Suppl 2):108–15.
  • Gotoh T, Endo M, Oike Y. Endoplasmic reticulum stress related inflammation and cardiovascular disease. Internat J Inflamm. 2011;2011: 259462.
  • Orrenius S. Further studies on the induction of the drug hydroxylating enzyme system of liver microsomes. J Cell Biol. 1965;26:725–33.
  • Conney AH. Pharmacological implications of microsomal enzyme induction. Pharmacol Rev. 1967;19:317–66.
  • Savolainen MJ, Arranto AJ, Hassinen IE, Luoma PV, Pelkonen RO, Sotaniemi EA. Relationship between lipid composition and drug metabolizing capacity of human liver. Eur J Clin Pharmacol. 1985;27:727–32.
  • Luoma PV, Savolainen MJ, Sotaniemi EA, Pelkonen RO, Arranto A, Ehnholm C. Plasma high- density lipoproteins and liver lipids and proteins in man. Acta Med Scand. 1983;214:103–9.
  • Sriburi R, Bommiasamy H, Buldak GL, Robbins GR, Frank M, Jackowski S, . Coordinate regulation of phospholipid biosynthesis and secretory pathway gene expression in XBP-(S)-induced endoplasmic reticulum biogenesis. J Biol Chem. 2007;282:7024–34.
  • Maiuolo J, Bulotta S, Verderio C, Benfante R, Borgese N. Selective activation of the transcription factor ATF6 mediates endoplasmic reticulum proliferation triggered by a membrane protein. Proc Natl Acad Sci U S A. 2011;108:7832–7.
  • Schuck S, Prinz WA, Thorn KS, Voss C, Walter P. Membrane expansion alleviates endoplasmic reticulum stress independently of the unfolded protein response. J Cell Biol. 2009;187:525–36.
  • Malhi H, Kaufman RJ. Endoplasmic reticulum stress in liver disease. J Hepatol. 2011;54:795–809.
  • Bommiasamy H, Back SH, Fagone P, Lee K, Meshinchi S, Vink E, . ATF6α induces XBP1-independent expansion of the endoplasmic reticulum. J Cell Sci. 2009;122:1626–36.
  • Brewer JB, Diehl JA. PERK mediates cell-cycle exit during the mammalian unfolded protein response. Proc Natl Acad Sci U S A. 2000; 97:12625–30.
  • Pirttiaho HI, Sotaniemi EA, Pelkonen RO, Pitkänen U. Hepatic blood flow and drug metabolism in patients on enzyme-inducing anticonvulsants. Eur J Clin Pharmacol. 1982;22:441–5.
  • Luoma PV, Sotaniemi EA, Pelkonen RO, Pirttiaho HI. Serum low-density lipoprotein and high-density lipoprotein cholesterol, and liver size in subjects on drugs inducing hepatic microsomal enzymes. Eur J Clin Pharmacol. 1985;28:615–8.
  • Szczesna-Skorupa E, Chen CC, Liu H, Kemper B. Gene expression changes associated with the endoplasmic reticulum stress response induced by microsomal cytochrome P450 overproduction. J Biol Chem. 2004;279:13953–61.
  • Luoma PV, Rautio A, Stengård J, Sotaniemi EA, Marniemi J. High-density lipoprotein subfractions, apolipoproteins and antipyrine clearance in normal subjects. Eur J Clin Pharmacol. 1990;38:625–7.
  • Luoma PV, Sotaniemi EA, Arranto AJ. Serum LDL cholesterol, the LDL/ HDL cholesterol ratio and liver microsomal enzyme induction evaluated by antipyrine kinetics. Scand J Lab Invest. 1983;43:671–5.
  • Xiao L, Xie X, Zhai Y. Functional crosstalk of CAR-LXR and ROR-LXR in drug and lipid metabolism. Adv Drug Deliv Rev. 2010;62:1316–21.
  • Luoma PV. Cytochrome P450—physiological key factor against cholesterol accumulation and the atherosclerotic vascular process. Ann Med. 2007;39:359–70.
  • Rader DJ, Lohse P, Ikewaki K, Thomas F, Harris WA, Zech LA, . Increased production of apolipoprotein A-I associated with elevated plasma levels of high-density lipoproteins, apolipoprotein A-I and lipoprotein A-I in a patient with familial hyperalphalipoproteinemia. Metabolism. 1993;42:1429–34.
  • Le NA, Ginsberg HN. Heterogeneity of apolipoprotein AI turnover in subjects with reduced concentrations of plasma high density lipoprotein cholesterol. Metabolism. 1988;37:614–17.
  • Miller M, Burgan RG, Osterlund L, Segrest JP, Garber DW. A prospective randomized trial of phenytoin in nonepileptic subjects with reduced HDL cholesterol. Arterioscler Thromb Vasc Biol. 1995;15:2151–6.
  • Chao YU, Pickett CB, Yamin TT, Guo LS, Alberts A, Kroon PA. Phenobarbital induces rat liver apolipooprotein A-I mRNA. Mol Pharmacol. 1985;27:394–8.
  • Luoma PV, Stengård J, Korpela H, Rautio A, Sotaniemi EA, Suvanto E, . Lipid peroxides, glutathione peroxidase, high density lipoprotein subfractions and apolipoproteins in young adults. J Intern Med. 1990;227:287–9.
  • Muller C, Salvayre R, Nègre-Salvayre A, Vindis C. HDLs inhibit endoplasmic reticulum stress and autophagic response induced by oxidized LDLs. Cell Death Differ. 2011;18:817–28.
  • Lahtela JT, Gachalyi B, Eksymä S, Hämäläinen A, Sotaniemi EA. The effect of enzyme inducing and inhibiting drugs on insulin mediated glucose metabolism in man. Br J Clin Pharmacol. 1986;21:19–26.
  • Dullens SPJ, Plat J, Mensink RP. Increasing apoA-I production as a target for CHD risk reduction. Nutr Metab Cardiovasc Dis. 2007;17:618–28.
  • Jimènez-Gomèz J, Marin C, Pèrez-Martinèz P, Hartwich J, Malczewska-Malec M, Gobalek I, . A low-fat, high-complex carbohydrate diet supplemented with long-chain (n-3) fatty acids alters the postprandial lipoprotein profile in patients with metabolic syndrome. J Nutr. 2010;140:1595–601.
  • Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, . Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. Diabetes Care. 1997;20:537–44.
  • Stampfer MJ. Cardiovascular disease and Alzheimer's disease: common links. J Intern Med. 2006;260:211–23.
  • Poikolainen K. Alcohol and mortality: a review. J Clin Epidemiol. 1995;48:455–65.
  • Luoma PV. Gene activation regresses atherosclerosis, promotes health, and enhances longevity. Lipids Health Dis. 2010;9:67.
  • da Luz G, Frederico MJ, da Silva S, Vitto MF, Cesconetto PA, de Pinho RA, . Endurance exercise ameliorates insulin resistance and reticulum stress in adipose and hepatic tissue of obese rats. Eur J Appl Physiol. 2011;111:2015–23.
  • Bray GA. Medical consequences of obesity. J Clin Endocrinol Metab. 2004;89:2583–9.
  • DeFronzo RA. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis. The missing links. The Claude Bernard Lecture2009. Diabetologia. 2010;53:1270–87.
  • Callow AD. Cardiovascular disease 2005—the global picture. Vascul Pharmacol. 2006;45:302–7.
  • Flegel KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999–2008. JAMA. 2010;303;235–41.
  • Brown MT, LeRoth D. Overcoming challenges in type 2 diabetes management to improve patient outcomes. Expert Rev Endocrinol Metab. 2010;5741–51.
  • Ji C, Kaplowitz N. ER stress: can the liver cope?J Hepatol. 2006;45: 321–33.
  • Ota T, Gayet C, Ginsberg HN. Inhibition of apolipoprotein B secretion by lipid-induced hepatic endoplasmic reticulum stress in rodents. J Clin Invest. 2008;118:316–32.
  • Yang X, Zhang X, Heckmann BL, Lu X, Liu J. Relative contribution of adipose triglyceride lipase and hormone-sensitive lipase to tumor necrosis factor-α (TNF-α)-induced lipolysis in adipocytes. J Biol Chem. 2011;286:40477–85.
  • Luoma PV, Arranto AJ, Ehnholm C, Sotaniemi EA. Liver histological changes and plasma high density lipoproteins in man. Res Commun Chem Pathol Pharmacol. 1981;33:163–73.
  • Lahtela JT, Arranto AJ, Stenbäck F, Sotaniemi EA. Insulin-mediated glucose metabolism is related to liver structure and microsomal function. Scand J Gastroent. 1986;21:737–43.
  • Ross R. Atherosclerosis—an inflammatory disease. New Engl J Med. 1999;340:115–26.
  • Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12:204–12.
  • Tabas I. The role of endoplasmic reticulum stress in the progression of atherosclerosis. Circ Res. 2010;107:839–50.
  • Hotamisligil GS. Endoplasmic reticulum stress and atherosclerosis. Nat Med. 2010;16:396–9.
  • McAlpine CS, Bowes AJ, Werstuck GH. Diabetes, hyperglycemia and accelerated atherosclerosis: evidence supporting a role for endoplasmic reticulum (ER) stress signaling. Cardiovasc Hematol Disord Drug Targets. 2010;10:151–7.
  • Thorpe E, Iwawaki T, Miura M, Tabas I. A reporter for tracking the UPR in vivo reveals patterns of temporal and cellular stress during atherosclerotic progression. J Lipid Res. 2011;52:1033–8.
  • Grundy SM. Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol. 2008;28:629–36.
  • Sha H, He Y, Yang L, Qi L. Stressed about obesity: IRE1α-XBP1 in metabolic disorders. Trends Endocr Metab. 2011;22:373–81.
  • Gregor MF, Yang L, Fabbrini E, Mohammed BS, Eagon JC, Hotamisligil GS, . Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss. Diabetes. 2009;58:693–700.
  • Gregor MF, Hotamisligil GS. Inflammatory mechanisms of obesity. Annu Rev Immunol. 2011;29:415–45.
  • Özcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Özdelen E, . Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004;306:457–61.
  • Thomas SE, Dalton LE, Daly ML, Malzer E, Marciniak SJ. Diabetes as a disease of endoplasmic reticulum. Diabetes Metab Res Rev. 2010;26:611–21.
  • Fonseca SG, Gromada J, Urano F. Endoplasmic reticulum stress and pancreatic β-cell death. Trends Endocr Metab. 2011;22:266–74.
  • Eizirik DL, Cardozo AK, Cnop M. The role for endoplasmic reticulum stress in diabetes mellitus. Endocr Rev. 2008;29:42–61.
  • Laybutt RD, Preston AM, Åkerfeldt MC, Kennch JG, Busch AK, Blankin AV, . Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes. Diabetologia. 2007;50:752–63.
  • Matus S, Glimcher LH, Hetz C. Protein folding stress in neurodegenerative diseases: a glimpse into ER. Curr Opin Cell Biol. 2011;23: 239–52.
  • Lindholm D, Wootz H, Korhonen L. ER stress and neurodegenerative diseases. Cell Death Differ. 2006;13:385–92.
  • Luchsinger JA, Gustafson DR. Adiposity, type 3 diabetes and Alzheimer's disease. J Alzheimers Dis. 2009;16:693–704.
  • Scheper W, Hoozemans JJM. Endoplasmic reticulum protein quality control in neuro-degenerative disease: the good, the bad and the therapy. Curr Med Chem. 2009;16:615–26.
  • Salminen A, Kauppinen A, Suuronen T, Kaarniranta K, Ojala J. ER stress in Alzheimer's disease: a novel neuronal trigger for inflammation and Alzheimer's pathology. J Neuroinflamm. 2009;6:41.
  • Suzuki H, Kanekura K, Levine TP, Kohno K, Olkkonen VM, Aiso S, . ALS-linked P56S-VAPB, an aggregated loss-of-function mutant of VAPB, predisposes motor neurons to ER stress-related death by inducing aggregation of co-expressed wild-type VAPB. J Neurochem. 2009;108:973–85.
  • Wang G, Yang ZQ, Zhang K. Endoplasmic reticulum stress response in cancer: molecular mechanism and therapeutic potential. Am J Transl Res. 2010;2:65–74.
  • Li X, Zhang K, Li Z. Unfolded protein response in cancer: the physician's perspective. J Hematol Oncol. 2011;4:8.
  • Luoma PV. Gene-activators prevent and regress atherosclerosis and reduce mortality. Cardiovasc Hematol Agents Med Chem. 2009;7: 295–304.
  • Knopp RH, Gitter H, Truitt T, Bays H, Manion CV, Lipka LJ, . Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J. 2003;24:729–41.
  • Goldstein JL, Brown MS. The LDL receptor. Arterioscler Thromb Vasc Biol. 2009;29:431–8.
  • Asztalos BF, Le Maulf F, Dallal GE, Stein E, Jones PH, Horvath KV, . Comparison of the effects of high doses of rosuvastatin versurs atorvastatin on the subpopulations of high-density lipoproteins. Am J Cardiol. 2007;99:681–5.
  • Fleming I. Vascular cytochrome P450 enzymes: physiology and pathophysiology. Trends Cardiovasc Med. 2008;18:20–4.
  • Ng V, Huang Y, Reddy LM, Falck JR, Lin ET, Kroetz DL. Cytochrome 450 eicosanoids are activators of peroxisome proliferator-activated receptor. Drug Metab Dispos. 2007;35:1126–34.
  • Shepherd J, Packard CJ, Patsh JR, Gotto AM Jr, Taunton OD. Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism. J Clin Invest. 1979;63:858–67.
  • Taskinen MR, Sullivan DR, Ehnholm C, Whiting M, Zannino D, Simes RJ, . Relationships of HDL cholesterol, apo A-I, and apo A-II with homocysteine and creatinine in patients with type 2 diabetes treated with fenofibrate. Arterioscler Thromb Vasc Biol. 2009;29:950–5.
  • Guillou H, Pascal M, Jan S, D’Andrea S, Roulet A, Catheine D, . Comparative effect of fenofibrate on hepatic desaturases in wild-type and peroxisome proliferator-activatedd receptor α-deficient mice. Lipids. 2002;37:981–9.
  • Shepherd J, Packard CJ.High density apolipoprotein metabolism. In: Miller NE, Miller GJ, editors. Clinical and metabolic aspects of high-density lipoproteins. Amsterdam: Elsevier; 1984. p. 247–74.
  • Nomura M, Ishii H, Kawakami A, Yoshida M. Inhibition of hepatic Niemann-Pick C1-like 1 improves hepatic insulin resistance. Am J Physiol Endocrinol Metab. 2009;297:E1030–8.
  • Erbay E, Babaev VR, Mayers JR, Makowski L, Charles KN, Snitow ME, . Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis. Nat Med. 2009;15:1383–91.
  • Özcan U, Ylimaz E, Özcan L, Furuhashi M, Vaillancourt E, Smith RO, . Chemical chaperones reduce ER stress and restore glucose homeostais in a mouse model of type 2 diabetes. Science. 2006;313: 1137–40.
  • Chen JC, Wu ML, Huang KC, Lin WW. HMG-CoA reductase inhibitors activate the unfolded protein response and induce cytoprotective GRP78 expression. Cardiovasc Res. 2008;80:138–50.
  • Luoma PV, Savolainen MJ, Sotaniemi EA, Arranto AJ, Pelkonen RO. Plasma HDL cholesterol and glucose in non-insulin-dependent diabetics related to liver lipids and microsomal enzyme activity. Acta Med Scand. 1985;217:473–9.
  • Kars M, Yang L, Gregor MF, Mohammed BS, Pietka TA, Finck BN, . Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes. 2010;50:1899–905.
  • Gao J, He J, Zhai Y, Wada T, Xie W. The constitutive androstane receptor is an anti-obesity nuclear receptor that improves insulin sensitivity. J Biol Chem. 2009;284:25984–92.
  • Dong B, Saha PK, Huang W, Chen W, Abu-Elbeiga LA, Wakil SJ, . Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease. Proc Natl Acad Sci U S A. 2009;106:18831–6.
  • Flamment M, Kammoun HL, Hainault I, Ferré P, Foufelle F. Endoplasmic reticulum stress: a new actor in the development of hepatic steatosis. Curr Opin Lipidol. 2010;21:239–46.
  • Wang D, Wei Y, Pagliassotti MJ. Saturated fatty acids promote endoplasmic reticulum stress and liver injury in rats with hepatic steatosis. Endocrinology. 2006;147:943–51.
  • Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga T, Fan W, . GRP120 is an omega-3 fatty acid receptor mediating potent anti- inflammatory and insulin-sensitizing effects. Cell. 2010;142:687–98.
  • Cao H, Gerhold K, Mayers JR, Wiest MM, Watkins SM, Hotamisligil GS. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell. 2008;134:933–44.
  • Wang I, Schuster GU, Hultenby K, Zhang Q, Andersson S, Gustafsson JA. Liver X receptors in the central nervous system: from lipid homeostasis to neuronal degeneration. Proc Natl Acad Sci U S A. 2002; 99:13878–83.
  • Fan J, Donkin J, Wellington C. Greasing the wheels of Aβ clearance in Alzheimer's disease. The role of lipids and apolipoprotein E. Biofactors. 2009;35:239–48.
  • Hartz AMS, Miller DS, Bauer B. Restoring blood brain barrier P-glycoprotein reduces brain amyloid-β in a mouse model of Alzheimer's disease. Mol Pharmacol. 2010;77:715–23.
  • Ricobaraza A, Cuadrado-Tejedor M, Péres-Mediavila A, Frechilla D, Del Rio J, Garcia-Osta A. Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer's disease mouse model. Neuropsychopharmacology. 2009;34:1721–32.
  • Singh-Manoux A, Gimeno D, Kivimaki M, Brunner E, Marmot MG. Low HDL cholesterol is a risk factor for deficit and decline in memory in midlife. Arterioscler Thromb Vasc Biol. 2008;28:1556–62.
  • Atzmon G, Gabriely I, Greiner W, Davidson D, Schechter C, Barzilai N. Plasma HDL levels correlate highly with cognitive function in exceptional longevity. J Gerontol A Biol Med Sci. 2002;57A:M712–5.
  • Ritchie K, Carriere I, Ritchie CW, Berr C, Artero S, Ancelin M-L. Designing prevention programmes to reduce of dementia: prospective cohort study of modifiable risk factors. BMJ. 2010;341:c3885.
  • Pullinger CR, Eng C, Salen G, Shefer S, Barra AK, Erickson SK, . Human cholesterol 7α-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype. J Clin Invest. 2002;110:109–17.
  • Cali JJ, Hsieh CL, Francke U, Russell DW. Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. J Biol Chem. 1991;266:7779–83.
  • Karvonen I, Stengård J, Saarni HU, Stenbäck F, Sotaniemi EA. Hepatic mixed function oxidase system and enzymatic glucose metabolism in rats. Diabetes Res. 1987;4:195–200.
  • Torres TP, Catlin RL, Chan R, Fujimoto Y, Sasaki N, Printz RL, . Restoration of hepatic glucokinase expression corrects hepatic glucose flux and normalizes plasma glucose in Zucker diabetic rats. Diabetes. 2009;58:78–86.
  • Butler PW, Mentuccia D, Celi FS. Stimulating brown fat: a potential future therapeutic approach for obesity and insulin resistance?Heart Metab. 2010;48:19–22.
  • Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, . Functional brown adipose tissue in healthy adults. New Engl J Med. 2009;360:1518–25.
  • Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, . Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57–63.
  • Naidoo N. ER and ageing-protein folding and the ER stress response. Ageing Res Rev. 2009;8:150–9.
  • Arai Y, Hirose N. Aging and HDL metabolism in elderly people more than 100 years old. J Atheroscler Thromb. 2004;11:246–52.
  • Ostlund RE, Staten M, Kohrt WM, Schultz, J, Malley M. The waist-to-hip circumference, plasma insulin level, and glucose intolerance as independent predictors of the HDL2 cholesterol levels in older adults. N Engl J Med. 1990;322:229–34.