The detail information of Narcolepsy
Basic Information
Disease Description: A neurological disorder characterized by falling asleep suddenly (collapse) which can occur during periods of activity and last for varying lengths of time. Seen in Doberman pinschers and Labrador retrievers.
Inherit Mode: -
Disease Symptom: In a narcoleptic episode, an animal may abruptly lose consciousness, fall on its side or stomach, and lie perfectly still, as if napping. Like in deep sleep, rapid closed eye movements (REM) may occur and muscles become slack, but the dog may still be aware of his surroundings. Often, the dog will abruptly come out of an episode after auditory or physical stimulation.
Disease Cause: Certain factors predispose a dog to narcolepsy. Dogs that are obese, inactive, or have immune system variations are more likely to be narcoleptic. There is also a heritable component to narcolepsy. Researchers have identified an inherited form of the disease in Doberman Pinschers, caused by a genetic defect involving a chemical neurotransmitter called hypocretin. Abnormalities in hypocretin receptors interrupt the regulation of normal sleep cycles. Abnormalities in hypocretin receptors in other dogs such as Labrador Retrievers, Poodles, and Dachshunds have also been identified.
Disease Diagnose: Narcolepsy is usually identified based on the symptoms alone, so a thorough history of your dog’s behavior and a detailed description of the attacks are critical. If you can film an incident, that’s even better. Since narcoleptic symptoms also occur with other medical problems, conditions such as heart disease, diabetes, and epilepsy must be ruled out. To arrive at an accurate diagnosis, your veterinarian will perform physical and neurologic exams, which are usually normal. Laboratory tests, including a blood chemical profile, a complete blood count, a urinalysis, and an electrolyte panel, will help rule out any underlying diseases.
Treat Method: There is no definitive cure for narcolepsy, but help is still available for affected dogs
Breeder Advice: -
Disease Description Source: Link
Associated Diseases
| Disease Name | Other Name | Mode of inheritance | Link ID | Possible OMIM ID | Gene |
|---|---|---|---|---|---|
| Narcolepsy | - | Autosomal Recessive | HCRTR2 |
Associated Breeds
| iDog Breed Number | Breed Name | Personality | Height | Weight | Breed Source |
|---|---|---|---|---|---|
| CB2 | Afghan Hound | Independent, sweet, silly | 63.5-68.6 cm | 22.7-27.2 kg | Afghanistan |
| CB3 | Airedale Terrier | Clever, confident, proud; friendly but courageous | 58.4 cm | 22.7-31.8 kg | United Kingdom (England) |
| CB5 | Alaskan Malamute | Affectionate, loyal, playful but dignified | 63.5 cm (male), 58.4 cm (female) | 38.6 kg (male), 34 kg (female) | United States |
| CB89 | Dogo Argentino | Loyal, trustworthy,courageous | 61-68.6 cm (male), 59.7-66 cm (female) | 36.3-45.4 kg | Argentina |
| CB98 | English Toy Spaniel | Affectionate, Alert, Merry | 22.9-25.4 cm | 3.6-6.4 kg | England |
| CB132 | Irish Terrier | Bold, dashing, even reckless; stouthearted at work, tenderhearted at home | 45.7 cm | 12.2 kg (male), 11.3 kg (female) | Ireland |
| CB148 | Lagotto Romagnolo(Romagna Water Dog) | Easygoing, affectionate, and eager to please | 43.2-48.3 cm (male), 40.6-45.7 cm (female) | 12.9-15.9 kg (male), 10.9-14.1 kg (female) | Italy |
| CB259 | Wire-Haired Vizsla | Calm and gentle around the house; an exuberant hunter on land or lake | 57.8-64.1 cm (male), 54-59.7 cm (female) | 24.9-29.5 kg (male), 20.4-24.9 kg (female) | Hungary |
References
| 2021 |
Mondino,A.,Delucchi,L.,Moeser,A.,Cerdá-González,S.,Vanini,G.: :
Sleep Disorders in dogs: A Pathophysiological and Clinical Review. Top Companion Anim Med 43:100516, 2021. Pubmed reference: 33556640 . DOI: 10.1016/j.tcam.2021.100516 . |
| 2013 |
Toth,L.A.,Bhargava,P.: :
Animal models of sleep disorders. Comp Med 63:91-104, 2013. Pubmed reference: 23582416 . |
| 2009 |
Chen,L.,Brown,RE.,McKenna,JT.,McCarley,RW.: :
Animal models of narcolepsy. CNS Neurol Disord Drug Targets 8:296-308, 2009. Pubmed reference: 19689311 . |
| 2008 |
Mishima,K.,Fujiki,N.,Yoshida,Y.,Sakurai,T.,Honda,M.,Mignot,E.,Nishino,S.: :
Hypocretin receptor expression in canine and murine narcolepsy models and in hypocretin-ligand deficient human narcolepsy. Sleep 31:1119-26, 2008. Pubmed reference: 18714784 . |
| 2007 |
Tonokura,M.,Fujita,K.,Nishino,S.: :
Review of pathophysiology and clinical management of narcolepsy in dogs. Vet Rec 161:375-80, 2007. Pubmed reference: 17873267 . |
| 2004 |
John,J.,Wu,MF.,Maidment,NT.,Lam,HA.,Boehmer,LN.,Patton,M.,Siegel,JM.: :
Developmental changes in CSF hypocretin-1 (orexin-A) levels in normal and genetically narcoleptic Doberman pinschers. J Physiol 560:587-92, 2004. |
| 2004 |
John,J.,Wu,MF.,Maidment,NT.,Lam,HA.,Boehmer,LN.,Patton,M.,Siegel,JM.: :
Developmental changes in CSF hypocretin-1 (orexin-A) levels in normal and genetically narcoleptic Doberman pinschers. J Physiol 560:587-92, 2004. Pubmed reference: 15308685 . DOI: 10.1113/jphysiol.2004.070573 . |
| 2003 |
Fujiki,N.,Yoshida,Y.,Ripley,B.,Mignot,E.,Nishino,S.: :
Effects of IV and ICV hypocretin-1 (orexin A) in hypocretin receptor-2 gene mutated narcoleptic dogs and IV hypocretin-1 replacement therapy in a hypocretin-ligand-deficient narcoleptic dog. Sleep 26:953-9, 2003. Pubmed reference: 14746368 . |
| 2003 |
Tonokura,M.,Fujita,K.,Morozumi,M.,Yoshida,Y.,Kanbayashi,T.,Nishino,S.: :
Narcolepsy in a hypocretin/orexin-deficient chihuahua Veterinary Record 152:776-9, 2003. Pubmed reference: 12846289 . |
| 2002 |
Fujiki,N.,Morris,L.,Mignot,E.,Nishino,S.: :
Analysis of onset location, laterality and propagation of cataplexy in canine narcolepsy Psychiatry & Clinical Neurosciences 56:275-276, 2002. |
| 2002 |
Gulyani,S.,Wu,M.F.,Nienhuis,R.,John,J.,Siegel,J.M.: :
Cataplexy-related neurons in the amygdala of the narcoleptic dog Neuroscience 112:355-365, 2002. Pubmed reference: 12044453 . |
| 2001 |
Hungs,M.,Fan,J.,Lin,L.,Lin,X.Y.,Grigoriadis,D.,Maki,R.A.,Mignot,E.: :
Identification and functional analysis of mutations in the hypocretin (Orexin) genes of narcoleptic canines (vol 11, pg 531, 2001) Genome Research 11:919, 2001. |
| 2001 |
Hungs,M.,Fan,J.,Lin,L.,Lin,X.Y.,Maki,R.A.,Mignot,E.: :
Identification and functional analysis of mutations in the Hypocretin (Orexin) genes of narcoleptic canines Genome Research 11:531-539, 2001. Pubmed reference: 11282968 . DOI: 10.1101/gr.161001 . |
| 2001 |
Nishino,S.,Fujiki,N.,Ripley,B.,Sakurai,E.,Kato,M.,Watanabe,T.,Mignot,E.,Yanai,K.: :
Decreased brain histamine content in hypocretin/orexin receptor-2 mutated narcoleptics dogs Neuroscience Letters 313:125-128, 2001. Pubmed reference: 11682143 . |
| 2001 |
Ripley,B.,Fujiki,N.,Okura,M.,Mignot,E.,Nishino,S.: :
Hypocretin levels in sporadic and familial cases of canine narcolepsy Neurobiology of Disease 8:525-534, 2001. Pubmed reference: 11442359 . DOI: 10.1006/nbdi.2001.0389 . |
| 1999 |
Coleman,E.S.: :
Canine narcolepsy and the role of the nervous system Compendium on Continuing Education for the Practicing Veterinarian 21:641-650, 1999. |
| 1999 |
Faraco,J.,Lin,X.,Li,R.,Hinton,L.,Lin,L.,Mignot,E.: :
Genetic studies in narcolepsy, a disorder affecting REM sleep Journal of Heredity 90:129-132, 1999. Pubmed reference: 9987919 . |
| 1999 |
Lin,L.,Faraco,J.,Li,R.,Kadotani,H.,Rogers,W.,Lin,X.Y.,Qiu,X.H.,de,Jong,P.J.,Nishino,S.,Mignot,E.: :
The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene Cell 98:365-376, 1999. Pubmed reference: 10458611 . |
| 1999 |
Ostrander,E.A.,Giniger,E.: :
Let sleeping dogs lie? Nat Genet 23:3-4, 1999. Pubmed reference: 10471483 . DOI: 10.1038/12591 . |
| 1999 |
Reilly,C.E.: :
Mutation in the hypocretin (orexin) receptor 2 gene causes canine narcolepsy Journal of Neurology 246:985-986, 1999. Pubmed reference: 10552257 . |
| 1999 |
Siegel,J.M.,Nienhuis,R.,Gulyani,S.,Ouyang,S.,Wu,M.F.,Mignot,E.,Switzer,R.C.,McMurry,G.,Cornford,M.: :
Neuronal degeneration in canine narcolepsy Journal of Neuroscience 19:248-257, 1999. Pubmed reference: 9870955 . |
| 1998 |
Cederberg,R.,Nishino,S.,Dement,W.C.,Mignot,E.: :
Breeding history of the Stanford colony of narcoleptic dogs Veterinary Record 142:31-36, 1998. Pubmed reference: 9481825 . |
| 1997 |
Honda,K.,Riehl,J.,Inoue,S.,Mignot,E.,Nishino,S.: :
Central administration of vitamin B-12 aggravates cataplexy in canine narcolepsy Neuroreport 8:3861-3865, 1997. Pubmed reference: 9462456 . |
| 1997 |
Nishino,S.,Arrigoni,J.,Shelton,J.,Kanbayashi,T.,Dement,W.C.,Mignot,E.: :
Effects of thyrotropin-releasing hormone and its analogs on daytime sleepiness and cataplexy in canine narcolepsy Journal of Neuroscience 17:6401-6408, 1997. Pubmed reference: 9236248 . |
| 1997 |
Nishino,S.,Mignot,E.: :
Pharmacological aspects of human and canine narcolepsy [Review] Progress in Neurobiology 52:27-78, 1997. Pubmed reference: 9185233 . |
| 1997 |
Nishino,S.,Tafti,M.,Sampathkumaran,R.,Dement,W.C.,Mignot,E.: :
Circadian distribution of rest/activity in narcoleptic and control dogs - assessment with ambulatory activity monitoring Journal of Sleep Research 6:120-127, 1997. Pubmed reference: 9377531 . |
| 1997 |
Tafti,M.,Nishino,S.,Liao,W.,Dement,W.C.,Mignot,E.: :
Mesopontine organization of cholinergic and catecholaminergic cell groups in the normal and narcoleptic dog Journal of Comparative Neurology 379:185-197, 1997. Pubmed reference: 9050784 . |
| 1996 |
Kanbayashi,T.,Nishino,S.,Tafti,M.,Hishikawa,Y.,Dement,W.C.,Mignot,E.: :
Thalidomide, a hypnotic with immune modulating properties, increases cataplexy in canine narcolepsy Neuroreport 7:1881-1886, 1996. Pubmed reference: 8905685 . |
| 1996 |
Reid,M.S.,Tafti,M.,Nishino,S.,Sampathkumaran,R.,Siegel,J.M.,Mignot,E.: :
Local administration of dopaminergic drugs into the ventral tegmental area modulates cataplexy in the narcoleptic canine Brain Research 733:83-100, 1996. Pubmed reference: 8891251 . |
| 1996 |
Tafti,M.,Nishino,S.,Aldrich,M.S.,Liao,W.N.,Dement,W.C.,Mignot,E.: :
Major histocompatibility class II molecules in the CNS - increased microglial expression at the onset of narcolepsy in a canine model Journal of Neuroscience 16:4588-4595, 1996. Pubmed reference: 8764647 . |
| 1995 |
Nishino,S.,Tafti,M.,Reid,M.S.,Shelton,J.,Siegel,J.M.,Dement,W.C.,Mignot,E.: :
Muscle atonia is triggered by cholinergic stimulation of the basal forebrain: Implication for the pathophysiology of canine narcolepsy Journal of Neuroscience 15:4806-4814, 1995. Pubmed reference: 7623112 . |
| 1995 |
Nitz,D.,Andersen,A.,Fahringer,H.,Nienhuis,R.,Mignot,E.,Siegel,J.: :
Altered distribution of cholinergic cells in the narcoleptic dog Neuroreport 6:1521-1524, 1995. Pubmed reference: 7579139 . |
| 1995 |
Shelton,J.,Nishino,S.,Vaught,J.,Dement,W.C.,Mignot,E.: :
Comparative effects of modafinil and amphetamine on daytime sleepiness and cataplexy of narcoleptic dogs Sleep 18:817-826, 1995. Pubmed reference: 8746387 . |
| 1994 |
Mignot,E.,Bell,R.A.,Rattazzi,C.,Lovett,M.,Grumet,F.C.,Dement,W.C.: :
An immunoglobulin switchlike sequence is linked with canine narcolepsy Sleep 17:S68-S76, 1994. Pubmed reference: 7701203 . |
| 1994 |
Nishino,S.,Reid,M.S.,Dement,W.C.,Mignot,E.: :
Neuropharmacology and neurochemistry of canine narcolepsy Sleep 17:S84-S92, 1994. Pubmed reference: 7701206 . |
| 1994 |
Reid,M.S.,Siegel,J.M.,Dement,W.C.,Mignot,E.: :
Cholinergic Mechanisms in Canine Narcolepsy .2. Acetylcholine Release in the Pontine Reticular Formation Is Enhanced During Cataplexy Neuroscience 59:523-530, 1994. Pubmed reference: 8008206 . |
| 1994 |
Reid,M.S.,Tafti,M.,Geary,J.N.,Nishino,S.,Siegel,J.M.,Dement,W.C.,Mignot,E.: :
Cholinergic Mechanisms in Canine Narcolepsy .1. Modulation of Cataplexy via Local Drug Administration into the Pontine Reticular Formation Neuroscience 59:511-522, 1994. Pubmed reference: 8008205 . |
| 1994 |
Reid,M.S.,Tafti,M.,Nishino,S.,Siegel,J.M.,Dement,W.C.,Mignot,E.: :
Cholinergic regulation of cataplexy in canine narcolepsy in the pontine reticular formation is mediated by M2 muscarinic receptors Sleep 17:424-435, 1994. Pubmed reference: 7991953 . |
| 1993 |
Mignot,E.J.M.,Dement,W.C.: :
Narcolepsy in Animals and Man Equine Veterinary Journal 25:476-477, 1993. Pubmed reference: 8275992 . |
| 1993 |
Mignot,E.,Nishino,S.,Sharp,L.H.,Arrigoni,J.,Siegel,J.M.,Reid,M.S.,Edgar,D.M.,Ciaranello,R.D.,Dement,W.C.: :
Heterozygosity at the canarc-1 Locus Can Confer Susceptibility for Narcolepsy - Induction of Cataplexy in Heterozygous Asymptomatic Dogs After Administration of a Combination of Drugs Acting on Monoaminergic and Cholinergic Systems Journal of Neuroscience 13:1057-1064, 1993. Pubmed reference: 8095066 . |
| 1993 |
Nishino,S.,Fruhstorfer,B.,Arrigoni,J.,Guilleminault,C.,Dement,W.C.,Mignot,E.: :
Further Characterization of the Alpha-1 Receptor Subtype Involved in the Control of Cataplexy in Canine Narcolepsy Journal of Pharmacology and Experimental Therapeutics 264:1079-1084, 1993. Pubmed reference: 8095546 . |
| 1992 |
Nishino,S.,Arrigoni,J.,Sharp,L.H.,Shelton,J.D.,Dement,W.C.,Mignot,E.: :
Serum Prolactin Response to a D2 Antagonist in Narcoleptic and Control Canines Sleep 15:474-475, 1992. Pubmed reference: 1455131 . |
| 1992 |
Valtier,D.,Dement,W.C.,Mignot,E.: :
Monoaminergic Uptake in Synaptosomes Prepared from Frozen Brain Tissue Samples of Normal and Narcoleptic Canines Brain Research 588:115-119, 1992. Pubmed reference: 1393561 . |
| 1991 |
Kornberg,M.,Kornberg,L.,Blanke,E.,Wagner,V.,Dahme,E.: :
A Case of Narcolepsy in a Giant-Schnauzer Kleintierpraxis 36:271, 1991. |
| 1991 |
Mignot,E.,Wang,C.,Rattazzi,C.,Gaiser,C.,Lovett,M.,Guilleminault,C.,Dement,W.C.,Grumet,F.C.: :
Genetic Linkage of Autosomal Recessive Canine Narcolepsy with a mu-Immunoglobulin Heavy-Chain Switch-Like Segment Proceedings of the National Academy of Sciences of the United States of America 88:3475-3478, 1991. Pubmed reference: 1673032 . |
| 1991 |
Nishino,S.,Arrigoni,J.,Valtier,D.,Miller,J.D.,Guilleminault,C.,Dement,W.C.,Mignot,E.: :
Dopamine-D2 Mechanisms in Canine Narcolepsy Journal of Neuroscience 11:2666-2671, 1991. Pubmed reference: 1831837 . |
| 1991 |
Renaud,A.,Nishino,S.,Dement,W.C.,Guilleminault,C.,Mignot,E.: :
Effects of SDZ NVI-085, a Putative Subtype-Selective alpha1- Agonist, on Canine Cataplexy, a Disorder of Rapid Eye Movement Sleep European Journal of Pharmacology 205:11-16, 1991. Pubmed reference: 1687464 . |
| 1991 |
Valtier,D.,Nishino,S.,Guilleminault,C.,Dement,W.C.,Mignot,E.: :
Platelet alpha2 Adrenoceptors in Human and Canine Narcolepsy Biological Psychiatry 29:376-382, 1991. Pubmed reference: 1645207 . |
| 1990 |
Miller,J.D.,Faull,K.F.,Bowersox,S.S.,Dement,W.C.: :
CNS Monoamines and Their Metabolites in Canine Narcolepsy - A Replication Study Brain Research 509:169-171, 1990. Pubmed reference: 1689603 . |
| 1990 |
Nishino,S.,Haak,L.,Shepherd,H.,Guilleminault,C.,Sakai,T.,Dement,W.C.,Mignot,E.: :
Effects of Central Alpha-2 Adrenergic Compounds on Canine Narcolepsy, a Disorder of Rapid Eye Movement Sleep Journal of Pharmacology and Experimental Therapeutics 253:1145-1152, 1990. Pubmed reference: 1972749 . |
| 1989 |
Dean,R.R.,Kilduff,T.S.,Dement,W.C.,Grumet,F.C.: :
Narcolepsy without unique MHC class II antigen association: studies in the canine model. Hum Immunol 25:27-35, 1989. Pubmed reference: 2523880 . |
| 1989 |
Fruhstorfer,B.,Mignot,E.,Bowersox,S.,Nishino,S.,Dement,W.C.,Guilleminault,C.: :
Canine Narcolepsy Is Associated with an Elevated Number of Alpha-2-Receptors in the Locus Coeruleus Brain Research 500:209-214, 1989. Pubmed reference: 2557958 . |
| 1989 |
Geisler,P.,Albert,E.: :
Immunogenetics of Narcolepsy Sleep 88 :117-122, 1989. |
| 1989 |
Motoyama,M.,Kilduff,T.S.,Lee,B.S.M.,Dement,W.C.,Mcdevitt,H.O.: :
Restriction Fragment Length Polymorphism in Canine Narcolepsy Immunogenetics 29:124-126, 1989. Pubmed reference: 2563354 . |
| 1989 |
Vanheerden,J.,Eckersley,G.N.: :
Narcolepsy in a Long-Haired Dachshund Journal of the South African Veterinary Association-Tydskrif Van Die Suid-Afrikaanse Veterinere Vereniging 60:151-153, 1989. |
| 1987 |
Bowersox,S.S.,Kilduff,T.S.,Faull,K.F.,Zeller-DeAmicis,L.,Dement,W.C.,Ciaranello,R.D.: :
Brain dopamine receptor levels elevated in canine narcolepsy. Brain Res 402:44-8, 1987. Pubmed reference: 3828787 . |
| 1986 |
Bowersox,S.S.,Kilduff,T.S.,Kaitin,K.I.,Dement,W.C.,Ciaranello,R.D.: :
Brain benzodiazepine receptor characteristics in canine narcolepsy. Sleep 9:111-5, 1986. Pubmed reference: 3010425 . |
| 1986 |
Kaitin,K.I.,Kilduff,T.S.,Dement,W.C.: :
Sleep fragmentation in canine narcolepsy. Sleep 9:116-9, 1986. Pubmed reference: 3704433 . |
| 1986 |
Kilduff,T.S.,Bowersox,S.S.,Kaitin,K.I.,Baker,T.L.,Ciaranello,R.D.,Dement,W.C.: :
Muscarinic cholinergic receptors and the canine model of narcolepsy. Sleep 9:102-6, 1986. Pubmed reference: 3704431 . |
| 1986 |
Lammers,G.J.: :
[Narcolepsy in dogs: an unusual disease]. Tijdschr Diergeneeskd 111:985-7, 1986. Pubmed reference: 3775753 . |
| 1986 |
Siegel,J.M.,Fahringer,H.,Tomaszewski,K.S.,Kaitin,K.,Kilduff,T.,Dement,W.C.: :
Heart rate and blood pressure changes associated with cataplexy in canine narcolepsy. Sleep 9:216-21, 1986. Pubmed reference: 3704445 . |
| 1984 |
Boehme,R.E.,Baker,T.L.,Mefford,I.N.,Barchas,J.D.,Dement,W.C.,Ciaranello,R.D.: :
Narcolepsy: cholinergic receptor changes in an animal model. Life Sci 34:1825-8, 1984. Pubmed reference: 6539848 . |
| 1983 |
Mefford,I.N.,Baker,T.L.,Boehme,R.,Foutz,A.S.,Ciaranello,R.D.,Barchas,J.D.,Dement,W.C.: :
Narcolepsy: biogenic amine deficits in an animal model. Science 220:629-32, 1983. Pubmed reference: 6188216 . |
| 1982 |
Baker,T.L.,Foutz,A.S.,McNerney,V.,Mitler,M.M.,Dement,W.C.: :
Canine model of narcolepsy: genetic and developmental determinants. Exp Neurol 75:729-42, 1982. Pubmed reference: 7199479 . |
| 1980 |
Foutz,A.S.,Mitler,M.M.,Dement,W.C.: :
Narcolepsy. Vet Clin North Am Small Anim Pract 10:65-80, 1980. Pubmed reference: 6996290 . |
| 1979 |
Foutz,A.S.,Mitler,M.M.,Cavalli-Sforza,L.L.,Dement,W.C.: :
Genetic factors in canine narcolepsy. Sleep 1:413-21, 1979. Pubmed reference: 574310 . |
| 1977 |
Darke,P.G.,Jessen,V.: :
Narcolepsy in a dog. Vet Rec 101:117-8, 1977. Pubmed reference: 562026 . |
| 1977 |
Mitler,M.M.,Dement,W.C.: :
Sleep studies on canine narcolepsy: pattern and cycle comparisons between affected and normal dogs. Electroencephalogr Clin Neurophysiol 43:691-9, 1977. Pubmed reference: 72649 . |
| 1976 |
Mitler,M.M.,Soave,O.,Dement,W.C.: :
Narcolepsy in seven dogs. J Am Vet Med Assoc 168:1036-8, 1976. Pubmed reference: 945254 . |
| 1974 |
Mitler,M.M.,Boysen,B.G.,Campbell,L.,Dement,W.C.: :
Narcolepsy-cataplexy in a female dog. Exp Neurol 45:332-40, 1974. Pubmed reference: 4472992 . |
| 1973 |
Knecht,CD.,Oliver,JE.,Redding,R.,Selcer,R.,Johnson,G.: :
Narcolepsy in a dog and a cat. J Am Vet Med Assoc 162:1052-3, 1973. Pubmed reference: 4736237 . |