A number of research interests are pursued within the Neuropathology Unit. The section has shared research interests (and funding) with other university departments, as well as other interstate and overseas institutions. There is a variety of projects, all of which are associated with the pathology of the nervous system.

 

Personnel

Clive G Harper, MD, FRCPA

Roger S Pamphlett, BSc(Med), MD ChB Cape T., FRACP, MRCPath

Roger Stankovic

Steve Kum Jew

Donna Sheedy

Equipment

VIDAS image analyser, Olympus 5-headed microscope, 6 x -80ÉC freezers, Olympus photomicrography microscope, Macroscopic photographic apparatus, 1 x Magellan semiautomatic image analysers, Cryostat, Tissue Processor, Leitz Operating microscope and Lynx EM tissue processor.

 

Funding

 

  • Head, Department of Pathology, 1987-1991, 1995 -1997

  • Foundation Professor of Neuropathology, University of Sydney and Royal Prince Alfred Hospital, 1986

  • Neuropathologist, Royal Perth Hospital, 1972 - 1985

  • Clinical Lecturer in Pathology, University of Western Australia, 1974 - 1985

  • Medical Director, Australian Brain Foundation (WA Div.), 1981 - 1985

  • Post-graduate Fellow in Neuropathology, University of Pennsylvania, 1979 - 1980

  • Assistant in Medicine, Division Anatomy de Neuropathologie, Hopital Cantonal, Universitaire de Lausanne, Switzerland, 1974

  • Lecturer in Neuropathology, University of Glasgow, 1973

  • Fellow of the Royal College of Pathologists of Australia, 1972

  • Resident Medical Officer and Registrar in Pathology, Royal North Shore Hospital, Sydney, 1967 - 1972

 

Professor Harper joined the Department of Pathology and The Royal Prince Alfred Hospital in 1986 (from Royal Perth Hospital) as Foundation Professor of Neuropathology. He was appointed Head of Department in 1986.

 

Alcohol-related brain damage

As part of his ongoing interest in the aetiology of alcohol-related brain damage, Professor Harper has combined neuropathological, neurochemical and pharmacological data obtained from many alcoholic cases to examine which factors are the most important in causing alcoholic brain damage. The research group have a particular interest in the role played by thiamin (vitamin B1) deficiency. He has a number of ongoing collaborative studies with Australian and International research groups.

Professor Harper is the Director of the NSW brain bank which is part of the Australian Network for Research into Mental Health Disorders. This is supported by the NH&MRC and NISAD and has led to a number of collaborative studies focusing on people with schizophrenia.

 

Recent Publications

1. Catts SV, Ward PB, Lloyd A, Huang X, Dixon G, Chahl I, Harper C, Wakefield D. Molecular biological investigations into the role of the NMDA receptor in the pathophysiology of schizophrenia. Aust NZ J Psychiatry 1997, 31:17-26.

2. Caine D, Kril JJ, Halliday GM, Harper CG. Operational criteria for the classification of chronic alcoholics for research and treatment. J Neurol Neurosurg and Psychiat. 1997, 62:1-51-60.

3. Dodd, PR, Eckert AL, Fletcher L, Kril, JJ, Harper CG, Halliday JW. Concentrations of transferrin and carbohydrate-deficient transferrin in post-mortem human brain from alcoholics. Addiction Biology 1997, 2:337-348.

4. Harper CH, Sheedy D, Lara A, Garrick T, Hilton J, Raisanen J. Is thiamin supplementation useful in preventing Wernicke's encephalopathy? Brain Pathology 1997, 7:4;1253-1255.

5. McKechnie, Harper C, Besser M. Durally based-occipital cavernous haemangioma indistinguishable from meningioma. Journal of Clinical Neuroscience 1998, 5:105-108.

6. Thomas GJ, Harper CG, Dodd P. Expression of GABAA receptor isoform genes in the cerebral cortex of cirrhotic and alcoholic cases assessed by S1Nuclease protection assays. Neurochemistry International 1998, 32:375-385.

7. Harper CG, Sheedy DL, Lara AI, Garrick TM, Hilton JM & Raisanen J. Prevalence of Wernicke-Korsakoff syndrome in Australia - has thiamine fortification made a difference? Medical Journal of Australia 1998, 168:542-545.

8. Harper C. The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain? Journal of Neuropathology and Experimental Neurology 1998, 57:101-110.

9. Kollar C, Johnston I, Parker G & Harper C. Dural arteriovenous fistula in association with heterotopic brain nodule in the transverse sinus. American Journal of Neuroradiology1998, 19: 1126-1128.

10. Raisanen J, Goodman HS, Ghougassian DF, Harper CG. Role of cytology in the intraoperative diagnosis of central demyelinating disease. A report of five cases. Acta Cytologica 1998, 42:907-912.

11. Garrick T, Sheedy D, Abernethy , Hodda A, Harper C. Accidental illicit drug deaths in Sydney.:how common are they? Medical Journal of Australia 1999, 170: 139.

12. Puvaneswary M, Floate D, Harper C. Creutzfeldt-Jacob disease: Magnetic resonance imaging findings. Australasian Radiology 1999, 43: 91-94.

13. Huang, WL, Dunlop SA, Harper CG. The effect of corticosteroids on the developing central nervous system: a review article. Obstetrical and Gynecological Survey 1999, 54 (5): 336-342.

14. Baker KG, Halliday GM, Kril JJ, Harper CG. Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke's Encephalopathy. Neuroscience 1999, 92:429-438.

15. Collins S, Boyd A, Fletcher A, Byron K, Harper C, McLean CA, Masters CL.et al Novel prion protein.gene mutation in an elderly "sporadic" case of Creutzfeldt-Jacob disease. Arch. Neurol 1999.

16. Sheedy D, Lara A, Garrick T, Harper C. The size of the mamillary bodies in health and disease. Alcoholism: Clinical and Experimental Research, 1999,23(10): 1624-1628.

17. Cappelen-Smith C, Reddell S, Halmagyi M, Harper C. Neuronal necrosis due to prolonged status epilepticus. A clinicopathological, neurophysiological and radiological study. Clinical Neurophysiology, 1999. 110: 2299.

18. Clark IA, Awburn M, Harper C, Whitten RO, Carr RA, Liomba GN, Molyneux ME, Taylor TE. Immunohistochemical evidence for nitric oxide production in fatal cases of falciparum malaria in Malawi. In Press

19. Dixon G, Dissanaike S, Harper C. Parvalbumin-immunoreactive neurons in the human anteroventral thalamic nucleus. Neuroreport, 2000, 11(1): 97-101.

20. Scolyer RA, Painter DM, Harper CG, Soon Lee C. Hepatocellular carcinoma metastasizing to the orbit diagnosed by fine needle aspiration cytology, Pathology, 2000, 31: 350-353.

21. Le Corre S,  Harper C, Lopez P, Ward P, Catts S. Increased level of expression of an NMDAR1 splice variant in the superior temporal gyrus in schizophrenia. Neuroreport, 2000, 11: 983-986.

22. Harper C.  The neuropathology of alcohol-related brain damage.  Fukushima Medical Journal 2000, 50:125-129.

23. Garrick T, Sheedy, DL, Abernethy J, Hodda AE, Harper C. Heroin related deaths in Sydney, Australia. How common are they? American Journal on Addictions, 9(2), 2000,:172-178.

24. Lo PA, Harper C, Besser M.  Intracavernous schwannoma of the abducens nerve : a review of the clinical features, radiology and pathology of an unusual case.  Journal of Clinical Neuroscience, 2001, 8: 357-360.

25. Barnett M, Prosser J, Sutton I, Halmagyi GM, Davies L, Harper C, Dalmau J.  Paraneoplastic brainstem encephalitis in a woman with anti-Ma2 antibody. Journal of Neurology, Neurosurgery and Psychiatry, 2001, 70: 222-225.

26. Harper CG  and Lee VK.  Mobile phones and your health. Pathology, 2001, 33:269-270.

27. Huang WL, Harper CG, Evans SF, Newnham JP, Dunlop SA. Repeated prenatal  corticosteroid administration delays astrocyte and capillary tight junction maturation in fetal sheep.  International Journal of Developmental Neuroscience. 2001, 19: 487-493.

28. Huang WL, Harper CG, Evans SF, Newnham JP, Dunlop SA. Repeated prenatal  corticosteroid administration delays myelination of the corpus callosum in fetal sheep.  International Journal of Developmental Neuroscience. 2001, 19: 415-425.

29. Buckland ME, Scolyer RA, Donellan MB, Brew S, MsGee-Collett M, Harper CG. Spinal chloroma presenting with triplegia in an aleukaemic patient. Pathology, 2001 33: 386-389.

30. Harper CG, Lee VK. Editorial: Mobile phones and your health. Pathology, 2001 33:269-270.

31. G Dixon, C Harper. High percentage of glutamic acid decarboxylase-immunoreactive neurons in the anterior thalamus of the human brain. Brain Research, 2001 In Press.

Book Chapters

1. Harper C, Butterworth RF. Nutritional and metabolic disorders. In: Greenfield's Neuropathology. 6th edition,. Lantos P, Graham D (Eds) Edward Arnold, Cambridge. 1997:601-655.

2. Harper CG, Corbett D. Alcoholism and dementia. In: The neuropathology of dementia. Esiri M , Morris H (Eds) Cambridge University Press, Cambridge. 1997:294-303.

3. Harper CG, Kril JJ, Sheedy D, Halliday GM, Double K, Dodd PR, Lewohl JM. Neuropathological studies: the relationship between alcohol and aging. In:Alcohol problems and aging. Gomberg ESL, Hegedus AM, Zucker RA (Eds) NIAAA Research Monograph No 33. Bethesda, Maryland, NIAAA. 1998:117-134

4. Harper C, Duckett S. Malnutrition and Alcoholism in the Aging Population.  In: The Pathology of the Aging Nervous System. 2nd Edition Eds. Duckett S and de la Torre J. Oxford University Press.

5. Harper C, Butterworth RF.  Nutritional and metabolic disorders. In: Greenfield's Neuropathology. 7th edition,. Lantos P, Graham D (Eds) Edward Arnold, Cambridge.

6. Harper CG, Scolyer, R.  Alcoholism and dementia. In: The neuropathology of dementia. 2nd. edition. Esiri M , Morris H, Trojanowski J (Eds)  Cambridge University Press, Cambridge.

 

 

Dr Roger Pamphlett practises as a Neurologist and a Neuropathologist at Royal Prince Alfred Hospital. He also teaches undergraduate and postgraduate Neuropathology and Neurology at the University of Sydney and Royal Prince Alfred Hospital.

Dr Pamphlett’s main clinical interest is in patients with Motor Neuron Disease, and he runs a weekly Research and Care MND Clinic for patients with this disorder.
 

 

 

Research Program in Motor Neuron Disease

Motor neuron disease (MND) kills one Australian every day. The disease causes a progressive loss of muscle strength, leading to death usually within 2 to 5 years. The weakness is due to a loss of motor neurons, the nerve cells in the spinal cord that activate muscle. In 10% of cases MND runs in families, but in 90% only one family member gets the disease, i.e. it is "sporadic".

The cause of sporadic MND is not known, but we think that either a toxin or a virus enters and destroys the motor nerve cells of susceptible individuals.

  1. Metal toxins are suspected in MND, since at low doses these toxins enter motor neurons selectively (i.e. other neurons are not affected). Possible environmental toxins in MND are lead, mercury, cadmium or copper. We have found that about 40% of adult humans have metal toxins in their motor neurons. However, many people are exposed to toxins, yet few get MND. So if metals are a cause of MND, a genetic susceptibility to these toxins is likely to underlie the disease.
  2. Viruses, especially those belonging to the family which includes poliovirus (the enteroviruses) have long been suspected in MND since they enter motor neurons selectively. However, these viruses are quite common infections, so some susceptibility to the virus must be present to cause MND.

To see if people with MND have a genetic susceptibility to metal toxins or viruses, we have set up an Australia-wide MND DNA bank. People both with and without MND contribute blood samples to the bank so that we can look for genetic differences between these groups. The research aims at look at the interactions between genes and environmental toxins or viruses that could underlie MND. We are therefore particularly interested in looking for abnormalities in genes that handle either toxic metals or genes for receptors for viruses that attack motor neurons.  

Recent Publications

  1. Pamphlett R, Kum-Jew S. Zinc in the spinal cord of a mutant SOD1 mouse model of ALS. Neuroreport 2003;14:547-549.
  2. Pamphlett R, Sjarif A. Is quantitation necessary for assessment of sural nerve biopsies? Muscle Nerve 2003;27:562-9.
  3. Pamphlett R, Todd E, Vink R, McQuilty R, Cheema S. Magnesium supplementation does not delay disease onset or increase survival in a mouse model of familial ALS. J Neurol Sci 2003;in press
  4. Halliday G, Ng T, Rodriguez M, Harding A, Blumbergs P, Evans W, Fabian V, Fryer J, Gonzales M, Harper C, Kalnins R, Masters CL, McLean C, Milder DG, Pamphlett R, Scott G, Tannenberg A, Kril J. Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria. Acta Neuropathol 2002;104:72-8.
  5. Pamphlett R. Mutations in the VEGF promoter and ALS in airline pilots: a link? J Occup Environ Med 2002;44:987.
  6. Pamphlett R, Kum-Jew S. Mercury vapor uptake into the nervous system of developing mice. Neurotoxicol Teratol 2001;23:191-196.
  7. Pamphlett R, McQuilty R, Zarkos K. Blood levels of toxic and essential metals in motor neuron disease. Neurotoxicology 2001;36:1-10.
  8. Wilmshurst JM, Bye A, Rittey C, Adams C, Hahn AF, Ramsay D, Pamphlett R, Pollard JD, Ouvrier R. Severe infantile axonal neuropathy with respiratory failure. Muscle Nerve 2001;24:760-768.
  9. Danscher G, Stoltenberg M, Kemp K, Pamphlett R. Bismuth autometallography. Protocol, specificity, and differentiation. J Histochem Cytochem 2000;48:1503-1510.
  10. Pamphlett R. Detection and cellular localization of enterovirus RNA sequences in spinal cord of patients with ALS. Neurology 2000;55:1420-1421.
  11. Pamphlett R, Danscher G, Rungby J, Stoltenberg M. Tissue uptake of bismuth from shotgun pellets. Environ Res 2000;82:258-262.
  12. Pamphlett R, Stoltenberg M, Rungby J, Danscher G. Uptake of bismuth in motor neurons of mice after single oral doses of bismuth compounds. Neurotoxicol Teratol 2000;22:559-563.
  13. Poljak A, Pamphlett R, Gurney ME, Duncan MW. Measurement of o- and m-tyrosine as markers of oxidative damage in motor neuron disease. Redox Report 2000;5:137-40.
  14. Stoltenberg M, Danscher G, Pamphlett R, Christensen MM, Rungby J. Histochemical tracing of bismuth in testis from rats exposed intraperitoneally to bismuth subnitrate. Reprod Toxicol 2000;14:65-71.
  15. Pamphlett R, Raisenen J, Kum Jew S. Vertebral artery compression due to head movement: a possible cause of the sudden infant death syndrome. Pediatrics 1999;103:460-468.
  16. Walker D, Pamphlett R. Prolonged survival and pulmonary metastasis after local cure of glioblastoma multiforme. J Clin Neurosci 1999;6:67-68.
  17. Pamphlett R, Coote P. Entry of low doses of mercury vapor into the nervous system. Neurotoxicology 1998;19:39-48.
  18. Pamphlett R, Ng YW. Does lead damage motor neurons? J Clin Neurosci 1998;5:66-69.
  19. Pamphlett R, Png FY. Shrinkage of motor axons following systemic exposure to inorganic mercury. J Neuropathol Exp Neurol 1998;57:360-366.
  20. Pamphlett R, Slater M, Thomas S. Oxidative damage to nucleic acids in motor neurons containing mercury. J Neurol Sci 1998;159:121-126.
  21. Pamphlett R, Waley P. Mercury in human spinal motor neurons. Acta Neuropathol 1998;96:515-519.
  22. Sue CM, Crimmins DS, Soo YS, Pamphlett R, Presgrave CM, Kotsimbos N, Jean-Francois MJ, Byrne E, Morris JG. Neuroradiological features of six kindreds with MELAS tRNA(Leu) A2343G point mutation: implications for pathogenesis. J Neurol Neurosurg Psychiatry 1998;65:233-240.