Skip to Content

Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

 

William M. Valentine, D.V.M, , Ph.D.

Associate Professor of Pathology, Microbiology and Immunology
Researcher

Contact Information:

Vanderbilt University Medical Center
1161 21st Ave, C-3321A MCN
Nashville, TN 37232-2561
615-343-5836
Fax: 615-343-9825

Research Description

Parkinson disease (PD) is the second most common neurodegenerative disease and the prevalence of PD is predicted to double in the US and more than double in developing countries during the next 25 years; however a definite etiology or unifying sequence of molecular events for the most common form of PD, late onset sporadic idiopathic PD, has not been established. Because a growing number of epidemiological studies have associated an increased risk for PD with various conditions, environmental factors must be considered as a risk for PD. The goal of our research is to identify mechanisms of environmental agents that contribute to increased risk for PD. We are currently investigating whether four classes of pesticides, that have established human exposure, can impair ubiquitin based protein processing and cell signaling that promotes neurodegenerative changes contributing to PD. Animal models are being used to determine whether these pesticides inhibit E1 activating enzyme through a common mechanism in vivo leading to nigrostriatal and extra nigral toxicity. These studies are determining the dose-response for changes in brain E1 enzyme activity, characterizing E1 covalent modifications by shotgun LC/MS/MS, mapping neurodegenerative changes both in the nigral striatal pathway and in potentially more sensitive nonmotor brain regions and enteric ganglia involved in PD using immunohistochemistry and silver degeneration staining. In vitro systems are being used to ascertain the cause and effect relationship for ubiquitin pathway inhibition and dopaminergic cell death through determining the influence of constitutively compromised and increased E1 function on viability and the localization and expression of the dopamine transporter and activation of the Cdk5 complex in differentiated MN9D cells exposed to either the proposed pesticides, their metabolites or specific pharmacologic E1 inhibitors. We believe that the mechanistic data and structure activity relationships derived from these studies will assist in the formulation of more informed risk management for the large population exposed to these agents and will facilitate strategies of intervention to decrease the risk of PD and slow the progression of disease in PD patients.

Publications
  • Harkins KD, Xu J, Dula AN, Li K, Valentine WM, Gochberg DF, Gore JC, Does MD. The microstructural correlates of T1 in white matter. Magn Reson Med [print-electronic]. 2016 Mar; 75(3): 1341-5. PMID: 25920491, PMCID: PMC4624612, DOI: 10.1002/mrm.25709, ISSN: 1522-2594.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25920491.
  • Dennis KE, Valentine WM. Ziram and sodium N,N-dimethyldithiocarbamate inhibit ubiquitin activation through intracellular metal transport and increased oxidative stress in HEK293 cells. Chem. Res. Toxicol [print-electronic]. 2015 Apr 4/20/2015; 28(4): 682-90. PMID: 25714994, PMCID: PMC4406076, DOI: 10.1021/tx500450x, ISSN: 1520-5010.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25714994.
  • Kraemer BR, Snow JP, Vollbrecht P, Pathak A, Valentine WM, Deutch AY, Carter BD. A role for the p75 neurotrophin receptor in axonal degeneration and apoptosis induced by oxidative stress. J. Biol. Chem [print-electronic]. 2014 Aug 8/1/2014; 289(31): 21205-16. PMID: 24939843, PMCID: PMC4118083, PII: M114.563403, DOI: 10.1074/jbc.M114.563403, ISSN: 1083-351X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24939843.
  • Caito SW, Valentine WM, Aschner M. Dopaminergic neurotoxicity of S-ethyl N,N-dipropylthiocarbamate (EPTC), molinate, and S-methyl-N,N-diethylthiocarbamate (MeDETC) in Caenorhabditis elegans. J. Neurochem [print-electronic]. 2013 Dec; 127(6): 837-51. PMID: 23786526, PMCID: PMC3830724, DOI: 10.1111/jnc.12349, ISSN: 1471-4159.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23786526.
  • Harkins KD, Valentine WM, Gochberg DF, Does MD. In-vivo multi-exponential T2, magnetization transfer and quantitative histology in a rat model of intramyelinic edema. Neuroimage Clin. 2013; 2: 810-7. PMID: 24179832, PMCID: PMC3777678, PII: S2213-1582(13)00075-2, DOI: 10.1016/j.nicl.2013.06.007, ISSN: 2213-1582.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24179832.
  • Viquez OM, Caito SW, McDonald WH, Friedman DB, Valentine WM. Electrophilic adduction of ubiquitin activating enzyme E1 by N,N-diethyldithiocarbamate inhibits ubiquitin activation and is accompanied by striatal injury in the rat. Chem. Res. Toxicol [print-electronic]. 2012 Nov 11/19/2012; 25(11): 2310-21. PMID: 22874009, PMCID: PMC3502677, DOI: 10.1021/tx300198h, ISSN: 1520-5010.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22874009.
  • Caito SW, Milatovic D, Hill KE, Aschner M, Burk RF, Valentine WM. Progression of neurodegeneration and morphologic changes in the brains of juvenile mice with selenoprotein P deleted. Brain Res [print-electronic]. 2011 Jun 6/29/2011; 1398: 1-12. PMID: 21636077, PMCID: PMC3114300, PII: S0006-8993(11)00808-0, DOI: 10.1016/j.brainres.2011.04.046, ISSN: 1872-6240.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21636077.
  • Dortch RD, Apker GA, Valentine WM, Lai B, Does MD. Compartment-specific enhancement of white matter and nerve ex vivo using chromium. Magn Reson Med. 2010 Sep; 64(3): 688-97. PMID: 20806376, PMCID: PMC2933086, DOI: 10.1002/mrm.22460, ISSN: 1522-2594.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20806376.
  • Valentine HL, Viquez OM, Valentine WM. Peripheral nerve and brain differ in their capacity to resolve N,N-diethyldithiocarbamate-mediated elevations in copper and oxidative injury. Toxicology [print-electronic]. 2010 Jul; 274(1-3): 10-7. PMID: 20452388, PMCID: PMC2900428, PII: S0300-483X(10)00206-4, DOI: 10.1016/j.tox.2010.04.018, ISSN: 1879-3185.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20452388.
  • Dula AN, Gochberg DF, Valentine HL, Valentine WM, Does MD. Multiexponential T2, magnetization transfer, and quantitative histology in white matter tracts of rat spinal cord. Magn Reson Med. 2010 Apr; 63(4): 902-9. PMID: 20373391, PMCID: PMC2852261, DOI: 10.1002/mrm.22267, ISSN: 1522-2594.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20373391.
  • Viquez OM, Lai B, Ahn JH, Does MD, Valentine HL, Valentine WM. N,N-diethyldithiocarbamate promotes oxidative stress prior to myelin structural changes and increases myelin copper content. Toxicol. Appl. Pharmacol [print-electronic]. 2009 Aug 8/15/2009; 239(1): 71-9. PMID: 19467251, PMCID: PMC2727155, PII: S0041-008X(09)00217-8, DOI: 10.1016/j.taap.2009.05.017, ISSN: 1096-0333.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/19467251.
  • Valentine HL, Viquez OM, Amarnath K, Amarnath V, Zyskowski J, Kassa EN, Valentine WM. Nitrogen substituent polarity influences dithiocarbamate-mediated lipid oxidation, nerve copper accumulation, and myelin injury. Chem. Res. Toxicol. 2009 Jan; 22(1): 218-26. PMID: 19093748, PMCID: PMC2665870, PII: 10.1021/tx8003714, DOI: 10.1021/tx8003714, ISSN: 1520-5010.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/19093748.
  • Viquez OM, Valentine HL, Amarnath K, Milatovic D, Valentine WM. Copper accumulation and lipid oxidation precede inflammation and myelin lesions in N,N-diethyldithiocarbamate peripheral myelinopathy. Toxicol. Appl. Pharmacol [print-electronic]. 2008 May 5/15/2008; 229(1): 77-85. PMID: 18284930, PMCID: PMC2429851, PII: S0041-008X(08)00021-5, DOI: 10.1016/j.taap.2008.01.005, ISSN: 0041-008X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18284930.
  • Valentine WM, Abel TW, Hill KE, Austin LM, Burk RF. Neurodegeneration in mice resulting from loss of functional selenoprotein P or its receptor apolipoprotein E receptor 2. J. Neuropathol. Exp. Neurol. 2008 Jan; 67(1): 68-77. PMID: 18172410, PII: 00005072-200801000-00007, DOI: 10.1097/NEN.0b013e318160f347, ISSN: 0022-3069.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18172410.
  • Valentine H, Amarnath K, Amarnath V, Li W, Ding X, Valentine WM, Ichihara G. Globin s-propyl cysteine and urinary N-acetyl-S-propylcysteine as internal biomarkers of 1-bromopropane exposure. Toxicol. Sci [print-electronic]. 2007 Aug; 98(2): 427-35. PMID: 17517825, PII: kfm126, DOI: 10.1093/toxsci/kfm126, ISSN: 1096-6080.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17517825.
  • Valentine HL, Does MD, Marshall V, Tonkin EG, Valentine WM. Multicomponent T2 analysis of dithiocarbamate-mediated peripheral nerve demyelination. Neurotoxicology [print-electronic]. 2007 May; 28(3): 645-54. PMID: 17350098, PMCID: PMC1976306, PII: S0161-813X(07)00029-0, DOI: 10.1016/j.neuro.2007.01.009, ISSN: 0161-813X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17350098.
  • Viquez OM, Valentine HL, Friedman DB, Olson SJ, Valentine WM. Peripheral nerve protein expression and carbonyl content in N,N-diethlydithiocarbamate myelinopathy. Chem. Res. Toxicol [print-electronic]. 2007 Mar; 20(3): 370-9. PMID: 17323979, PMCID: PMC2525616, DOI: 10.1021/tx6003453, ISSN: 0893-228X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17323979.
  • Valentine HL, Amarnath K, Amarnath V, Valentine WM. Dietary copper enhances the peripheral myelinopathy produced by oral pyrrolidine dithiocarbamate. Toxicol. Sci [print-electronic]. 2006 Feb; 89(2): 485-94. PMID: 16291825, PII: kfj047, DOI: 10.1093/toxsci/kfj047, ISSN: 1096-6080.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16291825.
  • Sills RC, Harry GJ, Valentine WM, Morgan DL. Interdisciplinary neurotoxicity inhalation studies: carbon disulfide and carbonyl sulfide research in F344 rats. Toxicol. Appl. Pharmacol. 2005 Sep 9/1/2005; 207(2 Suppl): 245-50. PMID: 16002115, PII: S0041-008X(05)00325-X, DOI: 10.1016/j.taap.2005.02.037, ISSN: 1096-0333.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16002115.
  • Valentine WM, Hill KE, Austin LM, Valentine HL, Goldowitz D, Burk RF. Brainstem axonal degeneration in mice with deletion of selenoprotein p. Toxicol Pathol. 2005; 33(5): 570-6. PMID: 16105800, PII: VK5307682H745882, DOI: 10.1080/01926230500243045, ISSN: 0192-6233.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16105800.
  • Ichihara G, Li W, Shibata E, Ding X, Wang H, Liang Y, Peng S, Itohara S, Kamijima M, Fan Q, Zhang Y, Zhong E, Wu X, Valentine WM, Takeuchi Y. Neurologic abnormalities in workers of a 1-bromopropane factory. Environ. Health Perspect. 2004 Sep; 112(13): 1319-25. PMID: 15345346, PMCID: PMC1247523, ISSN: 0091-6765.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15345346.
  • Tonkin EG, Valentine HL, Milatovic DM, Valentine WM. N,N-diethyldithiocarbamate produces copper accumulation, lipid peroxidation, and myelin injury in rat peripheral nerve. Toxicol. Sci [print-electronic]. 2004 Sep; 81(1): 160-71. PMID: 15187237, PII: kfh190, DOI: 10.1093/toxsci/kfh190, ISSN: 1096-6080.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15187237.
  • Zimmerman LJ, Valentine HL, Valentine WM. Characterization of S-(N,N-Dialkylaminocarbonyl)cysteine Adducts and Enzyme Inhibition Produced by Thiocarbamate Herbicides in the Rat. Chem. Res. Toxicol. 2004 Feb; 17(2): 258-67. PMID: 14967014, DOI: 10.1021/tx034209c, ISSN: 0893-228X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/14967014.
  • Johnson DJ, Amarnath V, Amarnath K, Valentine H, Valentine WM. Characterizing the influence of structure and route of exposure on the disposition of dithiocarbamates using toluene-3,4-dithiol analysis of blood and urinary carbon disulfide metabolites. Toxicol. Sci [print-electronic]. 2003 Nov; 76(1): 65-74. PMID: 12972631, PII: kfg226, DOI: 10.1093/toxsci/kfg226, ISSN: 1096-6080.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12972631.
  • Amarnath K, Amarnath V, Amarnath K, Valentine HL, Valentine WM. A specific HPLC-UV method for the determination of cysteine and related aminothiols in biological samples. Talanta. 2003 Aug 8/29/2003; 60(6): 1229-38. PMID: 18969150, PII: S0039-9140(03)00232-7, DOI: 10.1016/S0039-9140(03)00232-7, ISSN: 1873-3573.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18969150.
  • Thompson RW, Valentine HL, Valentine WM. Cytotoxic mechanisms of hydrosulfide anion and cyanide anion in primary rat hepatocyte cultures. Toxicology. 2003 Jun 6/30/2003; 188(2-3): 149-59. PMID: 12767687, PII: S0300483X03000799, ISSN: 0300-483X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12767687.
  • Tonkin EG, Valentine HL, Zimmerman LJ, Valentine WM. Parenteral N,N-diethyldithiocarbamate produces segmental demyelination in the rat that is not dependent on cysteine carbamylation. Toxicol. Appl. Pharmacol. 2003 Jun 6/1/2003; 189(2): 139-50. PMID: 12781632, PII: S0041008X03000930, ISSN: 0041-008X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12781632.
  • Nickols JC, Valentine W, Kanwal S, Carter BD. Activation of the transcription factor NF-kappaB in Schwann cells is required for peripheral myelin formation. Nat. Neurosci. 2003 Feb; 6(2): 161-7. PMID: 12514737, PII: nn995, DOI: 10.1038/nn995, ISSN: 1097-6256.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12514737.
  • Kapil Amarnath, Venkataraman Amarnath, Kalyani Amarnath, Holly L. Valentine and William M. Valentine. A specific HPLC-UV method for the determination of cysteine and related aminothiols in biological samples. Talanta. 2003; 60: 1229-38.
  • Thompson RW, Valentine HL, Valentine WM. In vivo and in vitro hepatotoxicity and glutathione interactions of N-methyldithiocarbamate and N,N-dimethyldithiocarbamate in the rat. Toxicol. Sci. 2002 Dec; 70(2): 269-80. PMID: 12441372, ISSN: 1096-6080.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12441372.
  • Zimmerman LJ, Valentine HS, Amarnath K, Valentine WM. Identification of a S-hexahydro-1H-azepine-1-carbonyl adduct produced by molinate on rat hemoglobin beta(2) and beta(3) chains in vivo. Chem. Res. Toxicol. 2002 Feb; 15(2): 209-17. PMID: 11849047, PII: tx015564a, ISSN: 0893-228X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11849047.
  • Amarnath V, Amarnath K, Graham DG, Qi Q, Valentine H, Zhang J, Valentine WM. Identification of a new urinary metabolite of carbon disulfide using an improved method for the determination of 2-thioxothiazolidine-4-carboxylic acid. Chem. Res. Toxicol. 2001 Sep; 14(9): 1277-83. PMID: 11559044, PII: tx010085x, ISSN: 0893-228X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11559044.
  • Tonkin EG, Erve JC, Valentine WM. Disulfiram produces a non-carbon disulfide-dependent schwannopathy in the rat. J. Neuropathol. Exp. Neurol. 2000 Sep; 59(9): 786-97. PMID: 11005259, ISSN: 0022-3069.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11005259.
  • Erve JC, Jensen ON, Valentine HS, Amarnath V, Valentine WM. Disulfiram generates a stable N,N-diethylcarbamoyl adduct on Cys-125 of rat hemoglobin beta-chains in vivo. Chem. Res. Toxicol. 2000 Apr; 13(4): 237-44. PMID: 10775322, PII: tx990191n, ISSN: 0893-228X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10775322.
  • Sills RC, Valentine WM, Moser V, Graham DG, Morgan DL. Characterization of carbon disulfide neurotoxicity in C57BL6 mice: behavioral, morphologic, and molecular effects. Toxicol Pathol. 2000 Jan; 28(1): 142-8. PMID: 10669001, ISSN: 0192-6233.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10669001.
  • Valentine WM, Valentine HL, Amarnath K, Amarnath V. Toluene-3,4-dithiol analysis of blood for assessing carbon disulfide exposure. Toxicol. Sci. 1999 Aug; 50(2): 155-63. PMID: 10478851, ISSN: 1096-6080.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10478851.
  • Lewis JG, Graham DG, Valentine WM, Morris RW, Morgan DL, Sills RC. Exposure of C57BL/6 mice to carbon disulfide induces early lesions of atherosclerosis and enhances arterial fatty deposits induced by a high fat diet. Toxicol. Sci. 1999 May; 49(1): 124-32. PMID: 10367350, ISSN: 1096-6080.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10367350.
  • Erve JC, Amarnath V, Sills RC, Morgan DL, Valentine WM. Characterization of a valine-lysine thiourea cross-link on rat globin produced by carbon disulfide or N,N-diethyldithiocarbamate in vivo. Chem. Res. Toxicol. 1998 Oct; 11(10): 1128-36. PMID: 9778308, PII: tx980077p, DOI: 10.1021/tx980077p, ISSN: 0893-228X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9778308.
  • Erve JC, Amarnath V, Graham DG, Sills RC, Morgan AL, Valentine WM. Carbon disulfide and N,N-diethyldithiocarbamate generate thiourea cross-links on erythrocyte spectrin in vivo. Chem. Res. Toxicol. 1998 May; 11(5): 544-9. PMID: 9585486, PII: tx980007i, DOI: 10.1021/tx980007i, ISSN: 0893-228X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9585486.
  • Amarnath V, Valentine WM, Montine TJ, Patterson WH, Amarnath K, Bassett CN, Graham DG. Reactions of 4-hydroxy-2(E)-nonenal and related aldehydes with proteins studied by carbon-13 nuclear magnetic resonance spectroscopy. Chem. Res. Toxicol. 1998 Apr; 11(4): 317-28. PMID: 9548802, PII: tx970176n, DOI: 10.1021/tx970176n, ISSN: 0893-228X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9548802.
  • Valentine WM, Amarnath V, Amarnath K, Erve JC, Graham DG, Morgan DL, Sills RC. Covalent modification of hemoglobin by carbon disulfide: III. A potential biomarker of effect. Neurotoxicology. 1998 Feb; 19(1): 99-107. PMID: 9498226, ISSN: 0161-813X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9498226.
  • Harry, G.J., Graham, D.G., Valentine, W.M., Moroan, D.L., and Sills, R.C. Carbon disulfide neurotoxicity in rats:VIII. Summary. Neurotoxicology. 1998; 19: 159-62.
  • Johnson, D.J., Graham, D.G., Amarnath, V., Amarnath, K., and Valentine, W.M. Release of carbon disulfide is a contributing mechanism in the axonopathy produced by N'-N'- diethyldithiocarbamate. Toxicol. Appl. Pharmacol. 1998; 148: 288-96.
  • Sills, R.C., Harry, G.J., Morgan, D.L., Valentine, W.M., and Grahanm, D.G. Morphology of axonal swelling, in the muscular branch of the posterior tibial nerve and spinal cord. Neurotoxicology. 1998; 19: 117-28.
  • Valentine WM, Amarnath V, Graham DG, Morgan DL, Sills RC. CS2-mediated cross-linking of erythrocyte spectrin and neurofilament protein: dose response and temporal relationship to the formation of axonal swellings. Toxicol. Appl. Pharmacol. 1997 Jan; 142(1): 95-105. PMID: 9007038, PII: S0041-008X(96)98028-X, DOI: 10.1006/taap.1996.8028, ISSN: 0041-008X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9007038.
  • Valentine, W.M., Amarnath, V., Graham, D.G., Morgan, D.L., and Sills, R.C. CS2-Mediated cross-linking of erythrocyte spectrin and neurofilament protein: dose response and temporal relationship to the formation of axonal swellings. Toxicol. Appl. Pharmacol. 1997; 142: 95-105.
  • Johnson D.J., Graham, D.G., Amarnath, V., and Valentine, W.M. The measurement of 2-thiathiozolidine-4 carboxylic acid as an index of the in vivo release of CS2 by dithlocarbamates. Chem. Res. Toxicol. 1996; 9: 910-6.
  • Montine, T.J., Huan-, D.Y., Valentine, W.M., Amarnath, V., Saunders, A., Weisgraber, K.H.,Graham, D.G., and Strittmatter, W.J. Cross-linking of apolipoprotein E by products of lipid peroxidation. J.Neuropath. Exp. Neurol. 1996; 55: 202-10.
  • Amarnath, V., Amarnath, K., Valentine, W.M., Eng, M., and Graham, D.G. Intermediates in the Paal-Knorr synthesis of pyrroles. 4-Oxoaldehydes. Chem. Res. Toxicol. 1995; 8: 234-8.
  • Graham, D.G. Amarnath, V., Valentine W.M., Pyle, S.J. and Anthony, D.C. Pathogenetic Studies of Hexane and Carbon Disulfide Neurotoxicity. CRC Crit. Rev. Toxicol. 1995; 25: 91-112.
  • Graham, D.G., Amarnath, V., Anthony, D.C., Eng., M.A., Kazaks, E.L., and Valentine, W.M. Biomolecular mechanisms of organic solvent toxicity in. Handbook of neurotoxicology: Effects and mechanisms; New York, Marcel Deker. 1995; 2: 401-12.
  • Montine, T., Valentine, W.M., and Graham, D.G. Central and peripheral nervous systems. The pathology of environmental and occupational disease; St. Louis, Mosby-Year Book, Inc. 1995; 511-31.
  • Montine, T.J., Underhill, M., Valentine, W.M., and Graham, D.G. Dialkyldlthiocarbamates inhibit tyrosine hydroxylase activity in PC 12 cells and in fibroblasts that express tyrosine hydroxylase. Neurodegeneration. 1995; 4: 283-90.
  • Valentine, W.M., Amarnath, V., Amarnath, K., and Graham, D.G. Characterization of protein adducts by N methyl dithiocarbamate and N-methyl dithiocarbamate esters. Chem. Res. Toxicol. 1995; 8: 254-61.
  • Amarnath, V., Valentine, W.M., Amarnath, K., Eng, M.A. and Graham D.G. The Mechanism of Nucleophilic Substitution of Alkylpyrroles in the Presence of Oxygen. Chem. Res. Toxicol. 1994; 7: 56-61.
  • Valentine, W.M., Graham, D.G. and Anthony, D.C. Covalent cross-linking of erythrocyte spectrin by carbon disulfide in vivo. Toxicol. Appl. Pharmacol. 1993; 121: 71-7.
  • Amarnath, V., Anthony, D.C., Amarnath, K., Valentine, W.M., Wetterau, L.A. and Graham, D.G. Intermediates in the Paal-Knorr synthesis of pyrroles. J. Org. Chem. 1991; 56: 6924-31.
  • Amarnath, V., Anthony, D.C., Valentine, W.M. and Graham, D.G. The molecular mechanism of the carbon disulfide mediated cross-linking of proteins. Chem. Res. Toxicol. 1991; 4((2)): 148-50.
  • Graham, D.G., Valentine, W.M., Amarnath, V. and Anthony, D.C. Molecular studies of n-hexane and carbon disulfide neuropathies. Vitro Toxicology - Mechanisms and New Technology, Alternative Methods in Toxicology, New York, Liebert. 1991; 8: 19-21.
  • Valentine, W.M. and Beasley, V.R. Electromyographic assessment of the neuromuscular blockade produced by anatoxin-a in the rat. Toxicon. 1991; 29: 347-57.
  • Valentine, W.M. Pyrethrin and Pyrethroid Insecticides. Veterinary Clincs of North America: Small Animal Practice. 1990; 20: 375-82.
  • Valentine, W.M. Short-Chain Alcohols. Veterinary Clinics of North America: Small Animal Practice. 1990; 20: 515-23.
  • Valentine, W.M. and Beasley, V.R. Pyrethrins and Pyrethroids. Current Veterinary Therapy X; W.B. Saunders Co., Philadelphia. 1989; 137-40.
  • Valentine, B., Steinschneider, A., Dhawan, D., Burgar, M.I. St. Amour, T. and Fiat D. Oxycen-17 NMR of peptides. Int. J. Pep. and Prot. Res. 1985; 25: 56-68.
  • Fiat D., Steinschneider, A., Valentine, B., Dhawan, D. and Gilboa, H. Hydrogen bonds in the tripeptide pro-leu-gly NH2 (MIF). 17 0 and1H studies. Biochem. Biophys. Acta. 1984; 800: 251-7.
  • Steinschneider, A., Valentine, B., Burgar, M.I. and Flat, D. NMR of carboxylic-170 in amino acids. Magn. Reson. Chem. 1984; 23: 104-10.
  • Valentine, B., St. Amour, T.E., and Fiat, D. A 170 NMR study of the protonation of urea. Org. Magn. Reson. 1984; 22: 697-700.
  • St, Amour, T.E., Burger, M.I., Valentine, B., and Fiat, D. 17 O NMR studies of substituted and hydrogen bonding effects in substituted acetophenones and benzaldhydes. J. Am. Chem. Soc. 1981; 103: 1128-36.
  • Valentine, B., St. Amour, T., Walter, R. and Fiat, D. 170 nuclear macnctic resonance studies of some amino acids at natural abundance. Org. Magn. Reson. 1980; 13: 232-3.
  • Valentine, B., St. Amour, T., Walter, R., and Fiat, D. PH dependence of oxygen-17 chemical shifts and linewidths of L-alanine and glycine. J. Magn. Reson. 1980; 38: 413-8.