Medical Toxicology Commons^™

Trichloroethylene And Cardiac Malformations, Robert L. Brent

The Selected Works of Robert Brent

No abstract.

Nucleic Acid Encoding Human Rev1 Protein, Zhigang Wang, Winston Lin, Hua Xin, Xiaohua Wu

Toxicology and Cancer Biology Faculty Patents

The present invention relates to a human cDNA homologous to the yeast REV1 gene. The sequence of human REV1 (hREV1) gene is described.

Commentary: Teratology In The 20th Century Environmental Causes Of Congenital Malformations In Humans And How They Were Established By Harold Kalter, Robert L. Brent

The Selected Works of Robert Brent

No abstract

Utilization Of Juvenile Animals Studies To Determine The Human Effects And Risks Of Environmental Toxicants During Postnatal Developmental Stages, Robert L. Brent

The Selected Works of Robert Brent

Toxicology studies utilizing animals and in-vitro cellular or tissue preparations have been used to study the toxic effects and mechanism of action of drugs and chemicals and to determine the effective and safe dose of drugs in humans and the risk of toxicity from chemical exposures. Testing in animals could be improved if animal dosing using the mg/kg basis was abandoned and drugs and chemicals were administered to compare the effects of pharmacokinetically and toxicokinetically equivalent serum levels in the animal model and human. Since alert physicians or epidemiology studies, not animal studies have discovered most human teratogens and toxicities …

Do Recent Data From The Seychelles Islands Alter The Conclusions Of The Nrc Report On The Toxicological Effects Of Methylmercury?, Alan H. Stern, Joseph L. Jacobson, Louise Ryan, Thomas A. Burke

Wayne State University Associated BioMed Central Scholarship

Abstract

In 2000, the National Research Council (NRC), an arm of the National Academy of Sciences, released a report entitled, "Toxicological Effects of Methylmercury." The overall conclusion of that report was that, at levels of exposure in some fish- and marine mammal-consuming communities (including those in the Faroe Islands and New Zealand), subtle but significant adverse effects on neuropsychological development were occurring as a result of in utero exposure. Since the release of that report, there has been continuing discussion of the public health relevance of current levels of exposure to Methylmercury. Much of this discussion has been linked to …

Phosphoglycan Messengers And Their Medical Uses (Lipidemia), Khalid M. Elased, Khalid A. Gumaa, Hassan Rahmoune, Thomas Rademacher

Pharmacology and Toxicology Faculty Publications

Phosphoglycan messengers (PGMs) which are carbohydrate derivatised phosphatidyl cyclitols are disclosed, together with the finding that these substances are biologically active, e.g. in lowering blood glucose levels. These compounds are distinct from GPI-anchors disclosed in the prior art as these GPI-anchors are protein linked and are not biologically active.

Phosphoglycan Messengers And Their Medical Uses (Sle), Khalid M. Elased, Khalid A. Gumaa, Hassan Rahmoune, Thomas Rademacher, J. B. De Souza

Pharmacology and Toxicology Faculty Publications

PPhosphoglycan messengers (PGMs) which are carbohydrate derivatised phosphatidyl cyclitols are disclosed, together with the finding that these substances are biologically active, especially in modulating plasma cholesterol, plasma triglycerides and/or high density lipoprotein levels and/or modulating the LDL:HDL ratio, and for the treatment of lipodystrophy or dyslipidemia. These compounds are distinct from GPI-anchors disclosed in the prior art as these GPI-anchors are protein linked and are not biologically active.

Medical, Social And Legal Implications Of Treating Nausea And Vomiting Of Pregnancy, Robert L. Brent

The Selected Works of Robert Brent

This article will deal with medical, social, and legal implications of treating nausea and vomiting of pregnancy (NVP). Clinical problems occur when the symptoms become exaggerated and result in debilitation, dehydration, and hospitalization. The treatment of NVP in its early stages has the implication that it will prevent the more serious complications, including hospitalization. Therapeutic modalities discussed in this conference that have been used or are being tested are primarily symptomatic treatments (antihistamines, Bendectin (Merrell Dow; Cincinatti, Ohio), phenothiazines, hyponosis, accupressure, relaxation behavioral modification, audiogenic feedback training, newer medications, diet, and nutritional support). Bendectin is probably the most studied medication …

Diagnostic Test And Therapy For Manganese Superoxide Dismutate (Msod) Associated Diseases, Daret K. St. Clair, Muneyasu Urano, Edward J. Kasarskis

Toxicology and Cancer Biology Faculty Patents

The present invention provides a diagnostic method and a kit for detection of mutations localized within the 5′ promoter region of the MnSOD gene. Such mutations are associated with diseases characterized by decreased MnSOD activity such as certain formes of cancer, and ALS. Accordingly, the diagnostic method this invention provides, comprising RFLP, direct sequencing, or PCR analysis of the region within 3 kb, the transcription initiation site will detect these disorders. This invention also provides a therapeutic method for such disorders comprising transfection of affected cells or tissues with high activity, MnSOD expression vectors, or the administration of exogenous MnSOD …

Treatment Of Diabetes, John H.L. Playfair, Khalid M. Elased, Joseph B. De Souza

Pharmacology and Toxicology Faculty Publications

The present invention provides methods for using a killed malaria parasite or an extract thereof in the treatment of non-insulin dependent diabetes mellitus (NIDDM).

Teratogen Update: Reproductive Risks Of Leflunomide (Arava); A Pyrimidine Synthesis Inhibitor: Counseling Women Taking Leflunomide Before Or During Pregnancy And Men Taking Leflunomide Who Are Contemplating Fathering A Child, Robert L. Brent

The Selected Works of Robert Brent

Arava™ (leflunomide) is a pyrimidine synthesis inhibitor used in the treatment of active rheumatoid arthritis (RA). The chemical name for leflunomide is N- (4’-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide. Because the drug has been successful in the treatment of rheumatoid arthritis (RA), it is being widely prescribed. In spite of the clear warning that the drug should not be prescribed for pregnant women, approximately 30 women have become pregnant while taking leflunomide as of December 1999. This commentary was prepared to aid teratology counselors and genetic counselors that might be contacted by physicians or patients about the risk of leflunomide exposure during pregnancy. Before the …

Nh4+ Inhibits K-Cl Cotransport In Low K Sheep Red Blood Cells, Peter K. Lauf, Suhail Ahmed, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Cation-Anion-Coupled Cotransport In An Immortalized Neuronal Cell Line (C6 Glioma), Kenneth B. E. Gagnon, Norma C. Adragna, Robert E.W. Fyffe, Peter K. Lauf

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Transient Nature Of The Stimulatory" Nem-Effect" On K-Cl Cotransport In Kccl-Transfected Hek293 And Primary Rat Aortic Smooth Muscle Cells, Peter K. Lauf, Jin Zhang, Jing Zhang, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.

K-Cl Cotransport: Membrane Immunofluorescence Localization By Confocal Microscopy Of The Kcc1 Protein, Before And After Truncation Of The Cooh-Terminal Domain, In Human Embryonic Kidney (Hek293) Cells, Peter K. Lauf, Kenneth B.E. Gagnon, Jin Zhang, Eric Delpire, Robert E.W. Fyffe, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Quantitative Analysis Of Changes In Cell Volume And Intracellular Ph Induced By Ammonia And Ammonium In Neuroblastoma Cells Studied With Fluorescent Probes, Vania D. Rosas, G. Boyarsky, S. Marquez, Francisco J. Alvarez-Leefmans

Pharmacology and Toxicology Faculty Publications

No abstract provided.

New Mechanism Of Regulation Of K+-Cl- Cotransport, Norma C. Adragna, H. Ahmed, C. M. Ferrell, J. Filosa, Peter K. Lauf

Pharmacology and Toxicology Faculty Publications

No abstract provided.

A Review Of The Anticoagulant Pesticide Pindone, Laurie E. Twigg, Tim J. Lowe, Gary R. Martin, Garry S. Gray

Books & book chapters

A review of the use of pindone for rabbit control in Western Australia is timely due to increased public concern over the use of this toxin, and because non-target deaths of some native Australian animals have been known to occur following its use. Pindone is one of the first generation indandione anticoagulant rodenticides which were developed in the late 1940' s. The toxicity of anticoagulants arises from their inhibition of vitamin K-dependent clotting factors in the blood. Thus therapeutic administration of vitamin K provides a reliable antidote against anticoagulant poisoning. Pindone is slow acting and works best with repeated small …

Review Of: Lewis' Dictionary Of Toxicology (Robert A. Lewis, Ed.; Lewis Publishers 1998), Dana E. Evans

RISK: Health, Safety & Environment (1990-2002)

Review of the book: Lewis' Dictionary of Toxicology (Robert A. Lewis, ed.; Lewis Publishers 1998). About the author, acknowledgments, alphabetical listing of terms defined. ISBN 1-56670-223-2; [1127 pp. $84.95. Hardbound. 2000 Corporate Blvd. N.W., Boca Raton, FL 33431.]

Vasodilators Activate Erythrocyte K-Cl Cotransport, Norma C. Adragna, H. Ahmed, Peter K. Lauf

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Significance Of The Kccl Cytoplasmic Cooh-Terminal Fragment For The Ph Dependence Of K-Cl Cotransport In Transfected Human Embryonic Kidney Cells, Norma C. Adragna, Jin Zhang, Peter K. Lauf

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Regulation Of The Rat Liver Sodium-Dependent Bile Acid Cotransporter Gene By Prolactin. Mediation Of Transcriptional Activation By Stat5, Tanmoy C. Ganguly, Michelle L. O'Brien, Saul J. Karpen, James F. Hyde, Fredrick J. Suchy, Mary Vore

Toxicology and Cancer Biology Faculty Publications

The intracellular mechanism(s) underlying the upregulation of the hepatic Na+/taurocholate cotransporting polypeptide (ntcp) by prolactin (PRL) are unknown. In this report, we demonstrate a time-dependent increase in nuclear translocation of phosphorylated liver Stat5 (a member of the ignal ransducers and ctivators of ranscription family) that correlated with suckling-induced increases in serum PRL levels. In electrophoretic mobility gel shift assays, nuclear Stat5 exhibited specific DNA-binding ability towards IFN-gamma-activated sequence (GAS)-like elements (GLEs; 5'TTC/A-PyNPu-G/TAA-3') located in the -937 to -904 bp region of the ntcp promoter. Transient cotransfections in HepG2 cells revealed that PRL inducibility (2.5-3-fold) required coexpression of the long form …

Dna-Protein Cross-Linking By Pyrrolizidine Alkaloids, Gail L. Drew

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Pyrrolizidine alkaloids (PAs) are natural plant compounds found in hundreds of plant species worldwide and are reported to have cytotoxic, carcinogenic, antimitotic, and genotoxic activity. PAs are metabolized by the cytochrome P450 (CYP) system to the pyrrole or the N-oxide form. The pyrroles are bifunctional electrophilic alkylators that bind cellular nucleophiles such as DNA and proteins and sirupt normal cell processes, including DNA replication and gene transcription and can cause megalocytosis. The pyrroles dehydrosenecionine (DHSN) and dehydromonocrotaline (DHMO) are among the most potent PA cross-linkers and inducers of megalocytosis. DHSN and DHMO-induced cross-links in cultured normal (MDBK) and neoplastic (MCF7) …

Aflatoxin B1 Metabolism In Mammalian Pulmonary Tissue, J. Michael Eichelberger

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Aflatoxin B₁ (AFB₁) is a potent dietary hepatocarcinogen and may be a lung carcinogen when inhaled. To study the relative ability of lung and liver to metabolize AFB₁, a susceptible (Swiss-Webster rat) and resistant species (Syrian golden hamster) were pretreated with inducing agents in order to identify specific AFB₁ metabolizing enzymes in each tissue.

Analysis of AFB₁-exo-epoxide (AFBO) formation, O-dealkynation assays, and protein immunoblots demonstrated that cytochrome P450 (CYP) 1A proteins were overexpressed in both the lung and liver of hamsters pretreated with 3-methylchyolanthrene (3-MC). Only CYP1A1 was expressed in the lung …

Proton (H) Modulation Of K-Cl Cotransport Through Both Internal And External Sites In Dids-Ph-Clamped Low Magnesium Lk Sheep Erythrocytes, Peter K. Lauf, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.

The Protective Role Of Manganese Superoxide Dismutase Against Adriamycin-Induced Acute Cardiac Toxicity In Transgenic Mice, Hsiu-Chuan Yen, Terry D. Oberley, Satit Vichitbandha, Ye-Shih Ho, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Adriamycin (ADR) is a potent anticancer drug known to cause severe cardiac toxicity. Although ADR generates free radicals, the role of free radicals in the development of cardiac toxicity and the intracellular target for ADR-induced cardiac toxicity are still not well understood. We produced three transgenic mice lines expressing increased levels of human manganese superoxide dismutase (MnSOD), a mitochondrial enzyme, as an animal model to investigate the role of ADR-mediated free radical generation in mitochondria. The human MnSOD was expressed, functionally active, and properly transported into mitochondria in the heart of transgenic mice. The levels of copper-zinc SOD, catalase, and …

A Thermodynamic Study Of Electroneutral K-Cl Cotransport In Ph- And Volume-Clamped Low K Sheep Erythrocytes With Normal And Low Internal Magnesium, Peter K. Lauf, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

Swelling-Induced human erythrocyte K-Cl cotransport is membrane potential independent and capable of uphill transport. However, a complete thermodynamic analysis of basal and stimulated K-Cl cotransport, at constant cell volume, is missing, This study was performed in low K sheep red blood cells before and after reducing cellular free Mg into the nanomolar range with the divalent cation ionophore A23187 and a chelator, an intervention known to stimulate K-Cl cotransport. The anion exchange inhibitor 4,4'diisothiocyanato-2,2'disulfonic stilbene was used to clamp intracellular pH and Cl or NO3 concentrations. Cell volume was maintained constant as external and internal pH differed by more than …

Sidedness Of H+ Action On K-Cl Cotransport In Dids Ph(I)-Clamped Low K Sheep Red Blood Cells With Reduced Mg(I), Peter K. Lauf, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Dependence Of Thiol-Stimulated K-Cl Cotransport On Redox State Of Low K Sheep Red Blood Cells, Peter K. Lauf, Norma C. Adragna, Nihal S. Agar

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Hypoglycemia And Hyperinsulinemia In Rodent Models Of Severe Malaria Infection, Khalid M. Elased, J. H. L. Playfair

Pharmacology and Toxicology Faculty Publications

Severe hypoglycemia developed during nonlethal Plasmodium chabaudi and lethal P. yoelii blood stage malaria infection in mice, always in association with hyperinsulinemia. Supernatants of lethal P. yoelii incubated overnight induced hypoglycemia and hyperinsulinemia in normal mice. In murine malaria, hypoglycemia may be largely secondary to increased insulin secretion.