toggle visibility Search & Display Options

Select All    Deselect All
 |   | 
Details
   print
  Records Links
Author Dargatz, D.A.; Traub-Dargatz, J.L. doi  openurl
  Title Multidrug-resistant Salmonella and nosocomial infections Type Journal Article
  Year (down) 2004 Publication The Veterinary Clinics of North America. Equine Practice Abbreviated Journal Vet Clin North Am Equine Pract  
  Volume 20 Issue 3 Pages 587-600  
  Keywords Animals; Anti-Bacterial Agents/*pharmacology; Cross Infection/prevention & control/*veterinary; Disease Outbreaks/prevention & control/veterinary; Drug Resistance, Bacterial; *Drug Resistance, Multiple, Bacterial; Horse Diseases/*drug therapy/transmission; Horses; Infection Control/methods; Microbial Sensitivity Tests/veterinary; Salmonella/*drug effects; Salmonella Infections, Animal/*drug therapy/transmission  
  Abstract Nosocomial infections are a serious threat to optimum patient care. In addition, nosocomial infections can have far-reaching consequences for the hospital personnel and the financial aspects of the hospital. Nosocomial infections with Salmonella spp have been described among hospitalized equine populations more frequently than any other agent. Salmonella spp associated with hospitalized equids often possess more antimicrobial resistance determinants than do Salmonella spp isolated from healthy horses in the general population. There is little evidence to suggest that resistant salmonellae are more virulent than nonresistant forms. MDR forms of Salmonella complicate the selection of appropriate antimicrobials when they are indicated, however. Furthermore, the use of some antimicrobials may apply selection pressure toward enhanced ability of MDR Salmonella to colonize equine patients. Further research should help to elucidate the risky uses of antimicrobials in the hospital setting and define the role of disinfectants and treatments such as NSAIDs in the ecology of MDR forms of nosocomial infections, including Salmonella. In the meantime, thoughtful selection of when and how to use antimicrobials in equine patients, together with deliberate selection of which antimicrobials to use based on monitoring data and other factors, such as safety and spectrum, is advised.  
  Address Animal and Plant Health Inspection Service, Veterinary Services, Centers for Epidemiology and Animal Health, United States Department of Agriculture, 2150 Centre Avenue, Building MS 2E7, Fort Collins, CO 80521, USA. david.a.dargatz@aphis.usda.gov  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0749-0739 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:15519820 Approved no  
  Call Number Equine Behaviour @ team @ Serial 2632  
Permanent link to this record
 

 
Author Touma, C.; Palme, R.; Sachser, N. openurl 
  Title Analyzing corticosterone metabolites in fecal samples of mice: a noninvasive technique to monitor stress hormones Type Journal Article
  Year (down) 2004 Publication Hormones and Behavior Abbreviated Journal Horm Behav  
  Volume 45 Issue 1 Pages 10-22  
  Keywords Adrenal Cortex/drug effects; Adrenal Cortex Function Tests; Adrenocorticotropic Hormone/pharmacology; Analysis of Variance; Animals; Circadian Rhythm; Corticosterone/*analysis/metabolism; Dexamethasone/pharmacology; Feces/*chemistry; Female; Immunoenzyme Techniques/*methods; Male; Mice; Mice, Inbred C57BL; Models, Animal; Reproducibility of Results; Stress, Psychological/*metabolism  
  Abstract In small animals like mice, the monitoring of endocrine functions over time is constrained seriously by the adverse effects of blood sampling. Therefore, noninvasive techniques to monitor, for example, stress hormones in these animals are highly demanded in laboratory as well as in field research. The aim of our study was to evaluate the biological relevance of a recently developed technique to monitor stress hormone metabolites in fecal samples of laboratory mice. In total, six experiments were performed using six male and six female mice each. Two adrenocorticotropic hormone (ACTH) challenge tests, two dexamethasone (Dex) suppression tests and two control experiments [investigating effects of the injection procedure itself and the diurnal variation (DV) of glucocorticoids (GCs), respectively] were conducted. The experiments clearly demonstrated that pharmacological stimulation and suppression of adrenocortical activity was reflected accurately by means of corticosterone metabolite (CM) measurements in the feces of males and females. Furthermore, the technique proved sensitive enough to detect dosage-dependent effects of the ACTH/Dex treatment and facilitated to reveal profound effects of the injection procedure itself. Even the naturally occurring DV of GCs could be monitored reliably. Thus, our results confirm that measurement of fecal CM with the recently established 5alpha-pregnane-3beta,11beta,21-triol-20-one enzyme immunoassay is a very powerful tool to monitor adrenocortical activity in laboratory mice. Since mice represent the vast majority of all rodents used for research worldwide and the number of transgenic and knockout mice utilized as animal models is still increasing, this noninvasive technique can open new perspectives in biomedical and behavioral science.  
  Address Department of Behavioural Biology, University of Muenster, D-48149 Muenster, Germany. touma@uni-muenster.de  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0018-506X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:14733887 Approved no  
  Call Number Equine Behaviour @ team @ Serial 4084  
Permanent link to this record
 

 
Author Dirikolu, L.; Lehner, A.F.; Karpiesiuk, W.; Hughes, C.; Woods, W.E.; Boyles, J.; Harkins, J.D.; Troppmann, A.; Tobin, T. openurl 
  Title Detection, quantification, metabolism, and behavioral effects of selegiline in horses Type Journal Article
  Year (down) 2003 Publication Veterinary Therapeutics : Research in Applied Veterinary Medicine Abbreviated Journal Vet Ther  
  Volume 4 Issue 3 Pages 257-268  
  Keywords Administration, Oral; Animals; Behavior, Animal/drug effects; Female; Horses/*metabolism; Mass Spectrometry/veterinary; Monoamine Oxidase Inhibitors/administration & dosage/blood/*pharmacokinetics/pharmacology/urine; Selegiline/administration & dosage/blood/*pharmacokinetics/pharmacology/urine; Substance Abuse Detection/veterinary  
  Abstract Selegiline ([R]-[-]N,alpha-dimethyl-N-2- propynylphenethylamine or l-deprenyl), an irreversible inhibitor of monoamine oxidase, is a classic antidyskinetic and antiparkinsonian agent widely used in human medicine both as monotherapy and as an adjunct to levodopa therapy. Selegiline is classified by the Association of Racing Commissioners International (ARCI) as a class 2 agent, and is considered to have high abuse potential in racing horses. A highly sensitive LC/MS/MS quantitative analytical method has been developed for selegiline and its potential metabolites amphetamine and methamphetamine using commercially available deuterated analogs of these compounds as internal standards. After administering 40 mg of selegiline orally to two horses, relatively low (<60 ng/ml) concentrations of parent selegiline, amphetamine, and methamphetamine were recovered in urine samples. However, relatively high urinary concentrations of another selegiline metabolite were found, tentatively identified as N- desmethylselegiline. This metabolite was synthesized and found to be indistinguishable from the new metabolite recovered from horse urine, thereby confirming the chemical identity of the equine metabolite. Additionally, analysis of urine samples from four horses dosed with 50 mg of selegiline confirmed that N-desmethylselegiline is the major urinary metabolite of selegiline in horses. In related behavior studies, p.o. and i.v. administration of 30 mg of selegiline produced no significant changes in either locomotor activities or heart rates.  
  Address Department of Biomedical Sciences, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL 36088, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1528-3593 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:15136987 Approved no  
  Call Number Serial 1901  
Permanent link to this record
 

 
Author Natalini, C.C.; Robinson, E.P. openurl 
  Title Effects of epidural opioid analgesics on heart rate, arterial blood pressure, respiratory rate, body temperature, and behavior in horses Type Journal Article
  Year (down) 2003 Publication Veterinary Therapeutics : Research in Applied Veterinary Medicine Abbreviated Journal Vet Ther  
  Volume 4 Issue 4 Pages 364-375  
  Keywords 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/administration & dosage/pharmacology; Alfentanil/administration & dosage/pharmacology; Analgesics, Opioid/administration & dosage/*pharmacology; Anesthesia, Epidural/*veterinary; Animals; Behavior, Animal/drug effects; Blood Pressure/drug effects; Body Temperature/drug effects; Butorphanol/administration & dosage/pharmacology; Cross-Over Studies; Female; Heart Rate/drug effects; Horses/*physiology; Injections, Epidural/veterinary; Male; Morphine/administration & dosage/pharmacology; Respiration/drug effects; Tramadol/administration & dosage/pharmacology  
  Abstract Heart rate, arterial blood pressures, respiratory rate, body temperature, and central nervous system excitement were compared before and after epidural administration of morphine (0.1 mg/kg), butorphanol (0.08 mg/kg), alfentanil (0.02 mg/kg), tramadol (1.0 mg/kg), the k-opioid agonist U50488H (0.08 mg/kg), or sterile water using an incomplete Latin square crossover design in five conscious adult horses. Treatments were administered into the first intercoccygeal epidural space. Significant (P <.05) reductions in respiratory rate were detected after epidural administration of morphine, alfentanil, U50488H, and sterile water. Additionally, significant (P <.05) head ptosis was observed within the first hour after administration of morphine, U50488H, and tramadol, but neither of these changes appeared to be of clinical significance. No treatment-related changes in motor activity or behavior were observed.  
  Address Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1528-3593 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:15136978 Approved no  
  Call Number Serial 1902  
Permanent link to this record
 

 
Author Dyson, S.; Murray, R. openurl 
  Title Pain associated with the sacroiliac joint region: a clinical study of 74 horses Type Journal Article
  Year (down) 2003 Publication Equine Veterinary Journal Abbreviated Journal Equine Vet J  
  Volume 35 Issue 3 Pages 240-245  
  Keywords Age Factors; Analgesia/veterinary; Anesthetics, Local/pharmacology; Animals; Body Height; Body Weight; Breeding; Female; Forelimb; Gait; Hindlimb; Horse Diseases/*diagnosis/radionuclide imaging; Horses; Lameness, Animal/*physiopathology; Lumbar Vertebrae/physiopathology; Male; Pain/diagnosis/drug therapy/radionuclide imaging/*veterinary; Sacroiliac Joint/*physiopathology; Sacrum/physiopathology  
  Abstract REASONS FOR PERFORMING STUDY: There has been no large study of horses with suspected sacroiliac (SI) joint region pain in which the clinical diagnosis has been supported by either abnormal radiopharmaceutical activity in the SI joint region or by periarticular infiltration of local anaesthetic solution. OBJECTIVES: To describe the clinical features of horses with SI joint region pain, to document the age, breed, sex, discipline, size and conformation of affected horses and to compare these with the author's (SD) normal case population and to document the results of infiltration of local anaesthetic solution around the SI joint region. METHODS: Horses were selected for inclusion in the study based upon the exclusion of other causes of lameness or poor performance, together with clinical signs suggestive of SI joint pain and abnormal radiopharmaceutical activity in the SI joint region and/or a positive response to periarticular infiltration of local anaesthetic solution. RESULTS: Sacroiliac joint region disease was identified in 74 horses between November 1997 and March 2002. Dressage and showjumping horses appeared to be at particular risk (P < 0.001). Affected horses were generally slightly older than the normal clinic population (P < 0.0001), taller at the withers (P < 0.0001) and of greater bodyweight (P < 0.01). There was a significant effect of breed (P < 0.001), with a substantially higher proportion of Warmblood horses (51%) in the SI pain group compared to the normal clinic population (29%). There was no correlation between conformation and the presence of SI joint region pain. The tubera sacrale appeared grossly symmetrical in most (95%) horses. Poor development of the epaxial muscles in the thoracolumbar region and asymmetry of the hindquarter musculature were common. Twenty-six horses (35%) showed restricted flexibility of the thoracolumbar region and 10 (16%) had an exaggerated response to pressure applied over the tubera sacrale. Fourteen horses (19%) were reluctant to stand on one hindlimb for prolonged periods. The majority of horses (75%) had a straight hindlimb flight and only 18% moved closely behind or plaited. In all horses restricted hindlimb impulsion was the predominant feature; invariably this was most obvious when the horse was ridden. Stiffness, unwillingness to work on the bit and poor quality canter were common. Sacroiliac joint region pain was seen alone (47%), or in conjunction with thoracolumbar pain (16%), hindlimb lameness (20%), forelimb lameness (7%) or a combination of problems (10%). Seventy-three horses (99%) had abnormalities of the SI joint region identified using nuclear scintigraphy. Infiltration of local anaesthetic solution around the SI joint region produced profound improvement in gait in all 34 horses in which it was performed. CONCLUSIONS AND POTENTIAL RELEVANCE: Careful clinical examination combined with scintigraphic evaluation of the SI joint region and local analgesia can enable a more definitive diagnosis of SI joint region pain than has previously been possible.  
  Address Centre for Equine Studies, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0425-1644 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:12755425 Approved no  
  Call Number Equine Behaviour @ team @ Serial 3723  
Permanent link to this record
 

 
Author Milgram, N.W.; Head, E.; Muggenburg, B.; Holowachuk, D.; Murphey, H.; Estrada, J.; Ikeda-Douglas, C.J.; Zicker, S.C.; Cotman, C.W. openurl 
  Title Landmark discrimination learning in the dog: effects of age, an antioxidant fortified food, and cognitive strategy Type Journal Article
  Year (down) 2002 Publication Neuroscience and Biobehavioral Reviews Abbreviated Journal Neurosci Biobehav Rev  
  Volume 26 Issue 6 Pages 679-695  
  Keywords Age Factors; Aging/*physiology; Analysis of Variance; Animals; Antioxidants/*pharmacology; Blood Chemical Analysis/methods; Cognition/*physiology; *Diet; Discrimination Learning/*drug effects/*physiology; Distance Perception/drug effects/physiology; Dogs/physiology; Female; Male; Psychomotor Performance/physiology; Retention (Psychology)/drug effects/physiology; Spatial Behavior/*drug effects/*physiology; Task Performance and Analysis; Time Factors; Vitamin E/blood  
  Abstract The landmark discrimination learning test can be used to assess the ability to utilize allocentric spatial information to locate targets. The present experiments examined the role of various factors on performance of a landmark discrimination learning task in beagle dogs. Experiments 1 and 2 looked at the effects of age and food composition. Experiments 3 and 4 were aimed at characterizing the cognitive strategies used in performance on this task and in long-term retention. Cognitively equivalent groups of old and young dogs were placed into either a test group maintained on food enriched with a broad-spectrum of antioxidants and mitochondrial cofactors, or a control group maintained on a complete and balanced food formulated for adult dogs. Following a wash-in period, the dogs were tested on a series of problems, in which reward was obtained when the animal responded selectively to the object closest to a thin wooden block, which served as a landmark. In Experiment 1, dogs were first trained to respond to a landmark placed directly on top of coaster, landmark 0 (L0). In the next phase of testing, the landmark was moved at successively greater distances (1, 4 or 10 cm) away from the reward object. Learning varied as a function of age group, food group, and task. The young dogs learned all of the tasks more quickly than the old dogs. The aged dogs on the enriched food learned L0 significantly more rapidly than aged dogs on control food. A higher proportion of dogs on the enriched food learned the task, when the distance was increased to 1cm. Experiment 2 showed that accuracy decreased with increased distance between the reward object and landmark, and this effect was greater in old animals. Experiment 3 showed stability of performance, despite using a novel landmark, and new locations, indicating that dogs learned the landmark concept. Experiment 4 found age impaired long-term retention of the landmark task. These results indicate that allocentric spatial learning is impaired in an age-dependent manner in dogs, and that age also affects performance when the distance between the landmark and target is increased. In addition, these results both support a role of oxidative damage in the development of age-associated cognitive dysfunction and indicate that short-term administration of a food enriched with supplemental antioxidants and mitochondrial cofactors can partially reverse the deleterious effects of aging on cognition.  
  Address Life Science Division, University of Toronto at Scarborough, 1265 Military Trail, Scarborough, Ont., Canada M1C 1A4. milgram@psych.utoronto.ca  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0149-7634 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:12479842 Approved no  
  Call Number Equine Behaviour @ team @ Serial 2806  
Permanent link to this record
 

 
Author McGreevy, P.D.; Webster, A.J.; Nicol, C.J. openurl 
  Title Study of the behaviour, digestive efficiency and gut transit times of crib-biting horses Type Journal Article
  Year (down) 2001 Publication The Veterinary record Abbreviated Journal Vet. Rec.  
  Volume 148 Issue 19 Pages 592-596  
  Keywords Animals; Behavior, Animal/*physiology; Case-Control Studies; *Digestion; *Gastrointestinal Motility/drug effects; Horse Diseases/*physiopathology; Horses/*physiology/psychology; Male; Stereotyped Behavior/*physiology; Sulfapyridine/blood; Sulfasalazine/diagnostic use/pharmacology  
  Abstract The spontaneous behaviour and the apparent digestibility of dry matter and fibre and transit times of digesta were compared in four normal horses and four crib-biters. A technique was developed for measuring total gut transit times (TGTT) by using single-stool analysis of the passage of radio-opaque polyethylene markers. Longer TGTT were recorded in the crib-biters than in the normal horses but the orocaecal transit times did not differ. The crib-biters rested less than the normal horses.  
  Address Department of Clinical Veterinary Science, University of Bristol, Langford  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0042-4900 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:11386445 Approved no  
  Call Number refbase @ user @ Serial 86  
Permanent link to this record
 

 
Author Madigan, J.E.; Bell, S.A. openurl 
  Title Owner survey of headshaking in horses Type Journal Article
  Year (down) 2001 Publication Journal of the American Veterinary Medical Association Abbreviated Journal J Am Vet Med Assoc  
  Volume 219 Issue 3 Pages 334-337  
  Keywords Animals; Anti-Allergic Agents/*therapeutic use; *Behavior, Animal/drug effects; Cyproheptadine/*therapeutic use; Data Collection; Diagnosis, Differential; Female; Horse Diseases/diagnosis/drug therapy/*etiology; Horses; Humans; Male; Questionnaires; Seasons  
  Abstract OBJECTIVE: To determine signalment, history, clinical signs, duration, seasonality, and response to various treatments reported by owners for headshaking in horses. DESIGN: Owner survey. ANIMALS: 109 horses with headshaking. PROCEDURE: Owners of affected horses completed a survey questionnaire. RESULTS: 78 affected horses were geldings, 29 were mares, and 2 were stallions. Mean age of onset was 9 years. Headshaking in 64 horses had a seasonal component, and for most horses, headshaking began in spring and ceased in late summer or fall. The most common clinical signs were shaking the head in a vertical plane, acting like an insect was flying up the nostril, snorting excessively, rubbing the muzzle on objects, having an anxious expression while headshaking, worsening of clinical signs with exposure to sunlight, and improvement of clinical signs at night. Treatment with antihistamines, nonsteroidal anti-inflammatory drugs, corticosteroids, antimicrobials, fly control, chiropractic, and acupuncture had limited success. Sixty-one horses had been treated with cyproheptadine; 43 had moderate to substantial improvement. CONCLUSIONS AND CLINICAL RELEVANCE: Headshaking may have many causes. A large subset of horses have similar clinical signs including shaking the head in a vertical plane, acting as if an insect were flying up the nostrils, and rubbing the muzzle on objects. Seasonality and worsening of clinical signs with exposure to light are also common features of this syndrome. Geldings and Thoroughbreds appear to be overrepresented. Cyproheptadine treatment was beneficial in more than two thirds of treated horses.  
  Address Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis 95616, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0003-1488 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:11497047 Approved no  
  Call Number refbase @ user @ Serial 1916  
Permanent link to this record
 

 
Author Yang, S. openurl 
  Title Melioidosis research in China Type Journal Article
  Year (down) 2000 Publication Acta Tropica Abbreviated Journal Acta Trop  
  Volume 77 Issue 2 Pages 157-165  
  Keywords Animals; Anti-Bacterial Agents/pharmacology; Burkholderia pseudomallei/drug effects/immunology/*pathogenicity; China/epidemiology; Cross Reactions; Glanders/immunology/microbiology; Horses; Humans; *Melioidosis/epidemiology/immunology/microbiology/veterinary; Seroepidemiologic Studies; Virulence  
  Abstract Research on melioidosis and its pathogen has been ongoing in China for more than two decades. It has been demonstrated that the natural foci are located predominantly in Hainan, Guangdong and Guangxi province, where there is a good correlation between soil isolation and the serum prevalence of antibodies to Burkholderia pseudomallei. The cases of melioidosis reported up to now are concentrated in the Hainan and Zhanjiang peninsula. Investigations on serotype, virulence, ecology, antibiotic susceptibility, whole cell analysis by gas chromatography, and genetics have led to a new understanding of the pathology of the disease. Immunological cross reactions between Burkholderia mallei and B. pseudomallei and the difference between melioidosis and glanders in horses is discussed.  
  Address Medical Research Institute, Yan-Ling (510507), Dongguanzhuang Road 91, Guangzhou, People's Republic of China. songyangch@hotmail.com  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0001-706X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:11080506 Approved no  
  Call Number Equine Behaviour @ team @ Serial 2649  
Permanent link to this record
 

 
Author Pierce, M.M.; Nall, B.T. doi  openurl
  Title Coupled kinetic traps in cytochrome c folding: His-heme misligation and proline isomerization Type Journal Article
  Year (down) 2000 Publication Journal of Molecular Biology Abbreviated Journal J Mol Biol  
  Volume 298 Issue 5 Pages 955-969  
  Keywords Amino Acid Sequence; Amino Acid Substitution/genetics; Binding Sites; Cytochrome c Group/*chemistry/genetics/*metabolism; *Cytochromes c; Enzyme Stability/drug effects; Fluorescence; Guanidine/pharmacology; Heme/*metabolism; Histidine/genetics/*metabolism; Hydrogen-Ion Concentration; Isomerism; Kinetics; Models, Molecular; Molecular Sequence Data; Mutation/genetics; Proline/*chemistry/metabolism; Protein Conformation/drug effects; Protein Denaturation/drug effects; *Protein Folding; Protein Renaturation; Saccharomyces cerevisiae/enzymology/genetics; Sequence Alignment; Thermodynamics  
  Abstract The effect of His-heme misligation on folding has been investigated for a triple mutant of yeast iso-2 cytochrome c (N26H,H33N,H39K iso-2). The variant contains a single misligating His residue at position 26, a location at which His residues are found in several cytochrome c homologues, including horse, tuna, and yeast iso-1. The amplitude for fast phase folding exhibits a strong initial pH dependence. For GdnHCl unfolded protein at an initial pH<5, the observed refolding at final pH 6 is dominated by a fast phase (tau(2f)=20 ms, alpha(2f)=90 %) that represents folding in the absence of misligation. For unfolded protein at initial pH 6, folding at final pH 6 occurs in a fast phase of reduced amplitude (alpha(2f) approximately 20 %) but the same rate (tau(2f)=20 ms), and in two slower phases (tau(m)=6-8 seconds, alpha(m) approximately 45 %; and tau(1b)=16-20 seconds, alpha(1b) approximately 35 %). Double jump experiments show that the initial pH dependence of the folding amplitudes results from a slow pH-dependent equilibrium between fast and slow folding species present in the unfolded protein. The slow equilibrium arises from coupling of the His protonation equilibrium to His-heme misligation and proline isomerization. Specifically, Pro25 is predominantly in trans in the unligated low-pH unfolded protein, but is constrained in a non-native cis isomerization state by His26-heme misligation near neutral pH. Refolding from the misligated unfolded form proceeds slowly due to the large energetic barrier required for proline isomerization and displacement of the misligated His26-heme ligand.  
  Address Center for Biomolecular Structure, Department of Biochemistry, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0022-2836 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:10801361 Approved no  
  Call Number refbase @ user @ Serial 3853  
Permanent link to this record
Select All    Deselect All
 |   | 
Details
   print