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Biomedical subjects

W J White

Publications and source records attributed to W J White.

At least 19 recordsLinked to original sources

Hyperkeratosis in athymic nude mice caused by a coryneform bacterium: microbiology, transmission, clinical signs, and pathology.

The purpose of this study was to characterize a spontaneous disease condition causing hyperkeratosis in nude mice and to explore the etiologic role of a particular species of coryneform bacteria in this disease, colloquially known as "scaly skin disease." The study was divided into two parts. In the first phase, a series of inoculation experiments was conducted with a field isolate of the coryneform species used to study the clinical and histopathologic development of the disease syndrome. Athymic nude mice (4 to 5 weeks old) were inoculated on the skin of the back with a suspension of a pure culture of the coryneform bacterium that had been isolated from a field case. The culture was applied with a sterile cotton swab in concentrations varying from 6.1 x 10(4)/ml to 5.0 x 10(7)/ml. All inoculated mice became persistently infected throughout the 33 days of the experiment. Clinically evident hyperkeratosis in inoculated animals developed more frequently in mice housed in a microisolator cage than in a semi-rigid isolator and more frequently in mice inoculated with higher numbers of organisms. In all animals in which hyperkeratosis developed, it was first noted on day 7 after inoculation. The second series of experiments was designed to determine the success of various housing methods in excluding the infection, mechanisms of transmission, susceptibility of other stocks and strains of mice to the organism, and whether the other strains might serve as a source of the organism. Results of the study in various strains indicated that both immunocompetent and immunodeficient mice, whether glabrous or hirsute, could be infected with the organism, but only glabrous animals developed hyperkeratosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Anaesthetic effects of chloral hydrate, pentobarbitone and urethane in adult male rats.

Chloral hydrate, pentobarbitone and urethane were evaluated and compared for onset, duration and depth of anaesthesia, cardiovascular and respiratory effects, nociception and mortality in adult male rats. Chloral hydrate (300 and 400 mg/kg) severely depressed the cardiovascular and respiratory systems. Duration of anaesthesia was linearly related to dose, and anaesthetic depth and analgesia were excellent. Pentobarbital (40 mg/kg) produced a short period of light surgical anaesthesia. Moderate to severe respiratory and cardiovascular depression occurred. Duration of anaesthesia was not related to dose. Urethane (1.2 and 1.5 g/kg) caused moderate cardiovascular depression. In addition, mortality was high at the 1.5 g/kg dose. Duration of anaesthesia was greater than 24 h for most animals. Anaesthesia depth and analgesia were excellent.

Anesthesia↗

Effectiveness of skin absorption of tincture of I in blocking radioiodine from the human thyroid gland.

Topical application of tincture of iodine (I) was found to be effective in blocking the thyroid uptake of orally administered 131I in humans. Abdominal skin application of tincture of I resulted in an approximately 82% reduction in the uptake of 131I by the thyroid gland. The effectiveness varied among individuals and may have depended on the quantity applied and on the application site. In each study group, elevated levels of serum I were observed.

Administration, Cutaneous↗

Use of cage space by guineapigs.

Cage space requirements for laboratory animals have been established by Government Regulation and Recommendations. In order to test the adequacy of these space allocations, the use of cage floor area by breeding groups of guineapigs was studied. A computer-coupled video tracking system capable of imaging in low light intensity as well as total darkness was used to determine the average per cent occupancy by guineapigs in all portions of a cage over 12-h light and dark cycles. Simultaneous time synchronized slow motion video recordings permitted an analysis of activity to be coordinated with cage use data. Results of the study revealed that breeding groups of guineapigs utilize the periphery of the cage almost to the total exclusion of the centre of the cage. Approximately 75-85% of all occupancy in both the day and evening hours occurred in 47% of the cage floor area located along the periphery. Analysis of video recordings revealed that the animals remained active throughout the day and night with no prolonged period of quiescence that could be associated with sleep. Results of this study suggest that while guidelines for housing guineapigs based on area allocation per animal can be formulated and are easy to administer, they cannot be supported by the behavioural characteristics of these animals or careful quantitation of their pattern of cage space utilization.

Animals↗

Three-year analysis of characteristics of learning disabled students in self-contained classrooms and resource rooms.

The present investigation examined the characteristics of school-identified learning disabled students from a large metropolitan school district in Tennessee. While it corroborated several findings of previous surveys of such students, this report also supplemented the literature by comparing the differences within a three-year span of time between school-identified learning disabled students who were assigned to self-contained classrooms and those who were assigned to resource rooms. Among the major findings were the presence of initial differences in IQ between self-contained and resource room students, the absence of differences in initial achievement scores between these two groups, and a decline over time in IQ, arithmetic, and spelling scores for both groups.

Achievement↗

An evaluation of intra-cage ventilation in three animal caging systems.

Although temperature and relative humidity have been quantitated and their effects on research data studied, few studies have measured the air turnover rates at cage level. We evaluated the air distribution and air turnover rates in unoccupied shoe-box mouse cages, filter-top covered cages and shoe-box mouse cages housed in a flexible film isolator by using discontinuous gas chromatography/mass spectrometry and smoke. Results showed that air turnover was most rapid in the unoccupied shoe-box mouse cage and slowest in the filter-top covered cage. Placing mice in the filter-top covered cage did not significantly improve the air turnover rate. Although filter-top covered cages reduce cage-to-cage transmission of disease, the poor airflow observed within these cages could lead to a buildup of gaseous pollutants that may adversely affect the animal's health.

Air Conditioning↗

Cilia-associated respiratory (CAR) bacillus infection of obese mice.

Cilia-associated respiratory (CAR) bacillus was identified in respiratory tract lesions of obese mice dying of chronic respiratory disease. Neither Mycoplasma pulmonis nor pathogenic bacteria were isolated from cultures of the lesions at necropsy, but there was serologic and histologic evidence of respiratory virus infection. Cranial-ventral areas of lung were firm and demarcated from unaffected lung at gross examination, and representative tissue sank in water. Microscopically, there was suppurative bronchopneumonia with extensive peribronchiole lymphocyte and plasma cell proliferation. The affected bronchiole epithelium was covered with a sheet of slightly basophilic, filamentous, gram negative bacteria. Bronchioles with lesser amounts of lymphocyte accumulations contained lesser amounts of filamentous bacteria. Bronchioles without filamentous bacteria lining the respiratory epithelium lacked peribronchiole lymphocyte accumulations. There was a high correlation between CAR bacillus-positive serology and the identification of diagnostic histologic lesions. CAR bacillus was readily stained using immunohistochemical methods, and the ultrastructural features were similar to that described in rat infections.

Animals↗

An evaluation of analgesia associated with the immobility response in laboratory rabbits.

The immobility response (IR) was studied in rabbits to evaluate its analgesic properties and reliability as a method of restraint. The participation of the endogenous opioid system in IR was studied indirectly by evaluating the effects of the narcotic antagonist naloxone on this phenomenon. Twenty-four adult New Zealand White rabbits were subjected to six noxious stimuli while restrained by IR and while restrained under control conditions. Testing on each animal was repeated under both conditions following the administration of naloxone. The noxious stimuli consisted of three levels of electric shock (10 volts, 30 volts, and 50 volts) applied to the shaved forearm, and mechanical pressure applied to the pinna, front toe, and hind toe. Withdrawal and changes in blood pressure, heart rate, and respiration were used as indicators of pain perception. Distress associated with noxious electrical and pressure stimulation was significantly reduced by IR, which suggested that the phenomenon does have a significant analgesic component. However, the rabbits showed wide variability in their susceptibility to IR induction, and even animals which did not withdraw in response to noxious stimulation under IR sometimes exhibited physiological changes suggestive of distress. Therefore, IR should not be considered as a reliable or humane alternative to analgesic/anesthetic drugs for laboratory rabbits. Naloxone had little effect on IR or IR-associated analgesia.

Analgesia↗

Further studies on the catalytic mechanism of human liver alpha-L-fucosidase.

Radiolabeling of human liver alpha-L-fucosidase (alpha-L-fucoside fucohydrolase, EC 3.2.1.51) with [1-3H]conduritol C trans-epoxide revealed that there are four active sites per tetrameric enzyme complex. Solvent isotope effect experiments give evidence for a proton transfer at the rate-limiting step in catalysis. Transglycosylase activity was observed using methanol as an alternative glycone acceptor to produce methyl alpha-L-fucoside, suggesting that alpha-L-fucose is formed when water is the acceptor. Initial burst kinetics experiments suggest that a glycosyl-enzyme intermediate is formed, although the magnitude of the burst is not stoichiometric with the number of active sites. These data, along with previous results, suggest a general acid-general base catalytic mechanism involving double inversion of stereochemistry at C-1 of fucose, as well as the formation of either a covalent glycosyl-enzyme intermediate or a tight ion pair between a charged active-site residue and a hypothetical fucosyl oxocarbonium ion intermediate.

Affinity Labels↗

Anesthesia and surgery of laboratory animals.

This article reviews anesthetics and anesthetic techniques applicable to small laboratory animals. Anesthetic and analgesic dosage tables are presented for each species to guide the practitioner. The actions of the various agents are reviewed in the text, and key references are presented. Surgical considerations are also reviewed.

Anesthesia↗

The effects of pentobarbital, fentanyl-droperidol, ketamine-xylazine and ketamine-diazepam on arterial blood pH, blood gases, mean arterial blood pressure and heart rate in adult male rats.

Although anesthetics are known to cause respiratory and cardiovascular depression in humans, these adverse effects rarely have been investigated in laboratory rodents. This study evaluated the effects of four different injectable drugs, pentobarbital, fentanyl-droperidol (Innovar-Vet), ketamine-xylazine and ketamine-diazepam on the respiratory and cardiovascular systems of rats. Results showed marked acidosis, hypercarbia and hypoxia with high doses of Innovar-Vet, moderate respiratory depression with all dosages of pentobarbital and minimal respiratory depression with ketamine-xylazine and ketamine-diazepam. Innovar-Vet, ketamine-xylazine and pentobarbital caused profound hypotension, particularly at high dosages, while ketamine-diazepam caused the least depression in mean arterial blood pressure of all drugs evaluated. None of the drugs studied produced significant alterations in heart rate. Throughout all dosages investigated, the ketamine-diazepam combination showed the least overall effects on ventilation and perfusion of the four parenteral drug combinations studied.

Analgesics↗

A comparison of pentobarbital, fentanyl-droperidol, ketamine-xylazine and ketamine-diazepam anesthesia in adult male rats.

Proper use of anesthetics is of paramount importance for humane animal care. Current research trends show a greater reliance on rats for laboratory investigations. This study compared several dosages for four different drugs, (pentobarbital, fentanyl-droperidol, ketamine-xylazine and ketamine-diazepam) for use in the laboratory rat. Each drug was evaluated in respect to its onset, duration of effect, recovery, adverse effects and mortality. A quantitative assessment of the depth of anesthesia also was obtained for all dosages of each drug. Results showed that all tested dosages of pentobarbital, ketamine-xylazine and ketamine-diazepam were suitable anesthetics for use in the laboratory rat. Low dosages of fentanyl-droperidol (Innovar-Vet), however, appeared to produce a state known as neuroleptanalgesia as opposed to anesthesia seen with the other agents.

Anesthesia, General↗

The effects of pentobarbital, fentanyl-droperidol, ketamine-xylazine and ketamine-diazepam on noxious stimulus perception in adult male rats.

The increased use of rats for laboratory studies has increased the urgency for a better understanding of their perception of painful or noxious stimuli and the means of obtunding such stimuli. Four different injectable drugs, pentobarbital, fentanyl-droperidol (Innovar-Vet), ketamine-xylazine and ketamine-diazepam, were evaluated in this study. Unlike previous studies in rodents, this study has quantitated noxious stimulus perception following a temporal sequence of observations. Results showed the greatest inhibition of noxious stimulus perception with Innovar-Vet, lesser inhibition with ketamine-xylazine and ketamine-diazepam, and the least obtunding of nociception with pentobarbital. Results of this study also suggested that a spatial orientation, similar to that present in man, exists within the CNS of rats for receipt of noxious stimulation.

Anesthesia↗

The effects of pentobarbital, fentanyl-droperidol, ketamine-xylazine and ketamine-diazepam on core and surface body temperature regulation in adult male rats.

Many commonly used anesthetics cause hypothermia by inhibiting central and peripheral thermoregulatory mechanisms. Although it is probable that a loss of thermal homeostasis contributes directly to the high mortality frequently reported following anesthesia of laboratory rodents, this adverse effect has been investigated rarely in the past. This study compared the effects of three parenteral anesthetics (pentobarbital, ketamine-xylazine and ketamine-diazepam) and a neuroleptanalgesic (fentanyl-droperidol) on core and surface body temperature regulation in rats. Results showed a profound hypothermia with all dosages of pentobarbital, while ketamine-xylazine and ketamine-diazepam caused a dose-dependent depression in core and surface body temperature. All dosages of fentanyl-droperidol (Innovar-Vet) caused minimal depression in thermoregulation, suggesting that it is the drug which requires the least external thermal support. Results of this study also suggested that inability to compensate for heat loss, particularly from the body core, may profoundly influence anesthetic toxicity and the safety of anesthetic procedures.

Analgesics↗

Pharmacokinetics of cefazolin in guinea pigs.

The occurrence of antibiotic-related enterocolitis in guinea pigs restricts the use of many common antibiotics in this species. Cephaloridine, an antibiotic frequently recommended for this species, is no longer available and a substitute has yet to be explored. In this study, the potential therapeutic efficacy of cefazolin, also a first generation cephalosporin, was evaluated in guinea pigs by assessing pharmacokinetics, toxicity and the minimal inhibitory concentration for selected animal pathogens. Pharmacokinetics and toxicity were evaluated in four phases: single intramuscular injections, multiple intramuscular injections over 30 hours, multiple intramuscular injections over 5 days, and serum-protein binding studies. Antibiotic-related enterocolitis and irritation at the injection site occurred following high (100 mg/kg) repeated doses. At all dose levels, blood values exceeded the minimum inhibitory concentration for Bordetella bronchiseptica for only 1 hour postinjection. For Streptococcus and Staphylococcus sp., the drug half-life was 0.5 hours with peak concentrations occurring within 0.25 hours of injection. The volume of distribution of 0.5 l/kg indicated that there was extensive tissue distribution. Serum protein binding was approximately 85%. The short half-life and rapid plasma clearance rate (10.4 ml/min/kg) indicated that cefazolin is eliminated very rapidly from the guinea pig and may be of questionable therapeutic value.

Animals↗

An evaluation of ampicillin pharmacokinetics and toxicity in guinea pigs.

Sodium ampicillin was administered subcutaneously to 350-550 g male Dunkin Hartley guinea pigs at doses of 6, 8 and 10 mg/kg tid for 5 days. Over a period of 12 days, the lowest ampicillin dose appeared to be tolerated well. However, significant body weight reduction and mortality occurred with the two higher dosage regimens. Cecal cultures of dead animals confirmed the presence of Clostridium difficile, an organism associated with antibiotic-induced enterotoxemia. Assay of serum collected from ampicillin-treated animals revealed ampicillin concentrations of approximately 10 micrograms/ml at 5 minutes post-dosing which fell precipitously to less than 0.2 micrograms/ml at 60 minutes. Determination of biliary ampicillin levels during the 60 minutes after administration of a single 10 mg/kg SQ dose revealed concentrations ranging from 18 micrograms/ml to 90 micrograms/ml. Estimates of total urinary ampicillin content after a single 10 mg/kg SQ dose were less than 500 micrograms/animal at 7.5 minutes, but increased to greater than 2000 micrograms/animal at 60 minutes after dosing. Results of this study indicated that due to its short serum half-life, sodium ampicillin probably has little systemic therapeutic efficacy in guinea pigs. Because high concentrations of ampicillin accumulated in the urine and bile, the antibiotic probably would have therapeutic efficacy for urinary and intestinal infections. However, its associated toxicity at large doses probably precludes its use. In view of the rapid clearance of ampicillin in guinea pigs in comparison to other species, the pharmacokinetics of other antibiotics, especially those reported to be less toxic for guinea pigs, should be considered.

Ampicillin↗

Active-site-directed inactivation of human liver alpha-L-fucosidase by conduritol C trans-epoxide.

Conduritol C trans-epoxide was found to inactivate human liver alpha-L-fucosidase (alpha-L-fucoside fucohydrolase, EC 3.2.1.51), exhibiting an apparent dissociation constant of 43 mM. The cis-isomer of the inactivator had no apparent effect on the enzyme's activity. The pH profile for the inactivation yielded two apparent pK values of approx. 3.7 and 6.1 alpha-L-Fucose (a competitive inhibitor) was effective in protecting the enzyme from inactivation. These results are consistent with a requirement for two amino acid side chains at the active site involved in the reaction of the enzyme with conduritol C trans-epoxide.

Binding Sites↗