The value of biomedical research training for veterinary anatomic and clinical pathologists.

Veterinary pathologists traditionally have been actively engaged in research as principal investigators and as collaborators. Pathologists frequently obtain advanced training in research; however, it appears that in the last 10 years there has been a reversal of a previous trend toward increasing numbers of pathologists obtaining PhD degrees. This has arisen despite an established shortage of veterinarians engaged in research. This article evaluates the benefits of research training for individual pathologists, including a wide spectrum of professional opportunities and additional skill development beyond that usually provided by diagnostic pathology training alone. Various training models are discussed, including combined and sequential diagnostic residency and research degree training as well as the nondegree research fellowship programs more commonly pursued in human medicine. Best-practice recommendations for program infrastructure, mentorship, time management, and a team approach to research and research training are advocated to facilitate the development of successful programs and to encourage a continued emphasis on integrated training for pathologists as both clinical diagnosticians and experimentalists. This article is intended to help prospective and active pathology trainees, their mentors, and educational administrators optimize opportunities to ensure the future vitality of veterinary pathologists, and their contributions, in basic and applied research.

Eosinophilic meningoencephalitis due to Angiostrongylus cantonensis as the cause of death in captive non-human primates.

Fatal eosinophilic meningoencephalitis due to Angiostrongylus cantonensis is reported in captive non-human primates. A howler monkey (Alouatta caraya) at the Audubon Park and Zoological Gardens, New Orleans, LA, died 21 days after initial clinical symptoms. A white-handed gibbon (Hylobates lar) died at the Ardastra Gardens and Zoo, Nassau, Bahamas, 17 days after onset of symptoms. Both had access to free-ranging gastropods within the zoos. These are the first reported cases of natural infection by A. cantonensis in non-human primates in the western hemisphere.

A space group assignment of ZrP2O7 obtained by 31P solid state NMR.

2-D 31P dipolar recoupling magic angle spinning NMR has been used to determine the true symmetry of the low temperature structure of ZrP2O7 for the first time.

Silicon-29 diffusion-ordered NMR spectroscopy (DOSY) as a tool for studying aqueous silicates.

The first use of silicon-29 diffusion-ordered NMR spectroscopy (DOSY) is reported, in a study of the speciation of aqueous silicates.

Sulfathiazole polymorphism studied by magic-angle spinning NMR.

The literature on sulfathiazole polymorphs has many confusions and inconsistencies. These are largely resolved by the distinctive appearance of (13)C magic-angle spinning NMR spectra, which immediately show the number of molecules in the crystallographic asymmetric unit. The spectra presented include those of a newly-recognized form. The assignments of the spectra are established and discussed in relation to such factors as electronic structure of the aromatic ring, second-order quadrupolar effects originating from the nitrogen nuclei, and hydrogen bonding. The results are compared to literature information on the crystal structures. When the amino group acts as a hydrogen bond acceptor, there is a shielding effect on C-4 to the extent of ca. 8 ppm (which should be compared to a further shielding by ca. 10 ppm for sulfathiazole sulfate). The fact that the spectrum of form III is similar to the sum of those of forms IV and V is rationalized in relation to the crystal structures. Some surprising variability of spectra with temperature and with specific sample is reported.

Effects of methanol vapor on human neurobehavioral measures.

Methanol could become an important motor fuel. The objective of this exploratory study was to provide preliminary information about whether or not acute exposure to methanol at 250 mg/m3 for 75 minutes would have adverse effects on human neurobehavioral functions important in everyday life. This concentration level was selected because it is at the upper limit of the traffic scenario estimates provided by the U.S. Environmental Protection Agency (EPA)2 (86 to 240 mg/m3), but is below the maximum concentrations for eight-hour average exposures currently recommended by the National Institute of Occupational Safety and Health (NIOSH) and the American Conference of Government and Industrial Hygienists (ACGIH) (260 mg/m3). Although traffic scenario exposure estimates suggest that such high levels of exposure last less than 15 minutes, we used a 75-minute exposure to increase the probability of identifying dependent measures that should be studied in more detail in a future confirmatory study. Twelve healthy young men, each serving as his own control, participated in two sham exposures and two methanol exposures under counterbalanced, double-blind control conditions. Because methanol is present in many foods, and because high preexposure levels of methanol or formate might obscure exposure effects, subjects were required to strictly limit their diets for 12 hours before each experimental session. The following endpoints were examined before, during, and after exposure to methanol and sham vapors: blood and urinary methanol; plasma formate; oral temperature; blood pressure; subjective mood, alertness, fatigue, workload, and symptom scales; spectral analysis of the electroencephalogram; visual- and auditory-event-related potentials; contingent negative variation; respiration; cardiac interbeat interval; Symbol Digit substitution task; three-choice reaction time; Stroop color-word test; simple reaction time; visual function; critical flicker fusion frequency; hand steadiness; visual search task; Gamberale reaction time task; visual tracking task; Sternberg memory task; interval production task; and speeded addition task. Two dual tasks were also included in the task batteries. These endpoints were selected from those indicated in the literature to be sensitive to solvents, and from those that are widely used in other neurobehavioral test batteries to identify the effects of environmental pollutants. Because the number of endpoints examined was large and the number of subjects was small, procedures designed to reduce the number of statistical tests performed were used. Mean methanol concentration in the exposure room during methanol exposures was 249 mg/m3 (SD +/- 7 mg/m3). Exposure produced significant increases in blood and urine methanol concentration. As expected, no changes in plasma formate were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Expression of cyclooxygenase-2 in transitional cell carcinoma of the urinary bladder in dogs.

OBJECTIVE: To evaluate expression of cyclooxygenase (COX)-1 and COX-2 in the urinary bladder epithelium of clinically normal dogs and in transitional cell carcinoma cells of dogs. ANIMALS: 21 dogs with transitional cell carcinoma of the urinary bladder and 8 dogs with clinically normal urinary bladders. PROCEDURE: COX-1 and COX-2 were evaluated by use of isoform-specific antibodies with standard immunohistochemical methods. RESULT: COX-1, but not COX-2, was constitutively expressed in normal urinary bladder epithelium; however, COX-2 was expressed in neoplastic epithelium in primary tumors and in metastatic lesions of all 21 dogs and in new proliferating blood vessels in 3 dogs. Also, COX-1 was expressed in the neoplastic cells. CONCLUSIONS AND CLINICAL RELEVANCE: Lack of expression of COX-2 in normal bladder epithelium and its substantial expression in transitional cell carcinoma cells suggest that this isoform may be involved in tumor cell growth. Inhibition of COX-2 is a likely mechanism of the antineoplastic effects of non steroidal antiinflammatory drugs.

Dental amalgam: success or failure?

A review of recent literature suggests that reasons for amalgam failure can generally be identified and avoided. These include: retentive failure, marginal breakdown, fracture of the tooth or restoration, reasons for sensitivity, poor surface characteristics, and contributions to periodontal disease. Materials themselves are least often the source of problems; rather, most of the failures can be attributed to lack of attention to detail in cavity preparation and handling of the materials.

Retentive pin systems: a laboratory comparison of effectiveness of seating and other characteristics.

An evaluation in vitro of a number of currently available pin systems used for retaining direct restorative materials was made in this study. The criteria used for evaluation of the systems were completeness of pin seating in the prepared channels and overall effectiveness of the design of the shoulder-stop-style pins. There was a wide range of difference in the ability to seat pins completely, and the seating of the shoulder-stops on the dentin floor was quite inconsistent.

Respiratory and pharyngo-esophageal iridovirus infection in a gopher tortoise (Gopherus polyphemus).

A free-living adult male gopher tortoise (Gopherus polyphemus) was found on Sanibel Island, Florida (USA), on 18 February 1992 with signs of upper respiratory disease. On necropsy after euthanasia on 27 February 1992, severe, extensive necrotizing ulcerative tracheitis, multifocal necrotizing pneumonia, and multifocal necrotizing ulcerative pharyngitis and esophagitis were observed. Large ovoid to round intracytoplasmic basophilic inclusions, which appeared to displace the nucleus to the cell periphery, occurred within degenerate and necrotic epithelial cells of the above tissues. On transmission electron microscopy of formalin-fixed trachea and lung, intracytoplasmic viral particles were observed within necrotic cells in the tracheal lumen and epithelial cells of the lung. Most infected cells also had a roughly spherical granular cytoplasmic inclusion that contained clusters of viral particles. Viral particles had an electron dense spherical to icosahedral core surrounded by a less electron dense icosahedral capsid. Mature extracellular virions were surrounded by an envelope and were 150 to 220 nm in diameter. Virions and cytoplasmic inclusions were morphologically similar to those of the Family Iridoviridae.

Toxoplasmosis in Atlantic bottle-nosed dolphins (Tursiops truncatus).

A female Atlantic bottle-nosed dolphin (Tursiops truncatus) and her calf were found beached on Picnic Island in Tampa Bay, Florida, USA. Despite therapy the animals died. Necropsy revealed severe pneumonia and lymphadenopathy in the mother and the calf, gastric ulcers and infection with the stomach digenean Braunina cordiformis in the mother, and a large, pale liver in the calf. Toxoplasma gondii was identified by light and electron microscopy and by immunohistochemistry in tissues of both animals. Toxoplasma gondii was associated with interstitial pneumonia, necrotizing adrenalitis, and cardiac myonecrosis in the mother and with lymphoid necrosis in both dolphins. The source of infection and the relationship to the recent dolphin beachings along the eastern seacoast of North America are unknown. This is the first report of toxoplasmosis in cetaceans.

Chronic upper respiratory tract disease of free-ranging desert tortoises (Xerobates agassizii).

Seventeen desert tortoises, Xerobates agassizii, with upper respiratory tract disease were examined; thirteen were euthanatized for necropsy. Four normal control desert tortoises from a clinically healthy population were similarly evaluated. Hemoglobin and phosphorus values were significantly (P less than or equal to 0.05) lower and serum sodium, urea, SGOT, and cholesterol values were significantly higher in ill tortoises compared to controls. No significant differences in concentrations of serum or liver vitamins A and E were found between the two groups. While no significant differences were found for concentrations of lead, copper, cadmium, and selenium, the livers of ill tortoises had higher concentrations of mercury and iron. Lesions were found consistently in the upper respiratory tract (URT) of ill tortoises. In all ill tortoises dense infiltrates of lymphocytes and histiocytes obscured the mucosal epithelium and underlying glands. The mucosal epithelium was variably dysplastic, hyperplastic, and occasionally ulcerated. Electron microscopic studies revealed small (350 to 900 nm), pleomorphic organisms resembling Mycoplasma sp., in close association with the surface epithelium of the URT of ill tortoises. Pasteurella testudinis was cultured from the nasal cavity of all ill tortoises and one of four control tortoises. A Mycoplasma sp. was cultured from the nasal passageways of four ill tortoises and was ultrastructurally similar to the pleomorphic organism present on the mucosa in tissue section.

Quantitative analysis of flavonol glycosides in Ginkgo biloba: a comparison of two analytical methods.

A comparison of testing methods for constituents of Ginkgo biloba was performed as part of the process for determining which of the many available analytical methods was most appropriate for inclusion in the American Herbal Pharmacopoeia (AHP). Three primary methods were reviewed: those adopted by the European Pharmacopoeia, the National Science Foundation-Institute for Nutraceutical Advancement (NSF-INA) and the United States Pharmacopeia. Methods were compared by evaluating sample preparation and hydrolysis, precision and methods of total flavonol glycoside calculation by two independent laboratories. The AHP adopted the method of NSF-INA for inclusion in the AHP monograph owing to observed superiority of this method in terms of precision, glycoside calculation, ease of sample preparation and chromatographic parameters.

Inhibition of malic enzyme by S-oxalylglutathione, a probable in vivo effector.

Various oxalyl thiol esters (RSCOCOO-), especially S-oxalylglutathione (GS-Ox), were found to be very effective inhibitors of chicken liver malic enzyme. When the conditions are similar to those encountered physiologically [high reduced nicotinamide adenine dinucleotide phosphate (NADPH) concentrations], inhibition is detectable with less than 1 microM concentrations of GS-Ox. The amount of inhibition is not reversed by excess glutathione, thus indicating that it is not due to oxalyl transfer to some enzymic thiol group with release of glutathione. Detailed kinetic studies show that the inhibition by GS-Ox can be treated as a simple reversible binding to the enzyme; the double reciprocal plot patterns indicate that the inhibition is linear noncompetitive (mixed type), vs. both L-malate in the oxidative decarboxylation reaction and pyruvate in the reverse reaction. At pH 7.4 and 25 degrees C in the presence of 100-200 microM NADPH, the Kis and Kii values for GS-Ox are 0.7 and 5 microM, respectively, and are the same for reactions run in either direction. The high specificity for GS-Ox is indicated by the observation that, under similar conditions, the Kis values for S-oxalyl coenzyme A and S-oxalyl-N-acetylcysteamine are 40 and 150 microM, respectively. Such high specificity indicates that the enzyme has evolved a specific binding site for the glutathione part of GS-Ox. The current results, when considered in conjunction with recent evidence that oxalyl thiol esters are present in animal tissues at concentrations up to 50 microM, imply that GS-Ox is an important in vivo regulator of malic enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of 1H-decoupling in two-dimensional multiple-quantum MAS NMR spectroscopy of 23Na in a hydrous layered silicate.

In order to check the efficiency of high-power 1H decoupling when used with the two-dimensional multiple-quantum MAS method recently proposed to obtain isotropic spectra from quadrupolar nuclei, we applied this new technique to 23Na NMR for a hydrous layered silicate compound, makatite, with and without 1H decoupling. A remarkable improvement of the spectral resolution in the isotropic dimension was observed by the decoupling, showing that it is effective in the 2D MQ-MAS method and suggesting that proton decoupling should be generally applied in 23Na experiments concerning these kinds of compound.

The diazo group as an example of an isolated 15N-14N nuclear spin pair: a static and variable spinning frequency investigation.

The 15N-14N heteronuclear spin pair present in the polycrystalline compound 5-methyl-2-diazobenzenesulphonic acid hydrochloride singly labelled with 15N at either the alpha- or the beta-position is investigated by solid-state nuclear magnetic resonance. The 15N spectrum is obtained both under static and spinning conditions. Unusually well resolved fine structure is observed in both cases and, in particular, the static spectra allow a direct and straightforward measurement of the 15N-14N internuclear dipolar coupling in addition to values of the principal components of the shielding tensors for 15N labelling (at either the alpha- or the beta-positions of the diazo moiety) and their orientation relative to a molecular frame. We also present a preliminary theoretical discussion concerning the origin of the observed spinning frequency dependence of the sideband fine structure.