CORRELATION OF ARTICULAR CARTILAGE THICKNESS MEASUREMENTS MADE WITH MAGNETIC RESONANCE IMAGING, MAGNETIC RESONANCE ARTHROGRAPHY, AND COMPUTED TOMOGRAPHIC ARTHROGRAPHY WITH GROSS ARTICULAR CARTILAGE THICKNESS IN THE EQUINE METACARPOPHALANGEAL JOINT.

Osteoarthritis of the metacarpophalangeal joint is common cause of lameness in equine athletes, and is hallmarked by articular cartilage damage. An accurate, noninvasive method for measuring cartilage thickness would be beneficial to screen for cartilage injury and allow for prompt initiation of interventional therapy. The objective of this methods comparison study was to compare computed tomographic arthrography (CTA), magnetic resonance imaging (MRI), and magnetic resonance arthrography (MRA) measurements of articular cartilage thickness with gross measurements in the metacarpophalangeal joint of Thoroughbred horses. Fourteen cadaveric, equine thoracic limbs were included. Limbs were excluded from the study if pathology of the metacarpophalangeal articular cartilage was observed with any imaging modality. Articular cartilage thickness was measured in nine regions of the third metacarpal bone and proximal phalanx on sagittal plane MRI sequences. After intra-articular contrast administration, the measurements were repeated on sagittal plane MRA and sagittal CTA reformations. In an effort to increase cartilage conspicuity, the volume of intra-articular contrast was increased from 14.5 ml, to maximal distention for the second set of seven limbs. Mean and standard deviation values were calculated, and linear regression analysis was used to determine correlations between gross and imaging measurements of cartilage thickness. This study failed to identify one imaging test that consistently yielded measurements correlating with gross cartilage thickness. Even with the use of intra-articular contrast, cartilage surfaces were difficult to differentiate in regions where the cartilage surfaces of the proximal phalanx and third metacarpal bone were in close contact with each other.

Mucopolysaccharidosis type VI in a juvenile miniature schnauzer dog with concurrent hypertriglyceridemia, necrotizing pancreatitis, and diabetic ketoacidosis.

A 7-month-old, neutered male miniature schnauzer dog with a history of cryptorchidism and umbilical hernia was referred for diabetic ketoacidosis. Clinical evaluation revealed stunted growth, skeletal abnormalities, hypertriglyceridemia, diabetic ketoacidosis, and acute necrotizing pancreatitis. Further testing was diagnostic for mucopolysaccharidosis type VI causing the stunted growth and skeletal deformities, but no connection between mucopolysaccharidosis type VI, hypertriglyceridemia, and pancreatic diseases was found.

Mucopolysaccharidose de type VI chez un jeune chien Schnauzer miniature atteint d'hypertriglycéridémie, de pancréatite nécrosante et d'acidocétose diabétique concomitantes. Un chien Schnauzer miniature castré âgé de 7 mois avec une anamnèse de cryptorchidie et d'hernie ombilicale a été référé pour une acidocétose diabétique. L'évaluation clinique a révélé une croissance arrêtée, des anomalies squelettiques, l'hypertriglycéridemie, l'acidocétose diabétique et une pancréatite nécrosante aiguë. Des tests supplémentaires ont permis de diagnostiquer une mucopolysaccharidose de type VI causant une croissance arrêtée et des difformités squelettiques, mais aucun lien avec la mucopolysaccharidose de type VI, l'hypertriglycéridémie et les maladies pancréatiques n'a été trouvé.(Traduit par Isabelle Vallières).

The onset of goiter in several species of sharks following the addition of ozone to a touch pool.

This report describes the onset of goiter in several species of shark following the addition of ozone to a touch pool. A detailed description of a female brown-banded bamboo shark (Chiloscyllium punctatum) that was presented with multinodular goiter is provided. Four other brown-banded bamboo sharks and 11 white-spotted bamboo sharks (Chiloscyllium plagiosum) housed in the same system developed clinical disease consistent with goiter, but two zebra bullhead sharks (Heterodontus zebra) did not. Plasma thyroxine (T4) concentration was 4.64 ng/ml before euthanasia, consistent with a diagnosis of hypothyroidism. The sharks had been chronically exposed to mean (+/- standard error) NO3-N concentrations of 35 +/- 5.12 mg/L before ozonation of the system. Ozonation of aquarium water causes a reduction in environmental iodide, which is required for thyroid hormone synthesis. Nitrate is goitrogenic and would further decrease I- absorption by competitive inhibition. Multinodular goiter is consistent with goiter caused by chronic iodide deficiency. Understanding the interaction between water chemistry and goiter development is critical to development of elasmobranch health management systems.

Excision of a congenital laryngeal cyst in a five-month-old dog via a lateral extraluminal approach.

CASE DESCRIPTION: A 5-month-old neutered male Golden Retriever was evaluated because of moderate stridor, exercise intolerance, and dyspnea. The dog had been neutered 3 weeks previously, and the referring veterinarian identified a large fluid-filled swelling on the left lateral aspect of the larynx during anesthetic intubation for that surgery. The referring veterinarian drained fluid from the mass by use of needle centesis via the oral cavity, which resulted in temporary improvement in clinical signs; however, the clinical signs returned soon thereafter. CLINICAL FINDINGS: A large, soft, spherical mass was located between the left arytenoid and thyroid cartilages and axial to the left ceratohyoid bone, thus causing partial obstruction of the rima glottidis. Laryngoscopic examination, computed tomography (CT), and cytologic evaluation of aspirates performed before surgery; examination during surgery; and histologic evaluation of tissues following surgical excision confirmed the diagnosis of a laryngeal cyst. TREATMENT AND OUTCOME: Complete surgical excision was successfully performed via a lateral extraluminal approach to the larynx. One week after surgery, the dog coughed only occasionally. Twelve months after surgery, the owner reported that the dog was clinically normal with no recurrence of clinical signs, and laryngoscopic examination revealed no recurrence of the cyst or other pathological changes in the laryngeal region. CLINICAL RELEVANCE: Congenital laryngeal cysts are rarely reported in domestic animals. The information provided here described the CT appearance of a laryngeal cyst and the use of CT in diagnosis and surgical planning. Congenital laryngeal cysts can be resected via a lateral submucosal approach.

Transmammary infection of free-ranging Florida panther neonates by Alaria marcianae (Trematoda: Diplostomatidae).

Two freshly-dead female Florida panther (FP) neonates, Puma concolor couguar (=Puma concolor coryi), an 11-day-old and a 17-day-old, were collected in the Florida Panther National Wildlife Refuge (26 degrees 14'N, 81 degrees 36'W), Collier County, Florida. The 2 neonates were siblings and had presumably fed only on milk from the dam since birth. A 12-day-old female FP neonate was collected in the Big Cypress National Preserve (26 degrees 05'N, 81 degrees 15'W), Collier County, Florida and had also fed only on milk from the dam since birth. Milk was the only food item found in the gastrointestinal tract of these neonates. Mesocercariae and diplostomula of Alaria marcianae were collected from the lungs of the 3 neonates, indicating a transmammary route of infection. No mesocercariae, diplostomula, or mature A. marcianae were seen in the stomach or small intestine. The probable paratenic host for the A. marcianae infection in the adult Florida panther is the raccoon (Procyon lotor).

Exotic Perkinsus sp. protozoa in an imported Vietnamese ornamental clam (Tridacna crocea) maintained in a home aquarium.

An adult, hermaphroditic Tridacna crocea ornamental clam imported from Vietnam into the USA became terminally moribund with sloughed byssal tissue and incomplete extension of the poorly responsive mantle and was necropsied. Necropsy findings included emaciation, visceral mass edema, and rare multifocal, 1-mm diameter, off-white to light tan gill nodules. Histopathology revealed marked inflammation and necrosis within the visceral mass and gills, with interstitial edema and atrophy of glandular, gonadal, and muscular tissues. Inflamed tissues contained large numbers of 10-15 microm extracellular, spherical organisms with a signet-ring morphology consistent with Perkinsus spp. trophozoites. The organisms often formed clusters of two to four cells and were surrounded by a host reaction consisting of a 1-4 microm rim of amorphous eosinophilic material and two to four host hemocytes. Incubation of infected host tissues in alternative Ray's fluid thioglycollate medium (ARFTM) confirmed the presence of Perkinsus sp. hypnospores that stained blue-black with Lugol's iodine. Polymerase chain reaction assays with sequencing of products revealed a high level of nucleotide similarity, but no exact match, to known P. olseni isolates. Perkinsus sp. organisms, including P. olseni and P. marinus, which are internationally reportable, are highly pathogenic destructive protozoa capable of disrupting ecosystems populated by naïve mollusks within the USA and negatively affecting both domestic and international shellfish industries. This is the first report of an exotic Perkinsus sp. pathogen in an imported ornamental clam maintained long term in a home aquarium. However, ongoing research indicates that T. crocea from Vietnam are commonly infected by such organisms. Veterinarians, aquarium facility mangers, and veterinary clients with hobby aquariums should use appropriate caution and responsible disposal practices for clam carcasses and for water in which imported ornamental clams have been housed. Such practices will reduce the possibility of dispersing viable, exotic Perkinsus sp. organisms into domestic waters.

Perkinsus olseni detected in Vietnamese aquacultured reef clams Tridacna crocea imported to the USA, following a mortality event.

Morbidity and mortality were observed in a group of 30 reef clams Tridacna crocea that were imported to Florida, USA, from a Vietnamese culture facility and held in research facility aquaria. Clinical signs included an incompletely extended mantle, slow mantle responses to stimuli, and sloughing of byssal tissue beginning 2 to 5 d prior to death. Necropsy findings included emaciation, visceral mass edema, and rare multifocal 1 mm off-white to light-tan gill nodules. Histopathology revealed marked inflammation and necrosis within the visceral mass and gills, with interstitial edema and atrophy of glandular, gonadal, and muscular tissues. Inflamed tissues contained large numbers of 10 to 15 microm extracellular round organisms consistent with Perkinsus sp. trophozoites. The organisms often formed clusters of 1 to 4 cells and were surrounded by a 1 to 3 microm rim of eosinophilic material variably forming a radiating corona pattern and by 3 to 4 host hemocytes with dense round nuclei. Polymerase chain reaction assays indicated the presence of Perkinsus sp. DNA in these animals, and species-specific assays indicated the presence of P. olseni, and possibly other Perkinsus spp., but not P. marinus. Identification of Perkinsus spp. other than P. marinus in T. crocea imported from Vietnam confirms that importation of untested and unquarantined ornamental reef clams has possibly allowed incursion of P. olseni into the USA.

A tough biodegradable elastomer.

Biodegradable polymers have significant potential in biotechnology and bioengineering. However, for some applications, they are limited by their inferior mechanical properties and unsatisfactory compatibility with cells and tissues. A strong, biodegradable, and biocompatible elastomer could be useful for fields such as tissue engineering, drug delivery, and in vivo sensing. We designed, synthesized, and characterized a tough biodegradable elastomer from biocompatible monomers. This elastomer forms a covalently crosslinked, three-dimensional network of random coils with hydroxyl groups attached to its backbone. Both crosslinking and the hydrogen-bonding interactions between the hydroxyl groups likely contribute to the unique properties of the elastomer. In vitro and in vivo studies show that the polymer has good biocompatibility. Polymer implants under animal skin are absorbed completely within 60 days with restoration of the implantation sites to their normal architecture.

Germ-line p53-targeted disruption inhibits helicobacter-induced premalignant lesions and invasive gastric carcinoma through down-regulation of Th1 proinflammatory responses.

p53 is a tumor suppressor gene that is mutated in many human malignancies, including gastric cancer. It remains unclear why patients with germ-line p53 mutations (i.e., Li-Fraumeni syndrome) are not at increased risk for gastric adenocarcinoma, despite the fact that they show a high rate of many other tumors. Furthermore, the precise relationship between germ-line p53 mutations and the response to chronic bacterial infections (such as Helicobacter spp.) has not been investigated. To assess the role of germ-line p53 deletions in modulating the progression to gastric cancer, p53(+/-) and wild-type (WT) C57BL/6 mice were infected with H. felis. The gastric pathology and immune response in these two groups of mice were analyzed for up to 15 months postinfection. The gastric fundus and antrum were evaluated independently using a 0-4 scale to score inflammation, parietal and chief cell loss, mucus metaplasia, and helicobacter colonization. Nonparametric statistical analysis was performed to determine the effects of p53(+/-), infection status, and postinoculation (p.i.) time on inflammation, preneoplastic changes, invasive lesions, and helicobacter colonization. mRNA expression for gammaIFN, interleukin (IL)-1, IL-10, and IL-4 was quantified by PCR. Sera were also evaluated for H. felis antibody by ELISA. Antral inflammation increased significantly with time in infected mice. There was a significant, protective effect on the development of preneoplastic fundic lesions and invasive carcinoma attributable to the deletion of one p53 allele (P < 0.05). Submucosal invasive foci were observed in 9 of 11 WT-infected mice ranging from 13 to 15 months p.i.; invasion of adjacent submucosal blood vessels by glandular epithelia also was present in 5 of these mice. None of these lesions were observed in 33 p53(+/-) mice, infected or not, at any time p.i. p53(+/-) mice had significantly higher helicobacter colonization consistent with a Th2 host response. In sera from WT mice, IgG2a, considered a proinflammatory Th1 response, continued to rise throughout the 15-month study (P < 0.004). In contrast, IgG2a levels of the p53(+/-) mice were 50-60% lower than those of the WT mice at each time point (P range, <0.012 to 0.002) and did not progress in magnitude between 12 and 15 months of chronic H. felis infection (P = 0.167). mRNA levels for gammaIFN and IL-1 were significantly up-regulated in WT mice infected with H. felis (P < 0.05) but were slightly elevated or were at background levels in p53(+/-) mice. IL-10 and IL-4 mRNA expression was not significantly different from control samples. Our results support the hypothesis that germ-line deletion of one p53 allele results in a down-regulated Th1 response to gastric helicobacter infection, possibly because of T-cell senescence, which may indirectly protect against the development of gastric cancer and other epithelial-derived neoplasms associated with chronic inflammation.

Characterization of (2R, 3S)-2-([[4-(2-butynyloxy)phenyl]sulfonyl]amino)-N,3-dihydroxybutanamide, a potent and selective inhibitor of TNF-alpha converting enzyme.

TNF-alpha converting enzyme (TACE) is a validated therapeutic target for the development of oral tumor necrosis factor-alpha (TNF-alpha) inhibitors. Here we report the pre-clinical results and characterization of a selective and potent TACE inhibitor, (2R, 3S)-2-([[4-(2-butynyloxy)phenyl]sulfonyl]amino)-N,3-dihydroxybutanamide (TMI-2), in various in vitro and in vivo assays. TMI-2 is a potent TACE inhibitor in an enzymatic FRET assay (IC50=2 nM). It is more than 250-fold selective over MMP-1, -7, -9, -14, and ADAM-10 in vitro. In cell-based assays and human whole blood, TMI-2 inhibits lipopolysaccharide (LPS)-induced TNF secretion with IC50s<1 uM. Importantly, TMI-2 inhibits the spontaneous release of TNF-alpha in human synovium tissue explants of rheumatoid arthritis patients with an IC50 of 0.8 microM. In vivo, TMI-2 potently inhibits LPS-induced TNF-alpha production in mice (ED50=3 mg/kg). In the adjuvant-induced arthritis (AIA) model in rats, treatment with TMI-2 at 30 mg/kg and 100 mg/kg p.o. b.i.d. was highly effective in reducing joint arthritis scores. In a semi-therapeutic collagen-induced arthritis (CIA) model in mice, TMI-2 is highly effective in reducing disease severity scores after oral treatment at 100 mg/kg twice per day. In summary, TMI-2 is a potent and selective TACE inhibitor that inhibits TNF-alpha production and reduces the arthritis scores in pre-clinical models. TMI-2 represents a novel class of TACE inhibitors that may be effective and beneficial in the treatment of rheumatoid arthritis as well as other TNF-mediated inflammatory autoimmune diseases.

High mortality due to Tetrahymena sp. infection in laboratory-maintained zebrafish (Brachydanio rerio).

A large colony of laboratory zebrafish (Brachydanio rerio) used in the study of early vertebrate embryogenesis began experiencing acute, unexplained mortality that approached 100% among approximately 30-day-old resident fry. The initial differential diagnosis included ammonia, nitrite, or chlorine toxicosis, as well as iatrogenically induced toxicosis associated with improper sanitation procedures of laboratory equipment. Necropsy of dead and moribund fry prior to fixation revealed swarms of ovoid-shaped, motile, ciliated protozoa with a "spiraling football" motion. Wet mount preparations of various water samples also contained high numbers of similar protozoa. Histologic examination of affected fry revealed numerous, periodic acid-Schiff-positive forms within the body coelom, and epithelial and muscle tissues. The protozoa were consistent morphologically with members of the genus Tetrahymena, which is usually a free-living, nonpathogenic ciliated protozoa in fresh and saltwater environments. Relevant disease associated with Tetrahymena spp. in viviparous fish has been reported as a result of concurrent disease, immunosuppression, or poor water quality conditions. To the authors' knowledge, this is the first report of an epizootic involving laboratory maintained zebrafish, and the diagnostic course and therapeutic interventions undertaken to alleviate Tetrahymena species-associated clinical disease.

Syrian hamsters (Mesocricetus auratus) with simultaneous intestinal Giardia sp., Spironucleus sp., and trichomonad infections.

A commercial facility producing hamsters with a history of infection by dwarf tapeworm (Hymenolepis nana) submitted 15 animals for necropsy and postmortem parasitological and microscopic examination. No tapeworms were detected grossly or microscopically. Fecal examination including gastrointestinal mucosal smears demonstrated mixed intestinal bacteria and low numbers of Giardia sp. Histologic examination of small intestine demonstrated filling of the small intestinal crypts by large numbers of 7-9 µm × 3 µm, rod to crescent or teardrop-shaped flagellates consistent with Spironucleus sp. These organisms had two 1-µm, basophilic, oval nuclei and multiple superficial flagella-like structures. Much larger 10-15 µm × 8-10 µm, oval to pear-shaped organisms were also present in lower numbers and usually located with the crypts. These larger flagellates had multiple flagella and a basophilic rod-shaped nucleus. The larger flagellates included Giardia sp., which had an intimate interface with the surface of the mucosal epithelium, bilaterally symmetry, and binucleation. Lower numbers of trichomonads were also present and were distinguished by an undulating surface membrane and a single nucleus. The mucosa was hyperplastic and moderately inflamed. Although the tapeworm infection was resolved, diagnosis of multiple intestinal flagellates by fecal examination is complicated by the varying sensitivity and diagnostic accuracy of different types of fecal analysis for different flagellate types. Key differences in the morphology and location of the different types of flagellates as observed by histology of intestinal tissues provide important additional diagnostic information to distinguish trichomonads, Spironucleus sp., and Giardia sp.

Report of wood decay fungus Inonotus tropicalis (phylum Basidiomycota) from a dog with a granulomatous mediastinal mass.

A 75.9-kg, 3.5-year-old male Irish Wolfhound dog with a 2-3-week history of gagging and eating difficulties was referred to the University of Florida Veterinary Medical Hospital (Gainesville, Florida) for evaluation of a large cranial mediastinal mass suspected to be a thymoma or lymphosarcoma. The patient had 4 months of nearly 10 kg progressive weight loss with severe flank sensitivity and radiographically apparent lumbar vertebral changes interpreted as discospondylitis. Lab work revealed hyperglobulinemia, mild proteinuria, normal T4, negative Brucella canis titer, and negative blood and urine bacterial cultures. A thoracotomy revealed a nonresectable, destructive, space-occupying mediastinal mass resulting in euthanasia without surgical recovery. Biopsies from the mass were collected during surgery for histology. Microscopic examination revealed extensive granulomatous cellulitis and lymphadenitis characterized by central cavitated necrotic areas containing debris and degenerate neutrophils, intermediate zones of fibrovascular proliferation with marked mixed inflammation, peripheral fibrosis, frequent multinucleated macrophages, and scattered mineralization. The necrotic material contained dense mats of 2 µm wide by 8-15 µm long fungal hyphae with parallel walls, acute angle branching, frequent septae, and occasional bulb-like dilations. DNA sequencing and phylogenetic analysis of the internal transcribed spacer region confirmed the presence of a fungus in the Inonotus tropicalis group. Inonotus tropicalis is primarily a wood decay fungus that is found on dead wood from angiosperms in tropical and subtropical habitats. Isolates of the I. tropicalis group have been detected a few times from immunosuppressed human beings with X-linked granulomatous disease.

Gastrointestinal small-cell lymphoma with gall bladder involvement in a cat.

A 13-year-old female spayed domestic shorthair cat presented for investigation of decreased appetite and increased serum liver enzyme concentrations. An abdominal ultrasound revealed multiple sessile hyperechoic structures along the luminal aspect of the gall bladder wall and a mildly enlarged liver with hyperechoic nodules. Cholecystectomy was performed and biopsies were obtained by laparotomy. Histopathologic examination with immunohistochemistry was consistent with a diagnosis of small-cell lymphoma of T cells within the gall bladder, liver and small intestine. Clonality testing confirmed the diagnosis. The cat remains clinically stable 23 months after institution of treatment with prednisolone, chlorambucil and ursodeoxycholic acid. This is the first report of small-cell lymphoma in the gall bladder of a cat.

Allele- and tir-independent functions of intimin in diverse animal infection models.

Upon binding to intestinal epithelial cells, enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli (EPEC), and Citrobacter rodentium trigger formation of actin pedestals beneath bound bacteria. Pedestal formation has been associated with enhanced colonization, and requires intimin, an adhesin that binds to the bacterial effector translocated intimin receptor (Tir), which is translocated to the host cell membrane and promotes bacterial adherence and pedestal formation. Intimin has been suggested to also promote cell adhesion by binding one or more host receptors, and allelic differences in intimin have been associated with differences in tissue and host specificity. We assessed the function of EHEC, EPEC, or C. rodentium intimin, or a set of intimin derivatives with varying Tir-binding abilities in animal models of infection. We found that EPEC and EHEC intimin were functionally indistinguishable during infection of gnotobiotic piglets by EHEC, and that EPEC, EHEC, and C. rodentium intimin were functionally indistinguishable during infection of C57BL/6 mice by C. rodentium. A derivative of EHEC intimin that bound Tir but did not promote robust pedestal formation on cultured cells was unable to promote C. rodentium colonization of conventional mice, indicating that the ability to trigger actin assembly, not simply to bind Tir, is required for intimin-mediated intestinal colonization. Interestingly, streptomycin pre-treatment of mice eliminated the requirement for Tir but not intimin during colonization, and intimin derivatives that were defective in Tir-binding still promoted colonization of these mice. These results indicate that EPEC, EHEC, and C. rodentium intimin are functionally interchangeable during infection of gnotobiotic piglets or conventional C57BL/6 mice, and that whereas the ability to trigger Tir-mediated pedestal formation is essential for colonization of conventional mice, intimin provides a Tir-independent activity during colonization of streptomycin pre-treated mice.

Nitrate-induced goiter in captive whitespotted bamboo sharks Chilosryllium plagiosum.

Elasmobranch susceptibility to goiter formation in captive environments has been well documented. Until recently, most public aquariums operated under the belief that the etiology of goiter in elasmobranchs was nutritional and specifically caused by insufficient dietary iodine. Recent studies have demonstrated that high environmental nitrate (NO3-N) inhibits the ability of the thyroid gland to utilize available iodide, resulting in thyroid gland overstimulation by thyroid stimulating hormone and ultimately leading to the development of goiter. The objective of this study was to evaluate the effects of high environmental nitrate concentrations on thyroid function in juvenile whitespotted bamboo sharks Chiloscyllium plagiosum. In July 2008, five juveniles (80-150 g) were exposed to a low-nitrate environment (NO3-N concentration < 1 mg/L of water) and five were exposed to an elevated-nitrate environment (NO3-N = 70 mg/L) for 29 d in a flow-through natural seawater system. Nitrate exposure did not affect growth rates (e.g., weight, length, and condition factor) and did not alter free plasma thyroxine concentrations during the 29-d experimental period. However, histological examination of thyroid glands from sharks exposed to elevated nitrate revealed the development of diffuse hyperplastic goiter. With increasing restrictions on water use, most modern aquaria operate as recirculating systems, which results in higher and more chronic nitrate exposure for captive animals. Goiter is one of the most common health problems in captive elasmobranchs, and this study suggests that nitrate exposure is an important factor in the etiology of this disease.

B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model.

We report the development of a mouse B cell-depleting immunoconjugate (anti-CD22 monoclonal antibody [mAb] conjugated to calicheamicin) and its in vivo use to characterize the kinetics of CD22+ B-cell depletion and reconstitution in murine primary and secondary lymphoid tissues. The effect of B-cell depletion was further studied in a murine collagen-induced arthritis (CIA) model and a respiratory syncytial virus (RSV) vaccination model. Our results show that (1) the immunoconjugate has B-cell-specific in vitro and in vivo cytotoxicity; (2) B-cell reconstitution starts in the bone marrow and spleen around day 30 after depletion and is completed in all tissues tested by day 50; (3) B-cell depletion inhibits the development of clinical and histologic arthritis in the CIA model; (4) depletion of type II collagen antibody levels is not necessary for clinical and histologic prevention of CIA; and (5) B-cell depletion does not adversely affect memory antibody responses after challenge nor clearance of infectious virus from lungs in the RSV vaccination model. These results demonstrate for the first time that only B-cell reduction but not type II collagen antibody levels correlate with the prevention of arthritis and represent key insights into the role of CD22-targeted B-cell depletion in mouse autoimmunity and vaccination models.

Helicobacter pylori infection and high dietary salt independently induce atrophic gastritis and intestinal metaplasia in commercially available outbred Mongolian gerbils.

Risk factors for development of gastric adenocarcinoma include high dietary salt and Helicobacter pylori infection. Few animal models exist for the laboratory investigation of these factors. We examined gastric pathology resulting from H. pylori infection and high dietary salt as independent variables in commercially available, outbred Mongolian gerbils. Gastric adenocarcinoma and its precursor lesion, intestinal metaplasia, have been previously reported in inbred Mongolian gerbils (MGS/Sea) infected either with clinical isolates of H. pylori or with the strain ATCC 43504. In contrast, we utilized outbred gerbils [Crl:(MON)] infected with the Sydney strain of H. pylori. After 37 weeks, five of five infected animals had atrophic gastritis and intestinal metaplasia. These lesions were similar in description and time of appearance to the lesions reported in inbred gerbils. Atrophic gastritis and intestinal metaplasia also developed in six of six uninfected, outbred gerbils fed a 2.5% salt diet for 56 weeks. In contrast to the H. pylori-infected animals, these lesions were present without concurrent gastric inflammation. The outbred Mongolian gerbil therefore provides an excellent animal model for the study of several gastric cancer risk factors.

Sexual dysfunction and sudden death in epileptic male EL mice: inheritance and prevention with the ketogenic diet.

PURPOSE: The EL mouse is an animal model for multifactorial idiopathic epilepsy. Although EL mice have been studied extensively for >45 years, the etiology of male sudden death and its relation to seizures have not been defined. Here we investigated the cause of EL male sudden death and its relation to epilepsy. METHODS: For histopathologic analysis, the terminally ill EL mice (n = 15) were killed, and the tissues were fixed. Blood chemical composition was compared between the terminally ill EL (n = 9) and the healthy age-matched EL (n = 17) and DDY (n = 11) males. To determine the effect of the ketogenic diet (KD) on sudden male death, young male EL mice (P30) were randomly separated into two groups that were fed ad libitum with either Agway lab chow (control n = 38) or with the KD (treated, n = 39) for 5 months. The genetic predisposition to sudden death was analyzed in the backcross generation (n = 106) of a cross between EL and the nonepileptic ABP strains. RESULTS: Sudden death coincided with the onset of seizures (70-80 days) and affected 94% of male EL mice by age 300 days. Urethral plugs were observed histologically in 13 of 15 longitudinally sectioned penises. Concentrations of blood urea nitrogen, creatinine, phosphorus, and calcium in the terminally ill mice were significantly elevated when compared with those of healthy animals. None of the mice treated with the KD experienced sudden death, whereas 15 (39%) of the untreated control mice died by age 5 months. The sudden death in male EL mice was inherited as an autosomal recessive sex-limited lethal trait. CONCLUSIONS: The cause of sudden death in male EL mice arises from abnormal ejaculation, which produces a urethral plug with consequent urinary retention and acute severe uremia. The coincident onset of seizures and sudden death in EL males suggests that a sexual dysfunction is associated with epilepsy in this model.