Staphylococcal meningoencephalitis, nematodiasis, and typhlocolitis in a squirrel monkey (Saimiri sciureus).

BACKGROUND: Seizures were observed in a 16-year old male Guyanese squirrel monkey with a history of inappetence and weakness. METHODS AND RESULTS: Complete blood count, biochemical profile, and urinalysis indicated systemic disease. Nematode larvae were detected in the feces. Cerebrospinal fluid (CSF) analysis revealed leukocytes and gram-positive cocci. Staphylococcus aureus was isolated from the CSF. Histopathological evaluation revealed systemic lesions with inflammation and nematodes in the small and large intestine. CONCLUSION: This is the first report describing spontaneous staphylococcal CNS infection in a squirrel monkey.

Progressive proliferative and dysplastic typhlocolitis in aging syrian hamsters naturally infected with Helicobacter spp.: a spontaneous model of inflammatory bowel disease.

Helicobacter spp. have been implicated in a variety of gastrointestinal tract diseases, including peptic ulcer disease, gastric cancer, and inflammatory bowel disease (IBD), in humans and animals. Although most models of IBD are experimentally induced, spontaneous or natural models of IBD are rare. Herein, we describe a long-term study of chronic, progressive lesions that develop in the distal portion of the large bowel of unmanipulated Syrian hamsters naturally infected with Helicobacter spp. Twenty-four Syrian hamsters of three age groups (group A, 1 month [n = 4], group B, 7-12 months [n = 12], group C, 18-24 months [n = 12]), underwent complete postmortem examination. Results of microbial isolation and polymerase chain reaction and restriction fragment length polymorphism analyses confirmed the presence of Helicobacter spp. infection in the distal portion of the large bowel of all animals. Additionally, confounding pathogens, such as Clostridium difficile, Lawsonia intracellularis, and Giardia spp. that can cause proliferative enteritis, were absent in the hamsters of this study. Histopathologic scores for inflammation (P < 0.01), hyperplasia (P < 0.01), and dysplasia (P < 0.05) were significantly higher in the ileocecocolic (ICC) junction of animals in group C, relative to group A. Dysplastic lesions of various grades were detected in 5 of 11 hamsters in group C. Interestingly, the segment of the bowel that is usually colonized by Helicobacter spp. in hamsters had the most severe lesions. One hamster of group C developed a malignant fibrous histiocytoma, whereas another hamster developed a round cell sarcoma originating from the ICC junction. Thus, lesions in the distal portion of the large bowel of aging hamsters naturally colonized with Helicobacter spp. warrants developing the hamster as an animal model of IBD and potentially IBD-related cancer.

Global gene expression profiling: a complement to conventional histopathologic analysis of neoplasia.

Transcriptional profiling of entire tumors has yielded considerable insight into the molecular mechanisms of heterogeneous cell populations within different types of neoplasms. The data thus acquired can be further refined by microdissection methods that enable the analyses of subpopulations of neoplastic cells. Separation of the various components of a neoplasm (i.e., stromal cells, inflammatory infiltrates, and blood vessels) has been problematic, primarily because of a paucity of tools for accurate microdissection. The advent of laser capture microdissection combined with powerful tools of linear amplification of RNA and high-throughput microarray-based assays have allowed the transcriptional mapping of intricate and highly complex networks within pure populations of neoplastic cells. With this approach, specific "molecular signatures" can be assigned to tumors of distinct or even similar histomorphology, thereby aiding the desired objective of pattern recognition, tumor classification, and prognostication. This review highlights the potential benefits of global gene expression profiling of tumor cells as a complement to conventional histopathologic analyses.

Gastritis-associated adenocarcinoma and intestinal metaplasia in a Syrian hamster naturally infected with Helicobacter species.

The objective of this study was to evaluate stomachs of 2-year-old Syrian hamsters that were naturally colonized by multiple Helicobacter species including Helicobacter aurati. A previous report on 7- to 12-month-old Syrian hamsters described chronic gastritis and intestinal metaplasia, a putative preneoplastic lesion in the stomach, without cancer. This report describes an invasive adenocarcinoma at the pyloric-duodenal junction in one of nine hamsters at a site of helicobacter-associated inflammation and marked intestinal metaplasia. Ceca of nine of nine animals were culture positive and polymerase chain reaction positive for Helicobacter spp. Furthermore, immunohistochemical analysis of the stomach using a H. pylori polyclonal antibody detected positive-staining bacteria within the pyloric region of three of nine hamsters including the neoplastic glands. However, argyrophilic bacteria were demonstrated only within the stomach of the hamster with gastric adenocarcinoma. This is a first report of gastric adenocarcinoma in helicobacter-infected hamsters. Syrian hamsters appear suitable as potential model for studying development of helicobacter-associated gastric adenocarcinomas.

Immunohistochemical detection of tumor suppressor gene p53 protein in feline injection site-associated sarcomas.

Sarcomas associated with injection sites are a rare but important problem in cats. Immunohistochemical detection of p53 protein may correlate to mutation of the p53 tumor suppressor gene, a gene known to be important in oncogenesis. The expression of nuclear p53 protein in 40 feline injection site-assocated sarcomas was examined by immunohistochemical staining. In 42.5% (17/40), tumor cell nuclei were stained darkly; in 20% (8/40), tumor cell nuclei were stained palely; and in 37.5% (15/40), tumor cell nuclei were unstained. Immunohistochemical detection of p53 protein in a proportion of injection site-associated sarcomas suggests that mutation of the p53 gene may play a role in the pathogenesis of these tumors.

Mutational analysis of tumor suppressor gene p53 in feline vaccine site-associated sarcomas.

OBJECTIVES: To investigate the role of tumor suppressor gene p53 mutation in feline vaccine site-associated sarcoma (VSS) development and to evaluate the relationship between p53 nucleotide sequence and protein expression. SAMPLE POPULATION: Formalin-fixed paraffin-embedded tissues of 8 feline VSS with dark p53 immunostaining (high p53 expression) and 13 feline VSS with faint or no staining (normal p53 expression). PROCEDURE: DNA was extracted from neoplastic and normal tissue from each paraffin block. The following 3 regions of the p53 gene were amplified by polymerase chain reaction: 379 base pair (bp) region of exon 5, intron 5, and exon 6, 108 bp region of exon 7, and 140 bp region of exon 8. Amplified p53 products were sequenced and compared with published feline p53. The p53 mutations identified were correlated with p53 mutations predicted by immunostaining. RESULTS: Neoplastic cells of 5 of 8 (62.5%) VSS that had high p53 expression harbored single missense mutations within the p53 gene regions examined. The p53 gene mutations were not detected in the 13 tumors with normal p53 immunostaining. Nonneoplastic tissues adjacent to all 21 VSS lacked mutations of these p53 gene regions. CONCLUSIONS: The p53 gene mutations were restricted to neoplastic tissue and, therefore, were unlikely to predispose to VSS. However, p53 mutations may have contributed to cancer progression in 5 of the 21 VSS. There was very good (kappa quotient = 0.67 with a confidence limit of 0.3 to 1.0), although not complete, agreement between prediction of mutation by p53 immunostaining and identification of mutations by sequencing of key p53 gene regions.

Differential expression of p16(INK4a) in azoxymethane-induced mouse colon tumorigenesis.

Alterations in the p16(INK4a) gene have been implicated in the pathogenesis of different human cancers and animal tumors. We postulated that alterations in the p16(INK4a) gene may also be involved in mouse colon tumorigenesis induced by the chemical carcinogen azoxymethane (AOM). In the present study, p16(INK4a) deletion status and its expression were examined in an AOM-induced mouse colon tumor model. Polymerase chain reaction-based deletion analysis of p16(INK4a) exon 2 showed no deletions in the colon tumors. The expression and localization of p16(INK4a) and its gene product were examined by reverse transcription-polymerase chain reaction and immunohistochemical analyses, respectively. The p16(INK4a) mRNA levels were low, and in some cases undetectable, in control colon tissue. However, colon tumors exhibited an eightfold increase in p16(INK4a) mRNA level when compared with control colon tissue (P < 0.01). Whereas control colon epithelium was uniformly negative for p16(INK4a) immunoreactivity, p16(INK4a)-immunoreactive cells were markedly increased in preneoplastic lesions and adenomas isolated from AOM-treated mice. To further examine the p16(INK4a) regulatory pathway, the retinoblastoma tumor-suppressor protein (Rb) was also examined immunohistochemically in these tissues. A heterogeneous Rb immunostaining was observed in preneoplastic lesions and adenomas. Immunohistochemical analysis also showed a reciprocal relationship between p16(INK4a) and Rb protein expression. These findings suggest that alterations in the p16(INK4a)/Rb pathway may play an important role in AOM-induced mouse colon tumorigenesis. Mol. Carcinog. 28:139-147, 2000.