Showing papers by "Edward J. Dick published in 2008"

Barbiturate euthanasia solution-induced tissue artifact in nonhuman primates

Abstract: Background Barbiturate euthanasia solutions are a humane and approved means of euthanasia. Overdosing causes significant tissue damage in a variety of laboratory animals. Methods One hundred seventeen non-human primates (NHP) representing 7 species including 12 fetuses euthanized for humane and research reasons by various vascular routes with Euthasol, Sodium Pentobarbital, Fatal Plus, Beuthanasia D, or Euthanasia 5 were evaluated for euthanasia-induced tissue damage. Lungs and livers were histologically graded for hemolysis, vascular damage, edema, and necrosis. Severity of tissue damage was analyzed for differences on the basis of agent, age, sex, dose, and injection route. Results Severity of tissue damage was directly related to dose and the intracardiac injection route, but did not differ by species, sex, and agent used. Conclusions When the recommended dose of agent was used, tissue damage was generally reduced, minimal, or undetectable. Barbiturate-induced artifacts in NHPs are essentially the same as in other laboratory species.

Nonhuman primates as models for studies of prostate specific antigen and prostatic diseases.

Abstract: BACKGROUND Because prostate specific antigen (PSA) is released at increased levels into the blood early in the development of prostate cancer, benign prostatic hyperplasia (BPH) and prostatitis, it is widely used as a marker for these diseases. However, PSA has clinical limitations as a screen for prostatic diseases due to its low sensitivity and specificity. There is a strong need to better understand the biology of PSA and factors affecting its serum levels. METHODS We evaluated cynomolgus macaques, rhesus macaques, baboons, and marmosets for their suitability as models for the study of PSA biology and prostatic diseases. RESULTS Prostates of several nonhuman primates are anatomically similar to the human counterpart. Anti-human PSA antibody detected PSA antigens in all the Old World monkeys (cynomolgus macaques, rhesus macaques, and baboons) but not in marmosets. Of the Old World monkeys, cynomolgus macaques have the highest serum PSA levels; baboons have the lowest. Serum PSA levels from macaques includes a number of outlier samples with unusually high values. We also report two cases of abnormal pathologies in macaques accompanied by high serum PSA levels. One case consisted of prostatic hyperplasia involving both glandular and basal cells in a cynomolgus macaque and another of glandular hyperplasia and atrophy in a rhesus macaque. The finding that pathological changes in the prostate of macaques may lead to increases in serum PSA is worthy of further exploration. CONCLUSION Cynomolgus macaques and rhesus macaques are promising animal models for PSA biology studies. Prostate 68: 1546–1554, 2008. © 2008 Wiley-Liss, Inc.

Trypanosoma cruzi in non-human primates with a history of stillbirths: a retrospective study (Papio hamadryas spp.) and case report (Macaca fascicularis)

Abstract: Background Congenital transmission of Trypanosoma cruzi has been described in humans and experimental work has been conducted with mice, but not with non-human primates (NHPs). Methods We conducted a retrospective study of female baboons (Papio hamadryas spp.) naturally seropositive or seronegative for T. cruzi with history of fetal loss, and we report a stillbirth in a cynomolgus macaque (Macaca fascicularis) with placental T. cruzi amastigotes. Results There were no differences in menstrual cycle parameters and the number of fetal losses between seropositive and seronegative baboons with history of fetal loss. The amount of parasite DNA detected using quantitative polymerase chain reaction (Q-PCR) in M. fascicularis placenta was within the range detected in infected baboon tissues. Conclusions There is no evidence that chronic maternal T. cruzi infection causes fetal loss in baboons. Q-PCR is a useful diagnostic tool to study archived NHP placentas.

Stillbirths in Macaca fascicularis.

Abstract: Background Stillbirths in non-human primates are a major problem and represent failure of the maternal–fetal–placental unit to maintain normal relationships because of various endogenous, undetermined or environmental factors. Methods Records of 236 stillborns and their dams in a Macaca fascicularis colony during a 7-year period were reviewed retrospectively. Results The 7-year stillbirth incidence was 11.99% (236 stillbirths, 1967 live births). Most (61.02%, n = 144) were of undetermined etiology. Fetal causes included trauma (22.46%, n = 53), fetal pneumonia (0.85%, n = 2) and congenital anomalies (0.42%, n = 1). Maternal causes included dystocia (9.75%, n = 23) and uterine rupture (0.42%, n = 1). Forty-nine placentas were available for histologic evaluation; there was placentitis in five, necrosis in five and placental abruption in two. Most stillbirths occurred close to term. First stillbirths usually occurred in 8- to 12-year-old animals during the first six pregnancies. Conclusions Most stillbirths were of undetermined etiology. Fetal trauma was the most common cause.

The frequency of lymphocytic and reflux esophagitis in non-human primates.

Abstract: We previously reported in humans a novel histologic phenotype of non-gastro-esophageal reflux disease called lymphocytic esophagitis. In this work, the esophagi of 121 non-human primates (103 baboons and 18 macaques) were investigated. 45 baboons (43.7%) and 9 macaques (50%) had lymphocytic esophagitis. The lymphocytic infiltration in the squamous epithelium involved not only papillary but also inter-papillary fields. Microscopic examination around the papillae revealed a mean of 52 intraepithelial lymphocytes (IELs) per high power field. Of the remaining baboons, 29 had reflux esophagitis (GERD). Among them, 25 (24.3%) 2 (1.9%) and 2 (1.9%) had grade1, 2 and 3 esophagitis, respectively. Of the remaining macaques, 4 had GERD: 1 (5.5%) with grade 1 and 3 (16.7%) with grade 2 esophagitis. None of the macaques had grade 3 esophagitis. The IEL population in lymphocytic esophagitis was composed of T cells, a subset of natural killer cells and of helper and inflammatory T cells. This investigation in non-human primates substantiates the identity of lymphocytic esophagitis as a subset of chronic esophagitis, as well as of reflux esophagitis. The antigenic agent(s) responsible for the marked immunological reaction in lymphocytic esophagitis in non-human primates (and in humans) remains unknown.

Characterization of spontaneous mammary gland carcinomas in female baboons

Abstract: Spontaneous mammary gland carcinomas occurred in five baboons during a 13-year period at Southwest Foundation for Biomedical Research. The affected baboons ranged in age from 21 to 33 years. Menopause in the baboon occurs at approximately 26 years of age. All five animals had typical invasive ductal carcinoma. Morphologically, the tumors were characterized by neoplastic cells arranged from pseudopapillary and cribiform to more poorly differentiated solid cellular growth patterns. Additional features included lack of tubule formation (4/5), marked nuclear pleomorphism (5/5), a high mitotic rate (4/5) and tumor necrosis (4/5). Applying a grading system used for breast cancer in women, four tumors were graded as poorly differentiated carcinomas and one was graded as moderately differentiated. Co-existent ductal carcinoma in situ (DCIS) was observed in three of the mammary tumors. Metastases to the regional lymph nodes were confirmed in two animals, both with histological evidence of lymphovascular invasion in the primary tumor. Distant metastases were observed in only one animal. Immunohistochemical staining for human therapeutic markers revealed 2/5 tumors strongly positive for estrogen receptor, 1/5 strongly positive for progesterone receptor and 4/4 negative for HER2 expression. Although the incidence appears to be low, these five cases of mammary carcinoma in female baboons suggest that when present baboon mammary carcinoma is usually of ductal origin and behaves similar to a human breast carcinoma.

Pathology of the male baboon (Papio spp.) urogenital system

Abstract: Background Comprehensive reports on male baboon urogenital pathology are not available. Methods We performed a retrospective study of 2246 male baboon necropsy records over 19 years. Results A total of 289 urogenital lesions were diagnosed in 197 (8.8%) baboons. The most frequently affected organs in decreasing order were kidney, testicle, urinary bladder, penis and prepuce, seminal vesicle, ureter, and prostate. Lesions were rare in the urethra, scrotum, and epididymis. The most common diagnoses in decreasing order were nephritis, urinary bladder cystitis, nephrocalcinosis, pyelonephritis, renal cysts, renal amyloidosis, testicular atrophy, penile/preputial dermatitis, hydronephrosis, orchitis/testicular abscess, glomerulonephritis, renal hemorrhage, hypospadia, nephrosis, renal infarct, hypospermia/aspermia, seminal vesicle mineralization, and hydroureter. We also report six cases of hypospadia, the first report in the baboon. Conclusions The male baboon has a low incidence of urogenital disease and renal disease is the most common malady. The role of herpesvirus papio 2 needs further study.

Incidence of lymphocytic esophagitis in baboons.

Abstract: Background: We previously reported a novel histologic al phenotype of chronic esophagitis, lymphocytic esophagitis, in patients without gastroesophageal reflux. The aim of the present study was to explore the possible occurrence of lymphocytic esophagitis in baboons. Material s and Methods: Filed hematoxylin and eosin (H&E)-stained sections from the esophagi of 103 consecutive baboons were reviewed. Lymphocytic esophagitis is characterized by high numbers of intraepithelial lymphocytes (IELs) gathered mainly around papillary areas and by none to occasional CD15+ intraepithelial granulocytes. Results: Forty-five of the 103 baboons (43.7%) had lymphocytic esophagitis. A mean of 52 IELs/high-power field were found around the papillae. Immunostains showed that the IEL population in lymphocytic esophagitis was composed of T-cells, a subset of natural killer cells and of helper and inflammatory T-cells. Conclusion: Since lymphocytic esophagitis is by far much more frequent in baboons tha n in humans, the baboon emerges as a good animal model to study the etiology of this inflammatory disease in humans. The esophagus in covered by a multilayer of nonkeratinized stratified squamous cells that protects the underlying tissues from noxious agents and irritants contained in passing solids and fluids (1). Low pH gastric juices refluxed into its lumen provide a major insult to the esophageal epithelium. This gastroesophageal reflux (GER) (2), if persistent, may severely alter the homeostasis of the esophageal microenvironment leading to mucosal inflammation followed, in severe cases, by ulceration and the replacement of deeper layers by fibrotic tissue (3). The sequence of these events is known as gastroesophageal reflux disease (GERD) (4).

Myxomatous neoplasms in the perineal region of baboons.

Abstract: Background In baboons, Papio sp. neoplasms tend to affect the hematopoietic system most commonly, with rare documentation of myxomatous neoplasms. In contrast, women can develop myxomatous masses within deep peripelvic tissues with some frequency during their reproductive years. Methods We have identified and examined, retrospectively, myxomatous perineal masses in twelve female baboons within one research facility and compared their histopathologic, immunohistochemical and electron microscopic features to their human variants. Results Our results indicate that these myxomatous neoplasms, in humans and non-human primates, share common features. Conclusion Further research, particularly molecular genetic analysis, may be needed to identify the baboon as a true animal model for myxomatous perineal neoplasms.

The prevalence of colonic amyloidosis in baboons. A 22-year survey at a large primate facility.

Abstract: Background Colonic amyloidosis has been previously reported in animals, however its prevalence rate has not yet been explored. The aim of the present work was to assess the prevalence of colonic amyloidosis at the Southwest National Primate Research Center since 1986. Materials and methods Colonic amyloidosis was sought in autopsy material from baboons collected under the diagnosis of systemic amyloidosis. Results Between 1986 and 2007, a mean of 3315 baboons per year (range 2578-3931) were housed at the Southwest National Primate Research Center. After examination, colonic amyloidosis was detected in 6 (6.8%) of the 88 baboons with systemic amyloidosis, yielding a prevalence rate of 0.27 cases per year since 1986. Colonic amyloid deposits were found in the interstitial aspect of the lamina propria, often replacing normal mucosal crypts of Lieberkuhn. Conclusion It was observed that only 6.8% of animals with systemic amyloidosis examined between 1986 and 2007 developed colonic amyloidosis. The apparent natural resistance to colonic amyloidosis in baboons presenting systemic amyloidosis deserves to be further investigated.

The frequency of lymphocytic gastritis in baboons.

Abstract: Background: In 1985, two independent reports highlighted a novel subtype of chronic inflammation in the gastric mucosa, characterized by the intraepithelial lymphocytic infiltration (ILI) both in the surface and the foveolar epithelium. The disease, subsequently called lymphocytic gastritis (LG) is a rare form of gastritis (0.8%-1.6% of cases), with unclear pathogenesis. More recently, LG was recorded in pigs and in non-human primates. Materials and Methods: The frequency of LG (>25 lymphocytes/100 epithelial cells) was assessed in gastric specimens from 92 consecutive baboons, initially filed under the diagnosis of "gastritis". Results: LG was found in 13 (14%) out of the 92 animals. Helicobacter pylori was not found. Discussion: LG mirrors an immunological phenomenon at the surface-foveolar cell level elicited by an uncertain etiological factor. In similarity to humans with LG, no Helicobacter pylori were found in baboons with LG. The search for the lymphocyte-attracting protein contained in affected cells might bring forward an alternative therapy capable of abrogating the specific surface-foveolar cell- lymphotaxis present in LG. The baboon emerges as a possible animal model to study the agent(s) leading to LG.

Morphological events found at the invading edge of colorectal carcinomas in baboons.

Abstract: Background: Earlier studies at the growing edge of colorectal cancer (CRC) in humans and rats have shown dilated neoplastic glands, some with a thin layer of flattened tumor cells (FTCs), some lacking one or more groups of consecutive lining tumor cells (called glandular pores, GPs). Materials and Methods: The characteristics of the neoplastic glands at the invading edge of CRCs were investigated in 39 baboons. A total of 190 neoplastic glands were studied in the 38 cases of glandular-forming adenocarcinomas. Results: In the studied neoplastic glands FTCs or GPs were recorded in 44.7% (85 glands). FTCs were found in 9.5% (18 glands) and GPs in 35.3% (67 glands). Only 7.9% or 3 out of the 38 animals showed neoplastic glands with GPs in the bulk of the tumor. Conclusion: In similarity to colorectal adenocarcinomas in humans, flattened tumor cells and glandular pores were found at the invading tumor edge of colorectal adenocarcinomas in baboons. A possible mechanism of host invasion is proposed.

The frequency of gastric amyloidosis in baboons. A 22-year survey at a large primate facility.

Abstract: Background: Systemic amyloidosis, caused by abnormal tissue accretion of plasma proteins, affects several organs of the gastrointestinal (GI) tract. Gastric amyloidosis, rare in humans, has only been reported once in animals. Materials and Methods: Gastric amyloidosis was sought for in baboons with systemic amyloidosis. Results: During the past 22 years (between January 1986 and January 2007) a mean of 3,315 baboons/year (range 2,578-3,931) were housed at the Southwest National Primate Research Center. Gastric amyloidosis was found in 9 (10.2%) of the 88 baboons having a diagnosis of systemic amyloidosis. Consequently, the prevalence of gastric amyloidosis occurring since 1986 at this facility was 0.41 baboons/year. Gastric amyloid deposits were found in the interstitial aspect of the lamina propria, replacing normal mucosal structures, in the submucosal stroma along the interface with the muscularis mucosae and in the interstitial tissue of submucosal lymphoid aggregates. In one of the animals, lumps of amyloid deposits with giant cells were found in the gastric mucosa. Conclusion: Baboons with systemic amyloidosis usually show increasing frequency of amyloid deposits in the liver, large intestine, lymph nodes, spleen and the small intestine.We now demonstrate that it may also involve the stomach. Why certain organs of the GI tract in baboons are more susceptible than others to be affected by the process of systemic amyloidosis remains unexplained. The apparent natural resistance of the stomach of baboons to be affected by systemic amyloidosis deserves further investigation. The review of the literature indicates that this is only the second report on gastric amyloidosis in baboons . Amyloidosis is a disease caused by abnormal tissue accretion mostly of insoluble plasma proteins conveyed by fibrillogenesis. The disease can be organ specific. When systemic, it affects several organs such as the heart, liver, spleen, kidneys, lymph nodes, adrenals, thyroid and the gastrointestinal (GI) tract. Amyloidosis affects not only humans but also animals.

The frequency of gastric pyloric cells with glassy cytoplasm in baboons. A comparison with human subjects.

Abstract: Background: Pyloric cells with "glassy" cytoplasm were detected 20 years ago in the human gastric mucosa, and subsequently in the gastric mucosa of two baboons and of transgenic mice. These pyloric cells, called glassy cells (GCs) show a homogeneous, eosinophilic material that pushes the nucleous towards the free border of the cell. Materials and Methods: The frequency of baboons having pyloric glands with GCs was assessed in the stomachs of 92 consecutive animals, dying of non-gastrointestinal disorders. Results: High power examination of the apparently normal gastric mucosa revealed that 10.9% (n=10) of the 92 baboons had GCs. Periodic acid Schiff (PAS) and PAS-diastase stains suggested that the glassy material might be a glycoprotein. Conclusion: The relatively high frequency of GCs in the gastric mucosa of baboons suggests that this animal might be a useful model for investigating the effect of the environment in the development of GCs, as well as ascertaining the true nature of the retained "glassy" material. In 1836 Boyd (1) described the normal structure of the human gastric mucosa. Since then, with the introduction of suitable tissue fixatives, embedding and staining procedures and the improvement of ancillary techniques, such as electron microscopy and immunohistochemistry, many workers have studied the normal histology of that mucosa in more detail (2-8). It is now known that the gastric mucosa operates through two main systems - the exocrine and the endocrine. The specialized exocrine cell system includes three glandular phenotypes, the cardia glands, not recognized by all authors (9), the fundic glands and the pyloric glands. Authors concur that the exocrine glands of the gastric antrum are lined by only one phenotype of pyloric epithelial cell (2-8). These cells have ill-defined borders with a mucus secreting, micro-vacuolated cytoplasm (7, 8). Recently, however, several reports have indicated the presence of other phenotypes of gastric cells in the gastric antrum, namely pyloric cells with cilia (10-11), with large (mucin negative) vacuoles (12), with small (mucin negative) vacuoles (12), with a dense luminal border (12), with eosinophilic granules (13) and with pancreatic features (14). We have also detected another phenotype of gastric cells in humans (13). These cells, which are characterized by a homogeneously eosinophilic cytoplasm with "ground- glass" appearance, are usually found in one gland or in a group of pyloric glands. The "glassy" material pushes the nuclei of the pyloric cells towards the free border of the cells. Because of their appearance, they were called "glassy cells" (GCs). In subsequent studies the frequency of GCs in populations dwelling in disparate geographical regions was investigated (15-19). In a more recent comparative survey of gastrectomies (20) it was found that GCs occurred in 2.1% of the 1,261 gastrectomies reviewed in the Pacific basin, but only in 0.6% of the 1,942 gastrectomies reviewed in the Atlantic basin (p<0.05). Interestingly, the proportion of gastrectomies with GCs was higher in Vancouver Canadians than in New Yorkers and in Chileans than in patients living in Buenos Aires, despite those populations residing at approximately the same geographic latitude, respectively, but in different basins (20). This results suggested that GCs occurred independently of the race of the individuals and that its presence might had been evoked by the dissimilar environmental exposures in the two basins. This suggestion seemed to be validated by the fact that other histological parameters influenced by environmental factors, such as extensive intestinal metaplasia (21) and ciliated metaplasia (22), were also higher in the same

The frequency of histological features mimicking reflux esophagitis: a study in non-human primates.

Abstract: Background: The frequency of histological changes mimicking those described for reflux esophagitis in humans was assessed in a cohort of non-human primates (NHP). Material s and Methods: A total of 121 consecutive esophagi (from 103 baboons and 18 macaques) were classified according to Ismail-Beiji for reflux esophagitis in humans into grade 1, grade 2 and grade 3 esophagitis. Results: Histological features compatible with reflux esophagitis were found in 28.2% of the baboons and in 22.2% of the macaques. Esophagitis grade 1 was more common in baboons (24%) than in macaques (6%), while esophagitis grade 2 was more common in macaques (17%) than in baboons (2%). Conclusion: Although the prevalence of reflux esophagitis in man is at least 2%, only a fraction of patients demonstrate histological features consistent with grades 1, 2 or 3 esophagitis. Hence, the finding that 27% of a cohort of consecutive, unselected NHP had grades 1, 2 or 3 esophagitis at histology is remarkable. The possible causes for the difference between species, such as the oblique position often adopted by NHP during the gastric phase of digestion, the diet, regurgitation and subsequent re-ingestion, as well as the stress of NHP when kept in captivity, are reviewed. A multilayer of non-keratinized stratified squamous cells covers the esophagus. This multilayer protects the underlying tissues from noxious agents and irritants contained in passing solids and fluids (1). Gastric juices of low pH refluxed into its lumen provide a major insult to the esophageal epithelium. The disease resulting from this gastroesophageal reflux (GER) is called gastroesophageal reflux disease (GERD (2)). Spechler (3) define GERD as any symptomatic condition ( e.g. heartburn), anatomic alteration ( e.g. esophagitis), or both that result from the reflux of noxious material from the stomach into the esophagus. The symptoms in GERD are due to mucosal inflammation of the distal esophagus and regurgitation and not to hiatus hernia, as most patients with hiatus hernia are asymptomatic (4).

Eosinophilic bronchitis-like lesion as the cause of death in a Macaca mulatta: a first case report.

Abstract: Background Eosinophilic bronchitis is a recently described, relatively benign condition in humans that is characterized by a corticosteroid-responsive chronic cough and sputum eosinophilia without the abnormalities of airway function seen in asthma The exact cause of this condition is currently unknown, however has been associated with various occupational exposures in humans It has also been reported to progress to irreversible airway obstruction This disease has been reported in dogs and horses, but not in non-human primates Methods Gross examination of an otherwise healthy 13-year-old, colony-born Macaca mulatta, which died of severe non-responsive respiratory distress revealed that the lungs were markedly inflated and moist Results Hematoxylin and eosin-stained sections from the lungs contained widespread accumulation of eosinophils, sloughed epithelial cells, and mucus centered around bronchioles and adjacent airways There was no evidence of mast cell infiltration of peribronchiolar smooth muscle, goblet cell hyperplasia, or basement membrane thickening Conclusions This ruled out recurrent episodes as would be expected in asthma, favoring the diagnosis of an eosinophilic bronchitis-like lesion We report a first case of eosinophilic bronchitis-like features in a M mulatta