Phylogenetic analysis of Histoplasma capsulatum var duboisii in baboons from archived formalin-fixed, paraffin embedded tissues.

Histoplasma capsulatum var. duboisii (Hcd) infections have been well documented to cause chronic granulomatous disease, mainly involving the skin of baboons and humans in African countries primarily. This retrospective study classified the subspecies of Histoplasma and developed a phylogenetic tree utilizing DNA sequences extracted from formalin-fixed, paraffin embedded (FFPE) tissues from 9 baboons from a research colony in Texas histologically diagnosed with Hcd. Based on sequence analysis of ITS-2, Tub-1, and ARF, Hcd isolated from the archived samples closely aligns with the African clade and has 88% sequence homology with a sample isolated from an individual in Senegal.

Pancreatic neuroendocrine tumors in twelve baboons (Papio spp.).

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are rare in nonhuman primates and in humans. METHODS: Twenty-one PNETs from twelve female baboons (Papio spp.) from the Southwest National Primate Research Center were evaluated using histopathology and immunohistochemistry. RESULTS: Histologically, all tumors were benign and had neuroendocrine packeting. Immunohistochemical staining for synaptophysin and chromogranin was positive in all tumors evaluated (17/17). Insulin was positive in 16 of 21 tumors. Somatostatin was positive in 9 of 20 tumors. Multifocal staining for glucagon and pancreatic polypeptide was evident in a minority of tumors (6/20 and 2/17, respectively). Gastrin and vasoactive intestinal peptide were negative in all tumors evaluated. Nine tumors expressed more than one hormone marker. CONCLUSIONS: This is the first detailed pathologic study of pancreatic endocrine tumors in the baboon. The findings suggest that these tumors are generally benign and have similar morphologic and immunohistochemical features as those described in people, including the ability to express multiple hormones.

Spontaneous Reproductive Tract Lesions in Aged Captive Chimpanzees.

Chimpanzees (Pan troglodytes) have served as an important model for studies of reproductive diseases and aging-related disorders in humans. However, limited information is available about spontaneously occurring reproductive tract lesions in aging chimpanzees. In this article, the authors present histopathologic descriptions of lesions identified in the reproductive tract, including the mammary gland, of 33 female and 34 male aged chimpanzees from 3 captive populations. The most common findings in female chimpanzees were ovarian atrophy, uterine leiomyoma, adenomyosis, and endometrial atrophy. The most common findings in male chimpanzees were seminiferous tubule degeneration and lymphocytic infiltrates in the prostate gland. Other less common lesions included an ovarian granulosa cell tumor, cystic endometrial hyperplasia, an endometrial polyp, uterine artery hypertrophy and mineralization, atrophic vaginitis, mammary gland inflammation, prostatic epithelial hyperplasia, dilated seminal vesicles, a sperm granuloma, and lymphocytic infiltrates in the epididymis. The findings in this study closely mimic changes described in the reproductive tract of aged humans, with the exception of a lack of malignant changes observed in the mammary gland and prostate gland.

Pleuro-pulmonary endometriosis in baboons (Papio spp.): insights into pathogenesis.

BACKGROUND: Human pleuro-pulmonary endometriosis (PPE) is rare. Recently, we identified several cases of abdominal endometriosis in baboons that developed PPE. MATERIALS AND METHODS: Ten cases of PPE and four of intra-abdominal endometriosis (three simultaneous) were identified at necropsy in baboons (Papio spp.) found dead due to natural causes. The endometriotic lesions were evaluated using immunohistochemistry. RESULTS: The stromal (CD10+) and epithelial cells in intra-abdominal cases were estrogen and progesterone receptor (ER/PR) positive and thyroid transcription factor 1 (TTF-1) negative similar to that seen in humans. In contrast, the PPE cases displayed TTF-1-positive epithelium lining the cystic spaces, while the stroma was ER/PR positive similar to that in abdominal endometriosis. Both lymph nodes and spindle cell rests in lung interstitium contained ER/PR-positive stromal cells. CONCLUSIONS: The lung lesions were different from the abdominal lesions in having a TTF-1-positive lining epithelium. The deep pulmonary interstitial and lymph node endometrial stromal rests probably arrive via lymphatic route. The endometrial stroma is the driving force in PPE upon which the lung-specific epithelium condenses and may require a novel approach to therapy.

Intracranial meningioma in a baboon (Papio spp.).

Meningioma is the most common intracranial non-glial tumour of cats, dogs and man. Few spontaneously arising brain tumours have been reported in non-human primates. This report describes a meningioma in a captive baboon. Clinical signs exhibited by the animal included head pressing, visual impairment and vestibular disease. The tumour arose from the ventral aspect of the cranial cavity and compressed the overlying left side of the cerebellum and brainstem. Microscopically, the mass was characterized by pleomorphic spindle-shaped to polygonal cells arranged in sheaths, vague whorls and occasional papillary structures on vascular cores. Nuclear cytoplasmic invagination, syncytial-like cells and areas of mineralization were also evident. Immunohistochemically, the neoplastic cells expressed vimentin and S-100 protein, but not pancytokeratin, glial fibrillary acidic protein or epithelial membrane antigen. The features of this tumour are similar to those of meningiomas in other species.

Spontaneous gallbladder pathology in baboons.

BACKGROUND: Gallbladder pathology (GBP) is a relatively uncommon, naturally occurring morbidity in both baboons and humans. METHODS: A retrospective analysis was performed on 7776 necropsy reports over a 20 year period to determine the prevalence of baboon GBP. RESULTS: Ninety-seven cases of GBP were identified, yielding a 20 year population prevalence of 1.25%. GBP is more common in adult female baboons, occurring with a female to male ratio of nearly 2:1. Among gallbladder pathologies, cholecystitis (35.1%) and cholelithiasis (29.9%) were the most prevalent abnormalities, followed by hyperplasia (16.5%), edema (15.5%), amyloidosis (5.2%), fibrosis (4.1%), necrosis (4.1%), and hemorrhage (1.0%). CONCLUSION: Many epidemiologic similarities exist between GBP in baboons and humans suggesting that the baboon may serve as a reliable animal model system for investigating GBP in humans.

Further studies on the frequency and length of the glandulo-metaplastic esophageal mucosa in baboons.

BACKGROUND: In previous studies, the length of the glandulo-metaplastic esophageal mucosa (GMEM) at the gastroesophageal junction was assessed in a selected group of baboons. In this study, the length of the GMEM was measured in the entire esophagus in a cohort of unselected adult baboons. MATERIALS AND METHODS: In 15 female baboons, the entire esophagus was removed en bloc at autopsy, from the tongue to the angle of His. No part of the stomach was included. The length of GMEM was measured using a calibrated ocular microscale. RESULTS: GMEM was found in 11 out of the 15 esophagi. The total length of GMEM recorded in the 11 cases was 115 mm (mean 10.5 mm, range 1-45 mm). The mean age for animals with GMEM was 15.5 years (range 7-32 years) and for animals without GMEM was 14.0 years (range 7-20 years); the difference was non-significant (p<0.6). No significant association was found between the length of the GMEM and the age of the animals (p<0.6). CONCLUSION: This study substantiates the notion that GMEM in baboons is a postnatal physiological adaptative process of the esophageal mucosa to daily regurgitation with rumination of gastric juices of low pH. The GMEM apparently progresses upwards, along the esophageal mucosa. The baboon might be an excellent animal model to study the series of histological events that take place in the distal esophagus under the influence of protracted gastroesophageal reflux.

Spontaneous pathology of the baboon endocrine system.

BACKGROUND: Study of endocrine pathology in animal models is critical to understanding endocrine pathology in humans. METHODS: We evaluated 434 endocrine-related diagnoses from 4619 baboon necropsies, established the incidence of spontaneous endocrine pathology, and analyzed the clinical and biochemical data associated with the individual cases. RESULTS: The most common diagnoses in descending order, were pancreatic islet cell amyloidosis (n = 259), ovarian cysts (n = 50), pituitary adenoma (n = 37), pancreatic islet cell adenoma (n = 20), granulosa cell tumor (n = 15), thyroid adenoma (n = 11), adrenal hyperplasia (n = 10), thyroid carcinoma (n = 8), and pheochromocytoma (n = 6). The incidence of pancreatic islet cell amyloidosis progressively increased with age. Pheochromocytomas were associated with renal and heart failure. The incidence of pancreatic islet cell amyloidosis and adrenal pathology was similar to humans; the incidence of pituitary adenoma and thyroid pathology was lower than in humans. CONCLUSIONS: Endocrine disease in baboons is common and shares clinical and biochemical characteristics with endocrine disease in humans.

Feto-placental adaptations to maternal obesity in the baboon.

Maternal obesity is present in 20-34% of pregnant women and has been associated with both intrauterine growth restriction and large-for-gestational age fetuses. While fetal and placental functions have been extensively studied in the baboon, no data are available on the effect of maternal obesity on placental structure and function in this species. We hypothesize that maternal obesity in the baboon is associated with a maternal inflammatory state and induces structural and functional changes in the placenta. The major findings of this study were: 1) decreased placental syncytiotrophoblast amplification factor, intact syncytiotrophoblast endoplasmic reticulum structure and decreased system A placental amino acid transport in obese animals; 2) fetal serum amino acid composition and mononuclear cells (PBMC) transcriptome were different in fetuses from obese compared with non-obese animals; and 3) maternal obesity in humans and baboons is similar in regard to increased placental and adipose tissue macrophage infiltration, increased CD14 expression in maternal PBMC and maternal hyperleptinemia. In summary, these data demonstrate that in obese baboons in the absence of increased fetal weight, placental and fetal phenotype are consistent with those described for large-for-gestational age human fetuses.

Neoplasia in the chimpanzee (Pan spp.).

BACKGROUND: Chimpanzees have over 98% genomic sequence homology with humans and may have a similar host response to malignancy. There is minimal information concerning cancer in the chimpanzee and such information would be valuable to individuals caring for and using them for research. METHODS: Spontaneous neoplasia that was documented in two chimpanzee colonies and in the literature were evaluated statistically. RESULTS: In all, 105 spontaneous and 12 experimental neoplasms were diagnosed. Seventy-four spontaneous tumors occurred in females, 24 in males,and seven in animals of undetermined sex. Of the spontaneous tumors 89 were benign, 14 were malignant, and two were undetermined. Neoplasia was most common in the urogenital system in females. CONCLUSIONS: Neoplasia is not uncommon in the chimpanzee, is generally benign, and occurs primarily in the urogenital system in females.

Gastrointestinal stromal tumors in a baboon, a spider monkey, and a chimpanzee and a review of the literature.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are believed to originate from the intestinal pacemaker cells (interstitial cells of Cajal) or their progenitor cells. Spontaneous tumors have been reported in dogs, horses, rhesus, and a chimpanzee and they have been produced experimentally in mice and rats. GISTs represent a diagnostic challenge because they cannot be differentiated from non-lymphoid mesenchymal tumors without using human c-kit (CD117) immunohistochemistry. METHODS: Three neoplasms were incidental findings at necropsy in the stomachs of a baboon and a spider monkey and in the rectum of a chimpanzee. RESULTS: The GISTs were initially diagnosed grossly and histologically with hematoxylin and eosin as leiomyomas. Immunohistochemical analysis revealed that all three were c-kit (CD117) positive. CONCLUSIONS: These are the first reports of GISTs in the baboon and spider monkey and the second in a chimpanzee. The occurrence of GISTs in non-human primates may provide a unique opportunity to study these tumors.

Endometriosis involving the ileocaecal junction with regional lymph node involvement in the baboon--striking pathological finding identical between the human and the baboon: a case report.

The baboon is an established model for endometriosis research. This report describes the occurrence of spontaneous endometriosis involving the ileocaecal junction and associated regional lymph nodes in the baboon. All endometriotic foci lacked the nuclear atypia, abnormal mitotic activity and altered nuclear-to-cytoplasmic ratio typical of malignancy. These findings are identical to reports in the human in which ileocaecal and colonic endometriosis is associated with endometriosis in pericolonic and mesenteric lymph nodes. The similarity between baboon and human colonic endometriosis in both location and pathology is striking and lends further evidence supporting the validity of the baboon as a model for human endometriosis.

In vivo evaluation of the effects of gravitational force (+Gz) on over-the-wire stainless steel Greenfield inferior vena cava filter in swine.

This study was done to determine the effect of exposure to gravitational force (acceleration stress) on in vivo over-the-wire stainless steel Greenfield inferior vena cava filters. Fifteen pigs underwent venous cut down and placement of a stainless steel Greenfield filter. A 4-week observation period simulated realistic convalescence and allowed sufficient time for epithelialization. Ten pigs were exposed to acceleration stress in a centrifuge (3G run for 15 sec followed by rest until return to baseline heart rate, then a 9G run for 15 sec), with inertial loading in a head-to-tail direction (+Gz). Fluoroscopy during acceleration stress allowed assessment for filter migration. Five pigs were not exposed to acceleration stress. AP and lateral abdominal radiographs were obtained at post-filter placement, convalescence, and centrifuge exposure to determine the position and integrity of the filter. All 15 IVCs were resected and evaluated for gross or histological injury to the vessel wall. IVC filter placement was technically successful in all 15 pigs. Radiographic measurements were limited secondary to differences in pig positioning. Fluoroscopy showed no filter migration. All filters were securely attached to the vena cava by the hooks without gross evidence of perforation or hemorrhage. There were varying degrees of fibroplasia involving the hooks and tip of the filters in both the control and experimental groups. Histologically, there was evidence of prior hemorrhage at the level of the hooks, which was similar between the control and experimental groups. It is concluded that Greenfield filter position and vena caval integrity at the implantation site is unaffected by high acceleration stress.

Record review of baboons with histologically confirmed endometriosis in a large established colony.

Spontaneous endometriosis was diagnosed in 43 baboons over a 14-year period. Thirty-seven have died; five remain alive; one was sold and lost to follow-up. The average age at diagnosis was 17.2 years; 29 (67%) were between 12 and 21 years of age. Fifteen (35%) were diagnosed by biopsy and received surgical excision of the endometriotic tissue; four of these were identified during caesarian section, confirming one prior report of endometriosis in pregnant animals. Twenty-eight (65%) were diagnosed at or shortly preceding necropsy. When diagnosed by a palpable abdominal mass, there was a significantly greater likelihood the animal died or was killed as a result of complications of endometriosis. When diagnosis was at necropsy, there was a significantly greater likelihood that the animal died from causes unrelated to endometriosis. Early identification with surgical removal appears to provide a benefit for both survival and delivering offspring after diagnosis. In twenty-one baboons (49%), endometriosis affected multiple sites within the peritoneal cavity. In the remaining baboons, lesions were more localized. Ovarian involvement was seen in sixteen (37%) of these baboons. This paper is the first to describe significant ovarian involvement in baboons, previously considered a limitation of the usefulness of this species as an animal model. We also describe the first reported endometriosis seeding of an abdominal surgery scar in a baboon. Many of these baboons were middle aged, had few or no offspring, or had evidence of a long duration of uninterrupted menstrual cycles, consistent with risk factors for women. Endometriosis was an incidental finding in 17 (40%) of these baboons, consistent with previous reports of minimal endometriosis as a common asymptomatic finding in baboons and in women. Overall, endometriosis in baboons presents a spontaneously occurring animal model that shares important features with the disease in women and the rhesus macaque.

Lack of effect of 94 GHz radio frequency radiation exposure in an animal model of skin carcinogenesis.

Although there is no evidence that electromagnetic energy in the radio frequency radiation (RFR) band is mutagenic, there have been suggestions that RFR energy might serve as either a promoter or co-promoter in some animal models of carcinogenesis. Recent developments in electromagnetic technology have resulted in the manufacture of RFR sources capable of generating frequencies in the millimeter wavelength (MMW) range (30-300 GHz). Because absorption of MMW energy occurs in the skin, it is to be expected that long-term detrimental health effects, if any, would most likely be manifest in the skin. In this study we investigated whether a single (1.0 W/cm(2) for 10 s) or repeated (2 exposures/week for 12 weeks, 333 mW/cm(2) for 10 s) exposure to 94 GHz RFR serves as a promoter or co-promoter in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced SENCAR mouse model of skin carcinogenesis. Neither paradigm of MMW exposure significantly affected papilloma development, as evidenced by a lack of effect on tumor incidence and multiplicity. There was also no evidence that MMW exposure served as a co-promoter in DMBA-induced animals repeatedly treated with 12-O-tetradecanoylphorbol 13-acetate. Therefore, we conclude that exposure to 94 GHz RFR under these conditions does not promote or co-promote papilloma development in this animal model of skin carcinogenesis.

Expression of stress proteins alpha B-crystallin, ubiquitin, and hsp27 in pallido-nigral spheroids of aged rhesus monkeys.

Ubiquitin and alpha B-crystallin belong to a class of proteins which are overexpressed in a variety of human neuropathological conditions associated with increased cellular stress. In this study we have examined the brains of aged rhesus monkeys (Macaca mulatta; n = 10, mean age: 29.7 years) using antibodies against the stress proteins ubiquitin, alpha B-crystallin, and heat shock protein 27 (hsp27). Here, we demonstrate an increased expression of ubiquitin, alpha B-crystallin, and hsp27 in spheroid bodies predominantly localized in the globus pallidus and pars reticulata of the substantia nigra. A portion of the pallido-nigral spheroids also contained ferric iron as highlighted by Perls' staining. On the basis of these findings we advance the hypothesis that expression of ubiquitin, alpha B-crystallin, and hsp27 in pallido-nigral spheroids of aged rhesus monkeys represents a stress response possibly related to increased iron-mediated oxidative stress.

Microvascular effects of oral interleukin-6 on ischemia/reperfusion in the murine small intestine.

Oral administration of interleukin-6 (IL-6) has been shown to reduce hemorrhage-induced bacterial translocation from the gut in mice and rats. To examine the intestinal microvasculature, mice were given the electron-dense tracer horseradish peroxidase (HRP) after hemorrhage and IL-6 or vehicle administration. In normal mice and in those hemorrhaged and given IL-6, the electron-dense marker, administered intravenously, could be found in intestinal capillaries and between mucosal epithelial cells, suggesting that the microvasculature was patent. In mice given saline after shock, however, no marker was present in the gut, suggesting that the intestinal microvasculature was unable to deliver the marker to the epithelia. When mice were given HRP intralumenally (il) the tracer was able to penetrate between intestinal epithelial cells only in mice given vehicle after hemorrhage. This finding suggests that hemorrhaged mice were susceptible to sepsis and endotoxic shock from the leaky gut. In normal and IL-6-treated mice, the tracer was unable to pass from the lumen between mucosal epithelial cells, because the presence of an intact zonula occludens prevented passage. Functional studies supported the electron microscopy findings. Bacteria were cultured from the livers of mice fed vehicle after hemorrhage, but not from those fed IL-6. These data support the conclusions that parts of the intestinal microvasculature remain diminished after hemorrhage and resuscitation and that oral IL-6 restores this circulation.

Acute ocular effects of mustard gas: ultrastructural pathology and immunohistopathology of exposed rabbit cornea.

Whole-body exposure to sulfur mustard (HD) produces cutaneous, respiratory and ocular impairment. Of these, ocular damage causes the most immediate incapacitation. Heretofore, characterization of HD ocular toxicity has been largely limited to gross and histological observations. In the present study we explore histological, ultrastructural and immunopathological acute effects of HD ocular exposure and establish correlations with HD toxicity data already documented for dermal exposure. Anesthetized rabbits were exposed to 0.4 microl of liquid HD placed directly on the cornea. Animals were euthanized at 6, 9 and 24 h post-exposure and the eyes were enucleated and processed for histopathology, ultrastructural and immunoperoxidase study. At 6 and 9 h, the most prominent histological feature was nuclear pyknosis, necrosis and loss of polarity of corneal epithelial basal cells to the exclusion of other epithelial cells. At 24 h, all corneal epithelial cells presented degenerative changes, with the epithelium eventually detaching from the underlying basement membrane at the level of the lamina lucida. Microblisters, a characteristic HD-induced skin pathology of the basement membrane zone of animals, were absent in this corneal study. Edema, degenerating fibroblasts and inflammatory cellular infiltrates were persistent stromal responses. Immunopathological effects included changes in antigenicity of bullous pemphigoid protein, laminin, desmosonal protein, Ki67 and p53. These morphological and immunopathological effects of corneal exposure to HD appear to be largely consistent with that previously reported for dermal exposures, perhaps providing shared anatomical considerations for the development of specific HD prophylaxis and therapy.

Differentially increased IL-6 mRNA expression in liver and spleen following injection of liposome-encapsulated haemoglobin.

Injection of the red cell substitute liposome-encapsulated haemoglobin (LEH) induces increased serum interleukin (IL)-6 in the absence of other inflammatory cytokines. In vitro studies found that IL-6 mRNA was increased in Mphi and endothelial cell lines by co-culture with LEH. In the present study, cytokine mRNA expression in extracts of livers, spleens, lungs and kidneys after LEH injection was determined by semi-quantitative RT-PCR. The distribution of cells expressing IL-6 mRNA in livers and spleens was visualized by in situ hydridization; extracts of kidney and lung did not show increased IL-6 mRNA and were not studied further. IL-6 mRNA accumulation in livers and spleens was increased at 4 h following LEH injection and had declined by 24 h. In the liver, cells expressing IL-6 mRNA were located in endothelia of hepatic and portal veins, and hepatic sinuses, Kupffer cells and epithelial cells of bile ducts. Endothelium of hepatic arteries did not express IL-6 mRNA. Lymphocytes, haematopoietic cells and macrophages expressed IL-6 mRNA in spleens. The data suggest that cells of the reticuloendothelial system (RES) might be a significant source of increased plasma IL-6 in vivo after LEH administration.

Acute and long-term response of the meniscus to partial meniscectomy using the holmium: YAG laser.

The purpose of this study was to evaluate the histological effects of holmium:YAG laser partial meniscectomy in an in vivo rabbit model and compare it with scalpel partial meniscectomy at selected time intervals. Twenty-four adult male New Zealand rabbits underwent bilateral partial medial meniscectomies through the avascular zone. In the right knee, partial medial meniscectomy was performed using a standard surgical blade; in the left knee, an anatomically similar partial medial meniscectomy was performed using a Ho:YAG laser (Coherent, Santa Clara, CA). All animals were randomized and three animals were killed at postoperative days I and 3, and postoperative weeks 1, 2, 3, 4, 6, and 10. Samples of all medial and lateral menisci, with attached synovium and vascular rim, from both knees were harvested and submitted for histological and/or ultrastructural examination. The results indicate that (1) at all time periods, laser cut menisci had more cell loss and matrix degradation; (2) synovial necrosis was more common in laser-treated knees; (3) the Ho:YAG laser creates three zones of damage in the meniscal fibrocartilage: a zone of fibrin and debris at the incision site, a zone of necrosis characterized by degeneration of the collagen and loss of viable cells, and a zone of thermal change characterized by collagen degeneration. The zone of thermal change, with its histological injury was thought at the time of surgery to be the viable border. The zone of thermal change may act as a barrier to delay healing, and the scalpel produced a consistently straighter cut.