Congenital cutaneous histiocytosis in a piglet.

A 2-week-old crossbred male piglet with numerous congenital, variably sized macules, plaques, and papules distributed all over the body was submitted for necropsy. Significant gross and histological lesions were restricted to the skin. On light microscopic examination, these cutaneous lesions corresponded to dermal and/or subcutaneous masses composed of spindle-shaped to round cells that multifocally contained hemosiderin; epidermotropism was not observed. Immunohistochemically, the neoplastic cells were strongly positive for CD204; moderately positive for CD163, lysozyme, and vimentin; and negative for Mac 387, α-1-antitrypsin, S-100 protein and E-cadherin; frozen tissues were not available for CD1a and CD11c. Transmission electron microscopic examination of sections from formalin-fixed tissues did not reveal Birbeck's granules. The clinical, morphological, and immunohistochemical results were consistent with a congenital cutaneous histiocytosis of non-Langerhans cell origin. The condition most resembled juvenile xanthogranuloma in humans, a generally skin-limited non-Langerhans histiocytic disorder that can be congenital. Cutaneous and/or systemic histiocytic disorders are well characterized in dogs and have been described in cats, and a case with some similarities to ours has been reported in a neonatal piglet, but this is to our knowledge the first immunohistochemically supported report of histiocytosis in the pig and congenital histiocytosis in animals.

Hypertrophy and hyperplasia of abdominal adipose tissues in women.

OBJECTIVE: To examine the expression of selected transcription factors involved in adipogenesis and genes related to lipid metabolism in abdominal subcutaneous and omental fat tissue. RESEARCH DESIGN AND METHODS: We obtained subcutaneous and omental adipose tissue samples from 40 women undergoing abdominal hysterectomies (age: 47+/-5 years; BMI 27.9+/-5.3 kg/m(2)). We measured isolated adipocyte size and metabolism, and detailed measures of body fat accumulation and body fat distribution were obtained (dual-energy X-ray absorptiometry and computed tomography, respectively). RESULTS: Adipocyte size of both subcutaneous and omental fat were increased with higher body fat mass values, with similar regression slopes in each compartment. In contrast, with higher body fat mass values, fat accumulation was progressively higher in the subcutaneous than in the visceral fat compartment, suggesting hyperplasia in the subcutaneous fat compartment. Messenger RNA levels of CEBPalpha, PPARgamma2, SREBP1c and genes related to lipid metabolism (LPL, FABP4, DGAT1, DGAT2, PLIN and HSL) were significantly higher in subcutaneous than in omental fat tissue (P< or =0.001 for all). Only subcutaneous expression of these genes tracked with obesity levels as reflected by significant positive associations between subcutaneous fat CEBPalpha, SREBP1c and DGAT2 expression and total body fat mass (r=0.37, r=0.41, r=0.57, respectively, P< or =0,05), fat percentage (r=0.40, r=0.39, r=058, respectively, P< or =0,05) and subcutaneous adipose tissue area (r=0.36, r=0.38, r=0.58, respectively, P< or =0,05). Omental adipose tissue expression levels of these genes were not significantly related to adiposity measures. CONCLUSIONS: These results show that in obese women, hyperplasia is predominant in the subcutaneous fat depot, whereas fat cell hypertrophy is observed both in the omental and subcutaneous compartments.

Unique responses to mitochondrial complex I inhibition in tuberoinfundibular dopamine neurons may impart resistance to toxic insult.

Tuberoinfundibular dopamine (TIDA) neurons are spared in Parkinson's disease (PD), a disorder that causes degeneration of midbrain nigrostriatal dopamine (NSDA) and mesolimbic dopamine (MLDA) neurons. This pattern of susceptibility has been demonstrated in acute complex I inhibitor-induced models of PD, and extrinsic factors such as toxin distribution, bioactivation, entry into the cell and sequestration into vesicles are postulated to underlie the resistance of TIDA neurons. In the present experiments, direct exposure to rotenone or 1-methyl-4-phenylpyridinium (MPP+) had no effect on mediobasal hypothalamic TIDA neurons, but significantly increased the percentage of apoptag immunoreactive neurons in midbrain primary NSDA and MLDA cultures. In vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure caused an initial decrease (by 4 h) in dopamine (DA) in brain regions containing axon terminals of TIDA (median eminence [ME]), NSDA (striatum [ST]) and MLDA (nucleus accumbens [NA]) neurons. By 16 h after MPTP treatment, DA concentrations in ME returned to control levels, while ST and NA DA levels remained low up to 32 h after treatment with MPTP. When mice and rats were chronically treated with MPTP and rotenone, respectively, the same pattern of susceptibility emerged. TIDA neurons were unaffected while NSDA neurons suffered loss of cell bodies and axon terminal DA. These experiments demonstrate that the resistance of hypothalamic TIDA neurons is not likely to be due to extrinsic factors, and that further examination of the intrinsic properties of these neurons may elucidate mechanisms that can be translated into neuroprotective strategies in PD.

Detection rates of porcine reproductive and respiratory syndrome virus, porcine circovirus type 2, and swine influenza virus in porcine proliferative and necrotizing pneumonia.

A retrospective study on pig lung tissues from 60 cases of proliferative and necrotizing pneumonia (PNP) was performed to determine the presence of porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), and porcine circovirus type 2 (PCV2) in these lesions. Cases selected included 30 cases diagnosed between 1988 and 1992 and 30 cases diagnosed between 1997 and 2001. In each group of 30 cases, 10 were from suckling piglets, whereas the other 20 were from postweaned animals representing either nursery or grower-finisher pigs. Immunohistochemistry using a monoclonal antibody to influenza virus type A was used to determine the presence of SIV, and in situ hybridization was used for the detection of PRRSV and PCV2 nucleic acids. PRRSV was detected in 55 of the 60 cases examined (92%), PCV2 in 25 cases (42%), and SIV in only 1 case (2%). In 30 cases (50%), PRRSV was the only virus detected, whereas in 25 other cases (42%), a combination of PRRSV and PCV2 could be detected in the lungs with PNP lesions. PCV2 could not be detected in the lungs of suckling pigs with PNP. All PCV2-positive cases were found in postweaned pigs and were always in combination with PRRSV. In this latter age group, PCV2 was detected in 63% of the cases (25/40). Data from our study indicate that SIV is rarely identified in PNP and that PCV2 infection is not essential for the development of PNP lesions. The results of the present study demonstrate that PRRSV is consistently and predominantly associated with PNP and should be considered the key etiologic agent for the condition.

Infectious agents identified in pigs with multifocal interstitial nephritis at slaughter.

One kidney was taken from each of 100 pigs at slaughter; 50 had gross lesions of multifocal interstitial nephritis and 50 had no gross lesions. Forty-nine of the affected kidneys had lesions that were characterised by the presence of either a few randomly distributed or numerous widely disseminated pale foci, 1 to 3 mm in diameter, on the cortical surface (white-dotted kidneys). Microscopically, these focal inflammatory lesions often had a distinct lymphofollicular pattern (follicular nephritis). Lesions of chronic vasculitis were observed in 21 of the affected kidneys. Histologically, the control kidneys had only small and sparse inflammatory foci. Standard bacterial cultures of kidneys of both groups were not significant, and cultures for the isolation of leptospires were all negative. Virological examination of the kidney homogenates by PCR did not reveal any porcine reproductive and respiratory syndrome virus and only a few cases were positive for the porcine circovirus type 1. However, porcine parvovirus (PPV) and porcine circovirus type 2 (PCV-2) were detected in many kidneys of both groups but in a significantly higher proportion of the kidneys with interstitial nephritis. There was a significant association between the lesions and the presence of PPV and PCV-2 with odds ratios of 7.5 (P<0.0001) and 3.4 (P=0.0074), respectively, and the odds ratio increased to 22.7 (P<0.0001) when both viruses were identified in the same kidney. However, a subsample of kidneys taken from both groups were negative by immunohistochemistry for the presence of PPV and PCV-2 antigens.

Equine proliferative enteropathy: a cause of weight loss, colic, diarrhoea and hypoproteinaemia in foals on three breeding farms in Canada.

Proliferative enteropathy (PE) is a transmissible enteric disease caused by Lawsonia intracellularis. An outbreak of equine PE was diagnosed in foals from 3 breeding farms. Most foals had been weaned prior to the appearance of clinical signs, which included depression, rapid and marked weight loss, subcutaneous oedema, diarrhoea and colic. Poor body condition with a rough haircoat and a potbellied appearance were common findings in affected foals. Respiratory tract infection, dermatitis and intestinal parasitism were also found in some foals. Haematological and plasma biochemical abnormalities included hypoproteinaemia, transient leucocytosis, anaemia and increased serum creatinine kinase concentration. Postmortem diagnosis of PE was confirmed on 4 foals based on the presence of characteristic intracellular bacteria within the apical cytoplasm of proliferating crypt epithelial cells of the intestinal mucosa, using silver stains, and by results of PCR analysis and immunohistochemistry. Antemortem diagnosis of equine PE was based on the clinical signs, hypoproteinaemia and the exclusion of common enteric infections. Faecal PCR analysis was positive for the presence of L. intracellularis in 6 of 18 foals tested while the serum of all 7 foals with PE serologically evaluated had antibodies against L. intracellularis. Most foals were treated with erythromycin estolate alone or combined with rifampin for a minimum of 21 days. Additional symptomatic treatments were administered when indicated. All but one foal treated with erythromycin survived the infection. This study indicates that equine PE should be included in the differential diagnosis of outbreaks of rapid weight loss, diarrhoea, colic and hypoproteinaemia in weanling foals.

Localization of type 1 17beta-hydroxysteroid dehydrogenase mRNA and protein in syncytiotrophoblasts and invasive cytotrophoblasts in the human term villi.

The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) play a key role in the synthesis of sex steroids. The hallmark of this family of enzymes is the interconversion, through their oxydoreductive reactivity at position C17, of 17-keto- and 17beta-hydroxy-steroids. Because this reaction essentially transforms steroids having low binding activity for the steroid receptor to their more potent 17beta-hydroxysteroids isoforms, it is crucial to the control of the physiological activities of both estrogens and androgens. The human placenta produces large amounts of progesterone and estrogens throughout pregnancy. The placental type 1 17beta-HSD enzyme (E17beta-HSD) catalyzes the reduction of the low activity estrogen, estrone, into the potent estrogen, estradiol. We studied the cell-specific expression of type 1 17beta-HSD in human term placental villous tissue by combining in situ hybridization to localize type 1 17beta-HSD mRNA with immunohistochemistry using an antibody against human placental lactogen, a trophoblast marker. Immunolocalization of E17beta-HSD was also performed. To ascertain whether other steroidogenic enzymes are present in the same cell type, cytochrome P450 cholesterol side-chain cleavage (P450scc), P450 aromatase, and type 1 3beta-hydroxysteroid dehydrogenase (3beta-HSD) were also localized by immunostaining. Our results showed that the syncytium is the major steroidogenic unit of the fetal term villi. In fact, type 1 17beta-HSD mRNA and protein, as well as P450scc, P450 aromatase, and 3beta-HSD immunoreactivities were found in these cells. In addition, our results revealed undoubtedly that extravillous cytotrophoblasts (CTBs), e.g. those from which cell columns of anchoring villous originate, also express the type 1 17beta-HSD gene. However, CTBs lying beneath the syncytial layer, e.g. those from which syncytiotrophoblasts develop, contained barely detectable amounts of type 1 17beta-HSD mRNA as determined by in situ hybridization. These findings, along with those from other laboratories confirm the primordial role of the syncytium in the synthesis of steroids during pregnancy. In addition, our results indicate for the first time that CTBs differentiating along the invasive pathway contain type 1 17beta-HSD mRNA.

Tissue- and site-specific gene expression of type 2 17beta-hydroxysteroid dehydrogenase: in situ hybridization and specificenzymatic activity studies in human placental endothelial cells of the arterial system.

Progesterone and estradiol are the most potent human sex steroid hormones of placental origin and are essential to the maintenance of pregnancy, the timing of parturition, the maturation of many fetal organs, and the preparation of the maternal reproductive system. Naturally, regulatory mechanisms must be in place to coordinate the synthesis and inactivation of these two hormones. We have previously shown that the highest levels of type 1 and type 2 17beta-hydroxysteroid dehydrogenase (17betaHSD) messenger ribonucleic acids (mRNAs) occur in the placenta, particularly in the villi. However, in contrast to type 1 17betaHSD mRNA, type 2 17betaHSD mRNA was not detectable in cell cultures of human cytotrophoblasts or syncytiotrophoblasts. Using in situ hybridization, we unequivocally identified endothelial cells as the only cell type expressing the type 2 17betaHSD gene in fetal villi. Moreover, type 2 17betaHSD mRNA was specifically detected in the endothelial cells of the arterial system, and at higher levels in the villi compared with endothelial cells of the cord arteries when the two tissue sections were cohybridized. In fact, both mRNA levels and enzymatic activity are at their highest levels in arterial endothelial cells. In conclusion, the endothelial cells of the villous arterioles are the primary site of type 2 17betaHSD gene expression. This suggests a regulatory role for these cells in the control of progestin, androgen, and estrogen levels during pregnancy, thus opening a whole new way of viewing regionalization and localization of steroidogenesis in the human villi.

Radiotelemetry system for apnea study in lambs.

Neonatal apneas are being studied in the laboratory using polysomnographic recordings in lambs. Standard equipment, requiring animal restraint, disrupts sleep and prevents development of spontaneous apneas. The aim of the current work was to develop and validate a wireless recording equipment to study freely moving lambs. Firstly, a radiotelemetry equipment composed of a multichannel FM transmitter and a receiver was developed. Secondly, to test the telemetry equipment, each biopotential - [electroencephalogram (EEG), electrooculogram (EOG), electrocardiogram (ECG), electromyograms (EMGs), nasal airflow] - was recorded simultaneously by standard equipment and by telemetry (5 lambs). The results indicated an excellent concordance between signals obtained by both systems. Finally, the 8-channel telemetry prototype was tested for polysomnographic recordings (16 lambs). Results obtained confirmed the possibility of recording frequent REM sleep periods and spontaneous apneas. In conclusion, this radiotelemetry polysomnographic equipment brings new possibilities for research on neonatal apneas.

Cutaneous and systemic necrotizing vasculitis in swine.

A systemic vasculitis involving particularly the skin and kidneys has been recently described in swine under the name dermatitis/nephropathy syndrome. Twelve pigs with gross cutaneous lesions typical of this condition were necropsied, and morphologic, immunohistochemical, microbiologic, and epidemiologic characteristics were studied. The pigs were divided into three groups comprising eight pigs with acute lesions, two with chronic lesions, and two with acute lesions kept for sequential skin biopsies. Acute skin lesions consisted of round to irregular, red to purple macules and papules that often coalesced to form large, irregular patches and plaques. With time, the lesions became covered by crusts and faded gradually, sometimes leaving scars. Characteristic distribution included the perineal area of the hindquarters, limbs, dependent parts of the abdomen and thorax, and margins of the ears. In the acute phase of the disease, necrotizing and leucocytoclastic vasculitis of small-caliber blood vessels were observed within the dermis and panniculus and in various extracutaneous locations such as the renal pelvis and synovial membranes. All pigs had macroscopic evidence of pneumonia and generalized lymphadenopathy. Microscopically, they had interstitial pneumonia and perivascular cuffing of mononuclear cells in various tissues including skin. The presence of immunoglobulins and complement was demonstrated by immunofluorescence in and around necrotic vessels of the skin in the early stages. Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) antigens were detected by immunohistochemistry in macrophages located around vessels of the tissues examined (skin and kidneys) in acute and chronic cases. PRRSV RNA was demonstrated by reverse transcription-polymerase chain reaction in lung and spleen homogenates from all pigs. The PRRSV was isolated in cell culture from 11 of the pigs. These findings suggest that PRRSV infection may play a role in the pathogenesis of this systemic vascular disease of swine.

Bilateral epiphysiolysis of the femoral heads in two dogs.

Two Shetland Sheepdogs that did not have a history of trauma were referred because of a gradual onset of lameness in the hind limbs. Bilateral slipped capital femoral epiphysis was diagnosed. Separation of the proximal femoral epiphysis that is not associated with trauma is recognized as a distinct clinical syndrome in adolescent human beings and swine, causing a condition called epiphysiolysis. The precise cause of this type of injury is unknown. Histologic lesions observed in the growth plates could have been the result of an abnormally high mechanical load imposed by obesity. It is not known whether cartilaginous lesions observed in the physis of 1 dog represented a preexisting cartilaginous defect (dyschondroplasia) or a late stage of repair after separation of the capital femoral epiphysis.

Helicobacter canis isolated from a dog liver with multifocal necrotizing hepatitis.

On the basis of biochemical, phenotypic, and 16S rRNA analysis, a novel gram-negative bacterium, isolated from normal and diarrheic dogs as well as humans with gastroenteritis, has been recently named Helicobacter canis. A 2-month-old female crossbred puppy was submitted to necropsy with a history of weakness and vomiting for several hours prior to death. The liver had multiple and slightly irregular yellowish foci up to 1.5 cm in diameter. Histologically, the liver parenchyma contained randomly distributed, occasionally coalescing hepatocellular necrosis, often accompanied by large numbers of mononuclear cells and neutrophils. Sections of liver stained by the Warthin-Starry silver impregnation technique revealed spiral- to curve-shaped bacteria predominantly located in bile canaliculi and occasionally in bile ducts. Aerobic culture of liver was negative, whereas small colonies were noted on Campylobacter selective media after 5 days of microaerobic incubation. The bacteria were gram negative and oxidase positive but catalase, urease, and indoxyl acetate negative; nitrate was not reduced to nitrite, and the organism did not hydrolyze hippurate. The bacteria were also resistant to 1.5% bile. Electron microscopy revealed spiral-shaped bacteria with bipolar sheathed flagella. By 16S rRNA analysis, the organism was determined to be H. canis. This is the first observation of H. canis in active hepatitis in a dog and correlates with recent findings of Helicobacter hepaticus- and Helicobacter bilis-related hepatic disease in mice. Further studies are clearly warranted to ascertain whether H. canis-associated hepatitis is more widespread in canines as well as a cause of previously classified idiopathic liver disease in humans.

Systemic necrotizing vasculitis and glomerulonephritis in grower pigs in southwestern Quebec.

This purpose of this study was to describe the clinical features and the pathological findings of an unusual condition observed in pigs of a fattening unit in southwestern Quebec. Two of these pigs were submitted for complete postmortem examination. The disease was characterized by a systemic necrotizing vasculitis and an exudative and proliferative glomerulonephritis. In the skin, the vascular lesions produced a conspicuous papular dermatopathy with a characteristic distribution. Bacteriological and virological results were inconclusive. In the glomeruli, there were extensive granular complement deposits with scattered immunoglobulin M. Transmission electron microscopy did not reveal any dense deposits in glomerular basement membrane. The cause of this newly recognized and potentially lethal condition remains unknown, although histological and immunopathological observations suggest an immune-mediated process.