Search

Friesian horses have a perceived high rate of congenital or hereditary diseases, including megaesophagus, that may lead to choke and death. A retrospective study was performed to determine the prevalence and pathologic characteristics of esophageal disease in 852 horses, including 17 Friesians, that had been necropsied over a 6-year period at the Diagnostic Center for Population and Animal Health. Forty-two horses had grossly described esophageal lesions (25 muscular hypertrophy, 7 hemorrhage, 6 megaesophagus, 4 erosion/ulceration, 3 obstruction, 2 tears, 2 secondary neoplasms, 2 lymphoid patches, 1 thin wall, 1 esophagitis). Some of these lesions occurred concurrently in the same horse. Ten of these horses died or were euthanatized because of severe esophageal disease (6 megaesophagus causing tears in 2 horses, 3 esophageal obstruction with food bolus, and 1 esophagitis). All 6 horses with megaesophagus were Friesians. No cause for megaesophagus was noted in the necropsy reports; however, 5 of these 6 Friesians had marked caudal esophageal muscular hypertrophy (wall thickness: 1.9 ± 0.3 cm). Microscopic review of the esophagus of these Friesians confirmed smooth muscle hypertrophy, with no obvious fibrosis, degeneration, or loss of myenteric plexi. Unlike the Friesians, the 4 non-Friesian horses with severe esophageal disease had esophageal obstruction with an intraluminal food bolus or severe esophagitis. None had caudal esophageal muscular hypertrophy. It is concluded that in comparison to other horse breeds, Friesians have a higher prevalence of severe esophageal disease, specifically megaesophagus, that is commonly associated with marked caudal muscular hypertrophy.

Objective—To evaluate the histologic diversity of epidermal laminae in hooves from horses without clinical signs of laminitis. Sample Population—Formalin-fixed samples of stratum internum obtained from the mid region of the dorsal aspect of the hoof wall from the forelimbs of 35Thoroughbred cadavers (including foals [n = 9], yearlings [5], 2 year olds [6], racing horses [5], and mares [10]). Procedures—Paraffin-embedded laminar tissues were stained with H&E for the evaluation of architectural variety of primary epidermal laminae (PEL) and secondary epidermal laminae (SEL). For detection of cytokeratin (CK) expression in epidermal laminae, immunohisto-chemical staining was performed by use of anti-CK14 and anti-CK8.12 antibodies. Results—The morphology of the PEL, SEL, and tips of PEL was classified into 3, 5, and 3 patterns, respectively. Differences in the predominant type of SEL depended on their location with respect to the laminar interface. In SEL attached to the sides of PEL, the basal cells were immunoreactive to CK14 and CK8.12, which was interpreted as a normal pattern. In some SEL at the tips of PEL, the suprabasal cells expressed CK14, CK8.12, or both, which constituted a hyperplastic pattern. Conclusions and Clinical Relevance—The histologic diversity of epidermal laminae from hooves of Thoroughbreds was attributable to the combined morphology of PEL and SEL. Detection of hyperplastic changes in the laminar interface does not justify a diagnosis of laminitis because such changes can develop independent of clinical disease. The classification system used here should aid investigators in making a more accurate histologic evaluation of laminae.

Epithelioid cells are found in lymph nodes in cases of metastatic carcinoma; however, epithelioid cells with benign features have also been discovered incidentally in lymph nodes. Epithelioid cells were observed in mediastinal lymph nodes of cattle without cancer during routine diagnostic necropsy. To explain this finding, the authors evaluated the prevalence and histopathologic, immunohistochemical, and ultrastructural features retrospectively using mediastinal lymph nodes from 110 cattle and found that 66 of the lymph nodes contained epithelioid cells. In all 66 nodes, most of the epithelioid cells were individual or aggregated in nodal sinuses; in 21 nodes, some epithelioid cells formed tubular structures. The individual and aggregated epithelioid cells were mostly considered to be mesothelial in origin by immunohistochemical and ultrastructural examination; presumably, they entered the lymph nodes via lymphatic vessels, because they were found in afferent lymphatic vessels and nodal sinuses. Although the presence of epithelioid cells in lymph nodes prompts suspicion of metastatic carcinoma, the epithelioid cells in these bovine lymph nodes did not disrupt nodal architecture, lacked atypia or mitotic figures, and did not invade nodal parenchyma.

To clarify the immunohistochemical characteristics of canine ovarian cysts, 109 canine ovarian cysts (57 cysts of subsurface epithelial structures: SES, 26 graafian follicle cysts, 12 cystic rete ovarii and 14 cysts difficult to classify morphologically) were examined regarding their lining cells immunohistochemically using antibodies against placental alkaline phosphatase (PLAP), S100, inhibin alpha, desmin and AE1/AE3. Both cysts of SES and cystic rete ovarii had a positive immunoreaction to desmin and AE1/AE3, whereas all cysts all but graafian follicle cysts were negative for inhibin alpha. PLAP-positive immunoreaction was observed only in cysts of SES. Graafian follicle cysts had a positive immunoreaction to inhibin alpha, but were negative for PLAP, desmin and AE1/AE3. Fourteen cysts were difficult to classify morphologically because these cysts had single-squamous lining cells and lacked other morphological characteristics. However, these unclassified cysts were immunohistochemically divided into two groups, including positive and negative cysts, by the reactivity of PLAP. The PLAP-positive cysts were considered large cysts of SES. These results suggest that PLAP was a useful marker for classification of cysts of SES, although cysts originating from SES are not always positive for this antigen.

Ophthalmoplegic migraine (OM) is a rare variant of migraine characterized by recurrent attacks of severe headache followed by oculomotor nerve palsy. The recent revision of the International Headache Classification has reclassified OM from a subtype of migraine, defined as a functional headache, to the neuralgia category. We describe a case of an 11-year-old girl with pathologically confirmed oculomotor nerve schwannoma who had been suffering from symptoms mimicking OM. For five years, she has been under treatment for OM, an initial diagnosis which was corroborated by brain magnetic resonance imaging (MRI). Usually, most OM attacks occur during one period in a lifetime and remit completely. In contrast, however, her attacks became more frequent and were not controlled by medication. After surgery, the frequency of OM attacks was reduced. From this experience, we hypothesize that optic nerve tumor is one condition that can mimic OM, without apparent signs suggestive of intracranial mass. To our knowledge, this is the first report to describe a pathologically confirmed case of oculomotor nerve schwannoma mimicking OM.

A member of the tumor necrosis factor (TNF) family, receptor activator of nuclear factor kappaB ligand (RANKL; also known as ODF, OPGL, and TRANCE), plays critical roles in osteoclast differentiation and activation in the presence of macrophage colony-stimulating factor (M-CSF). Recently, TNF-alpha has also been shown to induce the formation of multinucleated osteoclast-like cells (MNCs) in the presence of M-CSF from mouse macrophages. We demonstrated that mononuclear preosteoclast-like cells (POCs) were formed in the presence of conditioned medium of osteoblastic cells in a rat bone marrow culture depleted of stromal cells. Using this culture system, in this study we examined whether TNF-alpha affects differentiation into POCs from hematopoietic progenitor cells. Human TNF-alpha (hTNF-alpha) markedly stimulated the formation of POCs. Moreover, a concentration as low as 0.005 ng/mL of hTNF-alpha increased the level of mRNA for calcitonin receptor (CTR) and cathepsin-K of POCs. The POCs induced by hTNF-alpha formed MNCs, which showed dentine-resorbing activity after coculture with primary osteoblasts. Stimulation was observed after 24 h of treatment with hTNF-alpha only on day 1 or day 2 of the culture. After 24 h of hTNF-alpha treatment, expression of the receptor activator of nuclear factor kappaB (RANK) mRNA was markedly increased. The addition of soluble RANKL (sRANKL) to the preformed POCs efficiently induced MNCs. Interestingly, treatment of bone marrow cells with hTNF-alpha and sRANKL synergistically augmented the formation of MNCs. This formation was abolished by the addition of human osteoprotegerin (hOPG). These results suggest that cooperation of TNF-alpha and RANKL is important for osteoclastogenesis.

IL-15 shares many activities with IL-2 on stimulating lymphocytes, hematopoietic progenitor cells, and macrophages. However, the role of IL-15 in osteoclastogenesis has not been elucidated. The recent finding of abundant IL-15 in rheumatoid arthritis synovial fluids suggested a possible role for this cytokine in the pathological destruction of bone and prompted us to determine whether IL-15 stimulates osteoclast formation. IL-15 stimulated the formation of multinucleated osteoclast-like cells in rat bone marrow cultures. In stroma-free cultures, IL-15 increased the number of mononuclear preosteoclast-like cells in the early stage of osteoclast formation. The stimulation was observed even after treatment with IL-15 for only 24 or 48 h of culture. Moreover, low IL-15 concentration (0.1 ng/ml) strongly increased the level of calcitonin receptor mRNA of mononuclear preosteoclast-like cells. Although IL-15 is known as a potent stimulator of TNF-α, its activity was not abolished by addition of anti-TNF-α Ab. Interestingly, IL-2 and IL-7, which utilize some IL-15R components, had no effect on osteoclast differentiation, but pretreatment with IL-2 or IL-7 of bone marrow cells before the addition of IL-15 inhibited the enhancing activity of IL-15. In summary, IL-15 has a novel activity to stimulate the differentiation of osteoclast progenitors into preosteoclasts, which cannot be replaced by IL-2 but may use components in common with IL-2R to mediate its effects.

(1997). A NEW ROUTE FOR THE PREPARATION OF XANTHENE DERIVATIVES USING FRIEDEL-CRAFTS INTRAMOLECULAR CYCLOBENZYLATION. Organic Preparations and Procedures International: Vol. 29, No. 3, pp. 300-303.

Vitamin D3 is a potent regulator of cell growth, differentiation and death, tumour invasion, and angiogenesis. Production of matrix metalloproteinase (MMP)-9 and MMP-13 by tumour cells may promote tumour growth, invasion and metastasis.To investigate whether calcipotriol could suppress the expression of MMP-9 and MMP-13 in a human squamous cell carcinoma (SCC) cell line (DJM cells), and to examine the mechanism of modulation of MMP-9 and MMP-13 by calcipotriol in DJM cells treated with tumour necrosis factor (TNF)-α.Protein and mRNA levels of MMP-9 and MMP-13 were examined by ELISA and real-time PCR, respectively. Activation of signalling cascades was assessed using several inhibitors of signalling molecules and western blot analysis.Production of MMP-9 and MMP-13 markedly increased when the cells were treated with TNF-α. Calcipotriol suppressed the production of MMP-9 and MMP-13 mRNA and proteins significantly, in a dose-dependent manner. Induction of MMP-9 by TNF-α was suppressed by an extracellular signal-regulated kinase (ERK) inhibitor but not by a p38 inhibitor, whereas induction of MMP-13 was inhibited by a p38 inhibitor but not by an ERK inhibitor. Calcipotriol inhibited the phosphorylation of both ERK and p38, as shown by western blotting.Calcipotriol reduces MMP-9 and MMP-13 production through inhibiting the phosphorylation of ERK and p38, respectively.

A computer vision algorithm was developed based on a thinning technique for evaluating shapes of embryos in an automated somatic embryo production system. Normally shaped embryos thus selected will be further processed for transplants or artificial seed production. Carrot was used as a model plant. The “skeleton” of the embryo image was induced by “thinning” the image, and two parameters describing the shape of the skeleton were defined and used as selection criteria. These criteria were chosen because normal embryos have Y-shaped skeletons. The results were comparable to those based on human judgments. The developed algorithm gave results independent of the size and position of the embryo image.

A convenient preparation of fluorene derivatives based on a novel Friedel–Crafts intramolecular cyclobenzylation, involving the action of Cl 2 CHOMe and TiCl 4 on a variety of biphenyls (constructed such that electrophilic substitution occurs ortho to the biphenyl linkage), is described.

The majority of hepatic cysts identified in animals are considered to derive from the intrahepatic bile ducts (biliary cysts). An alternative origin is the peribiliary glands located in the hilum of the liver and large portal tracts (peribiliary cysts). The distinction between biliary and peribiliary cysts, and whether these have different clinical significance, has rarely been considered previously. This study reports the pathological features of five cystic porcine livers. Four of these five livers had both biliary and peribiliary cysts and the fifth had only biliary cysts. Biliary cysts were not associated with distortion of adjacent hepatic parenchyma, whereas peribiliary cysts appeared to cause local compression and circulatory disturbance. It would therefore appear that peribiliary cysts have greater potential clinical significance than those of biliary origin.

Contents In the present study, 15 canine ovaries without morphological lesions were examined histologically and immunohistochemically by using a large number of proteins including AE1/AE3, cytokeratin7 (CK7), CK13, CK20, vimentin, desmin, alpha smooth muscle actin (αSMA), calponin, S100, Neurofilaments, Inhibinα, placental alkaline phosphatase (PLAP) and neuron-specific enolase. Ovarian structures observed in this study included surface epithelium (SE), cortical tubules (CT), tunica albuginea (TA), stromal cells (SC), internal endocrine cells (IE), rete ovarii (RO) and fallopian tubes (FT). SE, CT, RO and FT were broadly immunoreactive for desmin. Besides AE1/AE3 and vimentin, desmin was also closely linked to these structures. Rete ovarii forming a reticular structure showed a positive reaction to S100. Surface epithelium was immunoreactive for PLAP at a significantly high level. In conclusion, these results indicate a specific segment of immunoreactivity as well as the broad range of immunoreactivity in canine ovary. The distinct patterns of immunoreactive for various kinds of proteins will play an important role in facilitating their identification and discrimination even in a normal canine ovary with a complex structure.

Histopathologic features of hepatic peribiliary cysts were described in a young slaughtered pig. The animal was an apparently healthy 6–month-old pig of mixed breed. Macroscopically, all lobes of the liver contained numerous cysts of varying size containing serous fluid in all lobes. Histopathologically, the cysts were located mainly around the large bile duct and in the connective tissue of the portal tracts. Within serial sections, these cysts were assumed to be solitary or multilocular, but they were separated from the bile duct. The cysts were lined by a single layer of columnar, cuboidal, and flattened epithelial cells. Occasionally, goblet cells were observed. The epithelial cells were stained with periodic acid—Schiff/alcian blue and high-iron diamine/alcian blue, indicating the presence of neutral mucin, sialomucin, and sulfomucin. Grimalius' method revealed the presence of endocrine cells in the lining epithelium. There was no bile pigment in the cysts by the Hall method.

In this study, the expression and distribution of monocarboxyolate transporter 1 (MCT1) along the intestines (duodenum, jejunum, ileum, cecum, colon and rectum) of dogs were investigated at both the mRNA and protein levels. The expression of MCT1 protein and its distribution were confirmed by Western blotting and immunohistochemical staining using the antibody for MCT1. We identified mRNA coding for MCT1 and a 43-kDa band of MCT1 protein in all regions from the duodenum to the rectum. Immunoreactive staining for MCT1 was also observed in epithelial cells throughout the intestines. MCT1 immunoreactivity was greater in the large intestine than in the small intestine. MCT1 protein was predominantly expressed on the basolateral membranes along intestinal epithelial cells, suggesting that MCT1 may play an important role in lactate efflux and transport of short-chain fatty acids (SCFAs) to the bloodstream across the basolateral membranes of the dog intestine.

AN aneurysm is a localised, abnormal dilation of any vessel. Aneurysms are most important when they affect the aorta in human beings and domestic animals (Robinson and Maxie 1993, Derksen and others 1998). In the horse, various lesions have been described in the aorta, including the formation of a dissecting aortic aneurysm (Holmes and others 1973, Shirai and others 1999), a ruptured aneurysm (Rooney 1979, Roby and others 1986) and a verminous aneurysm (Greatorex 1977), but reports of a mycotic aneurysm in the horse are uncommon. Mycotic aneurysms of the aorta caused by fungi are rare, and are frequently associated with a poor prognosis, as the diagnosis is usually based on an insidious presentation in human beings (Silva and others 2000). This short commu-nication describes a case of a horse with a mycotic aneurysm of the aortic arch caused by

We describe a patient with Sézary syndrome (SS) who was successfully treated with topical steroid and narrowband UVB. Sézary cells in peripheral blood correlated with severity of skin lesions. In addition, serum levels of CCL17 and CCL27 decreased as disease activity improved. These chemokines may be important for the pathogenesis of SS.

INTESTINAL obstruction is by far the most common cause of digestive disease in all species (Catherrine 1992). Obstruction can be induced by volvulus, torsion, hernias, strangulation or intussusception (Barker and others 1993). Volvulus has been widely reported in small and large domesticated animals (Andrews 1970, Todd and others 1977, Curtis 1988, Katiyar and others 1988, West and others 1988, Catherrine 1992, Barker and others 1993, Kemble and others 1994, Theyse and others 1998); it has resulted in different clinical presentations, depending on the segments and amounts of bowel involved (Catherrine 1992).Steller (northern) sea lions (

Psoriasis is a T-helper (Th)1 cytokine-mediated chronic skin disease and interleukin (IL)-12 has been shown to play a major role in the development of Th1 responses.To elucidate the role of IL-12 in the pathogenesis of psoriasis and to study the effect of ciclosporin A (CsA) on Th1 deviation of this disease.We investigated IL-12 production by stimulated monocytes from patients with psoriasis who were treated with or without CsA. Monocytes were stimulated with interferon-gamma plus lipopolysaccharide (LPS) or Staphylococcus aureus Cowan strain I (SAC). The amount of IL-12 p70 produced by stimulated monocytes was evaluated by enzyme-linked immunosorbent assay.Compared with those from normal controls, LPS- but not SAC-stimulated monocytes from patients with psoriasis produced significantly higher amounts of IL-12. Interestingly, LPS-stimulated monocytes from patients with psoriasis treated with CsA produced significantly decreased amounts of IL-12 compared with those patients not treated with CsA.Our results suggest that IL-12 production by monocytes may have a critical role in the pathogenesis of psoriasis, and that the therapeutic effect of CsA on psoriasis may be achieved by correcting the deviation of the Th1/Th2 balance.

Clinical symptoms and MR spectroscopic findings were studied on 4 cases of Pelizaeus-Merzbacher disease including 1 autopsy case. Common symptoms were severe mental retardation and spastic tetraplegia. These cases had nystagmus, and one had involuntary athetotic movement. Genetical diagnosis revealed in 2 cases, duplication of proteolipid protein (PLP) and deletion in 1, whereas one case had no abnormality of PLP gene. MRI indicated the reversal of signal intensities on T1- and T2-weighed images, a characteristic finding of PMD MR spectroscopy demonstrated a pattern of NAA in 3 cases. This was specific to PMD because other white matter diseases show a decrease in NAA. In conclusion, MRS was useful to differentiate PMD from other white matter diseases.

We report a patient with hemiparkinsonism associated with unilateral striatal necrosis of the contralateral side. The patient was an 18-year-old woman who had a two-month-history of difficulty in executing skilled movements with her right upper extremity. Neurological examination revealed that she had cogwheel rigidity and bradykinesia in her right upper and lower extremities. MRI revealed a well-delineated low signal intensity in T1-weighted and high signal intensity in T2-weighted images in the region of the putamen on the left side. Her laboratory data were unremarkable and mitochondrial gene mutation studies revealed no abnormality. It is extremely rare to encounter a case of parkinsonism associated with unilateral striatal necrosis.

Epidermal keratinocytes respond to injury by becoming activated, i.e. hyperproliferative, migratory, and proinflammatory. These processes are regulated by growth factors and cytokines. One of the markers of activated keratinocytes is keratin K6. We used a novel organ culture system to show that tumor necrosis factor alpha (TNFalpha) induces the expression of K6 protein and mRNA in human skin. Multiple isoforms of K6 are encoded by distinct genes and have distinct patterns of expression. By having shown previously that proliferative signals, such as epidermal growth factor (EGF), induce expression of the cytoskeletal protein keratin K6b, we here demonstrate that the same isoform, K6b, is also induced by TNFalpha, a proinflammatory cytokine. Specifically, TNFalpha induces the transcription of the K6b gene promoter. By using co-transfection, specific inhibitors, and antisense oligonucleotides, we have identified NFkappaB and C/EBPbeta as the transcription factors that convey the TNFalpha signal. Both transcription factors are necessary for the induction of K6b by TNFalpha and act as a complex, although only C/EBPbeta binds the K6b promoter DNA. By using transfection, site-directed mutagenesis, and footprinting, we have mapped the site that responds to TNFalpha, NFkappaB, and C/EBPbeta. This site is separate from the one responsive to EGF and AP1. Our results show that the proinflammatory (TNFalpha) and the proliferative (EGF) signals in epidermis separately and independently regulate the expression of the same K6b keratin isoform. Thus, the cytoskeletal responses in epidermal cells can be precisely tuned by separate proliferative and inflammatory signals to fit the nature of the injuries that caused them.

We describe a 31-year-old Japanese woman with generalized pustular psoriasis treated with PUVA who subsequently developed a bullous disease. Throughout the disease course, there was no phase of psoriasis vulgaris. Although several reports describe coexistence of psoriasis vulgaris and bullous disease such as bullous periphigoid, coexistence of generalized pustular psoriasis without any phase of psoriasis vulgaris and bullous disease is rare. As for the bullous disease, direct immunofluorescence study showed IgG and C3 deposition along the basement membrane zone. Indirect immunofluorescence disclosed IgG antibasement membrane zone antibodies. Indirect immunofluorescence on 1 mol/l sodium chloride-split skin demonstrated linear IgG staining almost exclusively on the dermal side of the split. Western immunoblot analysis revealed that the antibody was directed to neither epidermolysis bullosa acquisita antigen nor bullous pemphigoid antigens. Considering the unusual clinical course, we suspect the possibility of a novel autoimmune blistering disease.

A convenient, mild, one-pot synthesis of substituted dibenzo[a,d]cycloheptenes involving the action of ClCH 2 OMe and TiCl 4 on a variety of diphenylethanes,† which incorporates chloromethylation of a hydrocarbon followed by a Friedel–Crafts intramolecular cyclization reaction, is described.

A convenient preparation of fluorene derivatives based on a novel Friedel–Crafts intramolecular cyclobenzylation, involving the action of Cl 2 CHOMe and TiCl 4 on a variety of biphenyls (constructed such that electrophilic substitution occurs ortho to the biphenyl linkage), is described.