Retrospective characterisation of solitary cutaneous histiocytoma with lymph node metastasis in eight dogs.

OBJECTIVES: To describe a small subset of canine solitary cutaneous histiocytoma in which lymph node metastasis has been documented. METHODS: Cases of dogs with solitary cutaneous histiocytoma lesions and regional lymph node metastasis diagnosed via histopathology were found through a retrospective search of the databases of IDEXX Laboratories and the University of California, Davis Veterinary Medical Teaching Hospital Clinical Diagnostic Laboratories. Information on signalment, history and clinical follow-up was obtained from the submittal form and/or via a questionnaire to the submitting veterinarian. Slides were available for review in seven cases and when possible immunohistochemistry was reviewed or performed by a single pathologist. RESULTS: Eight cases met the inclusion criteria. The neoplasms had the typical appearance of histiocytomas. All tested samples were immunoreactive for CD18 and lacked immunoreactivity for other lymphocyte markers and CD11d. Immunoreactivity for E-cadherin varied among the neoplasms tested. Outcome was known for five dogs and at the time of manuscript preparation three of those dogs were alive 1682 days, 570 days and 318 days post-diagnosis. Of the other two dogs with known outcome, one was euthanased shortly after diagnosis and another was hit by a car. Of the dogs that were eventually lost to follow-up, one was reported to be disease-free 1003 days after diagnosis. CLINICAL SIGNIFICANCE: Metastatic histiocytoma is rarely reported and distinction from aggressive disease processes such as histiocytic sarcoma may be difficult. Based upon a small number of cases with known outcomes, some dogs with solitary metastatic histiocytoma may experience favourable outcomes.

p62/Sequestosome-1: Mapping Sites of Protein-Handling Stress in Canine Cutaneous Mast Cell Tumors.

Canine cutaneous mast cell tumors (MCT) are common, frequently malignant neoplasms that are currently graded histologically for provision of prognostic information. Continuing evidence of subsets of MCT within certain grades (with differing survival times) indicate the need for biomarkers that will facilitate better patient stratification and also provide further information on the biological processes involved in progression. We decided to investigate the expression of p62/sequestosome-1 (p62/SQSTM1), a stress-inducible "hub protein" found in all cell types that shuttles rapidly between the nucleus and cytoplasm and is known to play important roles in protein handling and tumorigenesis. The identity of canine p62/SQSTM1 was confirmed in silico and by validation of a commercial antibody using both Western blotting and functional (pharmaceutical-based) analyses in cell culture. Using immunohistochemistry, 3 patterns of p62 expression were identified based on the predominant intracellular localization, that is, nuclear, mixed (nuclear and cytoplasmic), and cytoplasmic. There was a highly significant association with the 2-tier (Kiupel) grade (P < .0001), with all p62-nuclear immunoreactivity being associated with low grade and most p62-cytoplasmic immunoreactivity (93%) with high grade. Most but not all mixed nuclear-cytoplasmic labeling occurred in low-grade MCT; in other (human) tumor types, this pattern has been interpreted as borderline malignant. These data indicate that there is a shift in protein-handling stress from the nucleus to the cytoplasm in association with increasing malignancy in MCT. Studies to identify the processes and drug-able targets involved in this progression are ongoing.

Congenital lymphangiomatosis and an enteric duplication cyst in a young dog.

A two-year-old female poodle with abdominal distention was diagnosed with concurrent enteric duplication cyst and lymphangiomatosis. Both lesions were shown as cystic structures, but some characteristic features of enteric duplication cyst were identified including a thick cyst wall and shared blood supply with the duodenum. Although it was challenging to discriminate between the types of cyst based on diagnostic imaging, this report describes the characteristics of each type of lesion using several different imaging modalities.

T-lymphocyte-rich thymoma and myasthenia gravis in a Siberian tiger (Panthera tigris altaica).

A 10-year-old captive male Siberian tiger (Panthera tigris altaica) presented with acute onset collapse, vomiting and dyspnoea, preceded by a 6-month period of progressive muscle wasting. Following humane destruction, post-mortem examination revealed a large multilobulated mass in the cranial mediastinum, which was diagnosed as a T-lymphocyte-rich thymoma with the aid of immunohistochemistry. Retrospective serology for acetylcholine receptor antibodies (titre 3.90 nmol/l) confirmed a diagnosis of thymoma-associated myasthenia gravis. Thymomas are reported rarely in wild carnivores, but when detected they appear to be similar in morphology to those seen in domestic carnivores and may also be accompanied by paraneoplastic syndromes. The clinical signs of myasthenia gravis in the tiger were consistent with those reported in cats and dogs and the condition is proposed as an important differential diagnosis for generalized weakness in captive Felidae.

The impact of social exclusion vs. inclusion on subjective and hormonal reactions in females and males.

BACKGROUND: The experience of social exclusion represents an extremely aversive and threatening situation in daily life. The present study examined the impact of social exclusion compared to inclusion on steroid hormone concentrations as well as on subjective affect ratings. METHODS: Eighty subjects (40 females) participated in two independent behavioral experiments. They engaged in a computerized ball tossing game in which they ostensibly played with two other players who deliberately excluded or included them, respectively. Hormone samples as well as mood ratings were taken before and after the game. RESULTS: Social exclusion led to a decrease in positive mood ratings and increased anger ratings. In contrast, social inclusion did not affect positive mood ratings, but decreased sadness ratings. Both conditions did not affect cortisol levels. Testosterone significantly decreased after being excluded in both genders, and increased after inclusion, but only in males. Interestingly, progesterone showed an increase after both conditions only in females. DISCUSSION: Our results suggest that social exclusion does not trigger a classical stress response but gender-specific changes in sex hormone levels. The testosterone decrease after being excluded in both genders, as well as the increase after inclusion in males can be interpreted within the framework of the biosocial status hypothesis. The progesterone increase might reflect a generalized affiliative response during social interaction in females.

Immunohistochemical expression of c-KIT protein in feline soft tissue fibrosarcomas.

C-KIT is the cellular homolog of the feline sarcoma viral oncogene v-KIT, which encodes the tyrosine kinase receptor protein KIT. Mutations and varied expression of this gene have been demonstrated within multiple neoplasms in people and domestic animals. The purpose of this study was to determine if KIT protein is expressed in feline soft tissue fibrosarcomas (ST FSA) using immunohistochemistry (IHC). The computer database at the Oklahoma Animal Disease Diagnostic Laboratory was searched from January 1, 2006, to December 31, 2007, for any domestic cat with an ST FSA. Routinely stained slides from 46 feline ST FSAs were reviewed and graded based on the scale outlined by Kuntz et al. Immunohistochemistry for KIT protein was performed on one representative section from each cat. There were a total of 12/46 (26%) cats that were immunoreactive for KIT. Immunoreactivity was detected in greater than 80% of the neoplastic cells in 4/46 (9%) cats. Immunoreactivity was detected in less than 10% of the neoplastic cells in 8/46 (17%) cats. Immunoreactivity was characterized by evenly distributed cytoplasmic stippling within the neoplastic spindle-shaped cells and/or multinucleated giant cells. Based on these results, KIT immunoreactivity can be detected within feline ST FSAs using IHC. The results of this study also indicate that KIT immunoreactivity in feline ST FSA does not correlate with the histologic grade (P = .141, X(2) = 2.166), survivability (P = .241, X(2) = 1.373), or whether the neoplasm was a spontaneous or an injection site FSA (P = .074, X(2) = 3.184).

Ovarian and intestinal angiomatosis in a horse.

Dozens of red, raised nodules scattered along the serosal surface of the small intestine and the right and left ovaries were observed as incidental findings on gross examination in a 21-year-old Thoroughbred mare euthanatized for severe lameness. Histologically, these nodules were composed of numerous, variably sized, redundant vascular profiles filled with red blood cells and fibrin thrombi. Based on the presence of multiple nodules composed of benign vascular channels scattered within the small intestine and ovary, a diagnosis of angiomatosis is proposed. To the authors' knowledge, this is the first report of small intestinal and ovarian angiomatosis in a horse.

Coronary aneurysms in patients with autosomal dominant polycystic kidney disease.

Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased risk of intracranial aneurysms. Reports on arterial aneurysms in other locations have not been conclusive. The present study was initiated to investigate the prevalence of coronary aneurysms. Thirty ADPKD patients who had undergone coronary angiography on clinical indication were identified, 15 after renal transplantation. For each ADPKD patient, a control patient was identified with end-stage renal disease, investigated by coronary angiography, and matched for age, sex, and time relation to transplantation. All angiograms were retrieved and reevaluated with respect to aneurysms, defined as an increase in artery diameter by 50% or more, as well as to pathologic ectasias not fulfilling this criterion. Aneurysms were detected in four ADPKD patients and two control subjects. Five more ADPKD patients, but none of the control subjects, had minor ectasias. One ADPKD patient had a dissecting aortic aneurysm, and another died of aortic dissection during bypass surgery. This study adds to the evidence of an increased risk of extracranial aneurysms in ADPKD patients.

Prediction of left ventricular dysfunction in coronary artery disease from clinical and exercise test findings.

We studied the ability to predict depressed left ventricular ejection fraction (LVEF) from clinical and exercise test findings prior to surgery in consecutive patients who underwent coronary artery bypass grafting (CABG) from 1988 to 1991 (n = 663). Multivariate analysis showed a history of myocardial infarction, pathological Q-wave in resting ECG, systolic blood pressure at maximal exercise and the degree of mitral regurgitation as significant independent predictors of impaired LVEF. The relative risk (RR) of depressed LVEF was markedly increased for a previous history of myocardial infarction (RR 3.3, p < 0.0001) and a pathological Q-wave in resting ECG (RR 2.4, p < 0.0001). All associations found between depressed LVEF and exercise test results were poor, and of little value for discriminating patients with depressed LVEF. Thus, clinical data appear to be better markers of low LVEF than the information obtained from the exercise test.

Magnetic resonance imaging in the follow-up of patients after aortic root reconstruction.

Long-term survival after replacement of the aortic root with a composite graft is improving. Late deaths are in several cases due to complications related to the previous surgery or to pathologies of the remaining aorta. Regular follow-up of these patients is of paramount importance. The purpose of this study is to evaluate the reliability of magnetic resonance imaging (MRI) in such cases. Twenty-seven patients (9 dissections and 18 aneurysms) who had undergone replacement of the aortic root with a composite graft were studied 20 to 167 months after surgery using magnetic resonance imaging with a 1.5 Tesla magnet. The left-ventricular outflow tract, the mechanical valve function, the proximal part of the coronary arteries, the graft, and the remaining aorta could be examined. No aortic insufficiency, ectasy of the proximal part of the coronaries, or pseudoaneurysms were seen. A widening of the remaining ascending aorta was noted in 4 cases. A still open, dissected pipe was visualized in 7 patients. Our conclusions are that MRI provides excellent images of the thoracic and abdominal aorta following surgical repair. The examination is becoming cost-competitive. More import is its very low risk for the patient group considered here: since it is non-invasive and requires no contrast medium or X-ray exposure, examinations can be repeated as required.

Quantification of Birbeck's granules in human Langerhans' cells.

A proper understanding of the function of Birbeck's granules requires that they should be counted under various conditions. We now present a simple quantification method which does not depend on specific assumptions concerning size, shape or location of the particles counted and can, moreover, be applied for counting other subcellular structures as well. A population of 69 serially sectioned human Langerhans' cells had an average of 290 granules and no cell contained fewer than 96 granules, indicating that as they degrade, granules are continuously formed. Suprabasal Langerhans' cells contained significantly more granules than did the basal cells.

Tracheal relaxant and cardiostimulant actions of xanthines can be differentiated from diuretic and CNS-stimulant effects. Role of adenosine antagonism?

Theophylline (1, 3-dimethylxanthine) and enprofylline (3-propylxanthine) have been examined for effects in the rat. Enprofylline was 3.8 times as potent as theophylline as a tracheal relaxant in vitro, and 1.3 times as potent as theophylline to increase the rate of isolated perfused hearts. An oral dose (5 mg/kg) of enprofylline to rats was almost completely recovered in the urine as unchanged drug, showing that this xanthine is well absorbed and negligibly metabolised. Theophylline (10 and 30 mg/kg p.o.) significantly and dose-dependently increased locomotor activity in rats whereas the same doses of enprofylline were without effect on behaviour. Theophylline ( 5-20 mg/kg p.o.) produced significant and dose-dependent natriuretic and volume diuretic effect with little augmentation of potassium excretion. Enprofylline up to 10 mg/kg was without diuretic effects. At the large dose of 20 mg/kg enprofylline decreased sodium excretion and produced some volume diuresis. It is suggested that lack of diuretic and CNS-stimulant behavioural effects by enprofylline is due to its low ability to antagonise adenosine receptor stimulation. Pharmacodynamic differences between enprofylline and the potent adenosine antagonist theophylline may indicate a functional importance of endogenous adenosine.