Cutaneous habronemosis in horses: First molecular characterization of Habronema muscae in Israel.

Draschia megastoma, Habronema microstoma, and Habronema muscae are the etiological agents of cutaneous habronemosis, commonly known as summer sores, an inflammatory cutaneous and ocular parasitic disease of horses and other equids transmitted by flies. Here, we describe a cluster of cutaneous habronemosis in five horses that showed single or multiple typical cutaneous ulcerative wounds located on the face, lower forelegs or hindquarters in Israel with the presence of typical "sulphur granules." All affected animals were confirmed by histopathological and/or molecular methods to be infected by H. muscae. This constitutes the first report of cutaneous habronemosis in Israel in which the causative nematode, H. muscae, was identified by molecular means. Cutaneous habronemosis should be considered as a differential diagnosis in equids with cutaneous ulcerative lesions during the summer months, especially when affected animals are refractive to antibiotic treatment alone.

Characterization of a porcine model of post-operative pain.

BACKGROUND: Management of acute pain related to surgical intervention, termed post-operative pain or POP, continues to be a major healthcare challenge. While the rat plantar incision model provides valuable data to researchers about the mechanisms mediating POP, the development of topical and localized treatments in small animal models is limited. To help address these issues, we describe here the characterization of a large animal model of incisional pain. METHODS: Pigs underwent full-skin incision or full-skin and muscle incision and retraction (SMIR). Withdrawal thresholds were determined using the Von Frey test at baseline, 0.5-12 h post-surgery and on days 1, 2, 3, 5 and 7 post-surgery. The analgesic effects of systemic morphine [0.1 or 1.0 mg/kg intramuscular (i.m.) dose] and local anaesthetic ropivacaine were studied. Spontaneous pain-like behaviours were scored and analysed. The effects on wound healing were evaluated by gross observation and by histopathological examination. RESULTS: Pigs incurring SMIR demonstrated significantly increased mechanical hypersensitivity compared with pigs that underwent full-skin incision only (p < 0.05). Maximal analgesia was achieved with morphine (1 mg/kg i.m. dose) at 0.5 h post-treatment. Local treatment with ropivacaine was effective at increasing the withdrawal threshold to Von Frey filaments compared with saline control (p < 0.05) for a period of at least 6 h. Wounds healed normally with no signs of infection, redness or swelling. CONCLUSIONS: We propose that the pig model of incisional pain can provide an appropriate translational model for validating new topical and localized treatments for POP in humans.

The evaluation of a novel technique to treat saphenous vein incompetence: preclinical animal study to examine safety and efficacy of a new vein occlusion device.

OBJECTIVES: We tested a novel technique to treat great saphenous vein (GSV) incompetence in an animal model. METHODS: V-block (VVT Medical Ltd, Kfar Saba, Israel), an occlusion device composed of a nitinol frame and anchoring hooks, was percutaneously deployed at the saphenofemoral junction in 12 sheep. Four of the 12 sheep were treated with adjunctive liquid sclerotherapy. Animals underwent duplex ultrasound, venography and histopathological evaluation immediately postimplantation at 30, 60 and 90 days. RESULTS: V-block was successfully deployed in all animals without adverse events. There was no device migration at follow-up. Histopathological analysis demonstrated V-block to be lodged within the GSV and surrounded by fibrous tissue in all samples. Obliteration of the GSV lumen, widespread intimal loss and multifocal medial smooth muscle loss was noted. CONCLUSIONS: In this animal study V-block was deployed without complications, remained in stable position and led to GSV occlusion. This device has promise for future use in humans.

Biopsy of the mouse prostate.

Many transgenic and knockout mouse models of prostate cancer have become available over the past decade. In this paper we describe a simple biopsy technique of the murine prostate. This technique allows sequential follow-up of the prostate in an individual mouse. Its use could also reduce the number of mice used in studies of the prostate gland.

Blocking of the placental immune-modulatory ferritin activates Th1 type cytokines and affects placenta development, fetal growth and the pregnancy outcome.

BACKGROUND: Placenta immunomodulatory ferritin (PLIF) cDNA was recently cloned from the human placenta, where it is expressed in syncytiotrophoblast and decidual mononuclear cells. PLIF and its subcloned bioactive domain (C48), expressed in Escherichia coli, are immunosuppressive proteins and induce pronounced IL-10 production in vitro and in vivo. METHODS AND RESULTS: PLIF serum level, measured by enzyme-linked immunosorbent assay, was elevated in pregnant mice throughout gestation and declined towards delivery. Blocking of PLIF activity by vaccination of mice with C48 prior to mating inhibited pregnancy development. Passive transfer of anti-C48 immunoglobulin (Ig) starting at 3.5-12.5 days post coitum (dpc) resulted in high rate of embryo resorption. Furthermore, treatment with anti-C48 Ig resulted in placental and embryonal growth restriction. At gestation day 13.5, growth retardation was especially notable in the placentae, while at 16.5 dpc it was pronounced in the embryos. Histopathological examination revealed that experimental placentae were globally hypoplastic and the labyrinth was strikingly pale and contained less maternal blood compared with control. Immune-activated spleen cells harvested at 13.5 dpc from anti-C48 Ig-treated pregnant mice secreted in vitro increased level of Th1 cytokines (IL-2, TNF-alpha, IL-12) and decreased level of Th2 cytokines (IL-10, IL-4, IL-5, IL-6) as compared with the level of the respective cytokines secreted by spleen cells from control pregnant mice. CONCLUSION: This study provides the first in vivo evidence that PLIF plays a major role in placentation and embryonic growth.

Lack of MHC expression and retention of ultrastructural characteristics by xenograft transmissible venereal tumor cells in SCID mice.

Canine transmissible venereal tumor (CTVT) is primarily a tumor of adult dogs with a high incidence of spontaneous regression. We recently reported a xenograft model of CTVT (XTVT) in NOD/SCID mice. XTVT cells retain cytological and histological features of CTVT as well as characteristic rearranged LINE/c-MYC junction [Am. J. Vet. Res. 62 (2001) 907]. In this paper, we demonstrate that XTVT cells maintain ultrastructural characteristics of CTVT and do not express MHC classes I and II molecules.

Spatial and temporal expression pattern of Runx3 (Aml2) and Runx1 (Aml1) indicates non-redundant functions during mouse embryogenesis.

The human RUNX3/AML2 gene belongs to the 'runt domain' family of transcription factors that act as gene expression regulators in major developmental pathways. Here, we describe the expression pattern of Runx3 during mouse embryogenesis compared to the expression pattern of Runx1. E10.5 and E14.5-E16.5 embryos were analyzed using both immunohistochemistry and beta-galactosidase activity of targeted Runx3 and Runx1 loci. We found that Runx3 expression overlapped with that of Runx1 in the hematopoietic system, whereas in sensory ganglia, epidermal appendages, and developing skeletal elements, their expression was confined to different compartments. These data provide new insights into the function of Runx3 and Runx1 in organogenesis and support the possibility that cross-regulation between them plays a role in embryogenesis.

Self prion protein peptides are immunogenic in Lewis rats.

Prion diseases are caused by abnormal folding of the prion protein. The paradigm is that the prion protein is not immunogenic because the immune system must be tolerant to such a self protein. In an attempt to identify immunogenic prion peptides, we immunized Lewis rats with peptides that fitted the MHC class II RT1.B(1)motif. Both humoral and cellular immunity to the prion peptides were obtained without any harmful effects to young animals. However, when 8-month-old rats were immunized, a sixth (6/36) of the rats developed severe skin inflammation with concomitant hair loss. These findings suggest that immunity to self-prion peptides can be readily induced in Lewis rats and that this immune response may have pathogenic consequences in older rats.

Alaskan Husky encephalopathy--a canine neurodegenerative disorder resembling subacute necrotizing encephalomyelopathy (Leigh syndrome).

The gross and histopathological findings in the brain and spinal cord of five Alaskan Husky dogs with a novel incapacitating and ultimately fatal familial and presumed hereditary neurodegenerative disorder are described. Four dogs presented with neurological deficits before the age of 1 year (7-11 months) and one animal at 2.5 years old. Clinical signs in all dogs were of acute onset and included ataxia, seizures, behavioral abnormalities, blindness, facial hypalgesia and difficulties in prehension of food. In animals allowed to survive, the disease was static but with frequent recurrences. Pathological findings were limited to the central nervous system. Grossly visible bilateral and symmetrical cavitated foci were consistently present in the thalamus with variable extension into the caudal brain stem. Microscopic lesions were more widespread and included foci of bilateral and symmetrical degeneration in the basal nuclei, midbrain, pons and medulla, as well as multifocal lesions at the base of sulci in the cerebral cortex and in the gray matter of cerebellar folia in the ventral vermis. Neuronal loss with concomitant neuronal sparing, spongiosis, vascular hypertrophy and hyperplasia, gliosis, cavitation and transient mixed inflammatory infiltration were the main histopathological findings. In addition, a population of reactive gemistocytic astrocytes with prominent cytoplasmic vacuolation was noted in the thalamus. Lesions of this nature in this distribution within the neuroaxis have not been reported in dogs. The neuropathological findings resemble Leigh's disease/subacute necrotizing encephalomyelopathy of man. Neuronal sparing in conjunction with apparently transient astrocytic vacuolation point to the possible pathogenetic role of astrocytes in the evolution of these lesions. An inherited metabolic derangement of unknown nature is postulated as the cause of this breed-specific disorder.

Subacute necrotising encephalopathy in an Alaskan husky.

A 29-month-old female Alaskan husky was presented recumbent, tetraparetic and in a state of dementia, with blindness and cranial nerve deficits. The dog's progress was followed for over two months, as the signs resolved to an non-progressive mild hypermetria with slight proprioceptive ataxia, a diminished menace response and inability to prehend food. Magnetic resonance imaging (MRI) revealed bilateral cavitation extending from the thalamus to the medulla, with less pronounced degenerative lesions in the caudate nucleus, putamen and claustrum. Cerebrospinal fluid lactate and pyruvate concentrations were in their normal ranges. Necropsy and histological examination confirmed the MRI findings as well as neuronal degeneration of the cerebellar cortex in the vermis and degenerative changes in the neocortex at the depths of the cerebral sulci. In view of the similarity of lesions to subacute necrotising encephalomyelopathy, known as Leigh's disease in humans, a tentative diagnosis of a mitochondrial encephalopathy was made.

The impact of perceptions and stereotypes on the managerial mobility of African Americans.

Although African Americans have made progress in reaching middle and upper management positions, a disproportionate number are stalled in lower levels of management where their remuneration often lags behind that of Whites in comparable positions. Further penetration into executive ranks may depend largely on the perceptions and attitudes of employers. Negative stereotypes held by top managers may have a deleterious effect on African American opportunities. Among a sample of White middle managers, Schein's (1973, 1975) descriptive index revealed a significant resemblance between ratings of Whites and ratings of managers (r' = .54), whereas the resemblance between ratings of Blacks and ratings of managers was nonsignificant (r' = .17). Managers were perceived to possess characteristics more commonly ascribed to Whites than to African Americans.

A canine encephalomyelopathy with morphological abnormalities in mitochondria.

A progressive encephalomyelopathy of insidious onset affecting a 16-month-old dog is described. Clinically, the dog was ataxic, stumbled into objects and showed mild behavioral abnormalities. Light microscopic findings included profound degeneration and astrogliosis of the optic pathways, loss of Purkinje neurons, focal bilateral and symmetrical brain stem spongiosis and diffuse neuroaxial astrogliosis with swollen and abnormally shaped nuclei. Ultrastructurally, there were giant and bizarre mitochondria within neuronal perikarya and axons as well as diffuse loosening of the cerebral and cerebellar neuropil. These neuropathological findings resemble the mitochondrial encephalomyopathies of man.

Hereditary polioencephalomyelopathy of the Australian cattle dog.

A vacuolar degeneration affecting primarily the gray matter in the central nervous system (CNS) of young Australian Cattle Dogs is described. An initial presentation of seizures was followed by a progressive spastic tetraparesis. Grossly evident bilateral and symmetrical foci of malacia were in the nuclei of the cerebellum and brain stem and the gray matter of the spinal cord. Microscopically, vacuolation of glial cells, dilation of the myelin sheaths and reactive astrocytosis characterized mild CNS changes. More advanced lesions displayed progressive dissolution of the neuropil, prominent vacuolation of reactive astrocytes, numerous glial fibrillary acidic protein-positive coiled astrocytic processes, neuronal vacuolation and loss with relative sparing of large neurons. Ultrastructurally marked mitochondrial accumulation and swelling were seen in astrocytes. In the appendicular muscles, changes interpreted as long-term denervation atrophy accompanied by widespread expression of the neonatal isoform of myosin were observed. The character of the neurological sings, the nature and the distribution of the lesions within the neuroaxis have not been reported in domestic animals. An inherited biochemical defect, possibly mitochondrial, is proposed as the cause. Selected conditions with a bilateral and symmetrical distribution affecting the gray matter of domestic animals are summarized.

Characterization of the dihydropyridine binding sites of rat neocortical synaptosomes and microvessels.

The dihydropyridine binding sites associated with rat neocortical synaptosomes and microvessels were compared using an in vitro [3H]PN 200-110 [(+)-[methyl-3H]-isopropyl 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-2,6-dimethyl-5- methoxycarbonylpyridine-3-carboxylate] binding assay. Saturation experiments yielded similar KD values (approximately 70 pM) and Bmax values (approximately 400 fmol/mg of protein) for the two membrane preparations. Interaction experiments with [3H]PN 200-110 and various calcium-modulating substances provided further evidence for the practically identical nature of the synaptosomal and microvascular dihydropyridine binding sites. These findings predict that lipophilic dihydropyridines, simultaneously occupying the two central binding sites, have the dual effect of altering neuronal function and local blood flow.

Predicting WRAT scores from the WISC-R for a selected sample of LD children and youth.

Investigated the concurrent validity of the WISC-R 11 subtests and three IQs as related to the WRAT standard scores. Correlations were computed for a sample of 28 children (20 boys, 8 girls), aged 7-9 to 16-5 (means of 11-8), who were diagnosed learning disabled by LEA placement terms according to state and federal guidelines. Regression analysis used all three Wide Range Achievement subtests as criteria, and the 11 subtests and three IQ scale scores of the WISC-R as predictors. The results did not support the concurrent validity of the WISC-R for this sample of disabled children and youth.

Modulation of [3H]muscimol binding in rat cerebellar and cerebral cortical membranes by picrotoxin, pentobarbitone, and etomidate.

Modulation of [3H]muscimol binding by picrotoxin, pentobarbitone, and etomidate was investigated in rat cerebellar and cerebral cortical membranes. In cerebellum, at 37 degrees C in the presence of chloride ions (150 mM), picrotoxin and picrotoxinin decreased specific [3H]muscimol binding to 43 +/- 3% of control, with an EC50 of 1.2 +/- 0.1 microM. [3H]Muscimol saturation experiments in the presence and absence of picrotoxin indicated that the picrotoxin effect was primarily due to a loss of high-affinity muscimol sites with KD approximately equal to 10 nM. Pentobarbitone enhanced specific [3H]muscimol binding to 259 +/- 3% of control, with EC50 = 292 +/- 37 microM, and etomidate increased binding to 298 +/- 18%, with EC50 = 7.1 +/- 1.0 microM. The influence of temperature and chloride ion concentration on these effects was investigated by comparing experiments at 37 and 0 degrees C in the presence or absence of chloride at constant ionic strength. The results indicate that studies at 0 degrees C underestimate the coupling between GABA receptors and barbiturate sites and that they greatly overestimate the importance of chloride ions in this phenomenon. In cerebral cortical membranes (37 degrees C, 150 mM Cl-), the effect of picrotoxin was similar to that observed in cerebellum, whereas the effects of pentobarbitone and etomidate were greater, but occurred at higher concentrations.

WISC-R profile analysis in differentiating LD from ED children.

Investigated the utility of profile analysis, using the WISC-R to differentiate learning disabled from emotionally disturbed and nonhandicapped children. Little evidence was found to support the use of WISC-R subtest scatter, and profile analysis was discussed. Research efforts that focus upon the meaning of WISC-R subtests in relation to the learning process were recommended.