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C N Hahn

Publications and source records attributed to C N Hahn.

At least 19 recordsLinked to original sources

Horses on pasture may be affected by equine motor neuron disease.

REASONS FOR PERFORMING STUDY: Equine motor neuron disease (EMND) was diagnosed in 3 horses maintained on lush, grass-based pasture. This contrasted with North American studies which identified limited or no access to green herbage as an important risk factor for EMND. HYPOTHESIS: Grazing horses that have an apparently adequate intake of pasture herbage to meet normal equine vitamin E requirements can develop EMND. METHODS: Owners of 32 European horses diagnosed with EMND completed a questionnaire regarding intrinsic, managemental, nutritional and environmental factors that could potentially be risk factors for EMND, and also regarding clinical signs, treatments and case outcome. Plasma/serum vitamin E data for these horses were supplied by the veterinarians. No control population was studied. RESULTS: Thirteen of 32 horses (termed the 'grazing' group) had part- or full-time access to grass-based pasture at the onset of EMND (median duration at pasture 12 h/day, range 3-24 h). Five of these horses were at pasture for at least 235 h/day at the onset of EMND, 2 of which were at pasture for at least 23.5 h/day throughout the year. Despite grazing, all these horses had a low vitamin E status. The remaining 19 horses resembled those cases reported from North America, in that they had no or limited access to pasture. CONCLUSIONS AND POTENTIAL RELEVANCE: A diagnosis of EMND should not be discounted on the basis that a horse has access, even full-time, to lush grass-based pasture. Inadequate vitamin E intake was probably not the sole cause of either the EMND or the low vitamin E status in the grazing horses; the latter was probably the result of abnormal bioavailability or excessive utilisation of vitamin E.

Animal Feed↗

Expression profiling reveals functionally important genes and coordinately regulated signaling pathway genes during in vitro angiogenesis.

Angiogenesis is a complex multicellular process requiring the orchestration of many events including migration, alignment, proliferation, lumen formation, remodeling, and maturation. Such complexity indicates that not only individual genes but also entire signaling pathways will be crucial in angiogenesis. To define an angiogenic blueprint of regulated genes, we utilized our well-characterized three-dimensional collagen gel model of in vitro angiogenesis, in which the majority of cells synchronously progress through defined morphological stages culminating in the formation of capillary tubes. We developed a comprehensive three-tiered approach using microarray analysis, which allowed us to identify genes known to be involved in angiogenesis and genes hitherto unlinked to angiogenesis as well as novel genes and has proven especially useful for genes where the magnitude of change is small. Of interest is the ability to recognize complete signaling pathways that are regulated and genes clustering into ontological groups implicating the functional importance of particular processes. We have shown that consecutive members of the mitogen-activated protein kinase and leukemia inhibitory factor signaling pathways are altered at the mRNA level during in vitro angiogenesis. Thus, at least for the mitogen-activated protein kinase pathway, mRNA changes as well as the phosphorylation changes of these gene products may be important in the control of blood vessel morphogenesis. Furthermore, in this study, we demonstrated the power of virtual Northern blot analysis, as an alternative to quantitative RT-PCR, for measuring the magnitudes of differential gene expression.

Bayes Theorem↗

Observations on the interstitial cells of Cajal and neurons in a recovered case of equine dysautonomia (grass sickness).

This paper describes the histopathological and immunohistochemical changes in the central, autonomic and enteric nervous systems in a well-documented case of equine dysautonomia (ED), after the animal had recovered without significant residual clinical signs. Evidence of neuronal degeneration, such as neuronal chromatolysis, glial scars or a decrease in density of neurons, was not observed in the midbrain, pons, medulla oblongata or spinal cord, including the nuclei of cranial nerves III, V, VII, X and XII. In addition, no evidence of muscle denervation or re-innervation, such as group atrophy of clusters of cells or grouping of cells of similar size in the triceps muscle, was observed. These findings support the hypothesis that the chromatolytic motor neurons may not progress to cell death in ED. The autonomic ganglia showed evidence of previous neuronal loss. In the myenteric and submucosal plexuses of the ileum there was significant loss of enteric neurons. However, in the ileum, a continuous network of interstitial cells of Cajal (ICC) was observed by means of immunohistochemical techniques. It is possible that recovery without significant residual clinical signs was associated with lack of damage to, or more likely recovery of, the ICC, which have a pacemaker function in the intestinal tract.

Animals↗

Thoracolaryngeal reflex latencies in Thoroughbred horses with recurrent laryngeal neuropathy.

Electrolaryngeography was used to study the latencies of the thoracolaryngeal adductor reflex in Thoroughbred horses with and without recurrent laryngeal neuropathy (RLN). Latencies were compared in horses with grades 1 and 2 RLN, diagnosed by endoscopy in resting horses. The reliability of the measurements, effect of sedation and correlations of latencies with age of the horse were also studied. There was no effect of sedation on reflex latency periods. The latency of the reflex period measured to a convolved peak of the electromyographic response was significantly different in horses with grades 1 and 2 disease; medians and quartile ranges were 0.067 (0.065-0.073) and 0.072 (0.068-0.074) s, respectively (P<0.05). Significant associations were found between reflex latencies and both horse age and the grade of RLN. Reflex latency measurements are reliable and sensitive, and may assist with the clinical appraisal of Thoroughbred horses with RLN.

Animals↗

Central neuropathology of equine grass sickness.

Equine grass sickness (EGS) is an acquired disease of unknown aetiology affecting horses kept at grass. The disease is characterised by postganglionic sympathetic and parasympathetic neuronal pathology and is categorised as a dysautonomia. This study undertook a systematic examination of brain stem cranial nerve nuclei in 59 cases of EGS. Pathology consisting of neuronal chromatolysis was most consistently noted in the lower motor neurons of the general visceral efferent nucleus of CN III and X and the general somatic efferent nuclei of CN III, V, VII and XII. The prevalence of chromatolysis differed significantly between the diagnostic categories and was inversely related to the age of the animal. Duration of disease had a small but significant negative effect on the proportion of nuclei with chromatolytic neurons in chronic cases. The distribution of chromatolytic neurons is unlike that reported in any other equine or human disease; however, it appears to be equivalent to that in other animals with primary dysautonomias. EGS should be classified as a multisystem disease.

Age Factors↗

Phenylephrine eyedrops as a diagnostic test in equine grass sickness.

The effect of an ocular administration of the alpha-1 adrenergic agonist phenylephrine was studied in 23 cases of grass sickness and 12 control horses. In the horses with grass sickness there was a significantly greater mean increase in the size of the palpebral fissure, as measured by the change in the angle of the eyelashes to the head observed from a frontal view.

Adrenergic alpha-Agonists↗

Osteoblast gene expression in rat long bones: effects of ovariectomy and dihydrotestosterone on mRNA levels.

The steroid sex hormones exert major effects on bone formation although the molecular events associated with their activity remain unclear. We have investigated the effects of ovariectomy and dihydrotestosterone (DHT) administration to both sham-operated and ovariectomized (ovx) rats on the bone mRNA levels of osteoblast genes. Rats were randomly allocated to either sham or ovariectomy operations and were administered either vehicle or 40 mg/ kg body weight DHT by silastic tube implants at the time of operation for 8 weeks, at which time they were killed and total RNA was extracted from the long bones. Northern blot analysis indicated that the mRNA levels of the bone cell genes alpha1(I) collagen, alkaline phosphatase, osteocalcin, and osteopontin were markedly increased in ovx rats between 6- and 30-fold. DHT administration to ovary-intact, estrogen-sufficient rats increased the mRNA levels of alpha1(I) collagen, alkaline phosphatase, osteopontin, and osteocalcin between 3- and 9-fold. In contrast, DHT did not alter levels of these mRNA species in ovx rats. The data demonstrate that estrogen deficiency increased mRNA levels of genes expressed during osteoblast development and suggest an interplay between estrogen and androgen action in regulating the expression of a number of bone cell genes.

Alkaline Phosphatase↗

Studies on the experimental induction of ptosis in horses.

The precise appearance of ptosis due to lesions at different sites was investigated in experimental ponies. The angles of the eyelashes to the head was used as an objective measurement of ptosis after local anaesthesia of the sympathetic trunk or the palpebral nerve and the administration of an ocular alpha agonist or antagonist. It was shown that ptosis is not an inevitable consequence of palpebral nerve pathology, that ocular alpha antagonists can induce ptosis, and that alpha agonist eyedrops have an inconsistent effect on the equine pupil, but are consistent at reversing ptosis induced by sympathetic denervation in unsedated horses.

Administration, Topical↗

Examination of the laryngeal musculature and recurrent laryngeal nerves of zebra (Equus burchelli) for evidence of idiopathic laryngeal hemiplegia.

AIMS: This study was undertaken in order to determine whether wild Burchell's Zebra (Equus burchelli) are affected by Idiopathic Laryngeal Hemiplegia (ILH). ILH has a high prevalence in the domestic horse and a negative control population has not been identified. METHODS: The work was conducted in two phases on two large farms in central Kenya during routine culls. The larynges of 42 zebra were removed and the left and right intrinsic laryngeal adductor and abductor muscles and recurrent laryngeal nerves were isolated. The muscles were weighed and biopsy samples of left and right recurrent laryngeal nerve and cricoarytenoideus lateralis muscles from 16 animals were taken for histological examination. RESULTS: Left adductor muscles were observed to be significantly lighter than right adductor muscles (p = 0.001). There was no significant difference between the weights of left and right laryngeal abductors (p = 0.260). There was no light microscopic evidence of pathological changes consistent with ILH in any of the muscle or nerve samples. CONCLUSIONS: Zebra do not appear to suffer from ILH and equids unaffected by ILH can have significantly lighter muscles on the left of the larynx. CLINICAL RELEVANCE: Mild asymmetries of the larynx on palpation may not be a reliable indicator of ILH. Zebra may be a potentially useful negative control animal for observational ILH studies.

Journal Article↗

Expression of vasoactive intestinal peptide, calcitonin gene-related peptide, substance P, and intermediate neurofilaments in nasal mucosal nerve fibers of horses without nasal disease.

OBJECTIVE: To determine the distribution of nerve fibers containing calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and intermediate neurofilaments in nasal mucosa of horses. ANIMALS: 6 horses without evidence of nasal disease. PROCEDURE: Full-thickness nasal tissue specimens were obtained from the rostral portion of the nasal septum at necropsy, and fluorescence immunohistochemistry was performed to assess mucosal distribution of nerve fibers. RESULTS: Nerve fibers with CGRP-like immunoreactivity (CGRP-Li) formed a dense subepithelial network, and a large number of fibers were found coursing between epithelial cells. Fibers with CGRP-Li were also associated with blood vessels and mucous glands. Fibers with SP-like immunoreactivity (SP-Li) had a similar distribution and density. In contrast, there were few fibers with VIP-like immunoreactivity. Fibers containing intermediate neurofilaments were prominent and appeared as large nerve fiber bundles mainly adjacent to the nasal septum but also close to mucous glands and within the lamina propria. Intermediate neurofilaments were also identified in single nerve fibers at all sites, but the density of fibers with intermediate neurofilaments did not match that of fibers with CGRP- or SP-Li. CONCLUSIONS: The density and distribution of nerve fibers containing SP- or CGRP-Li in nasal mucosa of horses was similar to that reported for other species. However, expression of VIP in nerve fibers was low. Antibodies against intermediate neurofilaments identified many nerve fibers in nasal mucosa of horses but did not appear to identify small diameter fibers expressing SP or VIP.

Animals↗

Do giraffe roar?

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Animals↗

The distribution of nerve fibres immunoreactive for vasoactive intestinal peptide, calcitonin gene-related peptide, substance P and dopamine beta-hydroxylase in the normal equine larynx.

The autonomic innervation of the mammalian respiratory system is complex, and involves a wide variety of peptide and non-peptide neurotransmitters which will have an important role in normal laryngeal function and the response to disease. This innervation has been partially described in the horse airway and lung, but there is no information on the equine larynx. This paper describes the expression and distribution of nerve fibres immunoreactive for vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP) and the adrenergic enzymatic marker dopamine beta-hydroxylase (DBetaH) in the mucosa of the equine larynx. The overall relative density of nerve fibres immunoreactive for the different antigens was VIP>>CGRP>SP>>DBetaH. There were differences in the distribution of nerve fibre types, although each antigen was found in nerve fibres adjacent to blood vessels and mucous glands. VIP -like immunoreactivity (VIP -Li) was particularly extensive in association with mucous glands. SP - and CGRP -like immunoreactivity (SP -Li, CGRP -Li) were also seen close to the epithelium, with occasional nerve fibres coursing beneath and between the epithelial cells. Fragments of SP -Li and CGRP -Li fibres were also present in large nerve fibre bundles and ganglionic cell clusters, but not in the neurons themselves. The density of nerve fibres immunoreactive for DBetaH was very low and restricted to blood vessels and mucous glands. There was marked variation in the density of nerve fibres at the different sites, with the greatest density, particularly for VIP, over the arytenoid cartilage. Immunoreactive nerve fibres were less plentiful over the epiglottis, and the density of all types of nerve fibres was low over the cricoid cartilage. Overall VIP -Li nerve fibres were the most plentiful.

Animals↗

Correction of murine galactosialidosis by bone marrow-derived macrophages overexpressing human protective protein/cathepsin A under control of the colony-stimulating factor-1 receptor promoter.

Galactosialidosis (GS) is a human neurodegenerative disease caused by a deficiency of lysosomal protective protein/cathepsin A (PPCA). The GS mouse model resembles the severe human condition, resulting in nephropathy, ataxia, and premature death. To rescue the disease phenotype, GS mice were transplanted with bone marrow from transgenic mice overexpressing human PPCA specifically in monocytes/macrophages under the control of the colony stimulating factor-1 receptor promoter. Transgenic macrophages infiltrated and resided in all organs and expressed PPCA at high levels. Correction occurred in hematopoietic tissues and nonhematopoietic organs, including the central nervous system. PPCA-expressing perivascular and leptomeningeal macrophages were detected throughout the brain of recipient mice, although some neuronal cells, such as Purkinje cells, continued to show storage and died. GS mice crossed into the transgenic background reflected the outcome of bone marrow-transplanted mice, but the course of neuronal degeneration was delayed in this model. These studies present definite evidence that macrophages alone can provide a source of corrective enzyme for visceral organs and may be beneficial for neuronal correction if expression levels are sufficient.

Animals↗

Lack of PPCA expression only partially coincides with lysosomal storage in galactosialidosis mice: indirect evidence for spatial requirement of the catalytic rather than the protective function of PPCA.

Protective protein/cathepsin A (PPCA) is a pleiotropic lysosomal enzyme that complexes with beta-galactosidase and neuraminidase, and possesses serine carboxypeptidase activity. Its deficiency in man results in the neurodegenerative lysosomal storage disorder galactosialidosis (GS). The mouse model of this disease resembles the human early onset phenotype and results in severe nephropathy and ataxia. To understand better the pathophysiology of the disease, we compared the occurrence of lysosomal PPCA mRNA and protein in normal adult mouse tissues with the incidence of lysosomal storage in PPCA(-/-) mice. PPCA expression was markedly variable among different tissues. Most sites that produced both mRNA and protein at high levels in normal mice showed extensive and overt storage in the knockout mice. However, this correlation was not consistent as some cells that normally expressed high levels of PPCA were unaffected in their storage capability in the PPCA(-/-) mice. In addition, some normally low expressing cells accumulated large amounts of undegraded products in the GS mouse. This apparent discrepancy may reflect a requirement for the catalytic rather than the protective function of PPCA and/or the presence of cell-specific substrates in certain cell types. A detailed map showing the cellular distribution of PPCA in nomal mouse tissues as well as the sites of lysosomal storage in deficient mice is critical for accurate assessment of the effects of therapeutic interventions.

Animals↗