Publications (3)11.53 Total impact
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Article: Replacing the enzyme alpha-L-iduronidase at birth ameliorates symptoms in the brain and periphery of dogs with mucopolysaccharidosis type I.
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ABSTRACT: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by loss of activity of α-l-iduronidase and attendant accumulation of the glycosaminoglycans dermatan sulfate and heparan sulfate. Current treatments are suboptimal and do not address residual disease including corneal clouding, skeletal deformities, valvular heart disease, and cognitive impairment. We treated neonatal dogs with MPS I with intravenous recombinant α-l-iduronidase replacement therapy at the conventional 0.58 mg/kg or a higher 1.57 mg/kg weekly dose for 56 to 81 weeks. In contrast to previous results in animals and patients treated at a later age, the dogs failed to mount an antibody response to enzyme therapy, consistent with the induction of immune tolerance in neonates. The higher dose of enzyme led to complete normalization of lysosomal storage in the liver, spleen, lung, kidney, synovium, and myocardium, as well as in the hard-to-treat mitral valve. Cardiac biochemistry and function were restored, and there were improvements in skeletal disease as shown by clinical and radiographic assessments. Glycosaminoglycan levels in the brain were normalized after intravenous enzyme therapy, in the presence or absence of intrathecal administration of recombinant α-l-iduronidase. Histopathological evidence of glycosaminoglycan storage in the brain was ameliorated with the higher-dose intravenous therapy and was further improved by combining intravenous and intrathecal therapy. These findings argue that neonatal testing and early treatment of patients with MPS I may more effectively treat this disease.Science translational medicine 12/2010; 2(60):60ra89. · 7.80 Impact Factor -
Article: Surveillance of amyloidosis and other diseases at necropsy in captive trumpeter swans (Cygnus buccinator).
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ABSTRACT: The purpose of this study was to characterize the incidence and diagnostic features of amyloidosis and other diseases found at necropsy in captive trumpeter swans (Cygnus buccinator). A search of Iowa State University's Department of Veterinary Pathology and Veterinary Diagnostic Laboratory databases yielded 31 trumpeter swan (C. buccinator) necropsy cases from captive swans in protected habitats. Eleven of the 31 birds had amyloid deposition most commonly in the spleen (8 of 11), liver (7 of 11), and kidney (6 of 11) and less often in the pancreas (2 of 11) and adrenal gland (2 of 11). Amyloid deposition effaced normal tissue with adjacent necrosis and hemorrhage in severe cases. Amyloidosis was most often diagnosed in February and March. Other disease diagnoses in the trumpeter swans included aspergillosis (5 of 31, 16%); bacterial infection (5 of 31, 16%); lead toxicosis (3 of 31, 10%); gout (2 of 31, 6%); parasitic infection (2 of 31, 6%); vitamin E deficiency (1 of 31, 3%); trauma (1 of 31, 3%); and ventricular foreign body (1 of 31, 3%). Histopathologic, toxicologic, and microbiologic analyses did not define an etiologic diagnosis in the deaths of 9 trumpeter swans. In these cases, necropsy lesions included emaciation (5 of 9), enteritis (1 of 9), pulmonary hemorrhage (1 of 9), and no lesions (3 of 9). The number of trumpeter swan case submissions was greatest in January and February. This study provides a reference for veterinary diagnosticians concerning incidence and diagnostic features of amyloidosis and other diseases in captive trumpeter swans of the midwestern United States.Journal of veterinary diagnostic investigation: official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 06/2005; 17(3):295-8. · 1.21 Impact Factor -
Article: Increased anionic peptide distribution and intensity during progression and resolution of bacterial pneumonia.
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ABSTRACT: Anionic peptides (APs) are small anionic antimicrobial peptides composed of 7 aspartic acid residues and are produced in the lungs of humans, sheep, and cattle. Although expression by epithelial cells of some antimicrobial peptides (e.g., beta-defensins) of humans and ruminants is increased in response to acute infection, AP expression is not increased during acute infection, which suggests that the expression of the latter peptide is constitutive. In this study, the degree of AP expression during the progression (acute, subacute, and chronic) of bronchopneumonia was determined. Mannheimia (Pasteurella) haemolytica, a known inducer of bovinebeta-defensins, was inoculated intrabronchially with a fiber-optic bronchoscope in nine 3-month-old sheep, and tissues were collected at 1, 15, and 45 days postinoculation (p.i.); nine control animals received pyrogen-free saline by the same procedure and were killed at the same time points. In the acute group (1 day p.i.), the lungs had lesions typical of bronchopneumonia and the distribution and intensity of AP immunoreactivity (AP-IR) were similar to those of previous studies (minimal intensity and distribution of AP-IR in bronchiolar epithelial cells). In the subacute group (15 days p.i.), there was prominent hyperplasia of bronchiolar and alveolar epithelial cells, and the chronic group (45 days p.i.) had yet more pronounced hyperplasia. In the subacute and chronic groups, the intensity and distribution of AP-IR in the cytoplasm of hyperplastic bronchiolar and type II alveolar cells were significantly increased compared to those of saline-inoculated and contralateral (noninoculated) lung lobes. Although AP expression appears constitutive, the constitutive production of AP is higher in hyperplastic, less differentiated cells than in fully differentiated, mature cells of the respiratory airways. The increased intensity and distribution of AP-IR in immature (hyperplastic) epithelial cells may be a mechanism by which production of a noninducible antimicrobial is increased temporarily during lesion progression and repair. This increased production of AP by hyperplastic cells may protect the lung against further infection until new, fully differentiated epithelial cells are capable of expressing their own inducible array of antimicrobial peptides.Clinical and Diagnostic Laboratory Immunology 02/2002; 9(1):28-32. · 2.51 Impact Factor
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2002–2005
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Iowa State University
- Department of Veterinary Pathology
Ames, IA, USA
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