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M M Sleeper

Publications and source records attributed to M M Sleeper.

8 recordsLinked to original sources
PubMed2004

Gene therapy ameliorates cardiovascular disease in dogs with mucopolysaccharidosis VII.

BACKGROUND: Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease caused by deficient beta-glucuronidase (GUSB) activity resulting in defective catabolism of glycosaminoglycans (GAGs). Cardiac disease is a major cause of death in MPS VII because of accumulation of GAGs in cardiovascular cells. Manifestations include cardiomyopathy, mitral and aortic valve thickening, and aortic root dilation and may cause death in the early months of life or may be compatible with a fairly normal lifespan. We previously reported that neonatal administration of a retroviral vector (RV) resulted in transduction of hepatocytes, which secreted GUSB into the blood and could be taken up by cells throughout the body. The goal of this study was to evaluate the effect on cardiac disease. METHODS AND RESULTS: Six MPS VII dogs were treated intravenously with an RV-expressing canine GUSB. Echocardiographic parameters, cardiovascular lesions, and biochemical parameters of these dogs were compared with those of normal and untreated MPS VII dogs. CONCLUSIONS: RV-treated dogs were markedly improved compared with untreated MPS VII dogs. Most RV-treated MPS VII dogs had mild or moderate mitral regurgitation at 4 to 5 months after birth, which improved or disappeared when evaluated at 9 to 11 and at 24 months. Similarly, mitral valve thickening present early in some animals disappeared over time, whereas aortic dilation and aortic valve thickening were absent at all times. Both myocardium and aorta had significant levels of GUSB and reduction in GAGs.

Animals↗
PubMed2001

Aortic root disease in four horses.

Clinical findings in 4 horses with aortic root disease are described. Three of the horses had aneurysms of the right aortic sinus, and in 2 of the 3, the aneurysm ruptured, creating a fistula between the aorta and right ventricle. One of these horses had had a murmur since birth, and the aortic sinus aneurysm may have been a congenital anomaly. In a second horse, the aneurysm may have been an acquired condition that developed secondary to chronic aortic regurgitation. Another horse had a large subendocardial hematoma associated with dissection of blood from the aorta to the interventricular septum because of a tear in the aortic root near the right aortic sinus. Ventricular ectopy and signs of abdominal pain were the most common initial signs in these horses.

Animals↗
PubMed2001

Vertebral scale system to measure heart size in growing puppies.

OBJECTIVE: To determine relative heart size in clinically normal puppies and assess whether relative heart size changes with growth. DESIGN: Prospective radiographic study. ANIMALS: 11 puppies without evidence of disease. PROCEDURE: Standardized measurements of the long and short axes of the heart, midthoracic vertebrae, and other structures were made at 3, 6, 12, and 36 months of age. Measurements were recorded in millimeters and number of thoracic vertebral lengths spanned by each dimension, measured caudally from T4 on lateral radiographic views. The long and short axis measurements of the heart, expressed in vertebral lengths, were added to yield vertebral heart size. RESULTS: Mean +/- SD vertebral heart sizes on lateral radiographic views at 3, 6, 12, and 36 months of age were 10.0 +/- 0.5, 9.8 +/- 0.4, 9.9 +/- 0.6, and 10.3 +/- 0.6 vertebrae, respectively. Significant differences were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: Vertebral heart size measurements in puppies are within the reference range for adult dogs (9.7 +/- 0.5 vertebrae) and do not change significantly with growth to 3 years of age. Standards for determining cardiac enlargement are similar in puppies and adult dogs.

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PubMedDate not supplied

Inheritance, biochemical abnormalities, and clinical features of feline mucolipidosis II: the first animal model of human I-cell disease.

Mucolipidosis II (ML II), also called I-cell disease, is a unique lysosomal storage disease caused by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase, which leads to a failure to internalize enzymes into lysosomes. We report on a colony of domestic shorthair cats with ML II that was established from a half-sibling male of an affected cat. Ten male and 9 female kittens out of 89 kittens in 26 litters born to clinically normal parents were affected; this is consistent with an autosomal recessive mode of inheritance. The activities of three lysosomal enzymes from affected kittens, compared to normal adult control cats, were high in serum (11-73 times normal) but low in cultured fibroblasts (9-56% of normal range) that contained inclusion bodies (I-cells), reflecting the unique enzyme defect in ML II. Serum lysosomal enzyme activities of adult obligate carriers were intermediate between normal and affected values. Clinical features in affected kittens were observed from birth and included failure to thrive, behavioral dullness, facial dysmorphia, and ataxia. Radiographic lesions included metaphyseal flaring, radial bowing, joint laxity, and vertebral fusion. In contrast to human ML II, diffuse retinal degeneration leading to blindness by 4 months of age was seen in affected kittens. All clinical signs were progressive and euthanasia or death invariably occurred within the first few days to 7 months of life, often due to upper respiratory disease or cardiac failure. The clinical and radiographic features, lysosomal enzyme activities, and mode of inheritance are homologous with ML II in humans. Feline ML II is currently the only animal model in which to study the pathogenesis of and therapeutic interventions for this unique storage disease.

Animals↗
PubMedDate not supplied

Cardiac troponin I in the normal dog and cat.

Cardiac troponin I (cTnI) has proven to be a highly specific and sensitive marker for myocardial cellular damage in many mammalian species. The structure of cTnI is highly conserved across species, and assays for human cTnI (including the one used in the current study) have been validated in the dog. Blood concentrations of cTnI rise rapidly after cardiomyocyte damage, and assay of cTnI potentially may be valuable in many clinical diseases. The purpose of this study was to establish the normal range of cTnI in heparinized plasma of dogs and cats. Forty one clinically normal dogs and 21 cats were included in the study. One to 3 milliliters of blood were collected by venipuncture into lithium heparin vacutainers for analysis of cTnI (Stratusz CS). The range of plasma cTnI concentrations in dogs was <0.03 to 0.07 ng/mL with a mean of 0.02 ng/mL, with the upper tolerance limit (0.07 ng/mL) at the 90th percentile with 95% confidence. In cats, the range was <0.03 to 0.16 ng/mL with a mean of 0.04 ng/mL, and the upper tolerance limit (0.16 ng/mL) at the 90th percentile as well with 90% confidence. This study establishes preliminary normal ranges of plasma cTnI in normal dogs and cats for comparison to dogs and cats with myocardial injury or disease.

Animals↗
PubMedDate not supplied

Familial dilated cardiomyopathy of young Portuguese water dogs.

A novel dilated cardiomyopathy (DCM) in 12 related Portuguese Water Dogs was identified by retrospective analysis of postmortem and biopsy case records. Male and female puppies born to clinically healthy parents typically died at 13 (+/- 7.3) weeks of age (range, 2-32 weeks) because of congestive heart failure. Puppies died suddenly without previous signs or with mild depression followed by clinical signs of congestive heart failure 1-5 days before death. There was no sex predilection. The hearts were enlarged and rounded, with marked left ventricular and atrial dilation. No other significant structural cardiac defects were noted. The histologic changes in the myocardium were diffuse and characterized by myofibers of irregular sizes separated by an edematous interstitium. The myofibers had multifocal swollen, cleared segments often involving perinuclear areas that contained granular, phosphotungstic-acid-hematoxylin-positive material consistent with mitochondria. There was loss of the cross-striation pattern, and intercalated discs were difficult to identify. There was no evidence of concurrent myocardial fibrosis; rare chronic inflammatory infiltrates were noted in one dog. Noncardiac skeletal muscles were not affected. The underlying cause is unknown. From the pedigree analysis, an autosomal recessive pattern of inheritance is suspected. Based on the histologic findings, this DCM is most likely due to an underlying molecular (biochemical or structural) defect. The early onset and rapid progression of the disease makes this a clinically distinctive form of canine DCM.

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