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Biomedical subjects

B J Cooper

Publications and source records attributed to B J Cooper.

At least 37 records · Page 2Linked to original sources
PubMed1991

Canine X-linked muscular dystrophy: selective involvement of muscles in neonatal dogs.

The development of lesions in dogs with canine X-linked muscular dystrophy (CXMD) was studied in dogs from birth to 8 weeks of age. Selective involvement of muscles was noted in dogs up to 4 weeks of age, after which lesions were noted in all muscles examined. Marked fiber hypertrophy was a consequence of the dystrophic process. Severe degenerative lesions were first detected in the tongue, diaphragm, trapezius, deltoideus, extensor carpi radialis, sartorius, and cranial tibial muscles, with relative sparing of the triceps, biceps femoris, and quadriceps muscles. Fiber necrosis and regeneration were present in the tongue muscle at birth, indicating onset of degeneration in utero. The propensity for early development of lesions in certain muscles could not be attributed to larger fiber diameter or to fiber maturity. It is suggested that early development of lesions in these muscles may be related to the activity of these muscles in neonatal dogs.

Adenosine Triphosphatases↗
PubMed1991

In vitro characteristics of normal and dystrophic skeletal muscle from dogs.

Explants were prepared from skeletal muscle tissue from 5 nondystrophic pups and from 5 pups with X-linked muscular dystrophy; pups were 2 to 17 weeks old. A serial reexplant method resulted in optimal cell density with minimal fibroblast growth. Cultures were examined daily by use of phase-contrast microscopy; differentiated (post-fusion) cultures were examined by electron microscopy. Moderate nuclear pleomorphism and cell clustering were observed in cultures of normal and dystrophic muscle cells. Cultures were maintained to 27 days after plating. Minimal myofilament synthesis was observed in multinucleate cells from nondystrophic and dystrophic pups, but spontaneous contraction of myotubes was not observed during this period. Differences in growth, fusion, or differentiation of myogenic cells into multinucleate cells and myotubes were not found between dystrophic and normal muscle.

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PubMed1990

Canine X-linked muscular dystrophy: morphologic lesions.

Gross pathologic lesions and light microscopic and ultrastructural features of skeletal muscle lesions in canine X-linked muscular dystrophy (CXMD) were studied in dogs from 3 months to 6 years of age. Necrosis and regeneration were present at all ages, but were most prominent in the youngest dogs studied. Increased intracytoplasmic calcium, as evidenced by positive alizarin red S staining, was associated with fiber necrosis, but was also seen in small numbers of otherwise normal fibers. Progressive changes included development of severe fiber size variation, endomysial and perimysial fibrosis, prominent cytoplasmic disorganization, internalization of myonuclei, mitochondrial proliferation, mild fat infiltration, and alterations in the fiber-type pattern. The most consistent early ultrastructural changes were dilatation of the sarcoplasmic reticulum and focal subsarcolemmal areas of degeneration. Convincing sarcolemmal defects were not found. Z-band streaming was present at all ages, and Z-band duplication and nemaline rods were seen in older dogs. Evidence for abnormal regeneration was found in the oldest dog, and was associated with extensive fibrosis. These findings document the progression of lesions in CXMD, and illustrate the profound alterations in fiber organization and fiber type that may occur in late stages of dystrophin-deficient muscular dystrophy.

Aging↗
PubMed1990

Equine motor neuron disease; a preliminary report.

A spontaneous motor neuron disease or neuronopathy was identified in 10 horses from the northeastern United States. Signs of generalized weakness, muscle fasciculations, muscle atrophy and weight loss progressed over 1 to several months in young and old horses of various breeds. Pathologic studies revealed that degeneration and loss of motor neurons in the spinal cord and brain stem resulted in axonal degeneration in the ventral roots and peripheral and cranial nerves and denervation atrophy of skeletal muscle. Many spinal neurons were swollen, chromatolytic and contained neurofilamentous accumulations. Other cell bodies were shrunken and undergoing neuronophagia and some were lost and replaced by glia. This fatal equine motor neuron disease has not been reported previously and its cause has not been determined. The progressive weakness and wasting and the neuronal degenerative changes in these horses were similar to those described in people with sporadic amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.

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PubMed1990

Mosaic expression of dystrophin in carriers of canine X-linked muscular dystrophy.

The expression of dystrophin was examined immunocytochemically in skeletal and cardiac muscle of canine carriers of X-linked muscular dystrophy, a model of Duchenne muscular dystrophy. In skeletal muscle, the expression of dystrophin was heterogeneous, individual fibers being strongly positive, negative, or intermediate in staining. Some fibers expressed dystrophin discontinuously along their length. Between 4 and 24 weeks of age, the expression of dystrophin in skeletal muscle of carriers became more uniform and the number of negative fibers declined. In the heart dystrophin was also expressed in a mosaic pattern, individual cells being either fully positive or negative by immunocytochemistry. There was no apparent change in the pattern of expression between 12 weeks and 4 years of age. These results indicate that in the mosaic skeletal muscle fibers of carriers dystrophin is initially expressed in a heterogeneous pattern and that, in time, it becomes more uniformly distributed. This change could be explained by recruitment of competent satellite cells or by gradual diffusion of the protein.

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PubMed1989

Intracellular calcium in canine muscle biopsies.

Intracellular staining for calcium was studied in muscle biopsies from 15 dogs by the alizarin red S (ARS) stain. Rare positive fibres were present in normal muscle and in denervation atrophy. The percentage of positive fibres was slightly increased in polymyositis, dermatomyositis and canine temporal/masseter myositis and markedly increased in progressive muscular dystrophy. Calcium-positive fibres were usually so-called large-dark (hypercontracted) fibres or necrotic fibres, although there was occasional staining of normal and atrophied fibres. These results indicate the probable involvement of calcium in muscle injury in canine inflammatory myopathies and in canine muscular dystrophy. In addition, use of the ARS stain appears to be useful for detecting the earliest lesions of acute muscle fibre injury.

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PubMed1989

Animal models of Duchenne and Becker muscular dystrophy.

Two animal models have been shown to be related to Duchenne and Becker muscular dystrophy at the molecular level. The mdx mouse is characterized by early onset of muscle degeneration and very mild clinical disease. The disease is minimally progressive and fibrosis of muscle is absent. Linkage studies, absence of dystrophin, and reduced levels of message indicate that the mutation in mdx lies in the gene for dystrophin, the gene that is defective in Duchenne and Becker muscular dystrophy. The xmd dog develops lesions that are essentially indistinguishable from those of Duchenne dystrophy, and there is progressive fibrosis and destruction of muscle tissue. Affected dogs develop severe clinical disease. The absence of dystrophin and its message in muscle, and the linkage of RFLPs recognized by Duchenne cDNA probes, indicate that the mutation in the xmd dog lies in the gene for dystrophin. Exploitation of these models should lead to a greater understanding of molecular and cellular events involved in the pathogenesis of Duchenne and Becker muscular dystrophies.

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PubMed1989

Clinical electromyographic studies of canine X-linked muscular dystrophy.

Clinical electromyographic studies were performed in dogs (6 weeks to 5.5 years old) with a degenerative myopathy analogous to Duchenne muscular dystrophy. Spontaneous activity, consisting primarily of complex repetitive discharges (pseudomyotonic discharges), was found in all dogs tested, but was most prominent in dogs greater than or equal to 10 weeks old. Myotonic discharges also were found, but were less frequent. Motor unit potentials were generally abnormally brief and frequently polyphasic. Ulnar nerve conduction velocities determined in two 4-month-old dogs were similar to those of unaffected littermates. It was concluded that canine X-linked muscular dystrophy is a primary myopathic process in which complex repetitive discharges and myotonic discharges are a prominent feature. The basis for this spontaneous activity is not known.

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PubMed1989

Development of Duchenne-type cardiomyopathy. Morphologic studies in a canine model.

The development of cardiac lesions was studied in xmd dogs aged from 1 day to 6 years. Cardiac lesions were not present in dystrophic dogs up to 3 months of age. Foci of mineralization were first seen at 6.5 months. A 1-year-old dog had foci of myocyte hypercontraction. Linear and anastomosing fibrosis was present in all dogs 1 year of age or older, most prominently and most consistently within the subepicardial region of the left ventricular (LV) free wall, the LV papillary muscles, and the right ventricular (RV) aspect of the septum. Ultrastructurally, endomysial fibrosis, decreased myofibrillar density, and prominence of mitochondria were consistent features. Severe degenerative changes were present in two dogs and included prominent intracytoplasmic myelin figures, lipid droplets, and lipofuscin. Immunocytochemical studies of an affected dog confirmed the absence of dystrophin in LV myocardium. Characteristic late-onset cardiac lesions, similar to those occurring in Duchenne dystrophy, are a consistent feature of canine X-linked muscular dystrophy (CXMD).

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PubMed1988

The homologue of the Duchenne locus is defective in X-linked muscular dystrophy of dogs.

Duchenne muscular dystrophy (DMD) is the most common and the most severe of the muscular dystrophies in man. It is inherited as an X-linked recessive trait and is characterized by ongoing necrosis of skeletal muscle fibres with regeneration and eventually fibrosis and fatty infiltration. Although the gene and gene product which are defective in DMD have recently been identified, the pathogenesis of the disease is still poorly understood. A myopathy has been described in the dog which has been shown to be inherited as an X-linked trait and which is therefore a potential model of the human disease. We have studied the phenotypic expression of the disease, canine X-linked muscular dystrophy (CXMD), and have examined the molecular relationship between it and DMD. We report here that dogs with CXMD faithfully mimic the phenotype of Duchenne muscular dystrophy and that they lack the Duchenne gene transcript and its protein product, dystrophin.

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PubMed1988

Canine X-linked muscular dystrophy. An animal model of Duchenne muscular dystrophy: clinical studies.

The progression of clinical disease and serum creatine kinase (CK) levels in canine X-linked muscular dystrophy (CXMD) was studied in 7 dogs from birth to 12-14 months and in 18 dogs at varying intervals from birth to 8 weeks. One affected male was studied from age 3.5 to 6 years, and all pups were descendants of this dog. A lethal neonatal form was recognized in some pups. In the more typical form, clinical signs of stunting, weakness and gait abnormalities were evident by 6-9 weeks and were progressive, leading to marked muscle atrophy, fibrosis and contractures by 6 months. Serum CK levels were markedly elevated, such that affected pups could be identified by 1 week. CK values increased until 6-8 weeks, then plateaued at approx. 100 times normal. Affected females and beagle-cross dogs were less severely affected than large breed-cross dogs. In the 2 adult dogs with cardiac insufficiency CK levels had decreased to 5-15 times normal. These studies show that CXMD and Duchenne muscular dystrophy have striking phenotypic as well as genotypic similarities. In addition, these studies of CXMD suggest that in females and in smaller dogs the same genetic defect results in a less severe clinical disease.

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PubMed1987

Epithelial odontogenic tumours in domestic animals.

Epithelial odontogenic tumours are uncommon, poorly understood and often difficult to diagnose, oral neoplasms. Dental organ pre-ameloblasts and basal lamina induce development of mesenchymal cells into odontoblasts, which produce dentin and induce pre-ameloblasts to mature into secretory ameloblasts. These reciprocal sequential inductive interactions between dental epithelium and mesenchyme form the basis for classifying epithelial odontogenic tumours. There are three tumours classified as non-inductive: ameloblastoma characterized by cords and islands of stellate reticulum with peripheral palisades of polarized columnar cells, adenomatoid ameloblastoma which has acini, rosettes and ducts of polarized columnar cells and stellate reticulum and calcifying epithelial odontogenic tumour which contains foci of Congo-red-positive material surrounded by pleomorphic polygonal epithelial cells. There are five tumours in which induction of mesenchymal tissue is evident: ameloblastic fibroma with characteristics of ameloblastoma plus proliferation of closely associated pulp-like mesenchyme; dentinoma consisting of masses of dentin, often with minimal cellular component; ameloblastic odontoma which contains palisaded epithelium and stellate reticulum as in ameloblastoma, as well as foci of dentin and/or enamel; complex odontoma which is a disorderly array of dentin, enamel, ameloblastic epithelium and odontoblasts; and compound odontoma containing denticles with well-organized tooth morphology. This paper reviews the embryogenesis of teeth and describes six types of epithelial odontogenic tumours in 13 animals. The literature concerning these tumours in nearly 250 animals is reviewed. The most commonly reported tumour is ameloblastoma and the species in which all types are most commonly reported is the dog.

Animals↗
PubMed1987

Expression of only one myelin basic protein allele in mouse is compatible with normal myelination.

Myelin deficiency (mld) is an autosomal recessive mutation in mice characterized by a severe myelin deficit in the central nervous system (CNS). The primary defect in mld is a reduction of the synthesis of the myelin basic protein (MBP) and probably lies in a regulatory element of the MBP gene. In young mld heterozygotes, the MBP mRNA and MBP levels are intermediate. In order to study whether reduced levels of MBP gene expression affect myelination, we determined the levels of MBP mRNA and MBP itself in mld heterozygous and control brains, at different ages during development. Total proteins and MBP were also measured in myelin isolated at 25 and 85 days of age. Myelin proteins were analyzed by SDS-PAGE. In addition, we carried out a morphometric analysis on 25- and 85-day-old optic nerves. Our results indicate that in spite of a roughly 50% reduction of MBP gene expression (compared to controls), the amounts of myelin isolated and the concentration of MBP in myelin were normal in heterozygous brains. Nevertheless, morphometric analyses of optic nerves, which myelinate later than the brainstem, showed thinner myelin sheaths in 25-day-old heterozygotes when compared to controls. This difference disappeared at 85 days of age. These results indicate that normal mice synthesize MBP in excess. The synthesis of this extramyelinic pool of MBP represents a safety factor allowing normal myelination to proceed even when MBP synthesis is severely reduced. In mld heterozygotes, a 30-50% reduction of this rate of synthesis can represent a limiting factor and locally delay myelin deposition without affecting the overall myelin content or myelin composition in heterozygous adult brains.

Aging↗
PubMed1986

Nemaline myopathy of cats.

An apparently inherited myopathy, characterized by the presence of large numbers of nemaline rods in skeletal muscle fibers, was investigated in five cats. Onset of signs varied from 6 months to 1.5 years of age and consisted of reluctance to move, jerky gait and muscle twitching, hyporeflexia, and muscle wasting, which was most prominent in the proximal muscles of the forelimbs. All of the cats, three males and two females, were from the same dam. In addition to the presence of rods, the myopathy was characterized by marked fiber size variation, with atrophy of type 1 and type 2a muscle fibers. In addition, there was infolding of the sarcolemma and fiber splitting. Ultrastructurally, the rods closely resembled those described in human nemaline myopathy.

Adenosine Triphosphatases↗
PubMed1986

Progressive muscular dystrophy in a golden retriever dog: light microscope and ultrastructural features at 4 and 8 months.

The clinical and morphological features of a congenital myopathy in a young male golden retriever dog were studied. Muscle biopsies at 4 and 8 months of age were examined with light and electron microscopy. Clinical features included early onset of generalized muscle weakness with selective muscle atrophy and hypertrophy, splaying of the limbs, stiff gait, and marked elevation of serum creatine kinase (CK). An electromyograph revealed spontaneous electrical activity characterized by sustained high-frequency activity, which was not abolished by neuromuscular blockade. Morphologically there was marked hypercontraction and segmental necrosis of muscle fibers with phagocytosis and regeneration. Ultrastructurally, dilatation of sarcoplasmic reticulum was the most consistent feature associated with early fiber degeneration. No abnormalities were noted in the central or peripheral nervous system. Progression of the disease was evident at 8 months. It was concluded that the findings are consistent with a dystrophic process of primary muscle origin. The probable genetics and comparison to other animal models of muscular dystrophy and to Duchenne dystrophy are discussed.

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