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Biomedical subjects

R E Bittner

Publications and source records attributed to R E Bittner.

27 records · Page 2Linked to original sources
PubMed1996

[Lactate determination at rest and during bicycle ergometry in healthy probands and in patients with mitochondrial myopathies].

Measuring lactate during moderate exercise is a useful tool in the diagnosis of mitochondrial disorders. It was the aim of this study, to develop reference limits for lactate at rest, during exercise and after the exercise. We investigated 18 healthy subjects and 6 patients with a mitochondrial disorder. In controls, serum lactate levels were comparable to already reported findings. In 4 patients lactate levels were markedly increased during the exercise. Measurement of serum lactate is a simple and useful step in the diagnosis of mitochondrial disorders.

Electron Transport↗
PubMed1996

[In vitro transformation of amniotic cells to muscle cells--background and outlook].

DNA analysis of peripheral blood leucocytes is routinely used to demonstrate mutations in the dystrophin gene in patients with Duchenne's muscular dystrophy. In approximately 35% of patients. DNA studies are not informative; in these patients immunochemical analysis of a muscle-biopsy specimen can determine whether dystrophin, the protein product of the gene for Duchenne's dystrophy, is absent. DNA analysis can be performed in amniocytes for the prenatal diagnosis; immunochemical testing for dystrophin cannot be performed because the protein is not expressed in these cells. To circumvent this limitation in prenatal diagnosis, we induced myogenesis in amniocyte cultures by addition of a rhabdomyosarcoma's cell line supernatant. Rhabdomyosarcomas are tumors of skeletal muscle and known to produce myogenic factors. After 6 weeks skeletal-muscle proteins could be detected in 10 amniocyte cultures. Cultures from fetuses with no family history of Duchenne's dystrophy expressed dystrophin, cultures from patients with Duchenne's dystrophy were dystrophin-deficient. Immunochemical analysis of dystrophin in genetically altered non-muscle cells may be applicable to the prenatal diagnosis of Duchenne's muscular dystrophy when conventional DNA analysis is not informative.

Amniocentesis↗
PubMed1995

Sarcolemmal expression of dystrophin C-terminus but reduced expression of 6q-dystrophin-related protein in two DMD patients with large deletions of the dystrophin gene.

Partial deletions of the dystrophin gene are the predominant genetic lesions in Duchenne (DMD) and Becker (BMD) muscular dystrophies. According to the reading frame hypothesis [1], any deletion disrupting the translational reading frame of the mRNA cannot result in expression of the dystrophin molecule and should lead to severe phenotypes of DMD. In contrast, deletions which maintain the reading frame across the deleted exons may give rise to truncated, semifunctional proteins and milder courses of the disease (i.e. BMD). Among the notable exceptions of this hypothesis are very large "in-frame" deletions by which functionally indispensable domains of the dystrophin molecule have been removed. Here, we report on two DMD patients with large intragenic in-frame deletions. Grossly truncated, but stable dystrophin molecules with preserved C-terminal domains were detected at the sarcolemma on cryosections in both patients. However, dystrophin organization on single-teased muscle fibers revealed disarrangement of the costameric pattern, if compared to normal skeletal muscle fibers. Compared to dystrophin-deficient DMD muscle, expression of chromosome-6-encoded dystrophin-related protein (DRP) was greatly diminished in skeletal muscle of both patients. We show, that loss of more than 50% of dystrophin seems to be deleterious for the protein's function and therefore, the extent of the deletions may have an impact on construction of dystrophin mini genes. Moreover, these findings shed new light on the functional significance of the C-terminal domain of dystrophin. They also suggest a negative correlation between sarcolemmal expression of the dystrophin C-terminus and DRP expression at the sarcolemma.

Blotting, Western↗
PubMed1995

[Congenital adrenal gland insufficiency and myopathy].

We report a rare case of a female newborn presenting with muscular hypotonia, pneumonia, and cardiovascular and renal insufficiency. Adrenal insufficiency was diagnosed clinically and proven by extremely low cortisone (0.4-0.8 microgram/dl) and high ACTH plasma levels. Myopathy was diagnosed clinically, as well as by muscular biopsy. DNA analysis of both X chromosomes showed no abnormality in the region of the genes for adrenal hypoplasia and Duchenne muscular dystrophy. After 4 weeks of intensive care therapy the patient died of multiorgan failure. At autopsy she had only microscopically visible fetal adrenal cells and multiple porencephalic lesions.

Adrenal Glands↗
PubMed1994

Coisogenic all-plus-one immunization: a model for identifying missing proteins in null-mutant conditions. Antibodies to dystrophin in mdx mouse after transplantation of muscle from normal coisogenic donor.

Specific antibody response against an alien protein is one of the basic immunologic mechanisms in immunecompetent organisms. They can be used as a first step in various approaches leading to the identification of proteins or even an antigen-encoding gene. Accordingly, we wanted to find out whether a null-mutant immunecompetent organism would produce specific antibodies against the missing gene product. We chose the mouse mutant mdx (X-linked muscular dystrophy) which represents a null-mutant condition for the gene product of the Duchenne muscular dystrophy (DMD) gene, dystrophin. When dystrophin-deficient mdx mice received dystrophin-containing muscle grafts from coisogenic normal mice, high titres of antibodies specific for dystrophin were detected in the transplanted animals' sera. Because dystrophin-containing muscle grafts were not rejected but have properly regenerated even in the presence of high titre antibodies against dystrophin, these findings have important bearings on all therapeutical strategies based on dystrophin supplementation. Using the mdx mouse as null-mutant model we showed that there was no immune tolerance for the missing protein but specific antibodies were produced when the organism came in contact with this protein. This simple approach may serve as a shortcut for identifying missing proteins presumably not only in neuromuscular disorders but in a wide range of diseases where null-mutant animal models and corresponding coisogenic inbred strains exist.

Animals↗
PubMed1992

Direct visualization of the dystrophin network on skeletal muscle fiber membrane.

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene locus, is expressed on the muscle fiber surface. One key to further understanding of the cellular function of dystrophin would be extended knowledge about its subcellular organization. We have shown that dystrophin molecules are not uniformly distributed over the humen, rat, and mouse skeletal muscle fiber surface using three independent methods. Incubation of single-teased muscle fibers with antibodies to dystrophin revealed a network of denser transversal rings (costameres) and finer longitudinal interconnections. Double staining of longitudinal semithin cryosections for dystrophin and alpha-actinin showed spatial juxtaposition of the costameres to the Z bands. Where peripheral myonuclei precluded direct contact of dystrophin to the Z bands the organization of dystrophin was altered into lacunae harboring the myonucleus. These lacunae were surrounded by a dystrophin ring and covered by a more uniform dystrophin veil. Mechanical skinning of single-teased fibers revealed tighter mechanical connection of dystrophin to the plasma membrane than to the underlying internal domain of the muscle fiber. The entire dystrophin network remained preserved in its structure on isolated muscle sarcolemma and identical in appearance to the pattern observed on teased fibers. Therefore, connection of defined areas of plasma membrane or its constituents such as ion channels to single sarcomeres might be a potential function exerted by dystrophin alone or in conjunction with other submembrane cytoskeletal proteins.

Actinin↗
PubMed1991

Histomorphometric studies in patients with facial palsy treated by functional muscle transplantation: new aspects for the surgical concept.

Whenever it was possible, muscle and nerve biopsies were performed in patients with irreversible, unilateral facial palsy treated by cross-face nerve grafting and free gracilis muscle transplantation with microneurovascular anastomoses. Planimetric analyses of cross-sections showed the following, to some extent, surprising, results: (1) Independent of the final functional result, approximately the same number of regenerated, thin nerve fibers (100-200) were found in the distal end of the cross-face nerve graft at the time of muscle transplantation. These are approximately 20% of the nerve fibers counted in the branches of the facial nerve at the healthy side used for reinnervation. (2) There is no correlation between the number or diameter of the nerve fibers in the distal end of the cross-face nerve graft and the functional recovery of the transplanted muscle, but there is good correlation between the morphology of the fibers of the muscle graft and the functional result. (3) Different portions of slow-contracting and fast-contracting muscle fibers in the reinnervated muscle grafts showed the strong influence of the quality of the nerve used for the crossover innervation. If a facial nerve branch innervating the slow buccinator muscle was used, the originally fast gracilis muscle was transformed to a slow muscle by this kind of reinnervation. These important findings are the basis of a new view of surgery in the treatment of irreversible facial palsy by functional free-muscle transplantation.

Biopsy↗
PubMedDate not supplied

Cerebrospinal fluid filtration and immunoglobulins in multifocal motor neuropathy.

Cerebrospinal fluid (CSF) filtration has been shown to be of benefit in chronic inflammatory, demyelinating polyneuropathy, but has not been applied to multifocal motor neuropathy (MMN) so far. Twenty-seven months after a 48-year-old male patient had developed slowly progressive, distally prominent monoparesis of the left arm, MMN was diagnosed. Conduction blocks were found in the left brachial plexus after median, ulnar, and radial nerve stimulation. Serum anti-GM1 antibody titers were markedly increased. Biopsy of the motor long thoracic nerve showed reduction of small caliber myelinated axons and irregularly shaped myelin lamellae. Treatment with immunoglobulins 29, 31, 36, and 39 months after onset was followed by a distinct improvement each time. Thirty-four months after onset, one liter CSF was filtered off by means of a bidirectional syringe pump with only minor therapeutic effect. In conclusion, immunoglobulins had a stronger therapeutic effect than CSF filtration on the MMN patient described.

Case-Control Studies↗