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Biomedical subjects

A Bornemann

Publications and source records attributed to A Bornemann.

At least 37 records · Page 2Linked to original sources
PubMed1999

Comparison of the muscle fiber diameter and satellite cell frequency in human muscle biopsies.

Satellite cells are responsible for the formation of postnatal muscle fibers. The number, mitotic activity, and differentiation potential of satellite cells and the muscle fiber diameter are tightly regulated events in normal muscle. The signal that induces satellite cells to stop proliferation once the determined muscle fiber size has been reached in normal growth is not known. The aim of the present study was to determine whether a correlation exists between satellite cell frequency and muscle fiber diameter in human muscle disease. Muscle biopsies from 7 cases of Duchenne muscular dystrophy (DMD), 8 other muscular dystrophies, 23 cases of inflammatory myopathy, and 22 cases of neurogenic atrophy were examined. The satellite cell number was elevated in DMD and neurogenic atrophy but not in other muscular dystrophies or inflammatory myopathies. Nevertheless, in all the diseased muscles, but not in normal controls, there was a significantly higher relative frequency of satellite cells with increasing fiber diameter. It has been shown before that satellite cells show ultrastructural and autoradiographic signs of activation and proliferation in myopathic and neurogenic conditions. We assume that we are dealing with activated, not quiescent, satellite cells in diseased muscle and that under these conditions the fiber diameter does not represent a stop signal for satellite cells to proliferate. The data suggest that not only the number of satellite cells matters in diseased muscle, as has been shown before, but that it is their behavior that influences, at least in part, progress and severity of muscle diseases.

Adolescent↗
PubMed1999

Intracranial inflammatory tumors: a survey of their various etiologies by presentation of 5 cases.

Due to similar clinical and neuroradiological features, intracranial inflammatory tumors (IITs) are frequently misdiagnosed as brain neoplasms, from which they notably differ in respect to therapy and prognosis. In this article, five cases of such tumors are presented. Three of the patients with brain tumors (cases 3, 4 and 5) presented a history of 'pararheumatic' syndromes but no diagnosis of defined immunopathies. On the basis of radiological findings, all processes were classified as genuine brain neoplasms, but histology showed reactive inflammatory features. The possible etiologies of these 'tumors' are discussed on the basis of all clinical and histological data of the patients. The spectrum of diseases potentially leading to the manifestation of an IIT is reviewed. Additionally, the presentation of case 5, who developed a highly malignant B-cell-lymphoma 6 months after the removal of an IIT without any histological signs of atypia, shows that this differential diagnosis always has to be kept in mind.

Adult↗
PubMed1999

NCAM, vimentin and neonatal myosin heavy chain expression in human muscle diseases.

The intermediate filament protein vimentin, the neonatal isoform of the myosin heavy chain gene (MHCn), and the neural cell adhesion molecule (NCAM) are developmentally and/or neurally regulated molecules that reappear transiently after the induction of necrosis, or denervation. Immunostaining using antibodies against these molecules helps to identify regenerating and/or denervated muscle fibres even if they are not recognized by conventional staining procedures. This study examined the expression of vimentin, MHCn, and NCAM using immunohistochemistry in 82 biopsy specimens from muscular dystrophies, inflammatory myopathies, and neurogenic atrophies. Anti-vimentin labelled significantly more fibres than anti-MHCn staining in the inflammatory myopathies (P<0.03) but not in the muscular dystrophies (P=0.58) and neurogenic atrophies (P=0. 58). The fraction of NCAM+ fibres was always more elevated than vimentin+ or MHCn+ fibres. In the necrotizing myopathies, most NCAM+ fibres were regenerating ones (co-expressing vimentin). In neurogenic atrophies, half the NCAM+ fibres were regenerating and half of them were NCAM+/vimentin- and thus were considered to be denervated. Taken together, anti-vimentin staining detects a broader spectrum of regenerating fibres than anti-MHCn, at least in the inflammatory myopathies. The number of anti-NCAM labelled fibres in the necrotizing myopathies is similar, but not identical, to the number of regenerating fibres. Co-staining with anti-vimentin (or anti-MHCn) and anti-NCAM identifies a subset of fibres that is considered to be denervated.

Adolescent↗
PubMed1999

Satellite cells as players and targets in normal and diseased muscle.

Satellite cells (SC), also termed adult myoblasts, are mononuclear cells of myogenic lineage. They are attached to the muscle fiber plasma membrane and surrounded by a common basement membrane. The characteristic localization differentiates them from embryonic and fetal myoblasts. SC are able to leave the G0 phase in which they usually reside in normal adult muscle, enter the mitotic cycle, and differentiate to express muscle-specific proteins. The activation of SC into the mitotic compartment and their progression to the differentiative compartment are processes which are tightly regulated by myogenic regulatory factors of the MyoD family and the cyclin-dependent kinases and their inhibitors. Those factors are in turn regulated by growth factors and innervation. SC are key features in muscle fiber growth, regeneration, and hypertrophy. Furthermore, they are targets in denervation atrophy, which results in SC loss in the long run. There is evidence from experimental work that SC age, and that they are a heterogeneous cell population in terms of mitotic cycle duration and have the ability to differentiate. Little is known of SC in human diseased muscle beyond their number. SC heterogeneity must be taken into account if future therapy strategies for muscular dystrophies are designed.

Adult↗
PubMed1999

Satellite cells on isolated myofibers from normal and denervated adult rat muscle.

Satellite cells (SCs) in normal adult muscle are quiescent. They can enter the mitotic program when stimulated with growth factors such as basic FGF. Short-term denervation stimulates SC to enter the mitotic cycle in vivo, whereas long-term denervation depletes the SC pool. The molecular basis for the neural influence on SCs has not been established. We studied the phenotype and the proliferative capacity of SCs from muscle that had been denervated before being cultured in vitro. The expression of PCNA, myogenin, and muscle (M)-cadherin in SCs of normal and denervated muscle fibers was examined at the single-cell level by immunolabeling in a culture system of isolated rat muscle fibers with attached SCs. Immediately after plating (Day 0), neither PCNA nor myogenin was present on normal muscle fibers, but we detected an average of 0.5 M-cadherin(+) SCs per muscle fiber. The number of these M-cadherin(+) cells (which are negative for PCNA and myogenin) increased over the time course examined. A larger fraction of cells negative for M-cadherin underwent mitosis and expressed PCNA, followed by myogenin. The kinetics of SCs from muscle fibers denervated for 4 days before culturing were similar to those of normal controls. Denervation from 1 to 32 weeks before plating, however, suppressed PCNA and myogenin expression almost completely. The fraction of M-cadherin(+) (PCNA(-)/myogenin(-)) SCs was decreased after 1 week of denervation, increased above normal after denervation for 4 or 8 weeks, and decreased again after denervation for 16 or 32 weeks. We suggest that the M-cadherin(+) cells are nondividing SCs because they co-express neither PCNA or myogenin, whereas the cells positive for PCNA or myogenin (and negative for M-cadherin) have entered the mitotic cycle. SCs from denervated muscle were different from normal controls when denervated for 1 week or longer. The effect of denervation on the phenotypic modulation of SCs includes resistance to recruitment into the mitotic cycle under the conditions studied here and a robust extension of the nonproliferative compartment. These characteristics of SCs deprived of neural influence may account for the failure of denervated muscle to fully regenerate. (J Histochem Cytochem 47:1375-1383, 1999)

Animals↗
PubMed1998

BCL-2 family protein expression in human malignant glioma: a clinical-pathological correlative study.

Malignant gliomas are rather refractory to current therapeutic approaches including surgery, radiotherapy, chemotherapy and immunotherapy. Acquired alterations in the pathways required for apoptotic cell death are thought to be responsible to the failure of glioma to respond to therapy. Here we have examined the expression of several proteins involved in the susceptibility to apoptosis in 20 human gliomas, including the BCL-2 family proteins BCL-2, BCL-X, BAX and MCL-1, as well as p53 and RB. Most gliomas expressed several BCL-2 family proteins. There was good correlation between expression of the functional antagonists, BCL-2/BCL-X and BAX, suggesting that changes in the BCL-2+BCL-X/BAX ratio are not responsible for the differential response of glioma patients to chemotherapy. The immunochemistry data were also analysed in regard to response to therapy and clinical outcome. All patients had cytoreductive surgery and received radiotherapy and nitrosourea-based adjuvant chemotherapy. There was no prominent association of outcome with the expression patterns of p53, RB, BCL-2, BCL-X or BAX. We find, however, that expression of the MCL-1 protein is associated with early tumour recurrence and shorter survival in this group of glioma patients. This preliminary observation will have to be confirmed in a larger independent sample of glioma patients.

Adolescent↗
PubMed1998

Abundant minute myotubes in a patient who later developed centronuclear myopathy.

Centronuclear myopathy (CNM) is a congenital myopathy which manifests itself as a severe neonatal (also termed myotubular myopathy), early-onset, or adult form. The histological pattern of each is marked by a considerable number of nuclei of muscle fibers being internally placed. Owing to their remote resemblance to myotubes, and their expression of developmentally regulated proteins, most authors now favor the concept that myogenesis is arrested or delayed in this disease. We here present two muscle biopsy specimens of a patient with early-onset CNM, taken at the age of 5 months and 14 years, respectively. The first biopsy sample contained internally placed nuclei in 7% of the muscle fibers, abundant minute myotubes, and hypertrophic muscle fibers. The second biopsy sample showed internally placed nuclei in 40% of the muscle fibers, and hypotrophic fibers. We suggest that the histological findings in early-onset CNM are the result of a complex dynamic process, which includes a delay in maturation.

Adolescent↗
PubMed1998

Humoral immune response to p53 in malignant glioma.

p53 immunoreactivity and humoral immune response to p53 were examined in 14 patients with malignant glioma, including 4 patients with leptomeningeal glioma cell dissemination. Twelve patients expressed p53 protein within the tumour tissue. p53 antibodies were detected in the serum in 2 of 14 patients but never in the cerebrospinal fluid (CSF). Soluble p53 protein was detected neither in serum nor in CSF of the glioma patients. CSF levels of the immunosuppressive cytokine, transforming growth factor (TGF)-beta, were elevated in the glioma patients, including those with a humoral response to p53. These preliminary findings raise the possibility of systemic humoral immune responses to antigens, including mutant p53, expressed by glioma cells in the central nervous system.

Adult↗
PubMed1998

Thymic myoid cell turnover in myasthenia gravis patients and in normal controls.

Thymic myoid cells (TMC) are sparse muscle-like cells in the thymic medulla, which are believed to trigger the autoimmune response in myasthenia gravis (MG). Ultrastructural investigations have revealed mature, degenerating, and immature TMC, but the number of TMC in MG patients does not differ from that in controls. We examined the turnover of TMC at the subcellular level, performing an immunocytochemical study with muscle-specific anti-desmin labelling of 10 thymuses derived from MG patients with lymphofollicular hyperplasia and from 8 normal controls. All thymuses examined revealed mature, immature, and degenerating TMC. Mature TMC contained desmin filaments in between Z-discs provided the sarcomeres were arranged in register. Morphological features of degenerating TMC included hypercontracted sarcomeres, cytoplasmic granular debris, chromatin clumping and, occasionally, membrane-bound bodies. Macrophages were not involved in the process. Immature TMC were of small diameter and contained myofilaments not arranged in myofibrils. In an MG thymus, small immature TMC were found clustered with dying TMC. It may be that degeneration of TMC is a stimulus for the generation of new TMC with faster turnover. This mechanism may mean that more antigen is available in MG patients than in normal controls, despite constant TMC numbers.

Adolescent↗
PubMed1998

Mosaicism for Charcot-Marie-Tooth disease type 1A: onset in childhood suggests somatic reversion in early developmental stages.

A 1.5 Mb duplication on chromosome 17p11.2 is typical for the great majority of patients suffering from Charcot-Marie-Tooth type 1A (CMT1A) disease. A female child of 4 years with clinical signs and symptoms of a demyelinating neuropathy was examined for the presence of this duplication. Analysis of MspI polymorphisms in DNA extracted from peripheral blood failed due to homozygosity for probes pVAW409R3a and pEW401HE. Also, no EcoRI/SacI 3.2 kb junction fragment or dosage difference with probe pLR7.8, characteristic of the CMT1A duplication, was found. However, fluorescence in situ hybridization (FISH) analysis with the PMP22 specific probe c132G8 revealed in peripheral blood lymphocytes 60% of interphase nuclei with CMT1A duplication indicating the probability of mosaicism. In interphase nuclei extracted from nerve tissue the duplication was detectable in 88%, in muscle tissue in 72% of the analyzed nuclei. This suggests the presence of a somatic CMT1A duplication mosaicism that can only be reliably detected by FISH. The early onset and severity of the phenotype indicates that the hypothesized somatic reversion is probably fixed to early developmental stages.

Age of Onset↗
PubMed1997

Congenital intracerebral teratoma: a rare differential diagnosis in newborn hydrocephalus.

Congenital hydrocephalus is caused by a broad spectrum of underlying disorders. In the majority of cases it is due to aqueductal stenosis and other distinct congenital anomalies, like Arnold-Chiari malformation. Nevertheless, in the differential diagnosis rare conditions such as cerebral malignancies must also be considered. We present two cases of congenital intracerebral teratoma as a differential diagnosis in congenital obstructive hydrocephalus. A teratoma is suggested when a rapidly growing hydrocephalus with a central calcified and vascularized mass is found sonographically. Regular cerebral structures usually cannot be detected. Early diagnosis in such cases is of clinical importance as the prognosis of congenital intracerebral teratoma is generally very poor.

Brain Neoplasms↗
PubMed1997

Spatial and temporal development of the gliovascular tissue in type II lissencephaly.

Type II lissencephaly is a complex cortical malformation in which mesenchymal and central nervous components are intermingled. It is generally believed that the histological pattern is created by migration of heterotopic neuroblasts into the leptomeninges through defects in the superficial basement membrane. Defects of the extracellular matrix have been suggested to be the primary cause of type II lissencephaly. To elucidate the underlying pathogenetic mechanisms, we immunostained extracellular matrix and basement membrane components of the cerebral cortex from six fetal and two infantile brains. We found that the pattern of collagen subtypes I, III and VI was not altered in type II lissencephaly brains when compared to normal controls. As to the pathogenesis of type II lissencephaly, a polymicrogyria-like pattern is created, which results in considerable cortical enlargement. The microgyri do not fuse but remain separated from each other by gliovascular tissue, i.e., leptomeninges which contain astrocytes. At the interface between the enlarged brain surface and the gliovascular tissue, neuronal migration takes place through gaps in the external basement membrane. Thus, the cortical dysplasia encountered in type II lissencephaly is only due to a limited amount to neuronal heterotopia in the leptomeninges.

Astrocytes↗
PubMed1997

Absence of integrin alpha 7 causes a novel form of muscular dystrophy.

Integrin alpha 7 beta 1 is a specific cellular receptor for the basement membrane protein laminin-1 (refs 1,2), as well as for the laminin isoforms -2 and -4 (ref. 3). The alpha 7 subunit is expressed mainly in skeletal and cardiac muscle and has been suggested to be involved in differentiation and migration processes during myogenesis. Three cytoplasmic and two extracellular splice variants that have been described are developmentally regulated and expressed in different sites in the muscle. In adult muscle, the alpha 7A and alpha 7B subunits are concentrated in myotendinous junctions but can also be detected in neuromuscular junctions and along the sarcolemmal membrane. To study the potential involvement of alpha 7 integrin, during myogenesis and its role in muscle integrity and function, we generated a null allele of the alpha 7 gene (Itga7) in the germline of mice by homologous recombination in embryonic stem (ES) cells. Surprisingly, mice homozygous for the mutation are viable and fertile, indicating that the alpha 7 beta 1 integrin is not essential for myogenesis. However, histological analysis of skeletal muscle revealed typical symptoms of a progressive muscular dystrophy starting soon after birth, but with a distinct variability in different muscle types. The observed histopathological changes strongly indicate an impairment of function of the myotendinous junctions. These findings demonstrate that alpha 7 beta 1 integrin represents an indispensable linkage between the muscle fibre and the extracellular matrix that is independent of the dystrophin-dystroglycan complex-mediated interaction of the cytoskeleton with the muscle basement membrane.

Animals↗
PubMed1997

Lymphocytic and granulomatous hypophysitis: experience with nine cases.

OBJECTIVE: Lymphocytic hypophysitis and granulomatous hypophysitis are rarely encountered. The aim of this study was to demonstrate their clinical peculiarities among pituitary disorders and to provide an approach for their clinical management. METHODS: In a retrospective study, we reviewed our surgical experience with nine patients harboring hypophysitis. The series included six cases of lymphocytic hypophysitis, two cases of granulomatous hypophysitis, and one case with evidence of coexisting lymphocytic and granulomatous hypophysitis. RESULTS: A striking similarity of clinical signs was found for our nine patients. Headache or aseptic meningitis, thickening of the sphenoid sinus mucosa, pituitary stalk enlargement, and tongue-shaped extension of the lesion along the basal hypothalamus were characteristic signs. Lymphocytic hypophysitis was not associated with pregnancy in any of the seven cases. No recurrence has been observed in six cases with total removal of the inflammatory tissue. CONCLUSION: Lymphocytic hypophysitis and granulomatous hypophysitis represent related inflammatory disorders. Their conspicuous clinical features frequently allow preoperative diagnosis of hypophysitis. In view of their sometimes insidious clinical course, early surgical exploration is justified.

Adolescent↗
PubMed1996

Fatal congenital myopathy with actin filament deposits.

We present the clinical and morphological findings in a case of progressive congenital myopathy. The symptoms present at birth included severe general muscular hypotonia, diffuse muscular atrophy, arthrogryposis, absence of spontaneous movements, and left ventricular hypertrophy. A biopsy specimen taken from the gastrocnemius muscle when the patient was 2 weeks old revealed deposits which consisted of actin filaments as shown by electron microscopy. The infant was occasionally respirator dependent but was mostly able to breathe unassisted. At the age of 5 months he died of respiratory failure. The actin filament deposits may explain the clinical findings.

Actins↗