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Biomedical subjects

A Bornemann

Publications and source records attributed to A Bornemann.

At least 19 recordsLinked to original sources
PubMed2006

Reinnervation-induced alterations in rat skeletal muscle.

Denervation-induced myofiber atrophy can be reversed by reinnervation. Growing reinnervated myofibers upregulate numerous molecules, many of which determine the muscle fiber type. In the present study we aimed at identifying factors that might contribute specifically to myofiber growth after reinnervation. The common peroneal nerve of 15 male Wistar rats was cut and resutured without delay (9 animals) or with a delay of 4 weeks (6 animals). We studied the transcriptional repertoire of intact reinnervated tibialis anterior muscle by microarray gene analysis. We assessed SC activation by immunolabeling using anti-MyoD and -myogenin antibodies. The percentage of SC expressing MyoD reached up to 50% of M-cadherin+ cells whereas the percentage of SC expressing myogenin was normal (<10%) in all muscles examined. The values of ipsi- and contralateral muscles did not differ significantly from one another between right and left leg (p<0.05). Thirteen known genes were differentially regulated after reinnervation compared with contralateral muscles. Five of them determine the slow-twitch fiber type (four and a half LIM domains 3, cardiac beta-myosin heavy chain, calsequestrin 2, troponin C (slow), and heart myosin light chain), and three of them are neurally regulated (thrombospondin 4, transferrin receptor, cardiac ankyrin repeat protein). The results strengthen the notion that reinnervaton affects the molecular repertoire of the myofibers directly, leading to fiber type transformation and partial reversal of the denervation phenotype. By contrast, SC do not appear to be affected by reinnervation directly. They can be activated both in reinnervated and contralateral muscles, and they do not fully differentiate. This makes them unlikely to contribute to myofiber growth.

Animals↗
PubMed2006

Patterns of SPARC expression and basement membrane intactness at the tumour-brain border of invasive meningiomas.

The matricellular glycoprotein SPARC (secreted protein, acidic and rich in cysteine), also termed osteonectin, has been found to regulate the invasive behaviour of several tumour types by interacting with basement membrane constituents. Brain invasive meningiomas are supposed to disrupt the pial-glial basement membrane. In the present study we aimed at determining the relationship of basement membrane intactness and SPARC protein expression at the meningioma-brain border. Sections of 51 brain-invasive meningiomas (31 meningothelial meningiomas WHO grade I, 11 atypical WHO grade II, and nine anaplastic WHO grade III tumours) were immunolabelled with antibodies against SPARC, epithelial membrane antigen (EMA), collagen IV and glial fibrillary acidic protein (GFAP). Twenty-two non-invasive WHO grade I meningothelial meningiomas were included in the study for comparison. At the tumour-brain border of invasive meningiomas, spindle-shaped tumour cells expressed SPARC. The number of tumours containing SPARC+ spindle cells did not differ significantly between WHO grades. By contrast, the number of WHO grade I tumours expressing collagen IV (15/31) was highly significantly elevated when compared with WHO grade II (1/11) and WHO grade III (0/9) (both P < 0.0001). There was an inverse relationship of the presence of SPARC+ spindle cells and basement membrane material. In conclusion, the destruction of the basement membrane is correlated with meningioma malignancy grade whereas the expression of SPARC protein at the tumour-brain border is not. Destruction of the basement membrane and appearance of SPARC+ spindle cells are not coincident during the course of brain invasion by meningiomas.

Adult↗
PubMed2005

Meningioma of the accessory nerve extending from the jugular foramen into the parapharyngeal space.

A 35-year-old man presented with pain in the right shoulder and neck for 18 months. The neurological examination revealed complete accessory nerve palsy on the right side without further deficits. Magnetic resonance imaging showed a right parapharyngeal tumour expanding into the posterior fossa through the jugular foramen without dural attachment and absence of invasion into the middle ear cavity or internal auditory meatus. Intraoperative inspection disclosed a tumour originating from the accessory nerve. Histological diagnosis revealed a meningothelial meningioma with invasion of the epineural space. To the knowledge of the authors this is the first report of an accessory nerve meningioma in the jugular foramen associated with a posterior fossa component and extension into the parapharyngeal space.

Accessory Nerve Diseases↗
PubMed2005

Long-term MRI and clinical follow-up of symptomatic and presymptomatic carriers of dysferlin gene mutations.

We report the results of a longitudinal study involving MRI and clinical follow-up in nine siblings from four families with Miyoshi myopathy (MM). All individuals carried pathogenic dysferlin gene (DYSF) mutations with six of them suffering from symptomatic disease and three being presymptomatic. In presymptomatic subjects, MRI was sensitive to detect alterations in muscle tissue years before disease onset. The first MRI alteration to disclose was evidence for myoedema in dorsal compartment muscles of the legs followed by fatty degeneration. Moreover, MRI changes anticipated the topography of subsequent clinical muscle involvement and progressed from distal to proximal dorsal leg muscles. In symptomatic subjects, MRI changes reflected the pattern and severity of clinical muscle involvement. MRI evidence, however, suggests that muscle involvement is much more prominent in early disease stages than clinically seen. Clinical follow-up up to 8 years made evident that MM onset occurs at a mean age of 18.4 years. The most prominent initial deficit was impaired tiptoe gait due to muscle plantarflexor dysfunction followed by impaired dorsiflexor function. Dorsal compartments were predominantly affected not only in distal but also in proximal leg muscles, and a more rapid progression was noticed during the early phase of the disease. Our data suggest that MRI is a helpful diagnostic tool for an early diagnosis of MM and other distal myopathies since it provides sensitive and topographic information about initial and even preclinical muscle involvement. This is of particular relevance in Miyoshi myopathy because distinct CK elevation is present long before its clinical onset and often misdiagnosed as "idiopathic".

Adolescent↗
PubMed2004

Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease.

BACKGROUND: Transcranial ultrasound may be used to detect increased iron levels of the substantia nigra (SN) in patients with Parkinson disease (PD) and in control subjects. It is not known whether iron accumulation in PD is a primary or secondary phenomenon. However, sequence variations in genes involved in iron metabolism have been linked to basal ganglia disorders. One of these is ceruloplasmin (Cp), which is vitally involved in iron transport across the cell membrane. METHODS: One hundred seventy-six patients with PD according to the UK Brain Bank criteria and 180 ethnically matched control subjects, who were previously examined for SN iron signal changes by transcranial ultrasound, were examined for mutations in the Cp gene using denaturing high-performance liquid chromatography and subsequent sequencing for verification of unequivocal signals. Immunohistochemistry of PD midbrains was performed to examine the presence of Cp in Lewy bodies. RESULTS: Five novel missense variations were detected. One of these (I63T) was found in a single PD patient. A known variation (D554E) was significantly associated with PD and the ultrasound marker for increased SN iron levels. Moreover, a third sequence variation (R793H) was found to segregate with the ultrasound marker for increased iron levels in patients and control subjects. Immunohistochemistry demonstrated that Cp co-localizes with Lewy bodies in PD. CONCLUSIONS: Detection of sequence variations in a single Parkinson disease (PD) patient or associated with the ultrasound marker for increased substantia nigra iron levels and the presence of ceruloplasmin (Cp) immunoreactivity in Lewy bodies underline a suspected role for Cp in the pathogenesis of PD. Further functional analyses are warranted to investigate whether these variations are causally linked to the complex pathogenesis of PD in a subset of cases.

Aged↗
PubMed2004

Primary melanocytic lesions of the CNS: report of five cases.

Primary melanocytic tumours of the central nervous system (CNS) form a rare entity which is histologically and clinically distinct from metastatic cutaneous or retinal malignant melanoma. They can be classified into diffuse melanocytosis (diffuse melanosis), malignant melanoma and benign melanocytoma with a small number of intermediate variants. In this paper, 5 cases treated neurosurgically in our department for spinal or cerebral primary CNS malignant melanoma are reported. Primary tumors and further metastases were ruled out. Radiological, histological and clinical features are discussed. Compared to metastatic disease, primary CNS malignant melanoma shows a more benign clinical course with long-term tumour control and a good quality of life. A review of the literature which mainly consists of individual case reports, confirms this assessment. Although therapeutic experience for primary melanocytic lesions of the CNS is based on a small number of published cases, prognosis seems highly dependent on complete tumour resection. Adjuvant radiation seems to be of additional therapeutic benefit. Except for meningeosis melanomatosa chemotherapy must be regarded as experimental. Unfortunately, a standardised therapy concept is still lacking.

Adult↗
PubMed2001

Ultrastructural findings at the satellite cell-myofiber border in normal and diseased human muscle biopsy specimens.

Satellite cells (SC) are mononuclear myoblasts located between the plasma membrane and the basement membrane of a myofiber. In normal adult muscle, SC are quiescent in the G0 phase of the cell cycle. The contact of the SC with the myofiber plasma membrane imposes a mitotic inhibition on the SC. Sarcolemmal molecules which might explain this membrane-imparted mitotic inhibition have not yet been identified. In this study we examined the border of the SC and the adjacent myofiber electron microscopically, assessing the number of SC showing encroachments of basement membrane (BM) material, secretion of cellular degradation products into the intercellular space, and caveolae. We studied normal and diseased muscle including Duchenne muscular dystrophy, Becker muscular dystrophy, idiopathic inflammatory myopathies, and neurogenic atrophies. Caveolae were present in SC from normal muscle, but they were more abundant in SC from diseased muscle, and they significantly prevailed at the outer surface of SC in all of the diseased muscle groups. Encroachments of BM material was only present in SC from diseased muscle, and mostly so in neurogenic atrophies. Secretion of cellular degradation products into the intercellular cleft occurred in normal and diseased muscle. We conclude that degradation products in the intercellular cleft do not disturb SC adhesion and that there is a neural influence on SC adhesion. The significance of the abundance of caveolae at the outer surface of the SC when compared with the inner surface in diseased muscle remains at present unknown.

Adolescent↗
PubMed2001

MRF4 protein expression in regenerating rat muscle.

The myogenic transcription factors of the MyoD family are not expressed in normal adult skeletal muscle. They are upregulated at the transcript and protein levels in a precisely coordinated manner during regeneration. While the cellular distribution of MyoD, myf-5, and myogenin expression in regenerating muscle is well documented, little is known about the exact localization of MRF4. It was the aim of this study to monitor the cellular distribution of MRF4 protein during regeneration. The soleus muscle of 6-week-old male Wistar rats was devascularized and allowed to regenerate for 2, 5, 10 or 14 days. Immunostaining revealed the presence of MRF4 throughout the time periods studied. Expression was detected in the nuclei of myofibers which had survived the devascularization procedure 2 days after necrosis was induced. In nuclei of newly formed myotubes and young myofibers, MRF4 was co-expressed with MyoD and myogenin. MRF4 protein was absent from satellite cells (SC), with anti-M-cadherin being used as a SC marker. Taken together, our results demonstrate that MRF4 protein expression in regenerated fibers is restricted to the time around and after fusion. The absence of MRF4 protein in SC suggests that the role of MRF4 during regeneration is distinct from myf-5, MyoD, and myogenin.

Animals↗
PubMed2001

Proton MR spectroscopy reveals lactate in infantile neuroaxonal dystrophy (INAD).

Changes of cerebral metabolites detected by proton MR spectroscopy in two cases of infantile neuroaxonal dystrophy are described. A 6 11/12-year-old boy and a girl (aged 4 1/12 years at the first and 5 2/12 years at the second examination) with infantile neuroaxonal dystrophy were investigated by magnetic resonance imaging and spectroscopy of the basal ganglia. The signal intensity of the cerebellar cortex was increased on T2-weighted, proton density, and fluid attenuated inversion recovery images. The long echo time (135 ms) spectra revealed the presence of lactate in the basal ganglia of both cases in all investigations. The N-acetylaspartate/creatine ratio was reduced in Case 1 and in the second investigation of Case 2. The choline/creatine ratio was always increased. As the diagnosis of infantile neuroaxonal dystrophy is made by a synopsis of various clinical, neuropathological, neurophysiological, and neuroradiological data, the presence of lactate in the basal ganglia spectra may help to narrow down the diagnosis and can support the decision to perform more invasive diagnostic procedures (such as biopsies of skin, conjunctiva or even of the brain).

Aspartic Acid↗
PubMed2001

Congenital myopathies.

Most congenital myopathies have been defined on account of the morphological findings in enzyme histochemical preparations. In effect, the diagnosis of this group of diseases continues to be made on the histological pattern of muscle biopsies. However, progress has been made in elucidating the molecular genetic background of several of the congenital myopathies. In this updated review we address those congenital myopathies for which gene defects and mutant proteins have been found (central core disease, nemaline myopathies, desminopathy, actinopathy, certain vacuolar myopathies, and myotubular myopathy) and the other disease with central nuclei (centronuclear myopathy).

Actins↗
PubMed2000

Altered expression of calcium- and apoptosis-regulating proteins in multiple system atrophy Purkinje cells.

The expression patterns of the calcium binding proteins calbindin and parvalbumin and of the apoptosis modulating proteins Bcl-2, Bax, and Bcl-x were studied in the cerebellum of patients with multiple system atrophy (MSA). Calbindin and parvalbumin immunoreactivity was markedly decreased in MSA Purkinje cells whereas Bax and Bcl-x protein expression was increased. Bcl-2 expression was restricted to a subpopulation of granule neurons, but no decrease of Bcl-2 was evident in MSA. Additional DNA end-labeling (ISEL) studies revealed only one possible apoptotic Purkinje cell nucleus, but nuclei in the cerebellar white matter, probably oligodendrocytes, in the cerebellum of patients with MSA. The present results suggest that a diminished calcium binding capacity of MSA Purkinje cells might lead to a change in the regulation of proteins of the bcl-2 family that could favor the pathologic initiation of apoptosis.

Apoptosis↗
PubMed2000

[Walker-Warburg syndrome in adulthood?].

BACKGROUND: Walker-Warburg-Syndrome (WWS) comprises malformations of the brain and the eyes with muscle dystrophy. Its course is usually lethal within the first 60 weeks of life. As far as we know there are no reports in the literature dealing with WWS in adults. CASE REPORT: A 70-year old female died because of cardio-pulmonary failure while she had an infection of the respiratory tract. The patient had been mentally deficient and had suffered from recurrent single convulsions. 17 years before death funduscopy had revealed an optic atrophy. Diabetes mellitus was known for ca. 15 years. The neuropathologists found a lissencephaly with a typical histology and a cerebellar malformation. Histologically, the eyes showed diabetic changes like vacuolization of the iris pigment epithelium and a thickening of basement membranes. There were marked deposits in the Pars plicata of the ciliary body and drusen formation in Bruch's membrane. The nerve fiber layer of the retina seemed to be thinned, and there was a considerable rarefication of optic ganglion cells. CONCLUSIONS: Taking the clinical and especially the morphological data into account, a Walker-Warburg-Syndrome was assumed. Within the eyes developmental and diabetic changes were combined. Because the cerebral and ocular malformations were comparably mild, the patient became unusually old, and visual function allowed at least good orientation. References were searched by medline and by the indices of known papers.

Abnormalities, Multiple↗
PubMed2000

Allograft inflammatory factor-1 is expressed by macrophages in injured skeletal muscle and abrogates proliferation and differentiation of satellite cells.

Secretion of regulatory peptides by macrophages in injured skeletal muscle constitutes a pivotal determinator of tissue homeostasis. We analyzed expression of a novel Ca2+- binding peptide expressed by activated macrophages, the allograft inflammatory factor-1 (AIF-1), in rat devascularized skeletal muscle. AIF-1 expression was observed in 94% of all macrophages at the site of the injury 48 hours postdevascularization. The physiological function of AIF-1 in injured skeletal muscle was analyzed using a rat in-vitro model of satellite cell proliferation and differentiation. Addition of AIF-1 to the culture medium resulted in a concentration-dependent and reversible reduction of the total number of cells expressing M-cadherin (p < or = 0.0001), a mediator of the differentiation process of skeletal muscle cells, the proliferation associated PCNA (p < or = 0.0001), and the initiator of muscle differentiation myogenin (p < or = 0.0001). These results provide convincing evidence that activated AIF-1 expressing macrophages constitute the predominant cell type in skeletal muscle 48 hours postinjury, and that AIF-1 regulates reduced proliferation, differentiation, and activation of satellite cells.

Animals↗
PubMed2000

Diagnostic protein expression in human muscle biopsies.

Using immunohistochemistry in diagnosing neuromuscular diseases is meant to enhance the diagnostic yield in two ways. The first application aims at visualizing molecules which are developmentally, neurally, and/or immunologically regulated and not expressed by normal muscle. They are upregulated in pathological conditions and may help assign a given muscular biopsy to one of the main diagnostic entities (muscular dystrophies, inflammatory myopathy, neurogenic atrophy). In the past, muscle-specific molecules with a defined expression pattern during fetal myogenesis served as antigens, with the rationale that the developmental program was switched on in new fibers. Recently, myofibers in diseased muscle are thought of as targets of stimuli which are released by macrophages in muscular dystrophy, by lymphocytes in inflammatory myopathies, or by a lesioned peripheral nerve in neurogenic atrophies. This has somewhat blurred the borders between the diagnostic groups, for certain molecules, e.g. cytokines, may be upregulated after experimental necrotization, denervation, and also in inflammatory myopathies. In the second part of this review we summarise the experiences of a Centre in the North of England that specialises in the diagnosis and clinical support of patients with muscular dystrophy. Emphasis is placed on the use of protein expression to guide mutation analysis, particularly in the limb-girdle muscular dystrophies (a group of diseases that are very difficult to differentiate on clinical grounds alone). We confirm that genetic analysis is essential to corroborate the results of protein analysis in certain conditions (particularly in calpainopathy). However, we conclude that analysing biopsies for abnormal protein expression is very useful in aiding the decision between alternative diagnoses.

Animals↗