H D Mennel

Publications (84)136.15 Total impact

• Article: Comparative experimental study of argon plasma and bipolar coagulation techniques.

  T Riegel, W Tirakotai, H D Mennel, D Hellwig, U Sure, H Bertalanffy, I Celik
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  ABSTRACT: Argon plasma coagulation (APC) is based on the principle of ionised argon creating conductive plasma between an activating electrode and tissue surface and is used as an effective alternative coagulation technique in various surgical disciplines. This trial aims to compare thermal injury in rat brain caused by APC and conventional bipolar coagulation technique. A controlled study design with constant power setting and application time was established. Twenty rats were randomised into the APC and bipolar groups. Each group of ten rats had 20 treated lesions. Early and late histopathological changes, as well as maximum extent of the lesion after 48 hours (h) and 12 days were studied in overall 20 lesions. Although the maximum depth of the lesions was different in APC (2.2 mm) and bipolar (1.8 mm) groups after 48 h, this did not achieve statistical significance (p=0.151). The superficially coagulated area was significantly larger after APC compared with the bipolar technique at the 48 h time point (p=0.032). After twelve days there were no differences in penetration depth (p=0.310) or coagulated area (p=0.222). Tissue defects after APC application on rat brains were comparable to conventional bipolar technique in this trial. The results suggest that argon plasma coagulation (APC) is an effective coagulation technique.
  Acta Neurochirurgica 08/2006; 148(7):757-62; discussion 762-3. · 1.52 Impact Factor
• Article: Primary and transplanted ENU induced rat tumors in neurooncology.

  H D Mennel, N Kosse, J T Heverhagen, H Alfke
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  ABSTRACT: In neurooncology transplanting, tumors can be used for many purposes e.g. to solve questions concerning the etiology and pathogenesis of such tumors or their management. Experimentally induced and transplanted tumors of the nervous system become reproducible in their morphology and growth parameters after about 12 subsequent intracerebral passages. During the period from the first to the 12th intracerebral generations, a simplification of the histology and a reduction of the induction times take place. Nowadays the growth behavior of such tumors can be followed by imaging methods such as MRI if specially adapted to small animals. Our results are based on the investigation of over 2350 experimentally induced tumors of the central and peripheral nervous system that were diagnosed according to the rules of human and rodent brain tumor classification and various subgroups of this sample, analyzed by electron microscopy, postmortal angiography and MRI.
  Experimental and Toxicologic Pathology 11/2004; 56(1-2):25-35. · 2.78 Impact Factor
• Article: The immunohistochemical expression of calcitonin receptor-like receptor (CRLR) in human gliomas.

  L Benes, C Kappus, G P McGregor, H Bertalanffy, H D Mennel, S Hagner
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  ABSTRACT: Gliomas are the most common primary tumours of the central nervous system and exhibit rapid growth that is associated with neovascularisation. Adrenomedullin is an important tumour survival factor in human carcinogenesis. It has growth promoting effects on gliomas, and blockade of its actions has been experimentally shown to reduce the growth of glioma tissues and cell lines. There is some evidence that the calcitonin receptor-like receptor (CRLR) mediates the tumorigenic actions of adrenomedullin. Aim: To determine whether CRLR is expressed in human gliomas and the probable cellular targets of adrenomedullin. Biopsies from 95 human gliomas of varying grade were processed for immunohistochemical analysis using a previously developed and characterised antibody to CRLR. All tumour specimens were positive for CRLR. As previously found in normal peripheral tissues, CRLR immunostaining was particularly intense in the endothelial cells. This was evident in all the various vascular conformations that were observed, and which are typical of gliomas. In addition, clear immunostaining of tumour cells with astrocyte morphology was observed. These were preferentially localised around vessels. This study has shown for the first time that the CRLR protein is present in human glioma tissue. The expression of the receptor in endothelial cells and in astrocytic tumour cells is consistent with the evidence that its endogenous ligand, adrenomedullin, may influence glioma growth by means of both direct mitogenic and indirect angiogenic effects. CRLR may be a valuable target for effective therapeutic intervention in these malignant tumours.
  Journal of Clinical Pathology 03/2004; 57(2):172-6. · 2.31 Impact Factor
• Article: [Pigmented form of orthochromatic leukodystrophy].

  J C Möller, I H Sünkeler, W H Oertel, H D Mennel
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  ABSTRACT: The pigmentary type of orthochromatic leukodystrophy (van Bogaert-Nyssen disease) is a hardly known neurological disorder usually with late onset that is very difficult to diagnose in vivo. Neuropathologically, the disorder features noninflammatory demyelination and the presence of pigmented macrophages and astrocytes that may contain iron. Clinically, van Bogaert-Nyssen disease can lead to death within a few years and is characterized by dementia, psychiatric abnormalities, epileptic seizures, spastic pareses, and occasionally extrapyramidal motor symptoms. This report presents a typical case and an overview of the literature. Furthermore, galactocerebroside could be documented in remaining macrophages and astrocytes by immunohistochemistry. This possibly indicates a dysfunction in sphingolipid breakdown and could relate the pigmented form of orthochromatic leukodystrophy to the genetically defined globoid cell leukodystrophy (Krabbe's disease). Thus, the rather heterogeneous pool of orthochromatic leukodystrophies could be further narrowed.
  Der Nervenarzt 01/2004; 74(12):1127-33. · 0.68 Impact Factor
• Article: Die pigmentierte Form der orthochromatischen Leukodystrophie

  J.C. Möller, I.H. Sünkeler, W.H. Oertel, H.D. Mennel
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  ABSTRACT: Die pigmentierte Form der orthochromatischen Leukodystrophie (M.van Bogaert-Nyssen) ist eine wenig bekannte neurologische Erkrankung, die in der Regel erst im Erwachsenenalter auftritt, in vivo kaum zu diagnostizieren ist und innerhalb weniger Jahre zum Tode fhren kann. Neuropathologisch ist sie hauptschlich durch den Nachweis einer nichtentzndlichen Demyelinisierung und von zum Teil eisenpositiven pigmentierten Makrophagen und Astrozyten gekennzeichnet. Klinisch stehen ein demenzielles Syndrom, psychiatrische Aufflligkeiten, epileptische Anflle, spastische Paresen und gelegentlich extrapyramidal-motorische Strungen im Vordergrund der Symptomatik. Die vorliegende Arbeit illustriert zum einen die diagnostischen berlegungen und gibt eine bersicht ber die Literatur. Zum anderen konnte in unserem Fall immunhistochemisch Galaktozerebrosid in noch vorhandenen Makrophagen und Astrozyten nachgewiesen werden. Mglicherweise liegt hier ein Hinweis auf die zugrunde liegende biochemische Strung vor. Vielleicht bestehen Beziehungen zur genetischen definierten Globoidzellleukodystrophie (M.Krabbe). Der heterogene Pool der orthochromatischen Leukodystrophien knnte in diesem Fall durch Ausgliederung dieser Form weiter eingeengt werden.The pigmentary type of orthochromatic leukodystrophy (van Bogaert-Nyssen disease) is a hardly known neurological disorder usually with late onset that is very difficult to diagnose in vivo. Neuropathologically, the disorder features noninflammatory demyelination and the presence of pigmented macrophages and astrocytes that may contain iron. Clinically, van Bogaert-Nyssen disease can lead to death within a few years and is characterized by dementia, psychiatric abnormalities, epileptic seizures, spastic pareses, and occasionally extrapyramidal motor symptoms. This report presents a typical case and an overview of the literature. Furthermore, galactocerebroside could be documented in remaining macrophages and astrocytes by immunohistochemistry. This possibly indicates a dysfunction in sphingolipid breakdown and could relate the pigmented form of orthochromatic leukodystrophy to the genetically defined globoid cell leukodystrophy (Krabbes disease). Thus, the rather heterogeneous pool of orthochromatic leukodystrophies could be further narrowed.
  Der Nervenarzt 11/2003; 74(12):1127-1133. · 0.68 Impact Factor
• Article: Intraspinal pannus formation at C6 in a patient with rheumatoid arthritis causing severe cervical cord compression. A case report.

  K Shiratori, H D Mennel, S Bien
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  ABSTRACT: We report a rare case of cervical cord compression caused by intraspinal pannus formation at C6 in a patient with long-term rheumatoid arthritis. No atlantoaxial abnormalities were seen. The imaging findings are presented and the pathology discussed.
  Rheumatology International 08/2003; 23(4):192-4. · 1.88 Impact Factor
• Article: Helium (argon) plasma coagulation in neurosurgery. morphology of tissue damage and reparation.

  H D Mennel, T Riegel, D Lonić, H Bertalanffy
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  ABSTRACT: Plasma coagulation, used in some neurosurgical operative settings, is currently under experimental investigation for the precise assessment of the kind and extent of tissue damage. We established a standardised trial to investigate the effects of helium (argon) plasma coagulation - H(A)PC - on rat brain tissue. The tissue reactions were observed with common methods of morphology including immunohistology and electron microscopy. A time dependent profile of the tissue reactions was performed from day 1 after operation up to 6 weeks. The tissue reaction consisted of clearly demarcated concentric zones. The depth of the lesion was about 1 mm maximally, at the beginning. Reparative forces acted at variance both in the different layers and at the edges versus the center of the damage. A manifold but reproducible picture emerges in the various compartments allowing the study of different aspects of organisation and/or elimination of tissue components. This study has demonstrated that a defined circumscribed and reproducible small lesion can be performed with H(A)PC. As in other areas of surgery, this technique has proven to be minimally traumatic. Clinical application of this technique in neurosurgery is therefore promising. In addition, H(A)PC lesions are obviously best suited for morphological studies of early and late reparative reactions in cells and tissues.
  Experimental and Toxicologic Pathology 12/2002; 54(3):255-63. · 2.78 Impact Factor
• Article: [Klaus Joachim Zülch: Partner to neurosurgery, advocate of neurology and the neuropathological basis].

  H D Mennel
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  ABSTRACT: Klaus Joachim Zülch (1910-1988) since 1959 head of a department of the german Max-Planck-Society, deeply influenced the neurological sciences in post-war Germany. The department with the name Abteilung für allgemeine Neurologie (i.e. department of general neurology) constituted a section of the renowned Max-Planck-Institut für Hirnforschung (i.e. institute for brain research) and found its place in Cologne. At the same time he was in charge of the local neurology unit of the municipal Cologne hospital, on the right Rhine riverside in Köln (Cologne) Merheim. In this double position he was able to focus his work as a neurologist on the major issues of this specialty, that at this time were not in the center of neurological interest: The connection of basic science i.e. morphology with important themes such as raised intracranial pressure, brain swelling and edema, brain and spinal chord circulation disturbances, head injuries and - in the first line - tumors of the central nervous system. This broad approach to essential issues in the field was probably due to his upbringing in german neurological tradition. His first contact with this specialty took place in Otfrid Foersters neurological clinic in Breslau, today in Poland, before World War II. Otfrid Foerster, a neurological encyclopedist, exerted a deep influence upon Klaus Joachim Zülch lifelong. Here he also came in contact with Percieval Bailey with whom he shared the obsession to classify brain tumors since then. This preoccupation became fruitful when he started collaboration with Wilhelm Tönnis 1936 at the time still in Würzburg. The collaboration continued, when Tönnis moved to Berlin, during and after World War II up to 1959, when Klaus Joachim Zülch became head of the mentioned department of the german Max-Planck-society. At this time, important contributions already existed concerning brain injuries, brain edema and tumor classification. The couple Wilhelm Tönnis and Klaus Joachim Zülch may well be compared to the team formed by Harvey Cushing and Percieval Bailey. Their respective philosophies were equally identical, namely to classify tumors of the central nervous system through a pragmatic approach that would facilitate the communication between neuropathologist, neurosurgeon, neurologist and of course be ultimately as helpful as possible to the patient. Since 1959 Zülchs research turned to the topics of brain hypoxia, circulatory disturbances and stroke, notwithstanding that his interest remained with the other items, whenever new or old questions came up. The occupation with tumors became even once more intense when the WHO installed a reference center for brain tumor classification at his place in Cologne. In the new field of brain circulation, Klaus Joachim Zülch tried once again to bring basic science and clinical practise together and to draw the neurologists attention upon these frequent and important conditions, a development that gained increasing importance under the heading of "stroke unit" in our days. Klaus Joachim Zülch therefore may be regarded as neurologist ahead of his time trying to cover the epidemiologically important and frequent themes and establishing equal partnership with neurosurgery The connection with the scientific basis, i.e. morphology in different variations at the time under a common roof was crucial in his understanding of the work as neurologist.
  Zentralblatt für Neurochirurgie 02/2002; 63(1):29-35. · 0.63 Impact Factor
• Article: Endothelial proliferation, neoangiogenesis, and potential de novo generation of cerebrovascular malformations.

  U Sure, N Butz, J Schlegel, A M Siegel, J P Wakat, H D Mennel, S Bien, H Bertalanffy
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  ABSTRACT: To date, both arteriovenous malformations (AVMs) and cavernomas have been considered to be congenital malformations. A recent survey of the literature has shown the potential for de novo generation of both familial and sporadic cavernomas as well as AVMs. Therefore, it was of interest to determine the biological behavior of these lesions in detail. The proliferative and angiogenic capacities of the endothelium of 13 cavernomas and 25 AVMs obtained in patients recently treated (1997-1998) at one institution were studied. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA), MIB-1, and vascular endothelial growth factor (VEGF) and its receptor Flk-1 was performed using standard staining procedures. Positive immunostaining of the nuclei of endothelial cells was observed in specimens of both AVMs and cavernomas for PCNA (80% of AVMs and 85% of cavernomas), and Flk-1 (80% of AVMs and 31% of cavernomas). Endothelial expression of VEGF in the 18 incompletely embolized AVMs was found in 72% of cases but only in 28% of the seven cases in which patients did not undergo endovascular treatment: it was found in 38% of cavernomas. Endothelial expression of MIB-1 was found in 12% of AVMs but in no cavernomas. These results indicate that there is endothelial proliferation as well as neoangiogenesis in cerebral cavernomas and AVMs. The increased level of angiogenesis in only partially obliterated AVMs underscores the need for radical and complete occlusion of cerebral AVMs to avoid recurrences and further risks of morbidity.
  Journal of Neurosurgery 07/2001; 94(6):972-7. · 2.96 Impact Factor
• Article: Early and late morphological effects of experimental HPNS--animal model of psychosis?

  G Stumm, H Geissel, J Wenzel, H D Mennel
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  ABSTRACT: The high pressure neurological syndrome (HPNS), a neurological condition during elevated pressure especially in deep diving, has been simulated with experimental animals. Rats were subjected to 61 bars with slow pressure increase and one or two hours constant high pressure; subsequently the pressure was released to sea level within 20 seconds--leading to immediate oxygen depletion and death of animals--or with slow decompression rates allowing survival. In all animals, brains and partly other organs were investigated morphologically. In animals sacrificed immediately, subtle changes in different brain regions were found: symmetrical occurrence of dark neurons in the hippocampus formation, cortex and brain stem, reduced expression of tyrosin hydroxylase in the substantia nigra and enhanced expression of Bax protein in some of these regions. The dark neurons were only observed after aldehyde fixation, otherwise the brains were unaltered despite ultrarapid decrease of highly elevated pressure. In animals that were allowed to survive for different time periods, some of these subtle changes were equally noted by light and electron microscopy. Furthermore, the ventricles were enlarged, the astrocytic reaction in the hippocampus increased and some signs of the destruction of the adrenal gland were visible. We conclude, that HPNS leads to minimal changes within the nervous system. The behaviour of animals during pressure was slightly altered, the weights after the experiments reduced, but no lasting sequelae were noted. Since both in human and experimental deep diving conditions signs of psychosis were reported, this HPNS model must be considered as a tentative animal model of human psychosis.
  Experimental and Toxicologic Pathology 05/2001; 53(1):45-55. · 2.78 Impact Factor
• Article: Treatment-induced neoangiogenesis in cerebral arteriovenous malformations.

  U Sure, N Butz, A M Siegel, H D Mennel, S Bien, H Bertalanffy
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  ABSTRACT: We investigated the angiogenetic and proliferative activity of the endothelium of 30 consecutive surgical cases of AVM treated at our institution by immunohistochemical detection of the PCNA, MIB-1, Flk-1 and VEGF antibodies. Endothelial positive immunostaining was observed in 87% of the cases for PCNA, in 20% for MIB-1, and in 80% for Flk-1. Of 22 individuals treated with incomplete embolization prior to surgery, 17 showed an expression of VEGF (77%), but only two of the eight patients (25%) who were treated without prior embolization exhibited such an immunoreaction (P=0.0086). The proliferation and growth of cerebral AVMs is documented by endothelial expression of PCNA and MIB-1. The statistically significantly higher expression of VEGF in partially obliterated (embolized) AVMs is most likely caused by transient regional hypoxia within the AVM nidus that mediates neoangiogensis. It points out the clinical relevance of a complete occlusion in order to avoid neovascularization associated with subsequent morbidity and mortality.
  Clinical Neurology and Neurosurgery 05/2001; 103(1):29-32. · 1.58 Impact Factor
• Article: Morphology of tissue damage caused by permanent occlusion of middle cerebral artery in mice.

  H D Mennel, H El-Abhar, M Schilling, J Bausch, J Krieglstein
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  ABSTRACT: In two series of experimental occlusion of the middle cerebral artery (MCA) in mice, the time course and the evolution of morphological changes were followed. Both series comprised control animals used in experiments for the screening of neuroprotective and therapeutic effects after focal ischemia. In both series the left MCA was permanently occluded and the animals were sacrificed by perfusion fixation at certain time intervals following occlusion. In the first series the follow up was continued until the 30th day after ischemia. In the second, the observation period was extended to two months. The general question was addressed, whether or not such experimental settings can contribute to the understanding of cellular (necrosis vs apoptosis) and tissue (resorption vs scar) reaction. In the two series the technical procedures were only slightly different. Nevertheless, the development of morphological sequelae was at variance. Differences in tissue reaction in both sets revealed features that were rarely observed in previous protocols. In the first series, infarct areas were different in size, often a central part near the meninges was preserved and gave rise to a prominent mesenchymal reaction. In the second series, infarcts had almost constant size and mesenchymal reaction changes were minimal. The end product in both series, however, was a shallow groove much smaller than the primary well-demarcated defect. We conclude that minor technical variations of MCA occlusion in the mouse demonstrate the variability of occlusion sequelae due to collateral irrigation known from human cerebral pathology. On the cellular level, neuronal death is obviously completed during the first 24 hours in the infarct core. Thus, the mechanism of neuronal damage can only be best observed by morphology at the transition between completed territorial necrosis and unchanged tissue: shrunken neuronal perikarya develop into pycnotic nuclei, that may be interpreted as apoptosis. A second area of partial damage is marked by gliosis. Astrocytic reaction extended far beyond the infarct border, even to the contralateral hemisphere and could represent a component of size compensation.
  Experimental and Toxicologic Pathology 11/2000; 52(5):395-404. · 2.78 Impact Factor
• Article: Immunohistochemically visualized localisation of gangliosides Glac2 (GD3) and Gtri2 (GD2) in cells of human intracranial tumors.

  H D Mennel, K Bosslet, H Geissel, B L Bauer
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  ABSTRACT: Antibodies against two major gangliosides detected in human brain and brain tumors--Glac2 (GD3) and Gtri2 (GD2)--were tested by immunohistochemistry in an unselected sample of intracranial tumors during the years 1986 through 1991. Two groups emerged as evaluable samples, namely gliomas of different grades and meningiomas. In a pilot series, it was shown that these gangliosides could be visualized in frozen sections of cells of gliomas and meningiomas (as well as neurinomas) and in some structures of the normal brain. It was however not possible in frozen sections to further analyze the cellular or subcellular expression pattern of the mentioned components and paraffin sections with conventional processing were only weakly and diffusely stained. A modified protocol therefore was created that replaced alcohol processing by acetone. With this protocol, interpretable results in paraffin sections were obtained. With this method, 133 single intracranial tumors were investigated as to their immunohistologically detectable ganglioside expression. The most consistent result was that the whole cytoplasm of highly fibrillary (gemistocytic) astrocytes in all grades of gliomas was stained by Gtri2 (GD2) and Glac2 (GD3) with high preponderance of Gtri2 (GD2) expression. In all meningiomas, Glac2 (GD3) had a higher expression than Gtri2. No constant pattern in the other entities emerged. By comparison with GFAP expression in gliomas and vimentin in meningiomas, the colocalisation of gangliosides and intermediary filament proteins is supposed.
  Experimental and Toxicologic Pathology 09/2000; 52(4):277-85. · 2.78 Impact Factor
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  Available from: maps.org

  Article: Amphetamines induce apoptosis and regulation of bcl-x splice variants in neocortical neurons.

  G Stumm, J Schlegel, T Schäfer, C Würz, H D Mennel, J C Krieg, H Vedder
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  ABSTRACT: Amphetamineanalogs have emerged as popular recreational drugs of abuse. The number of reports of these substances producing severe acute toxicity and death is increasing. In 'Ecstasy' -associated deaths, focal necrosis in the liver and individual myocytic necrosis has been reported. Furthermore, serotonergic and dopaminergic neuronal cell damage has been observed in experimental amphetamine intoxication in laboratory animals. Here we demonstrate that subchronic exposure to D-amphetamine, methamphetamine, methylenedioxyamphetamine, and methylenedioxymethamphetamine ('Ecstasy') results in significant neurotoxicity in rat neocortical neurons in vitro. This neuronal cell death is accompanied by endonucleosomal DNA cleavage and differential expression of anti- and proapoptotic bcl-xL/S splice variants. In addition, we observed pronounced induction of cell stress-associated transcription factor c-jun and translation initiation inhibitor p97 after amphetamine treatment. These data support that the neurotoxic effects of different amphetamines are extended to rat neocortical neurons and that apoptotic pathways are involved in amphetamine-induced neurotoxicity.
  The FASEB Journal 07/1999; 13(9):1065-72. · 5.71 Impact Factor
• Article: Molecular genetic characterisation of intracerebrally transplanted brain tumours.

  J Schlegel, G Piontek, C Kühne, H J Bartels, A Kraus, R Kappler, H D Mennel
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  ABSTRACT: The aim of the present study was the characterisation of genetic alterations in two different experimental gliomas, induced in rats from the inbred strain BDIX by transplacental ethylnitrosourea with subsequent serial transplantation. The genes investigated have been shown previously to be altered during human glial tumour progression and include the gene for the epidermal growth factor receptor (EGFR), the genes for the cell cycle regulators cyclin dependent kinase 4 (CDK4), cyclinD1 (cycD1), the p16 gene (MTS1/INK4) and the retinoblastoma gene (RB). Using a semi-quantitative PCR-based screening method no gross alterations could be detected in these genes, demonstrating that nitrosourea-induced glial tumours of rats do not harbour those genetic changes which typically arise in human malignant gliomas. Thus, the use of this tumour model for gene therapy trials is questionable.
  Experimental and Toxicologic Pathology 02/1999; 51(1):41-5. · 2.78 Impact Factor
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  Available from: Christoph G O Baerwald

  Article: Electron microscopy and capillaroscopically guided nailfold biopsy in connective tissue diseases: detection of ultrastructural changes of the microcirculatory vessels.

  A von Bierbrauer, P Barth, J Willert, C Baerwald, H D Mennel, J A Schmidt
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  ABSTRACT: The aims of the study were to describe and compare the frequency and nature of histologically detectable microvascular lesions in patients with various connective tissue diseases (CTD). An electron microscopic examination of specimens obtained by the technique of capillaroscopically guided nailfold biopsy was performed in 52 patients with CTD [nine systemic lupus erythematosus (SLE), eight mixed CTD, 18 scleroderma, 17 undifferentiated CTD] and 27 controls. The microvascular changes most frequently observed by electron microscopy were multilayering of the basal lamina (approximately 70% of the CTD patients), an increased amount of perivascular connective tissue, perivascular oedema formation, and an increased number of perivascular fibroblasts and mast cells (each in 30-37% of the CTD patients). In contrast, no particular histopathological feature was found in > 25% of the controls, multilayering (22.6%) being the most frequently observed. Comparing the different conditions studied, there were distinct differences in the frequency and nature of the histologically observed microvascular changes. In particular, SLE seems to be based on a separable type of vasculopathy consisting of significantly less frequent microvascular abnormalities. In conclusion, ultrastructural abnormalities of the microvascular system are a frequent finding in CTD. Electron microscopic examination of specimens obtained by capillaroscopically guided nailfold biopsy is able to disclose histopathological differences between defined entities. Therefore, this approach may be a useful tool to gain further insights into potentially separable aetiopathological mechanisms of the various types of CTD.
  British journal of rheumatology 01/1999; 37(12):1272-8.
• Article: Comparative genomic in situ hybridization discloses chromosomal copy number changes in a transplanted brain tumor line of the rat (Rattus norvegicus).

  R Kappler, J Schlegel, K Romanakis, H D Mennel, H Scherthan
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  ABSTRACT: We investigated chromosomal copy number changes in ethylnitrosourea-induced and serially transplanted gliomas of the rat by flow cytometry and Comparative Genomic in situ Hybridization (CGH). CGH analysis of a primary and four transplanted tumors revealed several genomic aberrations, including whole chromosome and subchromosomal gains and losses. Gains involved rat Chromosomes (RNO) 2, 3, 4, 5, 7, 9, 11, 12, 13, and Y, whereas losses affected RNO5, 13, 20, and Y. The primary tumor exhibited gain of RNO2q31qter and gain of RNO4. While gain of RNO2 was seen in nearly all investigated passages, gain of RNO4 was apparent in the primary tumor and in passage 2 and 5 tumors. Chromosomal alterations detected as single events were restricted to the transplanted tumors and included gain of RNO3q11, 3q41qter, 5q36, 7q34qter, 9q37, 11q, and Y, and loss of RNO5, 13, and 20q. Flow cytometry disclosed different aneuploid cell clones in the tumors investigated. The results are discussed in analogy to findings in human glial tumors.
  Mammalian Genome 03/1998; 9(3):193-7. · 2.89 Impact Factor
• Article: Early morphological findings in experimental high pressure neurological syndrome.

  H D Mennel, G Stumm, J Wenzel
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  ABSTRACT: HPNS (high pressure neurological syndrome) is considered to be reversible condition of the nervous system caused by elevated (atmospheric) pressure. Clinical observations and experimental findings gave rise to the belief that this syndrome at least partly functions as a model of a dopamin dependent psychosis. Morphological alterations during or after HPNS in man and animals have not been reported so far. We treated rats for three hours with an increasing pressure of helium-oxygen mixture up to 61 ATA in a pressure chamber. This pressure was subsequently maintained for one hour and then released to zero within twenty seconds. The rats died within the first three seconds of pressure release due to complete deoxygenation. Brains were immediately removed and either cooled in liquid nitrogen or fixed in formalin. In both instances the central nervous tissue was excellently preserved. In paraffin embedded formalin fixed specimens, dark neurons in different brain regions were found, especially within parts of the dentate gyrus, the CA 4 subfield of the ammons horn, in dopaminergic brainstem nuclei and in some cortical pyramidal cells. In dopaminergic cells, tyrosine hydroxylase was found to be absent in cells transformed into dark neurons. These dark neurons which have long been recognized in neuropathology, probably represent reversibly damaged neurons transformed into the dark configuration by aldehyde fixation. They may correspond to early apoptosis or they may be the consequence of cytoskeletal disruption.
  Experimental and Toxicologic Pathology 01/1998; 49(6):425-32. · 2.78 Impact Factor
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  Available from: bmj.com

  Article: Intravital microscopy and capillaroscopically guided nail fold biopsy in scleroderma.

  A F von Bierbrauer, H D Mennel, J A Schmidt, P von Wichert
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  ABSTRACT: To describe the frequency, extent, and nature of microvascular lesions in patients with scleroderma by means of capillaroscopy and capillaroscopically guided nail fold biopsy, and to determine the diagnostic value of the two methods and the pathophysiological significance of the lesions described. A cohort study was made of 24 consecutive patients with scleroderma and 10 healthy controls, using standardised clinical, serological, capillaroscopic, and histological (nail fold biopsy) techniques. All patients with scleroderma had distinct lesions of the microvascular system. Capillaroscopy revealed more than 90% of the patients to have the typical scleroderma pattern. Histologically, these changes most frequently consisted of splitting of the basal lamina, broadening of the perivascular connective tissue, perivascular round cell infiltrations, and immunoglobulin deposits (each in 60-75% of the patients). Electron microscopy was the most sensitive method of histological examination, detecting abnormalities in 87.5% of patients; with light microscopy and immunohistochemical techniques, abnormalities were revealed less frequently (83.3% and 75%, respectively). In contrast, normal findings were observed in most of the healthy controls: capillaroscopy = 90%; histology = 80%. Microvascular lesions are a predominant feature in scleroderma and seem to have a central pathogenetic role in the disease. Capillaroscopy is able to identify this microangiopathy noninvasively, and capillaroscopically guided nail fold biopsy can detect the frequency and nature of the underlying ultrastructural changes. This may therefore be a useful tool in describing the pathogenetic role of the microvascular system in scleroderma.
  Annals of the Rheumatic Diseases 06/1996; 55(5):305-10. · 8.73 Impact Factor
• Article: Quantitative DNA analysis of an intracerebrally transplanted brain tumour model after experimental chemotherapy with BCNU and CCNU.

  J Schlegel, G Stumm, J Ruschoff, H D Mennel
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  ABSTRACT: In the present study we investigated the susceptibility of high passages of the rat glial transplantation tumour G-XIII to chemotherapy using nitrosourea compounds. We observed a significant increase in lifespan (ILS) of animals treated with BCNU (37%, p < 0.01) and CCNU (27%, p < 0.01). There were no difference in the efficiency between these two substances. Using a semi-quantitative score system no histopathological changes were observed which were associated with the response to therapy. The only predicative parameter in the present study was the quantitative DNA distribution pattern. There was a close correlation between treatment and the occurrence of unimodal DNA distribution patterns indicating clonal regrowth of recurrent tumours. Moreover, we also observed a correlation of the DNA distribution pattern of recurrent tumours with the result of experimental chemotherapy. Survival times of animals suffering from tumours containing unimodal DNA histogram was significantly longer than survival times of rats with multimodal DNA distribution, i.e. bimodal or broad DNA histograms. A unimodal, near-diploid stem line was only present in treated animals suggesting that these clones are more resistant against therapy using nitrosourea compounds. Our data indicate DNA cytophotometry as comprehensive tool for the monitoring of therapy response and the design of experimental chemotherapy using rat glial tumours.
  Experimental and Toxicologic Pathology 10/1995; 47(4):313-8. · 2.78 Impact Factor