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Biomedical subjects

A Giese

Publications and source records attributed to A Giese.

At least 19 recordsLinked to original sources
PubMed2006

Synaptic organization in cochlear inner hair cells deficient for the CaV1.3 (alpha1D) subunit of L-type Ca2+ channels.

Cochlear inner hair cells (IHCs) release neurotransmitter onto afferent auditory nerve fibers in response to sound stimulation. Normal development and function of inner hair cells require the expression of alpha subunit 1.3 forming L-type voltage-gated Ca(2+) channel (Ca(V)1.3). Here, we used immunohistochemistry and reverse transcription-polymerase chain reaction to study the synaptic organization and expression of large conductance Ca(2+)-activated potassium channels in IHCs of mice lacking the Ca(V)1.3 Ca(2+) channel (Ca(V)1.3(-/-)). Despite the near complete block of evoked afferent synaptic transmission, hair cell ribbon synapses were formed and remained preserved for at least 4 weeks after birth. Moreover, these "silent" afferent synapses held major components of the synaptic machinery such as Bassoon, Piccolo, and CSP. Hence, the block of exocytosis might be solely attributed to the lack of Ca(2+) influx through Ca(V)1.3 channels. Later on, Ca(V)1.3 deficient IHCs subsequently lost their afferent synapses. This was probably due to a secondary degeneration of the postsynaptic spiral ganglion neurons. In line with a prolonged efferent synaptic transmission onto Ca(V)1.3 deficient IHCs, which normally ceases around onset of hearing, we found juxtaposed immunoreactive spots of efferent presynaptic synaptophysin and postsynaptic (IHCs) small conductance Ca(2+)-activated potassium channels (SK channels) up to six weeks after birth. Finally, we show a substantial reduction of mRNA for the alpha subunit of the large conductance Ca(2+)-activated potassium channel (BK) in the apical cochlea, suggesting a reduced transcription of its gene in Ca(V)1.3 deficient IHCs. Ca(V)1.3 deficient IHCs lacked the apical spot-like immunoreactivity of clustered BK channels, which normally contribute to the temporal precision of hair cell afferent synaptic transmission. In summary, these data indicate that the Ca(V)1.3 channels are crucially involved in regulation of the expression of BK and SK channels. Ca(V)1.3 channels seem not to be essential for ribbon synapse formation, but are required for the maintenance of ribbon synapses and spiral ganglion neurons.

Age Factors↗
PubMed2006

Time-domain and spectral-domain optical coherence tomography in the analysis of brain tumor tissue.

INTRODUCTION: Detection of residual tumor during resection of glial brain tumors remains a challenge because of a low inherent contrast of adjacent edematous brain, the surrounding infiltration zone, and the solid tumor. Therefore, new technologies that may facilitate an intraoperative analysis of the tissue at the resection edge are of great interest to neurosurgeons. MATERIALS AND METHODS: For ex vivo imaging of gliomas in a mouse model and human biopsy specimens of brain tumors and nervous system tissue we have used a time-domain Sirius 713 Tomograph with a central wavelength of 1,310 nm and a coherence length of 15 microm equipped with a mono mode fiber and a modified optical coherence tomography (OCT) adapter containing a lens system for imaging at a working distance of 2.5 cm. A spectral-domain tomograph using 840 nm and 930 nm superluminescence diodes (SLD) with a central wavelength of 900 nm was used as a second imaging modelity. RESULTS: Both time-domain and spectral-domain coherence tomography delineated normal brain, the infiltration zone and solid tumor in murine intracerebral gliomas. Histological evaluation of H&E sections parallel to the optical plain demonstrated that tumor areas of less than a millimeter could be detected and that not only solid tumor, but also brain invaded by a low-density single tumor cells produced an OCT signal different from normal brain. Spectral-domain OCT (SD-OCT) demonstrated a significantly more detailed microstructure of tumor and normal brain up to a tissue depth of 1.5-2.0 mm, whereas the interpretation of time-domain OCT (TD-OCT) was difficult at a tissue depth >1.0 mm. Because of rapid scanning times SD-OCT data could be acquired as 3D data maps, which allowed a multi-planar analysis of the tumor to brain interface. Similar to our findings in experimental gliomas, images of human nervous system tissue acquired using SD-OCT showed a characteristic signal of normal brain tissue and a detailed microstructure of tumor parenchyma. CONCLUSION: Spectral-domain OCT of experimental gliomas and human brain tumor specimens differentiates solid tumor, diffusely invaded brain tissue, and adjacent normal brain based on microstructure and B-scan signal characteristics. In conjunction with the rapid image acquisition rates of SD-OCT, this technology carries the potential of a novel intraoperative imaging tool for the detection of residual tumor and guidance of neurosurgical tumor resections.

Animals↗
PubMed2006

Optical coherence tomography for experimental neuroendoscopy.

Optical coherence tomography (OCT) is a non-invasive and non-contact imaging technology that has been applied to several biomedical applications. We have recently demonstrated that OCT allows discrimination of tumor adjacent brain, diffuse and solid tumor tissue and that this technology may be used to detect residual tumor within the resection cavity during resection of intrinsic brain tumors. Here we show that an OCT integrated endoscope can image the endoventricular anatomy and other endoscopically accessible structures in a human brain specimen. A Sirius 713 optical coherence tomography device was mounted to a modified rigid endoscope. A formalin-fixed human brain specimen was used to simulate endoscopic visualization of brain anatomy and two specimens of fixed malignant tumors with endoventricular growth patterns. Simultaneous OCT imaging and endoscopic video imaging of the visible spectrum was possible using a graded index rod endoscope. OCT imaging of a human brain specimen in water allowed an in-depth view into structures like the walls of the ventricular system, the choroid plexus or the thalamostriatal vein. OCT further allowed imaging of structures beyond tissue barriers or opaque media. In this fixed specimen OCT allowed discrimination of vascular structures down to a diameter of 50 mum. In vessels larger that 100 mum the lumen could be discriminated and within larger blood vessels a layered structure of the vascular wall as well as endovascular plaques could be visualized. This in vitro pilot study has demonstrated that OCT integrated into neuroendoscopes may add information that cannot be obtained by the video imaging alone. This technology may provide an extra margin of safety by providing cross-sectional images of tissue barriers within optically opaque conditions.

Brain↗
PubMed2005

Analysis of mouse brain using a clinical 1.5 T scanner and a standard small loop surface coil.

With increasing numbers of in vivo experiments in the field of neuroscience, the interest in methods for in vivo imaging of animal brains as small as those of mice has increased. Because highly specialized small bore scanners with high field strengths are not commonly available, clinical magnetic resonance imaging (cMRI) scanners have been used in the past to image rat and more recently also mouse brains in combination with specifically developed RF coils. These studies have demonstrated that imaging of small animal brains is feasible, and that tumor volumes measured by cMRI correlate well with histological tumor volume analysis. This protocol describes the cMRI settings at 1.5 T for imaging of mouse brain with resolutions up to 120 x 120 microm using an inexpensive, commercially available small loop surface coil. This allows easy establishment of a small animal MRI facility without the need for cost intensive dedicated small animal scanners or special custom made coils. In this study, we demonstrate high-resolution imaging of intracranial xenografts in a mouse glioma model and monitor the treatment effect of external field irradiation by cMRI.

Anesthesia↗
PubMed2005

Infarction of the right hemisphere in a patient with antiphospholipid antibody syndrome.

Hemicraniectomy as a surgical treatment for intracranial pressure following large ischemic lesions is widely practiced in selected patients. The antiphospholipid antibody syndrome (APS), a disorder characterized by recurrent arterial and venous thrombosis, is a very rare cause of space occupying ischemic lesions. We present a case of a 35 year old female diagnosed with APS who initially presented with small ischemic lesions and within days developed a massive near-total infarction of the right hemisphere. Because of central nervous system, skin and systemic manifestations Sneddon's syndrome and catastrophic antiphospholipid antibody syndrome (CAPS) remained a possible diagnoses. Sneddon's syndrome is a non-inflammatory occlusive arteriopathy of small and medium size arteries predominantly of the skin and brain, whereas the catastrophic antiphospholipid antibody syndrome is characterized by acute multi-organ system thrombosis of small and large vessels. In addition to the diagnostic criteria for APS a heterozygous factor V Leiden mutation was found in this patient, which may be a contributing risk factor for cerebral ischemia. When considering invasive decompressive procedures the neurosurgeon has to be aware of the poor prognosis of some forms of APS with systemic manifestations.

Adult↗
PubMed2005

Cerebellar haemorrhage and tension pneumocephalus after resection of a Pancoast tumour.

We present an unusual case of cerebellar haemorrhage followed by tension pneumocephalus several days after thoracotomy for resection of a Pancoast tumour. The postoperative course of the 32-year-old patient was complicated by a cerebellar haemorrhage and hydrocephalus caused by compression of the fourth ventricle. Immediate surgical evacuation of the haemorrhage and placement of an external ventricular drain was performed. Respirator ventilation maintaining a continuous positive airway pressure was required. Following weaning and extubation the patient rapidly deteriorated and became comatose. A cranial CT scan revealed a dilated ventricular system filled with air, and air in the subarachnoid space. Recovery of consciousness was observed after aspiration of intracranial air through the ventricular drainage. Recurrent deterioration of consciousness after repeated air aspiration indicated rapid refilling of the ventricles with air. The patient underwent emergency surgical re-exploration of the thoracic resection cavity: dural lacerations of the cervico-thoracic nerve roots C8 and Th1 were identified. Subarachnoid-pleural fistula, cerebellar haemorrhage and tension pneumocephalus after discontinuation of continuous positive airway pressure respiration are unusual complications of thoracic surgery. We discuss the putative pathomechanisms and present a brief review of the literature.

Adult↗
PubMed2005

CAD generated mold for preoperative implant fabrication in cranioplasty.

Intraoperative fabrication of acrylic cranial implants may be difficult and will increase operation time. In addition forming implants directly on the defect, intracranial tissues are exposed to heat of polymerization and residual monomer, that occurs, when autopolymerizing methyl methacrylate is used intraoperatively. Furthermore the cosmetical result may be unacceptable. Preoperatively formed acrylic implants may reduce these disadvantages compared to conventional techniques in cranioplasty. We will present methods for preoperative fabrication of cranial implants for a cadaver specimen. Implants were fabricated using a Rapid prototyping (RP) models of the skull built by Fused Deposition Modeling (FDM). In addition a mold of the defect was generated by CAD techniques, that can serve as a template for implant design.

Computer-Aided Design↗
PubMed2004

Fatal and non-fatal injuries caused by crossbows.

Today in modern times, traumatic injuries caused by crossbows are a rarity. The largest collection of cases so far is presented in this study, consisting of four fatalities (two homicides and two suicides) and two non-fatal injuries (grievous bodily harm and an accident). All the victims were male having an age between 31 and 54. The weapons, which were used, were mainly high-performance precision crossbows with telescopic sights and hunting bolts. The parts of the body involved were the facial/head area in three of the cases and the thorax in three of them. There were either deep or total penetration injuries to the cranium and thorax with the bolt remaining in the wound in four out of six cases. The persons with non-fatal crossbow injuries exhibited comparatively few symptoms, despite the sometimes extensive involvement of the interior of the cranium (cerebrocranial penetration, in one instance). The two cases of suicide favoured the body areas often found with gun-users. The aetiological classification of crossbow injuries may be difficult after the removal of the bolt. The external morphology is strongly dependent on the type of tip used. Multiple-bladed hunting broadheads produce radiating incised wounds, whereas conical field tips produce circular to slitlike defects. Correspondingly, the external injuries can be reminiscent of the effects of a violent attack by sharp force or of a gunshot wound. The possibility, supported by clinical data, that the victim might have the ability to act or even to survive for a period of time, even with penetration of the brain, should be taken into account when the cause of death is being investigated.

Accidents↗
PubMed2004

Inhibition of the arachidonic acid metabolism blocks endothelial cell migration and induces apoptosis.

Previous studies have demonstrated that inhibitors of the arachidonic acid metabolism block migration and sensitise human glioma cells to treatment inducing apoptosis. This paradigm may provide a new concept for anti-invasive treatment strategies targeting invasive glioma cells. However, the effect of such treatment on other cellular elements in glial tumours such as endothelial cells is unknown. In this study we have analysed the expression of metabolites of the arachidonic acid pathway in endothelial cells in vitro and in vivo and we have assessed the influence of inhibitors of this pathway on motility, capillary like tube formation, and apoptosis in human endothelial cells. Human endothelial cells (HUVEC) in culture showed expression for thromboxane synthase and both isoforms of cyclo-oxygenase, COX-1 and COX-2. Immunostaining demonstrated low levels of COX-1 expression in capillaries and larger vessels of normal brain and moderately elevated levels of this enzyme in small vessels of brain tumours of various grades. Both thromboxane synthase and COX-2 expression was limited to endothelial cells found in anaplastic gliomas and glioblastomas. Thromboxane synthase inhibitors strongly decreased endothelial cell migration in HUVEC in vitro and capillary like tube formation was strongly inhibited by the compound at a similar dose range. The non-selective cyclo-oxygenase inhibitor ASA and the selective COX-2 inhibitor sulindac only had a minor effect on endothelial cell migration, however, the COX-2 inhibitor sulindac showed a synergistic effect with the thromboxane synthase inhibitor. Thromboxane synthase inhibitors induced apoptosis in endothelial cells as demonstrated by intracellular histone-complexed DNA fragmentation. These data suggest that inhibitors of thromboxane synthase influence migration and apoptosis in both human glioma cells and human endothelial cells. An anti-invasive treatment strategy using this class of compounds may therefore not only sensitise glioma cells to conventional treatments inducing apoptosis but may also be supported by an anti-angiogenic effect.

Apoptosis↗
PubMed2003

Cost of migration: invasion of malignant gliomas and implications for treatment.

Tumors of glial origin consist of a core mass and a penumbra of invasive, single cells, decreasing in numbers towards the periphery and still detectable several centimeters away from the core lesion. Several decades ago, the diffuse nature of malignant gliomas was recognized by neurosurgeons when super-radical resections using hemispherectomies failed to eradicate these tumors. Local invasiveness eventually leads to regrowth of a recurrent tumor predominantly adjacent to the resection cavity, which is not significantly altered by radiation or chemotherapy. This raises the question of whether invasive glioma cells activate cellular programs that render these cells resistant to conventional treatments. Clinical and experimental data demonstrate that glioma invasion is determined by several independent mechanisms that facilitate the spread of these tumors along different anatomic and molecular structures. A common denominator of this cellular behavior may be cell motility. Gene-expression profiling showed upregulation of genes related to motility, and functional studies demonstrated that cell motility contributes to the invasive phenotype of malignant gliomas. There is accumulating evidence that invasive glioma cells show a decreased proliferation rate and a relative resistance to apoptosis, which may contribute to chemotherapy and radiation resistance. Interestingly, interference with cell motility by different strategies results in increased susceptibility to apoptosis, indicating that this dynamic relationship can potentially be exploited as an anti-invasive treatment paradigm. In this review, we discuss mechanisms of glioma invasion, characteristics of the invasive cell, and consequences of this cellular phenotype for surgical resection, oncologic treatments, and future perspectives for anti-invasive strategies.

Brain Neoplasms↗
PubMed2003

Glioma invasion--pattern of dissemination by mechanisms of invasion and surgical intervention, pattern of gene expression and its regulatory control by tumorsuppressor p53 and proto-oncogene ETS-1.

The capacity of glioma cells to invade normal brain leads to far reaching dissemination of these tumors limiting surgical resection and the prospect of local treatment strategies. The analysis of the dissemination pattern, the molecular substrates and mechanisms involved suggest that glioma invasion most likely represents independent cellular behaviors leading to distinct pattern of spread. The search for common denominators of the invasive phenotype has demonstrated that invasive cells show gene expression profiles indicating elevated expression of motility associated genes and genes involved in resistance to apoptosis whereas proliferation and apoptosis related gene expression is repressed. Confirming these findings, invasive cells in vitro show elevated motility and resistance to drug induced apoptosis. Obviously invasiveness is an early event in the progression of glial tumors. Therefore, the loss of control over invasion genes must involve key elements of molecular tumor progression. We have recently demonstrated that deregulation of invasion gene expression occurs as a consequence of functional impairment of tumor suppressor p53 leading to unrestrained activation of proto-oncogene Ets-1 dependent invasion-associated genes. In this article the prospect of limiting the dissemination of glial tumors by anti-invasive strategies and targets for modulation of the invasive phenotype to reconstitute chemo- and radiation sensitivity are discussed.

Animals↗
PubMed2003

Intracranial tuberculomas mimicking a malignant disease in an immunocompetent patient.

We present the unusual occurrence of multiple systemic and two central nervous system tuberculomas in an immunocompetent young patient. A large left frontal epidural tuberculoma with transcalvarian extension was removed surgically and chemotherapy was initiated. The patient remained on a chemotherapy with INH, RMP, and EMB and was followed clinically and with MRI scans for 24 months. Findings. The clinical presentation and neuroimaging studies initially suggested malignant disease. Surgical resection of the left frontal lesion was required to relieve the mass effect. The histological evaluation showed a granulomatous inflammation with epithelial and Langhans giant cells, but no acid-fast bacilli. Cultures of the specimens yielded a mixed infection with Corynebacterium species and Staphylococcus epidermidis. Based on the histological findings, chemotherapy for tuberculosis was initiated. Subsequently, Mycobacterium tuberculosis was cultured from the surgical specimen and sputum. Interpretation. Parenchymal CNS tuberculosis with or without extracerebral manifestations may present as a space-occupying lesion. Because a tuberculoma is rarely suspected especially if there is atypical morphology, biopsy is required to establish the diagnosis and expedite specific treatment.

Adolescent↗
PubMed2002

Cyclo-oxygenase inhibitors and thromboxane synthase inhibitors differentially regulate migration arrest, growth inhibition and apoptosis in human glioma cells.

We have previously identified thromboxane synthase as an important regulator of glioma cell migration. Inhibitors of this enzyme abrogate cell motility and induce apoptosis. However, the formation rate of thromboxanes is indirectly dependent on the activity of cyclo-oxygenase, which represents the rate-limiting step in the synthesis of prostaglandins and thromboxanes. In this study we have analyzed the expression of COX-1 and COX-2 in glioma cell lines and biopsies of glial tumors. In normal glia no expression of both COX isoforms was present, however, reactive astrocytes and glial tumors of all grades demonstrated expression of both COX-1 and COX-2. In contrast to inhibitors of thromboxane synthase, selective and non-selective cyclo-oxygenase inhibitors did not block cell motility. Specific COX-2 inhibitors resulted in growth inhibition and induction of intracellular DNA fragmentation indicative of apoptotic cell death. Treatment of glioma cells with thromboxane synthase inhibitors had a synergistic effect on induction of apoptosis by camptothecin, whereas COX inhibitors had not. Furthermore, combined treatment using COX-2 inhibitors and specific thromboxane synthase inhibitors did not show a synergistic increase of apoptosis. These data indicate that COX inhibitors and thromboxane synthase inhibitors influence apoptosis in glioma cells through different pathways. We hypothesize that, in contrast to the COX-2 inhibitors, thromboxane synthase inhibitors block the invasive phenotype of glioma cells and therefore increase the pro-apoptotic disposition of the cells and increase the susceptibility to induced apoptosis. This effect may be independent of prostaglandin synthesis controlled by cyclo-oxygenases.

Apoptosis↗
PubMed2002

Head injury by gunshots from blank cartridges.

BACKGROUND: Blank cartridge handguns are generally underestimated in their capacity to inflict serious and potentially life threatening injuries. The predominant reasons for these injuries are suicide or suicide attempts, followed by accidental injuries. METHODS: A series of 26 gas gunshots to the neurocranium is presented. The injury pattern relevant to neurosurgical practice is illustrated in a case summary of 7 selected cases and the clinical courses as well as outcomes are presented. RESULTS: The injury pattern demonstrates that the energy density of the gas jet and the high temperatures of the exploding gas volume cause extensive soft tissue injuries. In close-range shots the gas jet takes on physical properties of a projectile. In these injuries impression fractures and dislocation of bone fragments are common. CONCLUSIONS: Gas handguns, contrary to public opinion, are dangerous weapons and may inflict potentially fatal injuries to the neurocranium when fired at close range. These weapons are frequently used in criminal or careless activities predominantly by young males. Extensive CNS injuries including hematomas, subarachnoid hemorrhage, foreign body contamination, and increased intracranial pressure are frequently observed.

Adolescent↗
PubMed2001

Identification and validation of P311 as a glioblastoma invasion gene using laser capture microdissection.

The mRNA expression profiles from glioblastoma cells residing at the tumor core and invasive rim of a human tumor resection were compared. From a single tumor specimen, 20,000 single cells from each region were collected by laser capture microdissection. Differential expression of 50-60 cDNA bands was detected. One of the sequences overexpressed by the invasive cells showed 99% homology to the P311 gene, the protein product of which is reported to localize at focal adhesions. Relative overexpression of P311 by invading glioblastoma cells compared with tumor core was confirmed by quantitative reverse transcription-PCR of six glioblastoma specimens after laser capture microdissection collection of rim and core cells. In vitro studies using antisense oligodeoxynucleotides and integrin activation confirmed the role of P311 in supporting migration of malignant glioma cells. Immunochemistry studies confirmed the presence of the P311 protein in tumor cells, particularly at the invasive edge of human glioblastoma specimens.

Amino Acid Sequence↗
PubMed2001

Prion-induced neuronal damage--the mechanisms of neuronal destruction in the subacute spongiform encephalopathies.

Prion diseases are characterized by the accumulation of a specific disease-associated isoform of the prion protein (PrP), termed PrPSc, which is the main, if not the only, component of the infectious agent termed prion. PrPSc is derived by an autocatalytic post-translational process involving conformational changes from the normal host-encoded isoform of the prion protein, termed PrPC. PrPC is a copper-binding glycoprotein attached to the cell membrane of neurons and other cells by means of a GPI anchor. The pattern of neurodegeneration differs between variants of prion disease and is related to the pattern of PrPSc deposition and differences in susceptibility of different cell types to the disease process. The pattern of PrPSc deposition depends on the strain of the agent and the PrP genotype of the host. Strain properties of prions appear to be related to different pathological conformations of PrPSc. Neuronal cell death is a salient feature in the pathology of prion diseases. Histological and electron microscopical studies have shown that cell death in prion disease occurs by apoptosis. Apoptosis of neuronal cells can also be induced in vitro by exposure to PrPSc or a neurotoxic peptide fragment corresponding to amino acids 106-126 of human prion protein (PrP106-126). Both in vitro and in vivo, the toxicity of PrPSc and PrP fragments appears to depend on neuronal expression of PrPC and on microglial activation. Activated microglial cells release pro-inflammatory cytokines and reactive oxygen species. Cell culture experiments suggest an important role of microglia-mediated oxidative stress in the induction of neuronal cell death. Only limited data are available on direct effects of PrPSc on neuronal cells. Potential effects include increased formation of an aberrant transmembrane form of PrP, termed CtmPrP, and changes in plasma membrane properties. In addition to direct and indirect toxic effects of PrPSc, a loss of function of PrPC may contribute to neuronal cell death. Potential mechanisms include disturbances in cerebral copper metabolism and antioxidative defense mechanisms. A better understanding of the pathogenesis of neuronal cell death in prion diseases may also have important therapeutic implications in the future.

Amino Acid Sequence↗
PubMed2001

Treatment of malignant glioma: a problem beyond the margins of resection.

The treatment of malignant glioma remains problematic. Surgical removal followed by external beam irradiation represents a standard treatment that has demonstrated a prolonged time to progression and survival. However, the capacity to locally invade normal brain invariably leads to formation of a recurrent tumor most often immediately adjacent to the site of resection. This clinical everyday experience prompts the hypothesis that improved local control of the tumor may translate into a delayed time to progression and possibly survival, specifically because systemic chemotherapy for most of these tumors has failed to significantly improve survival. Local treatment strategies including chemotherapy, gene therapy, and immunotherapy are rapidly developing and progressing to clinical trials. Several theoretical considerations suggest that these approaches may be promising in the treatment of brain tumors.

Genetic Therapy↗