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Experimental treatment of stroke in spontaneously hypertensive rats by CD34+ and CD34- cord blood cells
Boltze, Johannes,Kowalski, Ina,Geiger, Kathrin,Reich, Doreen
GMS German Medical Science , 2005,
Abstract: Human umbilical cord blood as a source of stem cells has recently been reported in experimental treatment of cerebral disorders. However, little is known about the nature of cells and cellular mechanisms leading to neurofunctional improvement. Here we investigated the potential of separated CD34+ versus CD34- human umbilical cord blood cells (HUCBC) to promote functional recovery following stroke. The experiments were performed in spontaneously hypertensive (SH) rats, known for a risk profile comparable to stroke patients. After three weeks of behavioral training in the RotaRod and Beamwalk test arrays, stroke was induced by permanent middle cerebral artery occlusion (MCAO). For cell therapy, 1x106 cryopreserved cells were administered systemically between 8 and 10 hours after MCAO. The behavioral tests were performed together with a neurological severity score (mNSS) until day 29 to assess neurofunctional disabilities. Nearly complete functional remission was observed with both subpopulations CD34+ as well as CD34- cells. To localize cells histologically, they were labeled with a fluorescence dye (CFSE) before injection. Again, after administration of CD34+ as well as CD34- cells, CFSE labelled cells were found that accumulated in the border zone between the central necrosis of the ischemic lesion and functional brain tissue, thus indicating active attraction towards the lesion for both cell populations. Immunohistology with anti-CD68 and antibodies to human neuronal markers (NF-L, chromogranin) indicated an accumulation of human and rat monocytes in the border zone of the lesion while neuronal cells of human origin could not be detected in host brains.
Measurement Quantization Describes Galactic Rotational Velocities, Obviates Dark Matter Conjecture  [PDF]
Jody Geiger
Journal of High Energy Physics, Gravitation and Cosmology (JHEPGC) , 2019, DOI: 10.4236/jhepgc.2019.52028
Abstract: A physical description of the orbital mechanics of stars around a galactic core has proved difficult. Notably, there is insufficient mass to account for observed star velocities. The mystery is one of few in modern science that defy the known laws of physics. It has been conjectured that there is a new form of matter that interacts gravitationally while otherwise remaining undetectable. In this paper we resolve the mystery. The expressions do not modify the known laws of physics, contain no free variables or fitting and are entirely classical in nature. Using the notion of counts of the fundamental measures—length, mass and time—it is shown that measure is bounded. Accounting for this bound and the expansion of space reveal that the conjecture is unnecessary thus resolving the dark matter mystery.
SOX2-RNAi attenuates S-phase entry and induces RhoA-dependent switch to protease-independent amoeboid migration in human glioma cells
Felix Oppel, Nadja Müller, Gabriele Schackert, Sandy Hendruschk, Daniel Martin, Kathrin D Geiger, Achim Temme
Molecular Cancer , 2011, DOI: 10.1186/1476-4598-10-137
Abstract: Retroviral shRNA-vectors were utilized to stably knockdown SOX2 in U343-MG and U373-MG cells. The resulting phenotype was investigated by Western blot, migration/invasion assays, RhoA G-LISA, time lapse video imaging, and orthotopic xenograft experiments.SOX2 depletion results in pleiotropic effects including attenuated cell proliferation caused by decreased levels of cyclinD1. Also an increased TCF/LEF-signaling and concomitant decrease in Oct4 and Nestin expression was noted. Furthermore, down-regulation of focal adhesion kinase (FAK) signaling and of downstream proteins such as HEF1/NEDD9, matrix metalloproteinases pro-MMP-1 and -2 impaired invasive proteolysis-dependent migration. Yet, cells with knockdown of SOX2 switched to a RhoA-dependent amoeboid-like migration mode which could be blocked by the ROCK inhibitor Y27632 downstream of RhoA-signaling. Orthotopic xenograft experiments revealed a higher tumorigenicity of U343-MG glioma cells transduced with shRNA targeting SOX2 which was characterized by increased dissemination of glioma cells.Our findings suggest that SOX2 plays a role in the maintenance of a less differentiated glioma cell phenotype. In addition, the results indicate a critical role of SOX2 in adhesion and migration of malignant gliomas.Despite multimodal treatment the prognosis for glioblastoma (GBM), the most common and most malignant brain tumor remains poor, with the majority of patients dying within 1 year after diagnosis [1]. Glioblastomas, gliomas of WHO grade IV, diffusely spread into the surrounding brain and the invading tumor cells migrate along the white matter tracks and assemble satellites around neuron cell bodies, blood vessels and the subpial region [2,3]. Since glioblastoma cells infiltrate wide areas of the brain every resection of the bulk tumor is usually followed by a tumor re-initiation at the resection site or at another place in the brain [4,5]. The cellular origin of glioblastoma is still under investigation and it is h
An Extremely Rare, Remote Intracerebral Metastasis of Oral Cavity Cancer: A Case Report
Mario Leimert,Tareq A. Juratli,Claudia Lindner,Kathrin D. Geiger,Johannes Gerber,Gabriele Schackert,Matthias Kirsch
Case Reports in Medicine , 2013, DOI: 10.1155/2013/257046
Abstract: Distant brain metastases from oral squamous cell carcinomas (OSCC) are extremely rare. Here we describe a case of a 53-year-old man with a primary OSCC who referred to the neurosurgical department because of epileptic seizures. MR imaging revealed an enhancing lesion in the right parietal lobe. A craniotomy with tumor removing was performed. Histopathological examination verified an invasive, minimally differentiated metastasis of the primary OSCC. The patient refused whole brain radiation therapy and died from pulmonary metastatic disease 10 months after the neurosurgical intervention without any cerebral recurrence. To the authors’ knowledge, only two similar cases have been previously reported. 1. Introduction Remote brain metastases from oral squamous cell carcinomas (OSCC) are an extremely rare occurrence. To date, only few cases have been reported previously [1, 2]. In contrast, direct intracranial invasion is not infrequent in patients with nasopharyngeal carcinoma (NPC) at a locally advanced stage [3]. Incidence of brain metastases following NPC may be increasing secondary to advancements in the treatment of systemic disease and earlier detection by more sensitive imaging modalities [4]. Most distant metastases from squamous cell carcinoma (SCC) are reported to occur in the liver, lungs, and bones [5]. Therefore, preoperative tumor staging is focussed on these sites (CT scan of the chest, radionuclide bone scans, and ultrasound of the liver). In the following case study, we present a patient who developed a histologically confirmed brain metastasis of OSCC. The patient developed symptoms from his cerebral metastasis 29 months after the primary disease was diagnosed. 2. Case Description A 53-year-old man with a 29-month history of a slowly enlarging ulcer on the bottom of the right lateral oral cavity was referred to our Department of Head and Neck surgery. After biopsy, a radical surgical resection of the tumor with supraomohyoid and functional neck dissection in continuity and reconstruction with a radial forearm free flap was performed. Histopathological work-up diagnosed a primary oral squamous cell carcinoma stage T3N3 (Figure 3(a)). Based on the stage of this diagnosis, adjuvant radiotherapy was initiated with a total dose of 64?Gy delivered in 32 fractions to both sides of the neck and the primary site. A CT scan revealed bilateral small pulmonary nodules, which were diagnosed as pulmonary metastases, but the patient declined chemotherapy. After radiation therapy, he was well and with stable disease for 26 months. Then, after a 3-week
Atypical Central Neurocytoma with Recurrent Spinal Dissemination over a Period of 20 Years: A Case Report and Review of the Literature
Tareq A. Juratli,Kathrin Geiger,Mario Leimert,Gabriele Schackert,Matthias Kirsch
Case Reports in Neurological Medicine , 2013, DOI: 10.1155/2013/925647
Abstract: We present an unusual case of a late recurrent central neurocytoma that was rediagnosed as an ependymoma and neurocytoma in accordance with changes in histological classifications. Case Description. A 56-year-old male teacher presented with incomplete transverse syndrome due to several intradural extramedullary tumors at the level of lumbar vertebrae 1–3. The histological diagnosis at the time was atypical ependymoma. One year later, two additional tumors were removed at the L5-S1 vertebral level. For 12 years, the patient remained tumor free on followup. Fourteen years after the initial diagnosis, the patient presented with thoracic paresthesias due to two new extramedullary tumors in the C7-T1 and the T8-T9 vertebral levels. After complete removal of the tumors, a radiological survey revealed an intracranial lesion in the third ventricle. Five months later, an additional lesion recurrence was removed surgically. The most recent histological diagnosis revealed an atypical central neurocytoma. In retrospect, the previous tumors were reclassified as neurocytoma according to the additional immunohistochemistry evidence. Discussion. There is no standard adjuvant treatment regimen for atypical neurocytoma; therefore, the patient is currently under close followup. Modern histopathological diagnosis is essential in these cases. Potential routes for dissemination of the tumor should be considered upon first recurrence. 1. Introduction Central neurocytomas are rare benign tumors of the central nervous system, characterized by their intraventricular localization. They are considered to arise from precursor cells of the septum pellucidum. They predominantly occur in young adults and generally have a favorable outcome, although cases with an aggressive clinical course and recurrences have been described. Historically, many of these lesions were regarded as either intraventricular oligodendroglioma or as ependymoma until detailed immunohistological clarification of their neuronal phenotypes was established. Neurocytoma was first described by Hassoun et al. [1] and is now a well-established diagnosis included in the latest WHO Classification [2]. In the literature, only a few neurocytomas were reported with an extraventricular location, including cerebral hemispheres [3], thalamus [4], cerebellum [5], pons [6], amygdala [7], retina [8], and in some rare cases the spinal cord [9]. Herein, we report a case of an atypical central neurocytoma with recurrent spinal dissemination over a period of 20 years. 2. Case Report A 56-year-old Caucasian male teacher was first seen
Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model
Christof Renner, Nadine Zemitzsch, Beate Fuchs, Kathrin D Geiger, Matthias Hermes, Jan Hengstler, Rolf Gebhardt, Jürgen Meixensberger, Frank Gaunitz
Molecular Cancer , 2010, DOI: 10.1186/1476-4598-9-2
Abstract: A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu), were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 μl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p < 0.0003) than untreated animals, confirming that carnosine affects proliferation in vivo.As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level.Carnosine, a dipeptide discovered more than 100 years ago [1] is a naturally occurring substance synthesized by endogenous carnosine synthetase. It is present in mammalian brain at a concentration between 0.7 and 2.0 mM [2] and reaches concentrations of up to 20 mM in skeletal muscle [3]. However, not much is known about its physiological function but several possible roles have been considered since its first discovery (for detailed review see [4,5]). Among these functions ph-buffering [6], metal chelation [7] or neurotransmitter function [8] have been discussed and the currently most intensively de
Measurement Quantization Unites Classical and Quantum Physics  [PDF]
Jody A. Geiger
Journal of High Energy Physics, Gravitation and Cosmology (JHEPGC) , 2018, DOI: 10.4236/jhepgc.2018.42019
Abstract: Unifying quantum and classical physics has proved difficult as their postulates are conflicting. Using the notion of counts of the fundamental measures—length, mass, and time—a unifying description is resolved. A theoretical framework is presented in a set of postulates by which a conversion between expressions from quantum and classical physics can be made. Conversions of well-known expressions from different areas of physics (quantum physics, gravitation, optics and cosmology) exemplify the approach and mathematical procedures. The postulated integer counts of fundamental measures change our understanding of length, suggesting that our current understanding of reality is distorted.
Quantum Model of Gravity Unifies Relativistic Effects, Describes Inflation/Expansion Transition, Matches CMB Data  [PDF]
Jody A. Geiger
Journal of High Energy Physics, Gravitation and Cosmology (JHEPGC) , 2018, DOI: 10.4236/jhepgc.2018.44038
Abstract: Presenting a unified model of motion and gravity has proved difficult as current approaches to quantum and classical physics are incompatible. Using measurement quantization—a model that demonstrates the physical significance of Planck’s units of length, mass, and time—measure is expressed as counts of the fundamental units establishing a common framework for describing quantum and cosmological phenomena with expressions that are defined throughout the entire physical domain. Beginning with the Pythagorean Theorem, we demonstrate an understanding of measure with respect to static and moving references. The model is extended to include the measure of mass thus completing a single approach for describing the contraction and dilation of measure. With this new approach, relativistic effects are now described as properties of quantized finite units of measure. In support of the model, several descriptions of phenomena are resolved that match our most precise data such as the measure of dark energy, universal expansion, mass distribution, and the age of the Cosmic Microwave Background.
Identification of Hypoxia-Induced Genes in Human SGBS Adipocytes by Microarray Analysis
Kathrin Geiger, Andreas Leiherer, Axel Muendlein, Nicole Stark, Simone Geller-Rhomberg, Christoph H. Saely, Martin Wabitsch, Peter Fraunberger, Heinz Drexel
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0026465
Abstract: Hypoxia in adipose tissue is suggested to be involved in the development of a chronic mild inflammation, which in obesity can further lead to insulin resistance. The effect of hypoxia on gene expression in adipocytes appears to play a central role in this inflammatory response observed in obesity. However, the global impact of hypoxia on transcriptional changes in human adipocytes is unclear. Therefore, we compared gene expression profiles of human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes under normoxic or hypoxic conditions to detect hypoxia-responsive genes in adipocytes by using whole human genome microarrays. Microarray analysis showed more than 500 significantly differentially regulated mRNAs after incubation of the cells under low oxygen levels. To gain further insight into the biological processes, hypoxia-regulated genes after 16 hours of hypoxia were classified according to their function. We identified an enrichment of genes involved in important biological processes such as glycolysis, response to hypoxia, regulation of cellular component movement, response to nutrient levels, regulation of cell migration, and transcription regulator activity. Real-time PCR confirmed eight genes to be consistently upregulated in response to 3, 6 and 16 hours of hypoxia. For adipocytes the hypoxia-induced regulation of these genes is shown here for the first time. Moreover in six of these eight genes we identified HIF response elements in the proximal promoters, specific for the HIF transcription factor family members HIF1A and HIF2A. In the present study, we demonstrated that hypoxia has an extensive effect on gene expression of SGBS adipocytes. In addition, the identified hypoxia-regulated genes are likely involved in the regulation of obesity, the incidence of type 2 diabetes, and the metabolic syndrome.
Infrared Spectroscopic Studies of Cells and Tissues: Triple Helix Proteins as a Potential Biomarker for Tumors
Allison L. Stelling, Deirdre Toher, Ortrud Uckermann, Jelena Tavkin, Elke Leipnitz, Julia Schweizer, Holger Cramm, Gerald Steiner, Kathrin D. Geiger, Matthias Kirsch
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058332
Abstract: In this work, the infrared (IR) spectra of living neural cells in suspension, native brain tissue, and native brain tumor tissue were investigated. Methods were developed to overcome the strong IR signal of liquid water so that the signal from the cellular biochemicals could be seen. Measurements could be performed during surgeries, within minutes after resection. Comparison between normal tissue, different cell lineages in suspension, and tumors allowed preliminary assignments of IR bands to be made. The most dramatic difference between tissues and cells was found to be in weaker IR absorbances usually assigned to the triple helix of collagens. Triple helix domains are common in larger structural proteins, and are typically found in the extracellular matrix (ECM) of tissues. An algorithm to correct offsets and calculate the band heights and positions of these bands was developed, so the variance between identical measurements could be assessed. The initial results indicate the triple helix signal is surprisingly consistent between different individuals, and is altered in tumor tissues. Taken together, these preliminary investigations indicate this triple helix signal may be a reliable biomarker for a tumor-like microenvironment. Thus, this signal has potential to aid in the intra-operational delineation of brain tumor borders.
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