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A Mack

Publications and source records attributed to A Mack.

At least 19 recordsLinked to original sources
PubMed2006

Development of a 3-D convolution/superposition algorithm for precise dose calculation in the skull.

In this paper an algorithm for calculating 3-D dose distributions within the brain is introduced and adapted to the demands of modem radiosurgery. The dose calculation with this model is based on a 3-D distribution of the primary photon intensity which is calculated with a ray casting algorithm. A prelocated matrix takes into account field sizes as well as modifying elements as collimator positions (MLC), blocks, wedges and compensators. Monte Carlo precalculated monoenergetic kernels from 0.1 MeV to 50 MeV were at our disposal. The components of the spectrum were either determined by deconvoluting depth dose curves measured in water or analyzed with a Ge-Li detector system in the case of 60Co. The calculated fluence distribution has to be superposed to the complete kernel containing the spatial energy deposition. Inhomogeneities and tissue interface phenomena (rhoe, Z) have been investigated. The divergence of the rays and the curved surface of the patient are taken into account. Assuming homogenous media, it is possible to shorten the computation time by using the Fast Fourier Transformation (FFT) delivering a first overview within seconds. The algorithm was evaluated and verified under specific conditions of small fields as used in radiosurgery and compared to dose measurements and Monte Carlo calculations. In using both the fast algorithm (FFT) for mainly homogenous conditions on one hand and the very precise superposition for inhomogeneous cases on the other, this algorithm can be a very helpful instrument especially for critical locations in the skull.

Algorithms↗
PubMed2005

Quality assurance in stereotactic radiosurgery/radiotherapy according to DIN 6875-1.

The new DIN ('Deutsche Industrie-Norm') 6875-1, which is currently being finalised, deals with quality assurance (QA) criteria and tests methods for linear accelerator and Gamma Knife stereotactic radiosurgery/radiotherapy including treatment planning, stereotactic frame and stereotactic imaging and a system test to check the whole chain of uncertainties. Our existing QA program, based on dedicated phantoms and test procedures, has been refined to fulfill the demands of this new DIN. The radiological and mechanical isocentre corresponded within 0.2 mm and the measured 50% isodose lines were in agreement with the calculated ones within less than 0.5 mm. The measured absorbed dose was within 3%. The resultant output factors measured for the 14-, 8- and 4-mm collimator helmet were 0.9870 +/- 0.0086, 0.9578 +/- 0.0057 and 0.8741 +/- 0.0202, respectively. For 170 consecutive tests, the mean geometrical accuracy was 0.48 +/- 0.23 mm. Besides QA phantoms and analysis software developed in-house, the use of commercially available tools facilitated the QA according to the DIN 6875-1 with which our results complied.

Quality Control↗
PubMed2005

Development of an interactive graphical user interface for therapy simulation.

Because of the ongoing development to more complex non-coplanar techniques in radiotherapy, the use of modem computer graphics while designing a dose plan becomes increasingly essential and more important. In this paper, we describe a concept to simulate 3D conformal treatment techniques on the computer. All important components of the treatment device and relevant patient structures are mapped to an internal model, which allows simulation of motion sequences as well as the interactive adjustment of treatment parameters. The intention of this user interface is to save time by using mainly graphical modules in the optimization process instead of running through the dose calculation every time.

Algorithms↗
PubMed2004

High precision radiosurgery and technical standards.

BACKGROUND: A high degree of precision and accuracy in radiosurgery is a fundamental requirement for therapeutic success. Small radiation fields and steep dose gradients are clinically applied thus necessitating a dedicated quality assurance program in order to guarantee dosimetric and geometric accuracy. MATERIAL AND METHODS: A detailed analysis of the course of treatment independent of the irradiation technique used results in the so-called chain of uncertainties in radiosurgery (immobilisation, imaging, treatment planning system, definition of regions of interest, mechanical accuracy, dose planning, dose verification). Each link in this chain is analysed for accuracy and the established quality assurance procedures are discussed. A "System Test" was used to check the whole chain of uncertainties simultaneously. RESULTS: The tests described are compatible with published reports on quality assurance in radiosurgery. In terms of accuracy the weakest link in the chain of uncertainties is stereotactic MR imaging. Geometric overall accuracy measured in the "System Test" is less than 0.7 mm. CONCLUSION: The established quality assurance routines have clinically been validated. MR imaging dominates geometric overall accuracy in radiosurgery, which can be limited to less than 1 mm by an adequate quality assurance protocol.

Adenoma↗
PubMed2004

Stereotactic radiosurgery without radiation therapy providing high local tumor control of multiple brain metastases from renal cell carcinoma.

The aim of this study was to analyse treatment effects after stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT) as primary treatment for patients harboring brain metastases of renal cell carcinoma (RCC). During an 8-year period, 85 patients with 376 brain metastases from RCC underwent 134 outpatient SRS procedures. 65 % of all patients had multiple brain metastases. The median tumor volume was 1.2 cm (3) (range: 0.1 - 14.2 cm (3)). Mean prescribed tumor dose was 21.2 (+/- 3.2) Gy. Local/distant tumor recurrences were treated by additional SRS in cases of stable systemic disease. Overall median survival was 11.1 months after SRS. The local tumor control rate after SRS was 94 %. Most patients (78 %) died because of systemically progressing cancer. A KPS > 70 and RTOG class I were related to prolonged survival time. Patients of the RTOG groups I, II and III survived for 24.2 months, 9.2 months and 7.5 months, respectively. There was no permanent morbidity after SRS. 11 patients (12.9 %) showed transient radiogenic complications and 3 patients (3.5 %) died because of intratumoral bleedings after SRS. Stereotactic radiosurgery alone achieves excellent local tumor control rates for patients with small brain metastases from renal cell carcinoma.

Adult↗
PubMed2002

[Ambulatory radiosurgery in cerebral metastatic renal cell carcinoma. 5-year outcome in 58 patients].

Brain metastases (BM) indicate an advanced stage of renal cell cancer (RCC). They pose an increasing challenge to urologists as a result of improved survival due to modern therapy. Median survival of untreated patients with BM who often suffer from neurological deficits is 3 months. Radiosurgery with the Gamma Knife (GK) has increased in use as an alternative to whole brain radiation therapy (WBRT) and/or surgery. This study reports the results of a consecutive series of RCC patients treated for BM by GK radiosurgery during a 5-year period. Between 1994 and 1999, 58 patients with a total of 277 BM and 3.0 (1-19) BM/patient were treated. Because of recurrent BM, 23 (40%) patients received repeated (multiple) GK sessions. The median tumor volume was 3.4 cm3 (0.1-19.1). The median interval between diagnosis of RCC and GK treatment was 2.2 years (0.1-17.2). Symptomatic side effects were detected in 9 (16%) of 58 patients. The median actuarial survival time was 9.9 months. Local tumor control could be achieved in 95% of patients. The GK therapy induced a significant tumor remission accompanied by rapid neurological improvement in 70% of patients. Compared to standard radiotherapy, GK radiosurgery is more effective, less time consuming, and can be repeated. Compared to surgery, radiosurgery is less invasive and better suited to treat multiple metastases in one single session. Surgery and radiosurgery, however, are supplementary methods that are highly effective to control intracerebral metastasizing RCC.

Actuarial Analysis↗
PubMed2002

Quality assurance in stereotactic space. A system test for verifying the accuracy of aim in radiosurgery.

A detailed quality assurance (QA) program is essential for high precision single dose irradiations. The accuracy of stereotactic radiosurgery is limited by the errors of each step in the chain for optimal treatment beginning with the diagnostic imaging and target localization leading to the dose planning and ending up with the treatment of the patient. Two main goals were followed on the way to finding a concept for a suitable and sufficient quality assurance routine. First, the chain of items in terms of a complete patient simulation should be followed and second, the stereotactic MR image data should be verified against a reference in our case stereotactic radiographic projection images. Target point verifications were performed using the so-called, unknown target method based on MRI, CT, and stereotactic projection images. A marked radiochromic film, embedded between inserts of the phantom is fixed parallel to either the xy or the xz plane of the stereotactic coordinate system. After imaging and planning, the phantom is adjusted and irradiated. At the end, the film, dyed by the radiation field around the premarked cross, is evaluated. The measured distance between the unit center point (shadow) and the localization of the marked film leads to the deviation to be minimized. This is referred to as the displacement vector. The results, evaluating 170 system tests within 5 years. show that the mean displacement vector of the complete system is 0.48 mm +/-0.23 mm (mean+/- sd). Factors having a significant influence on the overall accuracy are associated with MRI parameters. Test results based on axial images (xy plane; 0.42 mm +/- 0.24 mm) are significantly superior to coronal images (xz plane; x = 0.60 mm +/- 0.02 mm). Further on, the 3D-mpr sequence (0.40 mm +/- 0.19 mm) is significantly superior to the T1 weighted SE sequences (0.66 mm +/- 0.24 mm). Given the high mechanical accuracy of the Leksell gamma knife, the most sensitive technical factor having an influence on the overall precision of radiosurgery is the MRI study. However, using the appropriate imaging sequences and parameters the dislocation error inferred by MRI can be kept very low and restricted to the rare patient inherent distortion factors. With these precautions in mind, MRI is recommended as the imaging method of choice in radiosurgery.

Biophysical Phenomena↗
PubMed2001

Thyroid hormone-deficient period prior to the onset of hearing is associated with reduced levels of beta-tectorin protein in the tectorial membrane: implication for hearing loss.

The genes for alpha- and beta-tectorin encode the major non-collagenous proteins of the tectorial membrane. Recently, a targeted deletion of the mouse alpha-tectorin gene was found to cause loss of cochlear sensitivity (). Here we describe that mRNA levels for beta-tectorin, but not alpha-tectorin, are significantly reduced in the cochlear epithelium under constant hypothyroid conditions and that levels of beta-tectorin protein in the tectorial membrane are lower. A delay in the onset of thyroid hormone supply prior to onset of hearing, recently described to result in permanent hearing defects and loss of active cochlear mechanics (), can also lead to permanently reduced beta-tectorin protein levels in the tectorial membrane. beta-Tectorin protein levels remain low in the tectorial membrane up to one year after the onset of thyroid hormone supply has been delayed until postnatal day 8 or later and are associated with an abnormally structured tectorial membrane and the loss of active cochlear function. These data indicate that a simple delay in thyroid hormone supply during a critical period of development can lead to low beta-tectorin levels in the tectorial membrane and suggest for the first time that beta-tectorin may be required for development of normal hearing.

Animals↗
PubMed2001

Biohybrid microarrays--impedimetric biosensors with 3D in vitro tissues for toxicological and biomedical screening.

To investigate the effectiveness of potential anticancer therapeutics or therapies, efficient screening methods are required. On the one hand, multicellular 3D aggregates (spheroids) are a powerful in vitro model for simulating the in vivo situation and on the other hand, planar electrode structures are generally highly suitable for automation and parallel testing. Here, the detection of the effect of active substances on spheroids positioned on electrodes of substrate integrated electrode arrays is exemplarily investigated. As a 3D tissue model a reaggregation system of T47D clone 11 tumor cells is used. The effect of cytotoxins (DMSO, Triton X-100) on spheroids can be detected by recording the effective impedance of planar electrodes covered by spheroids. The equivalent circuit model parameter of electrodes covered by cytotoxin treated spheroids are determined from recorded impedance spectra and compared to the parameter of electrodes covered by control spheroids as well as not covered electrodes. Spheroids on electrodes mainly influence the electrode impedance in the frequency range of 10 kHz to 1 MHz. The results are discussed in view of an optimal electrode/spheroid-interface for sensing the effects of therapeutics with high sensitivity.

Algorithms↗
PubMed2001

A multicellular spheroid-based sensor for anti-cancer therapeutics.

The progress in cellular engineering offers novel approaches for anti-cancer therapies. To investigate the effectiveness of potential therapies efficient screening methods are required. We propose an impedance measurement system which enables the use of multicellular spheroid models in bioelectronic screening systems either for non destructive life-time diagnostic or anti-cancer therapies. A biohybrid sensor system is created comprising gene-manipulated T47D clone 11 breast carcinoma spheroids positioned hydrodynamically in a capillary system with electrodes. A novel approach employing an antisense-5'butyrylcholinesterase expression system is probed on reaggregated tumor cells under simulated microgravity, inhibiting the gene transcription and translation of the embryonic proliferation marker butyrylcholinesterase expressed in different tumor types. Alterations in the morphology of cell aggregates e.g. apoptosis or necrosis can be detected by impedance spectroscopy monitoring the electric behavior of membranes and extracellular space with a high resolution and reproducibility. The hydrodynamic positioning of 3D in vitro cell aggregates and the short time for the measurements represent an innovative method for a synchronized multicapillary screening system. The combination of the measuring system with a bioreactor enables cyclic life time recordings of impedance spectra for monitoring the cell aggregate properties for a long period.

Antineoplastic Agents↗
PubMed2001

Functional dissection of the cis-acting sequences of the Arabidopsis transposable element Tag1 reveals dissimilar subterminal sequence and minimal spacing requirements for transposition.

The Arabidopsis transposon Tag1 has an unusual subterminal structure containing four sets of dissimilar repeats: one set near the 5' end and three near the 3' end. To determine sequence requirements for efficient and regulated transposition, deletion derivatives of Tag1 were tested in Arabidopsis plants. These tests showed that a 98-bp 5' fragment containing the 22-bp inverted repeat and four copies of the AAACCX (X = C, A, G) 5' subterminal repeat is sufficient for transposition while a 52-bp 5' fragment containing only one copy of the subterminal repeat is not. At the 3' end, a 109-bp fragment containing four copies of the most 3' repeat TGACCC, but not a 55-bp fragment, which has no copies of the subterminal repeats, is sufficient for transposition. The 5' and 3' end fragments are not functionally interchangeable and require an internal spacer DNA of minimal length between 238 and 325 bp to be active. Elements with these minimal requirements show transposition rates and developmental control of excision that are comparable to the autonomous Tag1 element. Last, a DNA-binding activity that interacts with the 3' 109-bp fragment but not the 5' 98-bp fragment of Tag1 was found in nuclear extracts of Arabidopsis plants devoid of Tag1.

Arabidopsis↗
PubMed2000

Detection of caspase-activation in intact lymphoid cells using standard caspase substrates and inhibitors.

Members of the caspase family of proteases are important in the implementation of apoptotic cell death. These caspases are intracellularly activated upon a death stimulus, and exhibit a distinctive proteolytic activity which transmits a death signal and readily detected by measuring the cleavage of synthetic substrates in cell extracts. In this report, we show that apoptosis-associated caspase activation can be recorded not only in cell lysates but also in intact lymphoid cells with commercially available peptides which are either biotinylated or carry an amino-methylcoumarin (AMC) group. Incubation of intact cells induced to undergo apoptosis with Ac-Asp-Glu-Val-Asp-AMC (DEVD-AMC) leads to the release of AMC in amounts very similar to the amounts released when cell extracts are prepared and incubated with DEVD-AMC. This release can be detected by a fluorescence read-out and is blocked by caspase-inhibitors such as Ac-DEVD-cho or Z-VAD-fmk. Similarly, labelling of intact cells with the biotinylated peptides Tyr-Val-Ala-Asp-cmk (YVAD-cmk) or YVAD-faom permits the detection of active caspases by affinity blotting and the detection of apoptotic cells by FACS analysis. These methods enable the investigator to detect at the single-cell level those cells which have activated their caspases and to evaluate such activation without the need for lysis of the cells.

Amino Acid Chloromethyl Ketones↗
PubMed2000

[Stereotaxic precision irradiation of large uveal melanomas with the gamma knife].

BACKGROUND: We report our experience with stereotactic radiosurgery using the Gamma-knife in large uveal melanoma unsuitable for brachytherapy (Ru106). PATIENTS AND METHODS: We treated 35 patients (16 male, 19 female; age: median 59 years (95% Confidence interval (CI): 31-84 years; 18 right eyes, 17 left eyes). 7 tumors were located juxtapapillary, 16 tumors were located in the mid-periphery and 12 tumors were located in the ciliary body, The localization and/or the dimension of the tumors did not allow for radiation brachytherapy (Ru106). All patients underwent regular clinical, echographical and neuroradiological follow-up examinations. RESULTS: The follow-up time was median 12 months (95% CI: 4-20 months). A local tumor control defined as either continuous tumor regression or stopping of tumor progression was achieved in 34 (97%) of the 35 treated patients within the observation period. The eye of one patient was enucleated due to tumor regrowth. Maximum apical tumor height according to standardized A-scan before treatment was median 9.1 mm (95% CI: 3.2-13.9 mm) and after treatment median 6.4 mm (95% CI: 2.1 bis 11.9 mm). The difference was statistically highly significant (p < 0.001, one-tailed paired t-test). CONCLUSIONS: Our results in 35 patients indicate that radiosurgery using the Gamma-knife is beneficial in retaining the eyes of patients with large uveal melanomas that are not suitable for brachytherapy (Ru106).

Adult↗
PubMed2000

The key role of butyrylcholinesterase during neurogenesis and neural disorders: an antisense-5'butyrylcholinesterase-DNA study.

The wide tissue distribution of butyrylcholinesterase (BChE) in organisms makes specific roles possible, although no clear physiologic function has yet been assigned to this enzyme. In vertebrates, it appears e.g. in serum, hemopoietic cells, liver, lung, heart, at cholinergic synapses, in the central nervous system. in tumors and not at least (besides acetylcholinesterase, AChE) in developing embryonic tissues. Here, a functional role of BChE can be found in regulation of cell proliferation and the onset of differentiation during early neuronal development--independent of its enzymatic activity. For studies concerning this point, we have established a strategy for a specific and efficient inhibition of BChE to investigate how the expected decrease of enzyme and, therefore, the manipulation of cellular cholinesterase-equilibrium influences embryonic neurogenesis--among others to gain information about the significance of noncholinergic, activity-independent and cell growth functions of BChE. The antisense-5'BChE-DNA strategy is based on inhibition of BChE mRNA transcription and protein synthesis. For this, the BChE gene is cloned into a suitable vector system; this is done in antisense-orientation, so that a transfected cell will produce their own antisense mRNA to inhibit gene expression. For such investigations in neurogenesis, the developing retina is a good model and we are able to create organotypic, three-dimensional retinal aggregates in vitro (retinospheroids) using isolated retinal cells of 6-day-old chicken embryos. Using this in vitro retina and "knock out" of BChE gene expression, we could show a key role of BChE during neurogenesis. The results are of great interest because in tumorigenesis and some neuronal disorders, the BChE gene is amplified or abnormally expressed. It has to be discussed how the antisense-5'BChE strategy can play a role in the development of new and efficient therapy forms.

Animals↗
PubMed2000

Agonist-induced cytoplasmic volume changes in cultured rabbit parietal cells.

Concomitant Na(+)/H(+) and Cl(-)/HCO(3)(-) exchange activation occurs during stimulation of acid secretion in cultured rabbit parietal cells, possibly related to a necessity for volume regulation during the secretory process. We investigated whether cytoplasmic volume changes occur during secretagogue stimulation of cultured rabbit parietal cells. Cells were loaded with the fluorescent dye calcein, and the calcein concentration within a defined cytoplasmic volume was recorded by confocal microscopy. Forskolin at 10(-5) M, carbachol at 10(-4) M, and hyperosmolarity (400 mosmol) resulted in a rapid increase in the cytoplasmic dye concentration by 21 +/- 6, 9 +/- 4, and 23 +/- 5%, respectively, indicative of cell shrinkage, followed by recovery to baseline within several minutes, indicative of regulatory volume increase (RVI). Depolarization by 5 mM barium resulted in a decrease of the cytoplasmic dye concentration by 10 +/- 2%, indicative of cell swelling, with recovery within 15 min, and completely prevented forskolin- or carbachol-induced cytoplasmic shrinkage. Na(+)/H(+) exchange inhibitors slightly reduced the initial cell shrinkage and significantly slowed the RVI, whereas 100 microM bumetanide had no significant effect on either parameter. We conclude that acid secretagoguges induce a rapid loss of parietal cell cytoplasmic volume, followed by RVI, which is predominantly mediated by Na(+)/H(+) and Cl(-)/HCO(3)(-) exchange.

Amiloride↗
PubMed2000

Localization of S-adenosylhomocysteine hydrolase in the rat kidney.

S-adenosylhomocysteine (SAH) hydrolase is a cytosolic enzyme present in the kidney. Enzyme activities of SAH hydrolase were measured in the kidney in isolated glomeruli and tubules. SAH hydrolase activity was 0.62 +/- 0.02 mU/mg in the kidney, 0.32 +/- 0.03 mU/mg in the glomeruli, and 0.50 +/- 0.02 mU/mg in isolated tubules. Using immunohistochemical methods, we describe the localization of the enzyme SAH hydrolase in rat kidney with a highly specific antibody raised in rabbits against purified SAH hydrolase from bovine kidney. This antibody crossreacts to almost the same extent with the SAH hydrolase from different species such as rat, pig, and human. Using light microscopy, SAH hydrolase was visualized by the biotin-streptavidin-alkaline phosphatase immunohistochemical procedure. SAH hydrolase immunostaining was observed in glomeruli and in the epithelium of the proximal and distal tubules. The collecting ducts of the cortex and medulla were homogeneously stained. By using double immunofluorescence staining and two-channel immunofluorescence confocal laser scanning microscopy, we differentiated the glomerular cells (endothelium, mesangium, podocytes) and found intensive staining of podocytes. Our results show that the enzyme SAH hydrolase is found ubiquitously in the rat kidney. The prominent staining of SAH hydrolase in the podocytes may reflect high rates of transmethylation. (J Histochem Cytochem 48:211-218, 2000)

Adenosylhomocysteinase↗
PubMed1999

A changing pattern of brain-derived neurotrophic factor expression correlates with the rearrangement of fibers during cochlear development of rats and mice.

The reorganization of specific neuronal connections is a typical feature of the developing nervous system. It is assumed that the refinement of connections in sensory systems requires spontaneous activity before the onset of cochlear function and selective sensory experience during the ensuing period. The mechanism of refinement through sensory experience is currently postulated as being based on the selective reinforcement of active projections by neurotrophins. We studied a presumed role of neurotrophins for rearrangement of afferent and efferent fibers before the onset of sensory function in the precisely innervated auditory end organ, the cochlea. We observed a spatiotemporal change in the localization of brain-derived neurotrophic factor (BDNF) protein and mRNA, which correlated with the reorganization of fibers. Thus, BDNF decreased in target hair cells during fiber retraction and was subsequently upregulated in neurons, target hair cells, and adjacent supporting cells concomitant with the formation of new synaptic contacts. Analysis of the innervation pattern in BDNF gene-deleted mice by immunohistochemistry and confocal microscopy revealed a failure in the rearrangement of fibers and a BDNF dependency of distinct neuronal projections that reorganize in control animals. Our data suggest that, before the onset of auditory function, a spatiotemporal change in BDNF expression in sensory, epithelial, and neuronal cells may guide the initial steps of refinement of the innervation pattern.

Afferent Pathways↗