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Klaus Hahn

Publications and source records attributed to Klaus Hahn.

At least 37 records · Page 2Linked to original sources
PubMed2004

Tissue-specific effects on uptake of 99mTc-sestamibi by breast lesions: a targeted analysis of false scintigraphic diagnoses.

UNLABELLED: The limited spatial resolution of gamma-cameras is commonly considered the main reason for the low sensitivity of scintimammography in the detection of small carcinomas. The present study assessed whether uptake of (99m)Tc-sestambi is affected by certain tissue-specific parameters besides the size of the tumor. METHODS: Surgical specimens from 75 patients (30 benign lesions, 8 of which had shown false-positive scintigraphic findings, and 45 carcinomas, 8 of which had shown false-negative scintigraphic findings) were subjected to a distinct histopathologic/immunohistochemical reevaluation. Tissue-specific parameters (lesion size, cellular density, vascularity, signs of inflammation, proliferative activity, multidrug resistance expression, and receptor status) were visually scored and correlated with the sestamibi uptake on scintimammograms. RESULTS: A clear relationship was found between sestamibi uptake and tumor size. As previously assumed, a lesion size of less than 1 cm in diameter was found to be one reason for false-negative scintigraphic diagnoses. In addition, a low cell count, low vascularity, and absence of inflammation in carcinomas had a negative effect on uptake of the radiopharmaceutical. The decisive factor for increased tracer uptake by benign lesions was the presence of inflammatory changes. No correlation could be found between sestamibi uptake and proliferative cellular activity, multidrug resistance expression, or the receptor status of the tumor. CONCLUSION: Because all mentioned findings were statistically significant only in part, it is to be supposed that uptake of (99m)Tc-sestambi by breast lesions is determined by various tissue parameters in interaction.

Breast↗
PubMed2003

Monitoring signaling processes in living cells using biosensors.

This collection of nine animations shows how different types of biosensors report changes in cellular processes through the production of a visually detectable signal. Biosensors can be created by attaching one or more fluorescent proteins (such as green fluorescent protein) to a target protein or peptide or by attaching a fluorescent dye that is sensitive to its environment to a protein or peptide. Conformational changes in proteins in response to ligand binding, changes in the concentration of cellular metabolites or signaling messengers, changes in protein localization, and changes in protein activity or covalent modification can all be detected with biosensors. These animations can be used separately or together to illustrate how molecular biology, chemistry, and microscopy have converged to allow cellular processes to be visualized in living cells. Several of the animations describe the production of a fluorescent resonance energy transfer (FRET) signal.

Biosensing Techniques↗
PubMed2003

Guidelines for direct radionuclide cystography in children.

These guidelines, which summarise the views of the Paediatric Committee of the European Association of Nuclear Medicine, provide a framework which may prove helpful to nuclear medicine teams in daily practice. They contain information on the indications, acquisition, processing and interpretation of direct radioisotope cystography in children. The guidelines should be taken in the context of "good practice" and any local/national rules which apply to nuclear medicine examinations.

Child↗
PubMed2003

Solvent-sensitive dyes to report protein conformational changes in living cells.

Covalent attachment of solvent-sensitive fluorescent dyes to proteins is a powerful tool for studying protein conformational changes, ligand binding, or posttranslational modifications. We report here new merocyanine dyes that make possible the quantitation of such protein activities in individual living cells. The quantum yield of the new dyes is sharply dependent on solvent polarity or viscosity, enabling them to report changes in their protein environment. This is combined with other stringent requirements needed in a live cell imaging dye, including appropriate photophysical properties (excitation >590 nm, high fluorescence quantum yield, high extinction coefficient), good photostability, minimal aggregation in water, and excellent water solubility. The dyes were derivatized with iodoacetamide and succinimidyl ester side chains for site-selective covalent attachment to proteins. A novel biosensor of Cdc42 activation made with one of the new dyes showed a 3-fold increase in fluorescence intensity in response to GTP-binding by Cdc42. The dyes reported here should be useful in the preparation of live cell biosensors for a diverse range of protein activities.

Biosensing Techniques↗
PubMed2003

Guidelines for radioiodinated MIBG scintigraphy in children.

These guidelines on the use of radioiodinated (99m)Tc-MIBG scintigraphy in children, which summarise the views of the Paediatric Committee of the European Association of Nuclear Medicine, provide a framework which may prove helpful to nuclear medicine teams in daily practice. They have been influenced by the conclusions of the "Consensus Guidelines for MIBG Scintigraphy" (Paris, November 6, 1997) of the European Neuroblastoma Group and by those of the Oncological Committee of the French Society of Nuclear Medicine. The guidelines should be taken in the context of "good practice" and any local/national rules which apply to nuclear medicine examinations.

3-Iodobenzylguanidine↗
PubMed2003

Shedding light on cell signaling: interpretation of FRET biosensors.

This Perspective compares recently developed approaches for studying live-cell signaling dynamics. It is now possible not only to study the changing localizations of proteins within living cells but to correlate these dynamics with quantitation of protein activities, including ligand interactions and phosphorylation. Initial applications of an increasingly varied toolchest of techniques have revealed strengths and weaknesses in each approach, clarifying which tool is best for which job.

Animals↗
PubMed2003

Sentinel node mapping in patients with malignant melanoma using melanoma Tc-99m colloidal rhenium sulfide.

PURPOSE: The aim of the study was to localize the sentinel lymph node using lymphoscintigraphy aided by Tc-99m colloidal rhenium sulfide. MATERIALS AND METHODS: Thirty consecutive patients with histologically proved melanoma, but no clinical evidence of metastases, were examined before operation by injecting 20 to 40 MBq (0.5 to 1.1 mCi) Tc-99m colloidal rhenium sulfide with a mean particle size of 100 nm (range, 50 to 200 nm) intradermally around the lesion. Lymphoscintigraphy was performed immediately after injection. In addition, blue dye was injected before operation. A hand-held gamma probe guided the sentinel node biopsy. RESULTS: Lymphoscintigraphy revealed hot spots in all patients. During surgery, the sentinel node was identified in all 30 patients. The number of sentinel nodes per patient ranged from 1 to 4 (mean, 1.9). Histologic examination confirmed the metastatic involvement of the sentinel lymph node in 11 of 30 patients. The sentinel lymph node-positive rate was 22.4%, which was comparable to findings using Tc-99m-labeled nanocolloids. CONCLUSION: The findings indicate that Tc-99m-bound colloidal rhenium sulfide is suitable for sentinel node mapping.

Adult↗
PubMed2003

Integrated imaging using MRI and 123I metaiodobenzylguanidine scintigraphy to improve sensitivity and specificity in the diagnosis of pediatric neuroblastoma.

OBJECTIVE: The objectives of this study were to compare MRI and iodine-123 ((123)I) metaiodobenzylguanidine (MIBG) scintigraphy in the detection of neuroblastoma lesions in pediatric patients and to assess the additional value of combined imaging. MATERIALS AND METHODS: Fifty MRI and 50 (123)I MIBG examinations (mean interval, 6.4 days) were analyzed retrospectively with regard to suspected or proven neuroblastoma lesions (n = 193) in 28 patients. MRI and MIBG scans were reviewed by two independent observers each. Separate and combined analyses of MRI and MIBG scintigraphy were compared with clinical and histologic findings. RESULTS: With regard to the diagnosis of neuroblastoma lesion, MIBG scintigraphy, MRI, and combined analysis showed a sensitivity of 69%, 86%, and 99% and a specificity of 85%, 77%, and 95%, respectively. On MRI, 15 false-positive findings were recorded: posttherapeutic reactive changes (n = 10), benign adrenal tumors (n = 3), and enlarged lymph nodes (n = 2). On MIBG scintigraphy, 10 false-positive findings occurred: ganglioneuromas (n = 2), benign liver tumors (n = 2), and physiologic uptake (n = 6). Thirteen neuroblastoma metastases and two residual masses under treatment with chemotherapy were judged to be false-negative findings on MRI. Two primary or residual neuroblastomas and one orbital metastasis were misinterpreted as Wilms' tumor, reactive changes after surgery, and rhabdomyosarcoma on MRI. Thirty-two bone metastases, six other neuroblastoma metastases, and one adrenal neuroblastoma showed no MIBG uptake. On combined imaging, one false-negative (bone metastasis) and three false-positive (two ganglioneuromas and one pheochromocytoma) findings remained. CONCLUSION: In the assessment of neuroblastoma lesions in pediatric patients, MRI showed a higher sensitivity and MIBG scintigraphy a higher specificity. However, integrated imaging showed an increase in both sensitivity and specificity.

Child↗
PubMed2002

Handedness and corpus callosum morphology.

Investigations of a relationship between callosal size and functional behavioral lateralization lead to the hypothesis that, as the size of the corpus callosum (CC) increases, interhemispheric information transfer is facilitated and behavioral laterality effects become smaller. The aim of our in vivo study was to investigate the relationship between functional asymmetry of handedness and CC size in healthy subjects. Magnetic resonance images of the CC and five CC subregions were obtained with a 1.5-T Magnetom using a three-dimensional T1 sequence in 46 healthy men. Handedness was determined using the 'handedness dominance test' (HDT). According to the HDT values, 32 consistent and 14 non-consistent right-handers were identified. No significant difference between handedness subgroups in CC regions and no significant correlations between HDT values and CC areas were detected.

Adolescent↗
PubMed2002

Dynamic lymph flow imaging in patients with oedema of the lower limb for evaluation of the functional outcome after autologous lymph vessel transplantation: an 8-year follow-up study.

The purpose of this study was to monitor the functional outcome of microsurgical intervention on lymph drainage by means of non-invasive, readily available lymphoscintigraphy. Eight patients with primary or secondary lymphoedema of the lower limb were investigated before and for 8 years after autologous lymph vessel transplantation. For scintigraphy, technetium-99m labelled nanocolloid was subcutaneously injected into the first interdigital space of the affected limb. Sequential images were acquired up to 6 h p.i.; for semiquantitative evaluation a numerical transport index was established by assigning scores of up to 9 on each of five criteria: lymphatic transport kinetics, distribution pattern of the radiopharmaceutical, time to appearance of lymph nodes, visualisation of lymph nodes and visualisation of lymph vessels/grafts. Ti values <10 were considered normal. In all eight patients, lymphatic function significantly (P</=0.01) improved after microsurgical treatment. Permanent function of vessel grafts was indicated by persistently low Ti values during the entire observation period, impressively demonstrating the success of this complex microsurgical technique. Patients with scintigraphic visualisation of the vessel graft (n=2/8) showed a substantially better postoperative outcome than those without visualisation of the vessel graft. The findings indicate that lymph vessel transplantation significantly improves lymph drainage in patients with primary or secondary lymphoedema of the lower limb. Thus, lymphoscintigraphy is helpful not only in planning microsurgical treatment but also in monitoring the postoperative outcome.

Adult↗
PubMed2002

Antiapoptotic Cdc42 mutants are potent activators of cellular transformation.

Cdc42 is a small GTP-binding protein which has been implicated in a number of cellular activities, including cell morphology, motility, cell-cycle progression, and malignant transformation. While GTPase-defective forms of Cdc42 inhibit cell growth, a mutation [Cdc42(F28L)] that allows the constitutive exchange of GDP for GTP and is GTPase-competent induces cellular transformation. These results suggest that Cdc42 must cycle between its GTP- and GDP-bound states to stimulate cell growth. In attempting to design Cdc42 molecules with more potent transforming activity, we set out to generate other types of Cdc42 mutants capable of constitutive GDP-GTP exchange. Here, we describe one such mutant, generated by changing a conserved aspartic acid residue at position 118 to an asparagine. The Cdc42(D118N) protein exchanges GDP for GTP more rapidly than wild-type Cdc42, but significantly more slowly than the Cdc42(F28L) mutant. Despite its slower rate of activation, the Cdc42(D118N) mutant is more potent at inducing cellular transformation than the Cdc42(F28L) protein, and causes a significant loss in actin stress fibers, reminiscent of what is observed with fibroblasts transformed by oncogenic Ras mutants. Effector-loop mutations made within the D118N background inhibit Cdc42-induced transformation and Cdc42-mediated antiapoptotic (survival) activity to similar extents. In addition, mutating aspartic acid 121 (to asparagine), which forms part of a caspase cleavage site (DLRD, residues 118-121 of Cdc42), in combination with the F28L mutation generates a Cdc42 molecule [Cdc42(F28L/D121N)] with transforming activity significantly stronger than that of Cdc42(F28L). Thus, mutations that combine some capacity for cycling between the GTP- and GDP-bound states with increased survival against apoptotic signals yield Cdc42 molecules with the maximum capability for inducing cellular transformation.

3T3 Cells↗
PubMed2002

Investigation of a possible diencephalic pathology in schizophrenia.

Absence of the adhesio interthalamica (AI) in schizophrenic first episode patients is suggestive for another marker of early developmental neuropathologic changes. Moreover, findings suggest that schizophrenic patients without AI are characterised by more severe negative symptoms. The study aims to investigate the presence vs. absence of AI in relation to brain measurements and clinical features. Presence or absence of AI and volumetric brain measurements were assessed in 50 patients with schizophrenia and 50 matched controls. No differences in the incidence of AI were found between the groups. Patients without AI revealed a strong trend towards a larger third ventricle and significantly higher scores for negative symptoms. Interestingly, the subgroup of healthy controls without AI also had larger third ventricles. The absence of AI may represent another early developmental marker of cerebral malformation in a clinical subgroup of schizophrenic patients.

Adolescent↗
PubMed2002

[Can supplemental imaging with SPECT technique improve the diagnostic value of preoperative Tc-99m-MIBI scintigraphy in primary hyperparathyroidism?].

BACKGROUND: The focus of this retrospective study was to evaluate if the additional use of SPECT improves the diagnostic value of the preoperative Tc-99m-sestamibi scintigraphy combined with sonography in patients presenting with primary hyperparathyroidism. PATIENTS AND METHODS: 62 patients (43 female, 19 male) were examined by visual analysis of planar Tc-99m-sestamibi scintigraphy, SPECT and ultrasound. 14/62 were suffering from superimposed thyroid disease, 22/62 patients underwent previous neck surgery. 12/62 presented with recurrent hyperthyroidism, in 8/62 cases dystopic parathyroid tissue had been localized. For statistic evaluation these imaging modalities were correlated with the histopathological examinations of the surgical specimens for single use as well as combined use for all patients (group 1) and for the subgroups "histologically confirmed adenoma" (group 2), hyperplastic disease (group 3) "recurrency and/or dystopic parathyroid tissue" (group 4) and "patients presenting with thyroid nodules and/or previous neck surgery" (group 5), respectively. RESULTS: For single use planar scintigraphy showed the highest sensitivity (72%) followed by SPECT (67%) and ultrasound (58%). The combination of planar imaging with ultrasound achieved 83% whereas the combined use of all three modalities increased the sensitivity up to a maximum of 85%. The combined use of the imaging modalities leads to the following results: The histologically proven parathyroid adenomas (group 2) could be detected by planar scintigraphy and sonography with a sensitivity of 87%, for group 3 the combined use of all three modalities reached 69% sensitivity. Group 4 achieved the highest sensitivity (69%) by means of planar scintigraphy and SPECT, whereas group 5 reached 82% by means of planar scintigraphy and ultrasound. CONCLUSION: Planar Tc-99m-sestamibi scintigraphy combined with ultrasound is superior regarding to sensitivity and to the costs for the noninvasive preoperative detection in patients presenting with primary hyperparathyroidism. Due to economic reasons the additional use of SPECT might be limited to patients presenting with recurrent hyperparathyroidism or atypically located parathyroid tissue.

Adult↗
PubMed2002

The delta subunit of AP-3 is required for efficient transport of VSV-G from the trans-Golgi network to the cell surface.

Vesicular stomatitis virus glycoprotein (VSV-G) is a transmembrane protein that functions as the surface coat of enveloped viral particles. We report the surprising result that VSV-G uses the tyrosine-based di-acidic motif (-YTDIE-) found in its cytoplasmic tail to recruit adaptor protein complex 3 for export from the trans-Golgi network. The same sorting code is used to recruit coat complex II to direct efficient transport from the endoplasmic reticulum to the Golgi apparatus. These results demonstrate that a single sorting sequence can interact with sequential coat machineries to direct transport through the secretory pathway. We propose that use of this compact sorting domain reflects a need for both efficient endoplasmic reticulum export and concentration of VSV-G into specialized post-trans-Golgi network secretory-lysosome type transport containers to facilitate formation of viral coats at the cell surface.

Adaptor Protein Complex 3↗
PubMed2002

Enlargement of the amygdala in patients with a first episode of major depression.

BACKGROUND: The amygdala plays a crucial role in the mediation of affective behavior in humans and is implemented in the limbic-thalamic-cortical network that is supposed to modulate human mood. The aim of the present study was to measure the amygdala volumes in patients with a first episode of major depression. METHODS: Thirty inpatients with a first episode of depression were compared with 30 healthy volunteers matched for age, gender, handedness, and education by performing structural magnetic resonance imaging (MRI) measures of the amygdala. RESULTS: Patients showed increased amygdala volumes in both hemispheres as compared to healthy control subjects. No significant correlations were found between amygdala volumes and age, age of onset, illness duration, or severity of depression in the patient group. CONCLUSIONS: Enlarged amygdala volumes in patients with a first episode of major depression might be due to enhanced blood flow in the amygdala rather than to a neurodevelopmental structural predisposition to major depression.

Adolescent↗
PubMed2002

Tpr is localized within the nuclear basket of the pore complex and has a role in nuclear protein export.

Tpr is a coiled-coil protein found near the nucleoplasmic side of the pore complex. Since neither the precise localization of Tpr nor its functions are well defined, we generated antibodies to three regions of Tpr to clarify these issues. Using light and EM immunolocalization, we determined that mammalian Tpr is concentrated within the nuclear basket of the pore complex in a distribution similar to Nup153 and Nup98. Antibody localization together with imaging of GFP-Tpr in living cells revealed that Tpr is in discrete foci inside the nucleus similar to several other nucleoporins but is not present in intranuclear filamentous networks (Zimowska et al., 1997) or in long filaments extending from the pore complex (Cordes et al., 1997) as proposed. Injection of anti-Tpr antibodies into mitotic cells resulted in depletion of Tpr from the nuclear envelope without loss of other pore complex basket proteins. Whereas nuclear import mediated by a basic amino acid signal was unaffected, nuclear export mediated by a leucine-rich signal was retarded significantly. Nuclear injection of anti-Tpr antibodies in interphase cells similarly yielded inhibition of protein export but not import. These results indicate that Tpr is a nucleoporin of the nuclear basket with a role in nuclear protein export.

Active Transport, Cell Nucleus↗
PubMed2002

Advances in molecular labeling, high throughput imaging and machine intelligence portend powerful functional cellular biochemistry tools.

Cellular behavior is complex. Successfully understanding systems at ever-increasing complexity is fundamental to advances in modern science and unraveling the functional details of cellular behavior is no exception. We present a collection of prospectives to provide a glimpse of the techniques that will aid in collecting, managing and utilizing information on complex cellular processes via molecular imaging tools. These include: 1) visualizing intracellular protein activity with fluorescent markers, 2) high throughput (and automated) imaging of multilabeled cells in statistically significant numbers, and 3) machine intelligence to analyze subcellular image localization and pattern. Although not addressed here, the importance of combining cell-image-based information with detailed molecular structure and ligand-receptor binding models cannot be overlooked. Advanced molecular imaging techniques have the potential to impact cellular diagnostics for cancer screening, clinical correlations of tissue molecular patterns for cancer biology, and cellular molecular interactions for accelerating drug discovery. The goal of finally understanding all cellular components and behaviors will be achieved by advances in both instrumentation engineering (software and hardware) and molecular biochemistry.

Animals↗