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Biomedical subjects

M Diehl

Publications and source records attributed to M Diehl.

At least 19 recordsLinked to original sources
PubMed2005

A late Eemian aridity pulse in central Europe during the last glacial inception.

Investigating the processes that led to the end of the last interglacial period is relevant for understanding how our ongoing interglacial will end, which has been a matter of much debate (see, for example, refs 1, 2). A recent ice core from Greenland demonstrates climate cooling from 122,000 years ago driven by orbitally controlled insolation, with glacial inception at 118,000 years ago. Here we present an annually resolved, layer-counted record of varve thickness, quartz grain size and pollen assemblages from a maar lake in the Eifel (Germany), which documents a late Eemian aridity pulse lasting 468 years with dust storms, aridity, bushfire and a decline of thermophilous trees at the time of glacial inception. We interpret the decrease in both precipitation and temperature as an indication of a close link of this extreme climate event to a sudden southward shift of the position of the North Atlantic drift, the ocean current that brings warm surface waters to the northern European region. The late Eemian aridity pulse occurred at a 65 degrees N July insolation of 416 W m(-2), close to today's value of 428 W m(-2) (ref. 9), and may therefore be relevant for the interpretation of present-day climate variability.

Atlantic Ocean↗
PubMed2005

Increased FDG bone marrow uptake after intracoronary progenitor cell therapy.

UNLABELLED: Patients with coronary artery disease who undergo FDG, PET for therapy monitoring after intracoronary progenitor cell infusion (PCT) show an increased bone marrow uptake in some cases. AIM of the study was to evaluate the systemic bone marrow glucose metabolism in this patient group after PCT. PATIENTS, METHODS: FDG bone marrow uptake (BMU), measured as standardized uptake value (SUVmax) in the thoracic spine, was retrospectively evaluated in 23 control patients who did not receive PCT and in 75 patients who received PCT 3 +/- 2.2 days before PET scanning. Five out of them were pretreated with granulocyte colony-stimulating factor (G-CSF) 5 days prior to PCT and 10 +/- 1.2 days before PET scanning. In 39 patients who received only PCT without G-CSF and underwent PET therapy monitoring 4 months later, baseline and follow up bone marrow uptake were measured. Leucocytes, C-reactive protein (CRP) levels and the influence of nicotine consumption were compared with the BMU. RESULTS: In patients (n = 70) who received PCT without G-CSF, BMU median (1.3) was slightly, but significantly higher than in the controls (1.0) (p = 0.02) regardless nicotine consumption. BMU did not change significantly 4 months later (1.2) (p = 0.41, n.s.). After G-CSF pretreatment, patients showed a significantly higher bone marrow uptake (3.7) compared to patients only treated with PCT (1.3) (p = 0.023). Leucocyte blood levels were significantly higher in patients with a BMU > or =2.5 compared to patients with a bone marrow SUVmax <2.5 (p<0.001). CRP values did not correlate with the BMU (rho -0.02, p = 0.38). CONCLUSION: Monitoring PCT patients, a slightly increased FDG BMU may be observed which remains unchanged for several months. Unspecific bone marrow reactions after PCT may be associated with increased leucocyte blood levels and play a role in the changed systemic glucose BMU. In addition, pretreatment with G-CSF shows an intense amplification of BMU.

Adult↗
PubMed2005

Real-time nonlinear feedback control of pattern formation in (bio)chemical reaction-diffusion processes: a model study.

Theoretical and experimental studies related to manipulation of pattern formation in self-organizing reaction-diffusion processes by appropriate control stimuli become increasingly important both in chemical engineering and cellular biochemistry. In a model study, we demonstrate here exemplarily the application of an efficient nonlinear model predictive control (NMPC) algorithm to real-time optimal feedback control of pattern formation in a bacterial chemotaxis system modeled by nonlinear partial differential equations. The corresponding drift-diffusion model type is representative for many (bio)chemical systems involving nonlinear reaction dynamics and nonlinear diffusion. We show how the computed optimal feedback control strategy exploits the system inherent physical property of wave propagation to achieve desired control aims. We discuss various applications of our approach to optimal control of spatiotemporal dynamics.

Bacteria↗
PubMed2004

The influence of thyroglobulin on functional imaging in differentiated thyroid cancer.

AIM: Recombinant human thyroid stimulating hormone (rhTSH) for an exogenous stimulation of TSH and consequent thyroglobulin (hTG) synthesis has reinitiated a discussion about the usefulness of diagnostic procedures for the follow-up of differentiated thyroid cancer (DTC). METHOD: Fifty consecutive patients with DTC who received whole-body iodine scintigraphy (WBS) and positron emission tomography (PET) were evaluated. RESULTS: The work-up was normal in 18/50. In 32 patients, functional imaging detected DTC. In 44% exogenous TSH stimulation with rhTSH was used and thyroxin was withdrawn in the others. The hTG under stimulation ranged from 0.8 to 5.004 ng x ml(-1). It was below 2 ng x ml(-1) in four (12.5%) patients. In total, 91 tumour sites were identified by positron emission tomography (PET) and 47 sites by WBS. PET and WBS showed corresponding uptake in 38% of lymph node, 48% of parenchymal and 43% of bone metastases. PET detected additional 53% of lymph node (WBS 9%), 38% of parenchymal (WBS 14%) and 28.5% of bone metastases. CONCLUSION: It is concluded that PET is more sensitive than WBS for the detection of DTC. The follow-up of DTC patients with hTG levels alone misses a significant number of true positive cases. Its use should therefore be restricted to selected low risk patients only.

Adult↗
PubMed2003

Monitoring the efficacy of iodine-131-MIBG therapy using fluorine-18-FDG-PET.

BACKGROUND: The purpose of this study was to assess the potential of fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG-PET) for monitoring the efficacy of iodine-131 metaiodobenzylguanidine (131I-MIBG) therapy in neuroendocrine tumours. METHODS: A total of seven 131I-MIBG therapies with 3.7 to 10.2 GBq were carried out in three patients suffering respectively from a phaeochromocytoma, a paraganglioma and a metastatic neuroendocrine tumour of an unknown primary. The post-therapeutic whole-body scintigrams were compared with the results of six 18F-FDG-PET studies performed at the time of the therapies. One patient received three PET scans prior to each one of the MIBG therapies, and one patient was studied twice. RESULTS: 18F-FDG uptake in tumour sites seemed to correlate well with tumour differentiation, showing no uptake in one patient with a highly differentiated neuroendocrine tumour, and moderate-to-intense uptake in the two other patients with metastatic disease. Those tumour sites that had a simultaneous positive uptake in both the MIBG scintigram and the PET scan showed response to therapy as a continuous reduction in MIBG uptake over time. They also showed a qualitative decrease in FDG accumulation during the follow-up. This was associated with a decrease in the mean and maximum standard uptake values of more than 50 % in some metastases, while the X-ray computed tomography showed no decrease in tumour volume. Two patients revealed additional metastases that were unknown on the basis of prior diagnostic or therapeutic PET scans and radiological follow-up. CONCLUSIONS: It may be concluded from these cases that 18F-FDG-PET is a valuable tool for an initial metabolic staging of neuroendocrine tumours prior to 131I-MIBG therapy, as it can reveal tumour sites beyond the reach of radioisotope therapy. It may also be of importance in assessing therapeutic potential in those tumour sites that do show positive MIBG uptake.

3-Iodobenzylguanidine↗
PubMed2003

Paraneoplastic syndromes: detection of malignant tumors using [(18)F]FDG-PET.

AIM: Paraneoplastic syndromes (PS) comprise a variety of clinical symptoms and diseases associated with underlying malignancy. Differentiation towards benign autoimmune diseases is necessary due to different therapeutic options. This diagnostic challenge includes cost- and time-consuming methods and is not successful in many cases. The aim of this study was the evaluation of [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) for detecting or ruling out malignancy in these patients. METHODS: In this retrospective work-up a total of 30 patients with suspected PS (m:f = 17:13, mean age 55, range 22-76 years) were examined with [(18)F]FDG-PET between 1996 and 2001. Diagnoses were erythrodermia, cerebellar degeneration, dermatomyositis, polyneuropathia and others. PET scans were compared to histopathological (n=14), radiological and follow up data (mean follow up 3.6 years, range 1-6 years). RESULTS: In 7 out of 30 patients (23%) an underlying malignancy was detected. Six out of 7 malignant neoplasms showed a distinctly increased glucose consumption. One benign neoplasm caused increased tracer uptake, another PET positive patient refused biopsy and showed no growth of a malignant tumour during clinical follow up of 28 months. The remaining 21 patients without suspicious glucose consumption did not demonstrate a malignancy in other diagnostic modalities or during subsequent clinical follow-up. CONCLUSION: [(18)F]FDG-PET seems to be a useful tool in the diagnostic work-up of patients with suspected paraneoplastic syndrome.

Adult↗
PubMed2003

[Positron-emission tomography in oncology].

This review analyses clinical results, new trends and recommendations of the leading medical centers concerning application of positron-emission tomography (PET) with F-18 fluorodeoxyglucose (F18 FDG) in cancer patients. This method of radionuclide visualization has been widely introduced for the last decade in diagnosis of cancer of unknown primary location, or CUP-syndrome, bronchogenic cancer of the lungs, cancer of the head and neck, malignant lymphoma and melanoma, colorectal and neuroendocrine cancer. Efficacy of this procedure, physiological grounds, performance are considered. Potentialities of F18 FDG PET are demonstrated in tumor screening, detection of metastases, recurrences after surgical, radiation or drug antitumor treatment or monitoring. In combination with CT, MRT, USI and other techniques, F18 FDG PET raises accuracy of the diagnosis of pathological changes at any stage of cancer with resulting improvement in further therapeutic and follow-up efficacy.

Colorectal Neoplasms↗
PubMed2001

Generalized parton distributions in the deuteron.

We introduce generalized quark and gluon distributions in the deuteron, which can be measured in exclusive processes like deeply virtual Compton scattering and meson electroproduction. We discuss the basic properties of these distributions and point out how they probe the interplay of nucleon and parton degrees of freedom in the deuteron wave function.

Journal Article↗
PubMed2001

Fluorine-18 fluorodeoxyglucose positron emission tomography in medullary thyroid cancer: results of a multicentre study.

The aim of this study was to evaluate the clinical use of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in medullary thyroid cancer (MTC) on the basis of comparison with findings obtained using indium-111 pentetreotide (SMS), pentavalent technetium-99m dimercaptosuccinic acid (DMSA), technetium-99m sestamibi (MIBI), computed tomography (CT) and magnetic resonance imaging (MRI). One hundred FDG-PET examinations in 85 patients (40 males, 45 females) with elevated tumour marker levels and/or pathological findings on other imaging methods were evaluated retrospectively. Eighty-two patients were examined after total thyroidectomy, and the remaining three patients prior to surgery. Overall, 181 lesions could be identified with at least one of the imaging techniques. Fifty-five lesions were confirmed histologically. FDG-PET detected 123 of 181 sites, which is a lesion detection probability of 68%. In the 55 cases with histological confirmation, we found 32 true positive, 3 false positive, 11 true negative and 9 false negative lesions using FDG-PET, resulting in a sensitivity of 78% and a specificity of 79%. Sensitivity and specificity were, respectively, 25% and 92% for SMS, 33% and 78% for DMSA, 25% and 100% for MIBI, 50% and 20% for CT and 82% and 67% for MRI. Compared with morphological techniques and functional imaging methods with single-photon emitters, FDG-PET showed the highest lesion detection probability for MTC tissue, with a high sensitivity and specificity. It is concluded that FDG-PET is a useful method in the staging and follow-up of MTC.

Adult↗
PubMed2001

Self-concept differentiation across the adult life span.

This study used 2 measures to examine 158 adults' (80 men, 78 women; ages 20 to 88 years) self-concept differentiation (SCD) across 5 role-specific self-representations. Findings revealed that the 2 measures did not assess SCD in similar ways and that they showed different associations with age. Specifically, the 1st measure was not significantly related to age, whereas the 2nd measure showed a curvilinear, U-shaped association with age. The 2nd SCD index also showed significant associations with several measures of emotional adjustment and 6 dimensions of psychological well-being. Additional analyses showed that age moderated the associations between SCD and positive and negative psychological well-being. A high level of SCD was associated with lower positive and higher negative psychological well-being for both young and older adults. However, this effect was significantly more pronounced in older adults.

Adult↗
PubMed2000

Thrombocyte HLA molecules retain nonrenewable endogenous peptides of megakaryocyte lineage and do not stimulate direct allocytotoxicity in vitro.

The origin and the function of HLA class I molecules present on the surface of human platelets are still unclear. In particular, it is controversial which fraction of these class I molecules represents integral membrane components derived from the megakaryocyte-platelet lineage versus soluble plasma HLA molecules acquired by adsorption. Results of the present study show that HLA-A2 ligands isolated from platelets possess the same peptide motif as described for HLA-A2-associated peptides obtained from nucleated cells. Sequencing of these platelet-derived peptides reveals that they originate mainly from ubiquitously expressed proteins also present in the megakaryocyte-platelet lineage. Moreover, one of these peptides derives from the GPIX protein, which is specifically expressed by platelets and their precursors. Platelet HLA molecules are unstable in vitro at 37 degrees C, but can be partially stabilized by addition of exogenous beta(2)-microglobulin and HLA class I binding peptide, suggesting that platelets cannot load HLA molecules with endogenous peptides. In in vitro experiments platelets were used to stimulate peripheral blood mononuclear cells. No allospecific cytotoxicity was observed after primary stimulation, or secondary restimulation, with allogenic resting or activated platelets, even in the presence of additional third-party helper activity. These data indicate that HLA class I molecules from platelets cannot directly induce allogenic CD8(+) cytotoxic T-cell response in vitro.

Blood Platelets↗
PubMed2000

Age differences in adult personality: findings from the United States and China.

This study used samples of adults from the United States (n = 285) and the People's Republic of China (n = 450) to examine age, gender, and culture differences in personality. Participants in both samples ranged from 20 to 87 years of age and responded to the California Psychological Inventory (CPI). Factor analyses of the CPI resulted in 4 personality factors (i.e., extraversion, control/norm orientation, flexibility, femininity/masculinity), with high congruence across cultures after targeted rotation. Multivariate analyses of variance with scale scores revealed significant Age Group 3 Culture and Gender 3 Culture interactions, and significant main effects of age, gender and culture. Specifically, negative age differences were found for scales that loaded on extraversion and flexibility, with older adults having lower scores on these scales. In contrast, positive age differences were found for scales indicative of control/norm orientation. In general, age differences were more pronounced for Chinese adults than for U.S. adults.

Adult↗
PubMed1998

Adult attachment styles: their relations to family context and personality.

This study used a sample of 304 adults to examine mean differences in family climate and personality variables on the basis of individuals' attachment styles. Also examined was whether mean differences varied by age group. Findings showed significant main effects of attachment style, but no Attachment Style x Age Group interactions. Compared with adults with an insecure attachment style, persons with a secure attachment style described their family of origin and their current family more positively and scored higher on personality variables indicative of self-confidence, psychological well-being, and functioning in the social world. When the family climate and personality variables were included in a discriminant function analysis, 2 significant functions were obtained. The 1st function discriminated adults with a positive self-model from those with a negative self-model. The 2nd function contrasted participants with a positive other-model from those with a negative other-model. Thus, this study provided evidence in support of the self- and other-models as the fundamental dimensions of adults' attachment system.

Adult↗
PubMed1998

Everyday competence in later life: current status and future directions.

This article reviews the literature on the antecedents and outcomes of everyday competence in later life and discusses future directions. It is argued that there is a fairly solid knowledge base with regard to the antecedents and outcomes but not in terms of the components and mechanisms of older adults' everyday competence. Five key issues are identified and discussed in terms of a future research agenda. For each key issue, directions for future research are outlined and a transactional approach is advocated. It is emphasized that older adults should be viewed as proactive individuals who are motivated to minimize the losses and maximize the gains associated with the aging process.

Activities of Daily Living↗
PubMed1997

Water-coupled low-frequency modes of myoglobin and lysozyme observed by inelastic neutron scattering.

Conformational changes of proteins often involve the relative motion of rigid structural domains. Normal mode analysis and molecular dynamics simulations of small globular proteins predict delocalized vibrations with frequencies below 20 cm(-1), which may be overdamped in solution due to solvent friction. In search of these modes, we have studied deuterium-exchanged myoglobin and lysozyme using inelastic neutron scattering in the low-frequency range at full and low hydration to modify the degree of damping. At room temperature, the hydrated samples exhibit a more pronounced quasielastic spectrum due to diffusive motions than the dehydrated samples. The analysis of the corresponding lineshapes suggests that water modifies mainly the amplitude, but not the characteristic time of fast protein motions. At low temperatures, in contrast, the dehydrated samples exhibit larger motional amplitudes than the hydrated ones. The excess scattering, culminating at 16 cm(-1), is suggested to reflect water-coupled librations of polar side chains that are depressed in the hydrated system by strong intermolecular hydrogen bonding. Both myoglobin and lysozyme exhibit ultra-low-frequency modes below 10 cm(-1) in the dry state, possibly related to the breathing modes predicted by harmonic analysis.

Animals↗
PubMed1996

Nonclassical HLA-G molecules are classical peptide presenters.

BACKGROUND: The physiological functions of the classical HLA (human leukocyte antigen) molecules, HLA-A, HLA-B and HLA-C, are to present peptides to T cells and to inhibit the activity of natural killer cells. In contrast, the functions of nonclassical HLA-molecules, such as HLA-E, HLA-F and HLA-G, remain to be established. The expression of HLA-G is largely limited to the placental trophoblast, where it might mediate protection of the fetus from rejection by the mother. Achieving the aim of understanding the function of HLA-G should be facilitated by information on the biochemical properties of HLA-G molecules, especially on their potential ability to act as peptide receptors. RESULTS: To study peptide presentation by HLA-G, we used stably transfected LCL721.221 cells as a source of HLA-G molecules and analysed the spectrum of extracted peptides by individual and pool sequencing. Our results indicate that HLA-G molecules, like classical HLA molecules, are associated with a wide array of peptides derived from cellular proteins. Peptides presented by HLA-G usually consisted of 9 amino acids, and adhered to a specific sequence motif, with anchor residues at position 2 (isoleucine or leucine), position 3 (proline) and the carboxy-terminal position 9 (leucine). Thus, the HLA-G peptide ligand motif follows the principles of classical HLA motifs, although it displays its own unique features. Peptide-binding assays indicated that two of the three anchor residues were sufficient for binding, and that the three natural HLA-G ligands that we identified bound, not only to HLA-G, but also to HLA-A2. This was not surprising, because the binding pockets of HLA-A2 and HLA-G overlap in their ability to recognize anchor residues at positions 2 and 9. Likewise, some, but not all, HLA-A2 peptide ligands could also bind to HLA-G. CONCLUSIONS: Nonclassical HLA-G molecules present peptides essentially in the same way as classical HLA molecules do. We determined the peptide motif that is specifically recognized by HLA-G; its basic features are described by the sequence XI/LPXXXXXL: This information should help to elucidate the physiological role of HLA-G molecules at the fetal-maternal interface. Most likely, this role is to protect fetal cells from lysis by natural killer cells, and possibly to present foreign peptides to a class of T cells that has not yet been identified.

Amino Acid Sequence↗