Biomedical subjects

K Reuter

Publications and source records attributed to K Reuter.

At least 19 recordsLinked to original sources

PubMed2006

Revisiting the structure of the p(4 x 4) surface oxide on Ag(111).

Scanning tunneling microscopy (STM) and density-functional theory are used to reexamine the structure of the renowned p(4 x 4)-O/Ag(111) surface oxide. The accepted structural model [C. I. Carlisle, Phys. Rev. Lett. 84, 3899 (2000)10.1103/PhysRevLett.84.3899] is incompatible with the enhanced resolution of the current STM measurements. An "Ag6 model" is proposed that is more stable than its predecessor and accounts for the coexistence of the p(4 x 4) and a novel c(3 x 5log3)rect phase. This coexistence is an indication of the dynamic complexity of the system that until now has not been appreciated.

Journal Article↗

PubMed2004

Kinetic hindrance during the initial oxidation of Pd(100) at ambient pressures.

The oxidation of the Pd(100) surface at oxygen pressures in the 10(-6) to 10(3) mbar range and temperatures up to 1000 K has been studied in situ by surface x-ray diffraction (SXRD). The results provide direct structural information on the phases present in the surface region and on the kinetics of the oxide formation. Depending on the (T,p) environmental conditions, we observe either a thin (sqrt[5]xsqrt[5])R27 degrees surface oxide or the growth of a rough, poorly ordered bulk oxide film of PdO predominantly with (001) orientation. By either comparison to the surface phase diagram from first-principles atomistic thermodynamics or by explicit time-resolved measurements we identify a strong kinetic hindrance to the bulk oxide formation even at temperatures as high as 675 K.

Journal Article↗

PubMed2004

The concepts of fatigue and depression in cancer.

A strong association between fatigue and depression in cancer patients has been reported repeatedly in clinical studies. The distinction remains difficult, mainly because of the similar phenomenology of fatigue and depression. It is the aim of this paper to work out similarities and differences in the conception of fatigue and depressive disorders. For that, a differentiation between depression as emotional distress and depression as clinical syndrome, according to the current classification systems, has to be made. Therefore, the classification of depressive disorders and their criteria is presented in the second section of this paper, especially in view of the diagnosis of depressive disorders in cancer patients. The comparison of the multidimensional fatigue construct and depression shows a strong overlap of symptoms. None of the fatigue symptoms are specific for fatigue, all being elements of depressive syndromes. It is in particular the psychological symptoms of depressive disorders that differentiate between the two concepts. To that end, the question is discussed whether fatigue in its current conceptualization can be defined as a diagnostic entity independent of depressive disorders. Additionally, research approaches are presented from the area of the chronic fatigue syndrome and neurasthenia, which could be adapted to cancer-related fatigue and help to clarify the clinical differences between fatigue and depression. In order to ensure better differential diagnostics in the future, criteria-orientated research in particular is needed.

Depression↗

PubMed2003

[Prevalence and risk factors of psychological burden and mental disorders in patients with musculoskeletal diseases -- a review of empirical studies].

A musculoskeletal disease frequently entails numerous physical, social and occupational limitations, e.g. reduction of physical capabilities, chronic pain, and loss of employment. A number of patients suffer from comorbid psychological strain or mental disorders, and it frequently remains unclear whether these psychological phenomena are unconnected to, a consequence of or even among the causes for the somatic disease. In order to diagnose, or possibly prevent, comorbid mental disorders, it is necessary to know risk factors which are associated with mental disorders. Studies published during the last twenty years are reviewed which examine sociodemographic, disease specific and psychosocial factors in connection with psychological strain or mental disorders among patients with musculoskeletal diseases. Due to the relatively small number of relevant studies (n = 12), the findings have to be interpreted carefully.

Geography↗

PubMed2002

Role of subsurface oxygen in oxide formation at transition metal surfaces.

We present a density-functional theory trend study addressing the incorporation of oxygen into the basal plane of the late 4d transition metals (TMs) from Ru to Ag. Occupation of subsurface sites is always connected with a significant distortion of the host lattice, rendering it initially less favorable than on-surface chemisorption. Penetration starts only after a critical coverage theta(c), which is lower for the softer metals towards the right of the TM series. The computed theta(c) are found to be very similar to those above which the bulk oxide phase becomes thermodynamically more stable, thus suggesting that the initial incorporation of O actuates the formation of a surface oxide on TM surfaces.

Journal Article↗

PubMed2002

[Epidemiology of comorbid mental disorders in rehabilitation patients with musculosceletal and cardiovascular diseases].

An association between mental disorders, musculoskeletal and cardiovascular diseases has been reported in many clinical studies with inpatients. However, no data exist about the prevalence of mental disorders in patients undergoing rehabilitation treatment for musculoskeletal and cardiovascular diseases. The present study investigates 4-week, 12-month and lifetime prevalence rates of comorbid mental disorders in more than 1700 patients out of 10 rehabilitation clinics. The patients were screened (GHQ-12, HADS) in the context of a two-stage epidemiological survey. In the second-stage examination a subsample of 369 patients was interviewed with a standardized clinical interview (CIDI) in order to obtain DSM-IV and ICD-10 diagnoses of mental disorders. 43 % (musculoskeletal) and 36 % (cardiovascular) of the patients have high GHQ-scores (cut off > 4). Furthermore, up to 24 % of the musculoskeletal and cardiovascular patients have elevated scores on the HADS subscales depression and anxiety (cut off > 10). For the 4-week period, prevalence rates of mental disorders in the sample of patients with musculoskeletal diseases are 31 % and 20 % in the sample of patients with cardiovascular diseases. The most frequent current disorders are affective and anxiety disorders. The high psychosocial burden expressed by the patients and the prevalence of depressive and anxiety disorders emphasize the importance of (1) effective diagnostic strategies to recognize mental disorders, (2) specialized psychological services in rehabilitation clinics, which provide psychological support and effective interventions for patients with musculoskeletal and cardiovascular diseases.

Adult↗

PubMed2001

Screening for anxiety, depressive and somatoform disorders in rehabilitation--validity of HADS and GHQ-12 in patients with musculoskeletal disease.

PURPOSE: The detection of patients with comorbid mental illness is of high clinical importance in orthopaedic rehabilitation. To simplify detection of cases, screening instruments are recommended. The study investigated the discriminant validity of the Hospital Anxiety and Depression Scale (HADS) and the General Health Questionnaire (GHQ-12) to identify patients with comorbid mental disorders, specifically anxiety, depressive and somatoform disorders. METHOD: Two hundred and six patients with musculoskeletal disease from four orthopaedic rehabilitation clinics participated in a two-stage survey: (1) patients were assessed with the GHQ-12 and HADS; and (2) they were examined for DSM-IV mental disorders by clinical standardized interview (CIDI). Validity of the two instruments regarding the detection of mental disorders was compared using ROC-analysis and CIDI-diagnoses as criteria. RESULTS: The HADS sumscale performed better in all analyses compared to the GHQ-12, specifically in detecting depressive and anxiety disorders. Best results are achieved for depressive disorders with an area under the curve (AUC) of 0.79, a sensitivity of 78% and a specificity of 71% (cut off point= 16). The positive predictive value (PPV) is best for the detection of any mental disorder with a cut-off point of 16 (46%). CONCLUSION: The HADS can be used as a screening instrument for the detection of comorbid depressive and anxiety disorders in patients with musculoskeletal disorders. Limitations in performance of screening instruments are due to: (1) different methodological approaches of tests (dimensional approach) and criterion (categorical approach); and (2) difficulties in diagnosing mental disorders in patients with prominent physical illness.

Adult↗

PubMed2001

A new target for shigellosis: rational design and crystallographic studies of inhibitors of tRNA-guanine transglycosylase.

Eubacterial tRNA-guanine transglycosylase (TGT) is involved in the hyper-modification of cognate tRNAs leading to the exchange of G34 at the wobble position in the anticodon loop by preQ1 (2-amino-5-(aminomethyl)pyrrolo[2,3-d]pyrimidin-4(3H)-one) as part of the biosynthesis of queuine (Q). Mutation of the tgt gene in Shigella flexneri results in a significant loss of pathogenicity of the bacterium, revealing TGT as a new target for the design of potent drugs against Shigellosis. The X-ray structure of Zymomonas mobilis TGT in complex with preQ1 was used to search for new putative inhibitors with the computer program LUDI. An initial screen of the Available Chemical Directory, a database compiled from commercially available compounds, suggested several hits. Of these, 4-aminophthalhydrazide (APH) showed an inhibition constant in the low micromolar range. The 1.95 A crystal structure of APH in complex with Z. mobilis TGT served as a starting point for further modification of this initial lead.

Binding Sites↗

PubMed2001

3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni: biological significance, three-dimensional structure and gene regulation.

3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase (3alpha-HSD/CR) catalyses the oxidoreduction at carbon 3 of steroid hormones and is postulated to initiate the complete mineralisation of the steroid nucleus to CO(2) and H(2)O in Comamonas testosteroni. The enzyme was found to be functional towards a variety of steroid substrates, including the steroid antibiotic fusidic acid. The enzyme also catalyses the carbonyl reduction of non-steroidal aldehydes and ketones such as a novel insecticide. It is suggested that 3alpha-HSD/CR contributes to important defense strategies of C. testosteroni against natural and synthetic toxicants. The 3alpha-HSD/CR gene (hsdA) is 774 base pairs long and the deduced amino acid sequence comprises 258 residues with a calculated molecular mass of 26.4 kDa. A homology search revealed 3alpha-HSD/CR as a new member of the short-chain dehydrogenase/reductase (SDR) superfamily. Upon gel permeation chromatography the purified enzyme elutes as a 49.4 kDa protein indicating a dimeric nature of 3alpha-HSD/CR. The protein was crystallised and the structure solved by X-ray analysis. The crystal structure reveals one homodimer per asymmetric unit, thereby verifying its dimeric nature. Dimerisation takes place via an interface essentially built-up by helix alphaG and strand betaG of each subunit. So far, this type of intermolecular contact has exclusively been observed in homotetrameric SDRs, but never in the structure of a homodimeric SDR. The formation of a tetramer is blocked in 3alpha-HSD/CR by the presence of a predominantly alpha-helical subdomain, which is missing in all other SDRs of known structure. The promoter domain was localised within the 93 bp region upstream of hsdA and the transcriptional start site was identified at 28 bp upstream of the translation start site. Interestingly, hsdA expression was found to be under negative control by two repressor proteins, the genes of which were found in opposite direction downstream or overlapping with hsdA. Based on our results, we propose that induction of hsdA expression in C. testosteroni by steroids actually appears to be a de-repression by preventing the binding of repressor proteins to regulatory regions.

3-Hydroxysteroid Dehydrogenases↗

PubMed2001

Psychiatric disorders and associated factors in cancer: results of an interview study with patients in inpatient, rehabilitation and outpatient treatment.

An association between mental disorders, especially affective and anxiety disorders, and cancer has been reported in many studies. The present study investigated current (4-weeks-, 12-months-, and lifetime-prevalence rates of comorbid mental disorders in cancer patients. Through a cross-sectional design, 517 patients (75% female patients) from two acute inpatient care clinics, two rehabilitation clinics and nine specialised practices for oncology were examined with standardised scales for psychological burden and quality of life. Somatic parameters were assessed through standardised medical records. In the second-stage-examination, a sample of 200 patients was interviewed with standardised clinical interview (CIDI) in order to obtain DSM-IV diagnoses of mental disorders. Differences in the type of mental disorders were examined for gender, treatment setting, severity of cancer and physical impairment. Prevalence rates of mental disorders were 23.5% for the 4-weeks, 40% for the 12-months, and 56.5% for the lifetime periods. The current and 12-months rates of affective and anxiety disorders were approximately 25-33% higher than prevalence rates found in recent epidemiological studies of the general population. These higher rates were, however, mainly due to the preponderance of female patients with a higher risk for mental disorders compared with males. The most prevalent current disorders were affective (9.5%), and anxiety disorders (13%). Female gender was associated with an approximately 2-fold risk of mental disorders during the patient's lifespan. Current diagnosis of affective disorders in women was highly related to the cancer. Physical impairment was also associated with the frequency of current psychiatric disorders, especially affective and anxiety disorders. The frequency of mental disorders in cancer patients does not differ from results of recent international epidemiological studies of the normal population. The slightly higher rates of anxiety disorders are mainly due to phobias (simple, social and agoraphobia) without urgent need for treatment. A relatively large portion of patients, however, fulfil the criteria of minor depressive disorder which deserves clinical attention.

Adolescent↗

PubMed2001

Chronically ill patients treated by spiritual healing improve in quality of life: results of a randomized waiting-list controlled study.

OBJECTIVE: Little is known about the effects of distant healing in chronically ill patients, the population most likely to see a healer in practice. This study investigated whether distant healing as found in normal practice with patients representative of those seeking treatment from healers changes patients' quality of life substantially. METHOD: Randomized, waiting-list controlled study of distant healing (anonymous, amulet, and allowing for personal contact) in chronically ill patients. OUTCOME MEASURE: Patient-reported quality of life as expressed by the sum of all MOS SF-36 health survey items. RESULTS: Sixty patients were treated by various methods of distant healing over 5 months; 59 patients were put on a waiting list (control). Quality of life improved significantly (p < 0.0005) in the treated group (10 points), while it remained stable in the control group. Positive expectation was significantly correlated with outcome. CONCLUSION: Chronically ill patients who want to be treated by distant healing and know that they are treated improve in quality of life.

Adult↗

PubMed2000

The crystal structure of 3alpha -hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni shows a novel oligomerization pattern within the short chain dehydrogenase/reductase family.

The crystal structure of 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni (3alpha-HSDH) as well as the structure of its binary complex with NAD(+) have been solved at 1.68-A and 1.95-A resolution, respectively. The enzyme is a member of the short chain dehydrogenase/reductase (SDR) family. Accordingly, the active center and the conformation of the bound nucleotide cofactor closely resemble those of other SDRs. The crystal structure reveals one homodimer per asymmetric unit representing the physiologically active unity. Dimerization takes place via an interface essentially built-up by helix alphaG and strand betaG of each subunit. So far this type of intermolecular contact has exclusively been observed in homotetrameric SDRs but never in the structure of a homodimeric SDR. The formation of a tetramer is blocked in 3alpha-HSDH by the presence of a predominantly alpha-helical subdomain which is missing in all other SDRs of known structure.

3-Hydroxysteroid Dehydrogenases↗

PubMed2000

Crystal structure of the human U4/U6 small nuclear ribonucleoprotein particle-specific SnuCyp-20, a nuclear cyclophilin.

The cyclophilin SnuCyp-20 is a specific component of the human U4/U6 small nuclear ribonucleoprotein particle involved in the nuclear splicing of pre-mRNA. It stably associates with the U4/U6-60kD and -90kD proteins, the human orthologues of the Saccharomyces cerevisiae Prp4 and Prp3 splicing factors. We have determined the crystal structure of SnuCyp-20 at 2.0-A resolution by molecular replacement. The structure of SnuCyp-20 closely resembles that of human cyclophilin A (hCypA). In particular, the catalytic centers of SnuCyp-20 and hCypA superimpose perfectly, which is reflected by the observed peptidyl-prolyl-cis/trans-isomerase activity of SnuCyp-20. The surface properties of both proteins, however, differ significantly. Apart from seven additional amino-terminal residues, the insertion of five amino acids in the loop alpha1-beta3 and of one amino acid in the loop alpha2-beta8 changes the conformations of both loops. The enlarged loop alpha1-beta3 is involved in the formation of a wide cleft with predominantly hydrophobic character. We propose that this enlarged loop is required for the interaction with the U4/U6-60kD protein.

Amino Acid Sequence↗

PubMed2000

[Comorbid psychiatric disorders in cancer patients in acute inpatient treatment and medical rehabilitation].

An association between mental disorders, especially affective and anxiety disorders, and cancer has been reported in many clinical studies with inpatients. However, no data exist about the prevalence of mental disorders in patients undergoing acute care or rehabilitation treatment for cancer in Germany. The present study investigated 4-week, 6-month and lifetime prevalence rates of comorbid mental disorders in cancer. 256 patients from 2 rehabilitation clinics and 2 acute care hospitals were examined with standardized screening scales for psychological burden (GHQ-12, HADS) and quality of life (SF-36). Somatic parameters and interventions were assessed through standardized medical records from the attending oncologists. In the second-stage examination a subsample of 120 patients were interviewed with standardized clinical interview (CIDI) in order to obtain DSM-IV diagnoses of mental disorders. 44% (acute care) and 49% (rehabilitation) of the patients have high GHQ scores (cut-off > 4). Furthermore, more than 20% of the cancer patients have elevated scores on the HADS subscales depression and anxiety (cut-off > or = 11). Prevalence rates of mental disorders in the rehabilitation sample are 34% for the 4-week (vs. 24% in the acute care sample), 45% for the 6-month period (vs. 38%), and 79% for lifetime (vs. 49% in the acute care sample). The most frequent current disorders are affective (13% rehabilitation vs. 11% acute care) and anxiety disorders (17% in both samples). The rates of affective and anxiety disorders are much higher than the frequency of these disorders in recent epidemiological studies of the normal population in Germany. The high psychosocial burden expressed by the patients and the frequency of depressive and anxiety disorders emphasize the importance of (1) effective diagnostic strategies to recognize mental disorders, and (2) specialized psychosocial services in oncology, which provide psychological support and effective interventions for cancer patients in acute care and rehabilitation.

Adult↗

PubMed2000

Screening orthologs as an important variable in crystallization: preliminary X-ray diffraction studies of the tRNA-modifying enzyme S-adenosyl-methionine:tRNA ribosyl transferase/isomerase.

The genes encoding the tRNA-modifying enzyme S-adenosylmethionine:tRNA ribosyl transferase/isomerase (QueA) from 12 eubacterial sources were overexpressed in Escherichia coli and the resulting products were purified to homogeneity and subjected to crystallization trials. Using the hanging-drop vapour-diffusion method, crystals suitable for X-ray diffraction experiments were only obtained for the queA gene product from Bacillus subtilis. The crystals belong to the space group P422, with unit-cell parameters a = b = 100.7, c = 150.9 A. Using highly focused synchrotron radiation from the EMBL/ESRF beamline ID13 (Grenoble, France), diffraction to at least 3.2 A could be achieved. A selenomethionyl derivative of the protein was prepared and crystallized for future multiwavelength anomalous diffraction (MAD) experiments.

Bacteria↗

PubMed1999

Crystal structure of the surfactin synthetase-activating enzyme sfp: a prototype of the 4'-phosphopantetheinyl transferase superfamily.

The Bacillus subtilis Sfp protein activates the peptidyl carrier protein (PCP) domains of surfactin synthetase by transferring the 4'-phosphopantetheinyl moiety of coenzyme A (CoA) to a serine residue conserved in all PCPs. Its wide PCP substrate spectrum renders Sfp a biotechnologically valuable enzyme for use in combinatorial non-ribosomal peptide synthesis. The structure of the Sfp-CoA complex determined at 1.8 A resolution reveals a novel alpha/beta-fold exhibiting an unexpected intramolecular 2-fold pseudosymmetry. This suggests a similar fold and dimerization mode for the homodimeric phosphopantetheinyl transferases such as acyl carrier protein synthase. The active site of Sfp accommodates a magnesium ion, which is complexed by the CoA pyrophosphate, the side chains of three acidic amino acids and one water molecule. CoA is bound in a fashion that differs in many aspects from all known CoA-protein complex structures. The structure reveals regions likely to be involved in the interaction with the PCP substrate.

Amino Acid Sequence↗

PubMed1999

Identification, characterization and crystal structure analysis of the human spliceosomal U5 snRNP-specific 15 kD protein.

The U5 small ribonucleoprotein particle (snRNP) contains various proteins involved in catalytic activities mediating conformational rearrangements of the spliceosome. We have isolated and characterized the evolutionarily highly conserved human U5 snRNP-specific protein U5-15kD. The crystal structure of U5-15kD determined at 1.4 A resolution revealed a thioredoxin-like fold and represents the first structure of a U5 snRNP-specific protein known so far. With respect to human thioredoxin the U5-15kD protein contains 37 additional residues causing structural changes which most likely form putative binding sites for other spliceosomal proteins or RNA. Moreover, a novel intramolecular disulfide bond replaces the canonical one found in the thioredoxin family. Even though U5-15kD appears to lack protein disulfide isomerase activity, it is strictly required for pre-mRNA splicing in vivo as we demonstrate by genetic depletion of its ortholog in Saccharomyces cerevisiae. Our data suggest that the previously reported involvement of its Schizosaccharomyces pombe ortholog Dim1p in cell cycle regulation is a consequence of its essential role in pre-mRNA splicing.

Amino Acid Sequence↗

PubMed1999

Mutagenesis and crystallographic studies of Zymomonas mobilis tRNA-guanine transglycosylase to elucidate the role of serine 103 for enzymatic activity.

The tRNA modifying enzyme tRNA-guanine transglycosylase (TGT) is involved in the exchange of guanine in the first position of the anticodon with preQ1 as part of the biosynthesis of the hypermodified base queuine (Q). Mutation of Ser90 to an alanine in Escherichia coli TGT leads to a dramatic reduction of enzymatic activity (Reuter, K. et al. (1994) Biochemistry 33, 7041-7046). To further clarify the role of this residue in the catalytic center, we have mutated the corresponding Ser103 of the crystallizable Zymomonas mobilis TGT into alanine. The crystal structure of a TGT(S103A)/preQ1 complex combined with biochemical data presented in this paper suggest that Ser103 is essential for substrate orientation in the TGT reaction.

Crystallography↗