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Biomedical subjects

R Klinger

Publications and source records attributed to R Klinger.

At least 19 recordsLinked to original sources
PubMed2006

Impact of low back pain on functional limitations, depressed mood and quality of life in patients with rheumatoid arthritis.

Low back pain (LBP) and rheumatoid arthritis (RA) are common orthopedic problems, but there is little information on the importance of LBP in RA patients. The aim of this study was to investigate how LBP affects functional limitations, depressed mood, and quality of life in patients with RA. A complex questionnaire was answered by 281 RA patients, including questions about their RA and their experience of LBP. Functional limitations were assessed using the Hannover Activities of Daily Living questionnaire (ADL), depressed mood using the Center for Epidemiological Studies Depression Scale (CES-D) and health-related quality of life using the Short Form 12 health questionnaire (SF-12). The prevalence of LBP in RA patients was 53.4%. RA patients with LBP displayed a significantly higher degree of disability and depression than RA patients without LBP. There were no differences between the two groups with regard to the duration of RA, the number of operations or medication. LBP is an important factor for the physical and psychological behavior of RA patients. Therefore, the onset of LBP should not be overlooked or underestimated.

Arthritis, Rheumatoid↗
PubMed2006

The interaction of disturbances and small mammal community dynamics in a lowland forest in Belize.

1. Three floods (July 2000, August 2002, September 2003) and a hurricane (October 2001) that occurred in a lowland forest in the southern Maya Mountains of Belize presented an opportunity to evaluate the influence of these disturbances on the structure of a small mammal assemblage. 2. Four terrestrial and four primarily scansorial/arboreal species were trapped July 2000-March 2005 in six grids over 14 irregularly spaced trapping periods. 3. Community dynamics were characterized more by changes in species composition than changes in diversity. The dynamics were driven by species-specific variation in abundance, with changes in composition generally, but not exclusively, due to the occurrence or disappearance of species at low abundance. Despite the disturbances, species richness remained relatively constant. Evenness within the assemblage was consistently low, primarily as a result of dominance by one species, Heteromys desmarestianus. 4. Effects of flooding on community structure were direct but relatively brief (< 1 year), and varied with the duration and intensity of flooding. Effects from the hurricane were indirect but long-lasting and strongly related to severely reduced food resources. 5. This study suggests that long-term dynamics in the structure of many animal communities in the tropics often results from interactions between direct and indirect effects of disturbance. It also suggests that community resistance will depend on variation in disturbance type and regime, but resilience will be determined by the life-history characteristics of each species.

Animals↗
PubMed2004

Proatrial natriuretic peptide (1-98), but not cystatin C, is predictive for occurrence of acute renal insufficiency in critically ill septic patients.

INTRODUCTION: N-terminal prohormone of atrial natriuretic peptide ((proANP(1-98)) has been extensively analyzed in patients with chronic renal failure. It has been found to be closely related to the renal function and to interdialytic hydration status. The clinical relevance of proANP(1-98) and cystatin C, a novel marker of glomerular filtration, has not been investigated in the subgroup of critically ill septic patients with no history of chronic renal impairment. METHODS: We measured plasma level ofproANP(1-98) and cystatin C in 29 critically ill septic patients on admittance to the surgical intensive care unit and correlated it with the occurrence of acute renal failure. RESULTS: The proANP(1-98) plasma level was significantly higher in the group of patients who developed renal failure (12,722 +/- 12,421 vs. 2,801+/- 2,023 fmol/ml, p < 0.05). Multiple regression analysis shows that proANP(1-98) on the first day in the intensive care unit has a superior predictive value for the occurrence of renal failure to diuresis, calculated creatinine clearance or cystatin C (r = 0.42, p < 0.039). proANP(1-98) is also higher in non-survivors (9,303.8 +/- 11,053 vs. 2,448.5 +/- 1,803 fmol/ml, p < 0.018). CONCLUSION: proANP(1-98) is possibly a better predictor of acute renal failure to calculated creatinine clearance or diuresis among critically ill septic patients. Cystatin C was not correlated with occurrence of acute renal failure in this subgroup of patients.

Acute Kidney Injury↗
PubMed2002

[Guidelines in pain treatment--methodical quality of guidelines for treatment of pain patients].

The committee for quality assurance of the German IASP chapter (DGSS) evaluated all relevant guidelines concerning pain treatment. Quality of guidelines was analysed according to the checklist "Methodical quality of guidelines" by Ollenschläger and the user manual released by the German Medical Centre for Quality Assurance. The guideline for the treatment of back pain released by the German Medical Association was examined as well as the one released by the German Association for physical therapy and rehabilitation, the guideline on cervical and lumbal nerve root compression syndrome of the German Association of Neurosurgeons, the guideline for cancer pain of the Drug Committee of the German Medical Association was compared with the one of the German Interdisciplinary Association for Pain Treatment. The guideline for the treatment of chronic headache and facial pain of the Medical Association was evaluated and the guideline for the treatment of trigeminal neuralgia of the German Association of Neurosurgery and Neurology, also the guideline for the treatment of acute postoperative and posttraumatic pain. All guidelines show deficiencies in different aspects and of different severity. At first there are deficiencies in interdisciplinary formulation of the guidelines and identification and interpretation of evidence of multimodal pain treatment options. The most prominent deficiency is the lack of implementation and application trials or impulses by all author associations. This way all expenditure on releasing guidelines is given away without improving quality of pain treatment. The authors' recommendation is to adjust to guidelines and, if they are working or not, tell the authors and improve interdisciplinary in pain treatment guidelines.

Analgesics↗
PubMed2002

Influence of the sagittal advancement of mandibulae on myofibrillar ATPase activity and myosin heavy chain content in the masticatory muscles of pigs.

Endurance muscle stress leads to polymorphic expression of myosin heavy chains (MyHC). Histochemical and electrophoretic analyses were performed on different masticatory muscles (masseter, temporal, geniohyoid and medial pterygoid) of 10 weeks old pigs after 28 days of chronic sagittal advancement of the mandibulae. The differentiation between fiber types was investigated histochemically with the myofibrillar ATPase (mATPase) method and by immunohistochemistry. Expression of different MyHC isoforms was also assessed by means of immunoblotting with monoclonal antibodies. The results of both methods were compared. Chronic sagittal advancement of the mandibulae led to an increase in the cross-sectional area of type I fibers and type I MyHC in the anterior part of the masseter, the distal part of the temporal and the medial pterygoid muscle. In the present study, clear differentiation between type I and type II muscle fibers in all histological analyses was possible. However, mATPase classification of subtypes of type II fibers may lead to misinterpretations. Additionally, a direct correlation between the type I MyHC concentration and the type I fibers was seen in enzyme histochemical and immunohistochemical staining. The defined cross section of fibers is important for the histological investigation in small muscles. The immunoblot method seems to be more sensitive and less subjective for measurement of muscle changes. It can be concluded that the immunoblot method used for measuring the MyHC content is a valid alternative for fiber typing in small muscles as it is less time-consuming and more sensitive than qualitative histochemistry.

Adenosine Triphosphatases↗
PubMed2001

Anionic phospholipids are involved in membrane targeting of PI 3-kinase gamma.

Phosphoinositide 3-kinases (PI 3-kinases) have critical roles in diverse cellular signaling processes and in protein trafficking. In contrast to the class I PI 3-kinases alpha, beta, and delta which bind via src homology 2 (SH2) domains of adaptor proteins to tyrosine kinase receptors, the mechanism of recruitment of the PI 3-kinase gamma to membranes is unknown. We report in vitro experiments using immobilized proteins and small unilamellar vesicles which suggest an involvement of anionic phospholipids in membrane association of PI 3-kinase gamma. Furthermore we provide evidence that the enzyme displays beside the catalytic center a phospholipid binding domain which is essential for enzyme activity.

Animals↗
PubMed2001

Multiple PIP2 binding sites in Kir2.1 inwardly rectifying potassium channels.

Inwardly rectifying potassium channels require binding of phosphatidylinositol-4,5-bisphosphate (PIP2) for channel activity. Three independent sites (aa 175-206, aa 207-246, aa 324-365) were located in the C-terminal domain of Kir2.1 channels by assaying the binding of overlapping fragments to PIP2 containing liposomes. Mutations in the first site, which abolished channel activity, reduced PIP2 binding of this fragment but not of the complete C-terminus. Point mutations in the third site also reduced both, channel activity and PIP2 binding of this segment. The relevance of the third PIP2 binding site provides a basis for the understanding of constitutively active Kir2 channels.

Animals↗
PubMed1999

Retinoic acid induces selective expression of phosphoinositide 3-kinase gamma in myelomonocytic U937 cells.

Retinoic acid provokes growth inhibition and differentiation of the human leukemic cell line U937 to macrophage-like cells. We report that treatment of U937 cells with all-trans retinoic acid (ATRA), but not the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, results in an increased gene expression of the phosphoinositide 3-kinase (PI3K) species PI3Kgamma. PI3Kgamma expression was transcriptionally elevated, indicating that the PI3Kgamma gene may be a direct target for ATRA. In contrast to its effect on PI3Kgamma expression, ATRA did neither affect the levels of the PI3K species beta and delta nor the adapter proteins p85 and p101. Enhanced expression by ATRA of PI3Kgamma correlated with an increase of PI3K lipid kinase activity. Additionally, ATRA induced significant and lasting stimulation of mitogen-activated protein kinase/Erk2 activity. This effect was sensitive to the PI3K inhibitors wortmannin or LY294002 and, therefore, attributed to the upregulation of PI3Kgamma expression. Our findings suggest that sustained MAPK activation via PI3Kgamma precedes ATRA -dependent differentiation or growth inhibition.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Identification of 55 kDa phosphatidylinositol 4-kinase in HaCaT cells: comparison with the epithelial cell line A431.

Phosphatidylinositol kinases play a crucial role in signal transduction in many cell types. The 55 kDa isoform of phosphatidylinositol 4-kinases is a key enzyme in the metabolism of phosphoinositides, which work as regulators of cell function itself or as precursors of signal molecules. The experiments with HaCaT cells presented suggest that the phosphatidylinositol 4-kinase activity in this cell line corresponds to the 55 kDa isoform concerning kinetic parameters and specific activity in comparison with the malignant cell line A431. Km (for ATP and phosphatidyl-inositol) and Ki values (for Ca2+ and adenosine) are in good agreement with the parameters described for other cells. The findings support the idea that the 55 kDa phosphatidylinositol 4-kinase represents a key enzyme in the inositide signal transduction pathway.

1-Phosphatidylinositol 4-Kinase↗
PubMed1997

[Quality control in the therapy of chronic pain. Results obtained by a task force of the German Section of the International Association for the Study of Pain on psychological assessment of chronic pain. XI. Assessment and multiaxial classification of pain].

This paper reviews instruments in German language for the psychological assessment and classification of pain. Usually chronic pain syndromes are classified within the International Classification of Diseases (ICD). Instead of the psychiatric chapter of the ICD, it is possible to use the Diagnostic and Statistical Manual of Mental Disorders (DSM). The proposed classification system of the International Association of the Study of Pain (IASP) is based on a multiaxial solution. The numerous ways to classify chronic pain include many problems and limits, especially in the case of an interdisciplinary assessment. They provide no specific system for classifying pain syndromes. They are impractical to handle and restrict classifying pain as either somatogenic or psychogenic. It is not possible to describe both sides in one diagnosis without loss of information. As a result of this situation, a task force of the German Chapter of the International Association for the Study of Pain developed a Multiaxial Classification of Pain (Multiaxiale Schmerzklassifikation; MASK) as an advanced system of pain assessment and an alternative to the common classification systems. MASK embraces a somatic (MASK-S) and a psychological (MASK-P) part. Both parts constitute an 'interdisciplinary diagnosis'. MASK-S enables classifying a pain syndrome using hierarchical levels, with progredient specific degrees of differentiation. In addition there are 6 axes to describe pain syndromes qualitatively and quantitatively (e.g. localization, quality). The psychosocial part (MASK-P) embraces 5 main levels (1. behavioral, 2. emotional, 3. cognitive, 4. stress-related, 5. habitual personal factors) and 2 additional levels (6. functional coherence, 7. ICD/DSM-diagnosis additional). The MASK-P part of the diagnosis is composed of graduation on these levels. Differential axis of the pain syndromes are described phenomenologically and specifically. MASK provides the possibility of establishing an integrative, interdisciplinary diagnosis.

English Abstract↗
PubMed1997

Lipid kinase and protein kinase activities of G-protein-coupled phosphoinositide 3-kinase gamma: structure-activity analysis and interactions with wortmannin.

Signalling via seven transmembrane helix receptors can lead to a massive increase in cellular PtdIns(3,4,5)P3, which is critical for the induction of various cell responses and is likely to be produced by a trimeric G-protein-sensitive phosphoinositide 3-kinase (PI3Kgamma). We show here that PI3Kgamma is a bifunctional lipid kinase and protein kinase, and that both activities are inhibited by wortmannin at concentrations equal to those affecting the p85/p110alpha heterodimeric PI3K (IC50 approx. 2 nM). The binding of wortmannin to PI3Kgamma, as detected by anti-wortmannin antisera, closely followed the inhibition of the kinase activities. Truncation of more than the 98 N-terminal amino acid residues from PI3Kgamma produced proteins that were inactive in wortmannin binding and kinase assays. This suggests that regions apart from the core catalytic domain are important in catalysis and inhibitor interaction. The covalent reaction of wortmannin with PI3Kgamma was prevented by preincubation with phosphoinositides, ATP and its analogues adenine and 5'-(4-fluorosulphonylbenzoyl)adenine. Proteolytic analysis of wortmannin-prelabelled PI3Kgamma revealed candidate wortmannin-binding peptides around Lys-799. Replacement of Lys-799 by Arg through site-directed mutagenesis aborted the covalent reaction with wortmannin and the lipid kinase and protein kinase activities completely. The above illustrates that Lys-799 is crucial to the phosphate transfer reaction and wortmannin reactivity. Parallel inhibition of the PI3Kgamma-associated protein kinase and lipid kinase by wortmannin and by the Lys-799-->Arg mutation reveals that both activities are inherent in the PI3Kgamma polypeptide.

Adenosine Triphosphate↗
PubMed1997

[Quality assurance in chronic pain therapy. Results obtained by a task force of the German Chapter of the International Association for the Study of Pain on psychological Assessment of chronic Pain. Psychological instruments for the assessment of pediatric pain].

The present paper is one in a series of publications reviewing German instruments for the psychological assessment of pain. Part X deals with pain measurement of acute and chronic pain in infants and children. German assessment instruments of pediatric pain together with frequently used instruments of American origin are examined and described. The survey contains self-report and behavioral pain measures. Multidimensional pain interviews for both children and parents, diaries and rating scales, as well as observation measures especially for infants, are examined. Since the selection of pain-assessment instruments is dependent on the age and cognitive level of the children, for each instrument a minimum age limit is given. In cases in which quantitative indices of reliability, validity and objectivity are still needed, the evaluation is based on qualitative quotations.

English Abstract↗
PubMed1997

Dependence on intracellular Ca2+ on mass and turnover of phosphoinositides and phosphatidate in human erythrocytes.

Effects of a calcium-load on mass and turnover of phosphoinositides and phosphatidate were investigated in human erythrocytes by short-term labeling with [32P]Pi. The labeling of phosphatidate was accelerated at normal mass by short-term elevation of free intracellular [Ca2+] up to 1 microM and inhibited by the reduction of normal free [Ca2+]. Thus, the labeling of phosphatidate is a Ca2+-regulated process and not only the consequence of a net synthesis of diacylglycerol by other Ca2+-dependent reactions. Persisting elevation of free intracellular [Ca2+] between 1-40 microM induced an increase of the mass of phosphatidylinositol 4-phosphate with a concomitant decrease of the mass of phosphatidylinositol 4,5-bisphosphate. Under these conditions, the normal steady-state turnover of phosphoinositides was not altered by Ca2+, but mass and turnover of phosphatidate continuously rose. The increase in phosphatidate mass by far exceeded the decrease of the mass of phosphoinositides, indicating that phosphatidate was generated to a great extent by hydrolysis of other phospholipids in addition to the action of phosphoinositidase C with subsequent phosphorylation of diacylglycerol to phosphatidate. The results demonstrate that different phospholipid phosphodiesterases of human erythrocytes are activated by Ca2+-concentrations in the microM range as is known from various other cell types. In contrast to current explanations, Ca2+-dependent phospholipid phosphodiesterases of human erythrocytes did not exhibit an unusually low affinity against rising cytosolic Ca2+-concentrations.

Binding Sites↗
PubMed1996

[Quality assurance in therapy of chronic pain. Results obtained by a task force of the German Section of the Association for the Study of Pain on psychological assessment of chronic pain. IX. Multidimensional instruments for the assessment of aspects relating to pain and recommendations on standard procedures for diagnosis].

Four multidimensional inventories used as instruments for the assessment of pain are examined: "Fragebogen zur Erfassung der Schmerzverarbeitung' [Questionnaire for Assessment of Level of Coping with Pain], "Kieler Schmerzverarbeitungs-Inventar' [Kiel Inventory of Coping with Pain], "Fragebogen zur Schmerzregulation' [Questionnaire on Pain Regulation], and the German version of the "Multidimensional Pain Inventory'. None of these questionnaires assesses all domains that are important in chronic pain. The recommended standardized assessment routine for pain centres includes the use of a diary, the rating of actual, average and maximum pain intensity, the application of the PDI, a measure of disability, and the FESV, which records cognitive processing and coping. As measures of general psychological dysfunction the ADS for the assessment of depression and the B-L, a symptom checklist, are suggested as instruments suitable for routine use in diagnosis and evaluation.

English Abstract↗
PubMed1996

Dependence on intracellular pH and Mg2+ of metabolic compartmentation of phosphoinositides in human erythrocytes.

Effects of intracellular pH and Mg2+ on turnover and extent of metabolic compartmentation of phosphomonoester groups of phosphoinositides and phosphatidate were investigated in human erythrocytes by short-term and equilibrium labeling with [32P]Pi under steady-state conditions. At pH 6.7, the specific radio-activities of phosphoinositides reached apparent equilibrium values, in the range of 70% of that ATP-gamma-P after long-term labelling. At pH 7.2, these values were in the range of 40-50% of that ATP-gamma-P. This demonstrates a decreased accessibility of phosphoinositides to enzymatic phosphorylation and dephosphorylation at the transition from acidic to normal incubation conditions. These changes were more pronounced at pH 7.8. High intracellular [Mg2+] initially activated the turnover of phosphoinositides at pH 7.2. The activation changed into an inhibition and an increase of metabolic compartmentation after three hours preincubation of erythrocytes at high [Mg2+]. The long-term Mg2+ effects are reversible to a great extent by a subsequent re-reduction of [Mg2+]. In conclusion, deprotonation of phosphoinositides by low [H+] or high intracellular [Mg2+] at normal pH induces a decreased accessibility for their specific lipid kinases and phosphatases. This effect may be the result of lateral phase separation of acidic phospholipids as a consequence of divalent cation complexation under both experimental conditions, high pH and high [Mg2+] at normal pH.

Erythrocytes↗
PubMed1994

Regulation of human type II phosphatidylinositol kinase activity by epidermal growth factor-dependent phosphorylation and receptor association.

Epidermal growth factor (EGF) stimulates phosphatidylinositol PtdIns) hydrolysis in many cell types by effecting the specific interaction between the EGF receptor and phospholipase C gamma. Several studies have suggested that PtdIns 4-kinase activity can also be regulated by EGF, but the mechanism of this stimulation was unclear. We report here that EGF treatment of intact A431 cells increased the association of type II PtdIns kinase with the EGF receptor within 1 min at 37 degrees C. Phosphorylation of immunoprecipitated EGF receptor also increased the association of PtdIns 4-kinase. Furthermore dephosphorylation of phosphoserine residues on the stimulated receptor immune complex led to inactivation of the bound PtdIns 4-kinase, while dephosphorylation of phosphotyrosine residues led to activation. Unlike the stimulated activity measured in total cell and plasma membrane lysates, the changes in activity of the immunoprecipitates were apparent at high substrate concentration. Metabolic labeling was used to show that a 55-kDa phosphoserine and phosphotyrosine-containing protein comigrated with renatured PtdIns 4-kinase activity on SDS-polyacrylamide gel electrophoresis, while in vitro labeling revealed only serine phosphorylation. These data are discussed with reference to the direct regulation of PtdIns 4-kinase by phosphorylation, PtdIns compartmentalization, and the formation of a multienzyme signal transduction complex.

1-Phosphatidylinositol 4-Kinase↗
PubMed1992

[Chronic use of glucomannan in the dietary treatment of severe obesity].

Two groups of 25 severely obese patients underwent 3 months of hypocaloric diet therapy either alone or associated with a glucomannan-based fibrous diet supplement (approx. 4 g/die in 3 doses). The comparative analysis of the results obtained in both groups showed that the diet + glucomannan group had a more significant weight loss in relation to the fatty mass alone, an overall improvement in lipid status and carbohydrate tolerance, and a greater adherence to the diet in the absence of any relevant side effects. Due to the marked ability to satiate patients and the positive metabolic effects, glucomannan diet supplements have been found to be particularly efficacious and well tolerated even in the long-term treatment of severe obesity.

Adult↗