PubMed Health⌕ Search

Biomedical subjects

S Kellner

Publications and source records attributed to S Kellner.

At least 19 recordsLinked to original sources
PubMed2005

Paroxetine serum concentrations in depressed patients and response to treatment.

INTRODUCTION: There is no established relationship between the serum concentration of selective serotonin reuptake inhibitors (SSRIs) and clinical response in depressed patients. METHODS: We analyzed paroxetine concentrations in serum of 46 depressed patients during treatment with a fixed dosage of 40 mg paroxetine. RESULTS: After 5 weeks 29 patients responded to treatment, while 17 did not. Analysis of variance with repeated measures (ANOVA-rm) revealed a significant effect of "response" with responders having lower serum concentrations throughout the treatment period, when compared to non-responders. After 2, 3, and 4 weeks of treatment, we could define an upper threshold of paroxetine serum concentrations (week 1 : 22.7 ng/mL; week 2 : 43 ng/mL; week 3 : 53.4 ng/mL; week 4 : 39.1 ng/mL) above which response to treatment was unlikely. CONCLUSION: We conclude that -- in contrast to other pharmacological approaches -- high rather than low drug serum concentrations may be associated with non-response in paroxetine treatment of depressed patients.

Adult↗
PubMed2000

Binding of flavin adenine dinucleotide to molybdenum-containing carbon monoxide dehydrogenase from Oligotropha carboxidovorans. Structural and functional analysis of a carbon monoxide dehydrogenase species in which the native flavoprotein has been replaced by its recombinant counterpart produced in Escherichia coli.

The carbon monoxide (CO) dehydrogenase of Oligotropha carboxidovorans is composed of an S-selanylcysteine-containing 88. 7-kDa molybdoprotein (L), a 17.8-kDa iron-sulfur protein (S), and a 30.2-kDa flavoprotein (M) in a (LMS)(2) subunit structure. The flavoprotein could be removed from CO dehydrogenase by dissociation with sodium dodecylsulfate. The resulting M(LS)(2)- or (LS)(2)-structured CO dehydrogenase species could be reconstituted with the recombinant apoflavoprotein produced in Escherichia coli. The formation of the heterotrimeric complex composed of the apoflavoprotein, the molybdoprotein, and the iron-sulfur protein involves structural changes that translate into the conversion of the apoflavoprotein from non-FAD binding to FAD binding. Binding of FAD to the reconstituted deflavo (LMS)(2) species occurred with second-order kinetics (k(+1) = 1350 M(-1) s(-1)) and high affinity (K(d) = 1.0 x 10(-9) M). The structure of the resulting flavo (LMS)(2) species at a 2.8-A resolution established the same fold and binding of the flavoprotein as in wild-type CO dehydrogenase, whereas the S-selanylcysteine 388 in the active-site loop on the molybdoprotein was disordered. In addition, the structural changes related to heterotrimeric complex formation or FAD binding were transmitted to the iron-sulfur protein and could be monitored by EPR. The type II 2Fe:2S center was identified in the N-terminal domain and the type I center in the C-terminal domain of the iron-sulfur protein.

Aldehyde Oxidoreductases↗
PubMed1998

Analysis of the DNA content in Bowen's disease.

The aim of this study was to evaluate the DNA content in Bowen's disease in comparison to healthy epidermis applying image cytophotometry. The material investigated was derived from 50 patients with Bowen's disease and 10 patients with healthy skin. For comparison of both groups the Kruskal-Wallis test was applied. Slides were stained with Feulgen and were evaluated with CAS-200 image analyzer. Only 7/50 morbus Bowen cases represented euploid histogram. The others 43/50 were either conspicious to be aneuploid (29/50) or clearly aneuploid (14/50). In contrast, all normal epidermis (10/10) were clearly euploid. Morbus Bowen cases demonstrated significantly higher 5c exceeding rate (p=0.0012) and significantly more cells in the S-phase (p=0.017). High aneuploidy rate and increased proliferative activity in morbus Bowen cases support the classification of these lesion as carcinoma in situ.

Aged↗
PubMed1998

Prognostic relevance of histologic grading, the cell cycle-associated antigen Ki-S1 and cell cycle regulators in malignant fibrous histiocytomas: a multivariate analysis.

The main aim of this study was to compare the prognostic impact of different histologic grading systems, the expression of the cell cycle-associated antigen DNA-topoisomerase-II-alpha (Ki-S1) and the expression of cell cycle regulators in malignant fibrous histiocytomas (MFH) using multivariate analyses. Paraffin-embedded tissue of 161 cases of MFH were studied immunohistochemically for the expression of the proliferation marker Ki-S1, cell cycle regulators (p53, MDM2, waf-1, pRb, p16) and the oncoprotein EGFR. The percentage of immunolabelled tumor cells (index) was assessed. The histologic grade was determined by the two-level grading systems of Costa, Tsujimoto and Pezzi, by the three-level grading systems of Coindre and Van Unnik and by the grading system presented here. Univariate analyses using the LOG rank test showed that all of the applied grading systems produce highly significant differences in survival between the grades of malignancy. Multivariate analyses with COX regression demonstrated that only the grading system presented here, based on the parameters necroses, mitoses and cellularity, had independent prognostic relevance. Moreover, the inclusion of the proposed grading system, the Ki-S1-index and a prognostic index primarily based on the expression of cell cycle regulators into the COX regression was suited for predicting survival in MFH. The grading system presented shows considerable advantages over the grading systems compared in this study for use in the routine pathology of MFH. The prognostic power of the proposed grading system can be enhanced by the combined study of cell cycle regulators and Ki-S1.

Adolescent↗
PubMed1998

The role of nm23 in melanoma progression and its prognostic significance.

The nm23 monoclonal antibody directed to specific antigen was applied for investigation of 29 benign naevi, 59 melanomas of different Clark level and locations, 4 lymph node and 28 organ metastases, using quantitative immunohistochemistry. The reduced expression of nm23 protein was associated with the tumor progression. A statistically significant difference (p = 0.0014) was found in nm23 protein expression between naevi and malignant melanomas. Additionally, a reduced protein level in metastases was found. A strong correlation was found between nm23 expression and survival of patients as well as the presence of metastasis (p = 0.0003).

Adolescent↗
PubMed1997

Defects of insulin and IGF-1 action at receptor and postreceptor level in a patient with type A syndrome of insulin resistance.

The action of insulin and IGF-1 in comparison to non-diabetic controls was studied in cultured fibroblasts of a patient with an inherited syndrome of insulin resistance (Type A syndrome). Insulin binding was reduced due to decreased receptor affinity, but sequence analyses revealed no alterations of splicing or primary insulin receptor (IR) structure. Most likely due to the IR affinity defect analyses of signal transduction pathways showed an impairment of insulin action on glucose uptake, total RNA synthesis and phosphorylation as well as activity of MAP-kinase. In addition inducibility of c-fos mRNA level was strongly impaired by insulin and IGF-1, but comparable to controls by PDGF indicating a postreceptor defect. In conclusion, we provide evidence that genetic syndromes of insulin resistance can be associated with both, receptor and postreceptor defects.

Cells, Cultured↗
PubMed1995

Recombinant human insulin receptor substrate-1 protein. Tyrosine phosphorylation and in vitro binding of insulin receptor kinase.

Insulin receptor substrate-1 (IRS-1) is a major endogenous substrate of the insulin receptor. To study the interaction of the insulin receptor with IRS-1 in vitro, we expressed in Escherichia coli the amino acids 516-777 of human IRS-1 (hIRS-p30) covering five potential tyrosine phosphorylation sites within YXXM motifs. Kinetic data for tyrosine phosphorylation of hIRS-p30 by partially purified insulin receptor and insulin-like growth factor I receptor and by baculovirus-expressed insulin receptor kinase domain were determined. Native insulin receptor demonstrated the highest affinity to hIRS-p30 (Km = 6.8 +/- 0.6 microM), followed by the insulin-like growth factor I receptor (Km = 9.9 +/- 1.0 microM). We used the soluble recombinant insulin receptor kinase domain, which phosphorylated hIRS-p30 with high affinity (Km = 11.9 +/- 0.8 microM), and affinity columns prepared by coupling hIRS-p30 to NHS-activated Sepharose for binding assays. The insulin receptor kinase domain phosphorylated the hIRS-p30 on the column, was bound by the immobilized hIRS-p30, and was eluted with high salt buffer. Autophosphorylated and EDTA-inactivated insulin receptor kinase domain was bound only by immobilized hIRS-p30 protein that has been prephosphorylated. Our results indicate that the recombinant hIRS-p30 protein is a high affinity substrate for insulin receptor and insulin-like growth factor I receptor in vitro. Moreover, we show that only tyrosine-phosphorylated hIRS-p30 is able to bind to the insulin receptor.

Amino Acid Sequence↗
PubMed1995

[Screening for increased cholesterol values in blood donors].

OBJECTIVE: In a pilot study blood donors were screened on HDL, LDL, and total cholesterol. The practicability and significance of such a screening in a blood bank should be tested. DESIGN: For this purpose, current methods to determine HDL, LDL, and total cholesterol were adapted on microtiter plates and validated. In a period of about 4 weeks all blood donors were tested for the three cholesterol parameters. SETTING: Red Cross blood bank in Baden-Baden, Germany with about 150,000 donations per year. PARTICIPANTS: The HDL, LDL, and total cholesterol results of 10,006 blood donors could be evaluated. INTERVENTIONS: None. RESULTS: The mean total cholesterol was 192 +/- 36 mg/dl, the mean HDL cholesterol 56 +/- 15 mg/dl, and a mean LDL cholesterol of 123 +/- 39 mg/dl was found. The known age-dependency of the measured cholesterol fractions could be confirmed in our blood donor population. According to the current recommendations, more than 20% of the tested blood donors need a therapy. CONCLUSIONS: The study shows that the screening of blood donors for increased total cholesterol for prevention of coronary heart disease could be done with a minimum of costs.

Adolescent↗
PubMed1994

Relative efficiency of leucocyte removal procedures for the production of leucocyte-poor red cell concentrates assessed by flow cytometry.

Flow cytometry was used to: (1) determine residual leucocyte numbers in red cell suspensions following the range of leucocyte depletion procedures used in our organisation, and (2) to characterize phenotypically the leucocytes using direct immunofluorescence with monoclonal antibodies to cell surface receptors. Under the conditions used, a lower limit of detection of 2.5 leucocytes per microliter (equivalent to 3.43 log10 or 99.96% removal) could be achieved. Filtration through polyester filters was found to remove up to > 99.96% of the initial leucocytes; however, a significant differential efficacy was observed between filters from different manufacturers even when filters with similar costs were compared. The order of filter brands with respect to leucocyte removal found was Pall BPF4 = Erypur Optima G-O > Sepacell R500 > Pall RC50. Phenotyping revealed that increasing filtration efficacy was associated with a preferential removal of lymphocytes; conversely, a second filtration over one brand of filter allowed proportionately more lymphocytes to pass through compared with the first filtration. A saline wash following filtration removed a further 0.5% of the initial leucocyte content, and was associated with a preferential loss of granulocytes. Freeze-thawing the red cell suspension removed fewer leucocytes (96.3%) than did filtration (98.74% to > 99.6%) or filtration followed by washing (99.22%), and also led to preferential loss of granulocytes. Flow cytometry provides a reliable tool for the quality control of leuco-depleted red cells, and allows a qualitative assessment of the residual leucocytes. This information is of value in choosing procedures aimed at decreasing the risk of alloimmunisation and post-transfusion reactions.

Cell Separation↗
PubMed1993

Vitamin K in breast milk: no influence of maternal dietary intake.

There is limited information available on the vitamin K intake of lactating mothers, concentration of vitamin K1 in breast milk, and the effect of long-term vitamin K1 supplementation of lactating mothers on the vitamin K1 concentration in breast milk. In a randomized study, we followed 20 mothers who received a daily oral vitamin K1 supplement (average 88 micrograms, supplemented group) and 16 mothers receiving no supplement (control group) from 4 throughout 91 days postpartum. Maternal vitamin K intakes (weighed dietary intake) at 4-6, 25-29 and 87-91 days postpartum ranged between 73 and 1735 micrograms/day. Differences between the groups were statistically not significant. Average intake exceeded the recommended dietary intake for lactating women of 55 micrograms/day by 670%. In the supplemented group, mean breast-milk vitamin K1 concentrations (HPLC) at 5, 26 and 88 days postpartum were 1.73 (SD 0.74), 1.36 (SD 0.81) and 1.67 (SD 2.01) ng/ml, respectively. Corresponding values in the control group were 1.44 (SD 0.57), 1.68 (SD 0.70) and 1.78 (SD 1.05) ng/ml. The latter were not statistically different from values in the supplemented group. Mean daily vitamin K1 intakes of infants breast-fed by supplemented mothers were 0.69 (SD 0.42), 0.93 (SD 0.51) and 1.25 (1.53) micrograms, respectively on days 5, 26 and 88. Corresponding values in the control group were 0.69 (SD 0.30), 1.07 (SD 0.58) and 1.31 (SD 0.95) micrograms and were statistically not different from values in the supplemented group. Average vitamin K1 intakes corresponded to 7-13% of the recommended dietary intake of 10 micrograms/d for infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Improved in-vitro quality of platelet concentrates stored in a dextrose-free synthetic medium.

The licensed balanced salt solution Plasma-Lyte, buffered with a clinical solution of sodium bicarbonate, was evaluated as a suspending fluid for platelet concentrates. Platelets suspended in this medium showed better pH maintenance over 5 days of storage compared to platelets stored in plasma (7.0 vs 6.45, P < 0.001). This was reflected in improvements in in-vitro indicators of platelet viability-hypotonic shock response (79 vs 48%, P < 0.05), aggregation to paired agonists (86 vs 62%, P < 0.05); and platelet size distribution (104 vs 119%, P < 0.001). Dissolved bicarbonate measurement showed less depletion of bicarbonate in the synthetic medium compared to plasma, which suggests a lower rate of lactate formation. A synthetic medium containing dextrose showed inferior platelet storage characteristics when compared to the plasma-lyte/bicarbonate medium in a paired study (Day 5, pH 6.53 vs 6.9, P < 0.05). The results suggest that utilization of substrates other than dextrose allows platelets to metabolize without the accumulation of lactate that leads to pH drops during storage in plasma, and continue to support the feasibility of storing platelets in a non-plasma environment.

Bicarbonates↗
PubMed1990

Large-scale gel filtration chromatography for the production of a solvent/detergent-treated high-purity factor VIII concentrate.

To produce a tri(n-butyl)phosphate/sodium-cholate-treated intermediate-purity factor VIII (FVIII) concentrate with a specific activity of about 1 IU/mg, we used a simple gel filtration step with Sephadex G25 to remove the solvent/detergent reagents from the final product. By exchanging the Sephadex G25 gel for a new high-resolution gel (Sephacryl S400 HR), we obtained a high-purity FVIII concentrate, by simultaneous elimination of about 98% of the extraneous proteins and removal of the solvent/detergent reagents, without reducing the FVIII:c yield and without altering the production scheme. With different protein analysis techniques we analysed the resulting FVIII concentrate and, comparing it to the formerly produced intermediate-purity FVIII concentrate, demonstrated improved purity.

Cholic Acid↗
PubMed1989

Chemical and immunochemical characterization of polymers of aggregates in preparations of human serum albumin.

The polymer/aggregate fractions of three human serum albumin preparations (HSA) from different manufacturers were isolated by size-exclusion high-performance liquid chromatography (HPLC) and analyzed by different electrophoretic and immunochemical methods. All of these polymer/aggregate fractions contained only 30-50% albumin. The rest seemed to be mainly heat-denatured haptoglobin which did not react with an anti-haptoglobin serum, whereas the albumin part reacted with an anti-albumin serum. It could be shown that these polymers or aggregates are formed by disulfide bonds between albumin and the small amounts of denatured impurity globulins (haptoglobin, transferrin) during the pasteurization step. The higher the amount of these heat labile globulins in the final preparation before the pasteurization step, the higher was the polymer/aggregate content of the pasteurized albumin preparation.

Blood Protein Electrophoresis↗