PubMed Health⌕ Search

Biomedical subjects

J Koster

Publications and source records attributed to J Koster.

At least 19 recordsLinked to original sources
PubMed2006

Symmetry properties of vibrational modes in mesoporphyrin IX dimethyl ester investigated by polarization-sensitive resonance Raman and CARS spectroscopy.

The symmetry properties of selected vibrational modes of mesoporphyrin IX dimethyl ester (MP-IX-DME) in solution are investigated under different electronic resonance conditions. The Raman band parameters of the macrocycle modes nu(2), nu(10), nu(11), and nu(19) are determined from a quantitative analysis of polarized spontaneous resonance Raman (RR) and polarization-sensitive (PS) multiplex coherent anti-Stokes Raman scattering (CARS) spectra obtained with pre-resonant B band and resonant Qx band excitation, respectively. Additionally, the molecular geometry and the vibrational modes of MP-IX-DME are calculated by employing density functional theory (DFT) on the B3LYP/6-31G(d) level. Both the DFT-derived structure and the Raman spectroscopic parameters of MP-IX-DME indicate minor deviations from an ideal D2h macrocycle symmetry. To assess the influence of the beta substitution pattern on the in-plane symmetry, calculated normal-mode vectors and several experimentally detected parameters, such as peak positions, depolarization ratios, and coherent phases, are analyzed. The effects of the macrocycle substitution pattern are different for the selected vibrational modes: nu(2) in particular is very sensitive to subtle perturbations of the in-plane symmetry. The considerable activity of totally symmetric vibrations observed in the PS CARS spectra of MP-IX-DME and the correlation of mode symmetries with coherent phases confirm earlier PS CARS results on octaethylporphine (OEP) acquired under the same electronic resonance conditions.

Absorption↗
PubMed2003

Role of binding of plectin to the integrin beta4 subunit in the assembly of hemidesmosomes.

We have previously shown that plectin is recruited into hemidesmosomes through association of its actin-binding domain (ABD) with the first pair of fibronectin type III (FNIII) repeats and a small part of the connecting segment (residues 1328-1355) of the integrin beta4 subunit. Here, we show that two proline residues (P1330 and P1333) in this region of the connecting segment are critical for supporting beta4-mediated recruitment of plectin. Additional binding sites for the plakin domain of plectin on beta4 were identified in biochemical and yeast two-hybrid assays. These sites are located at the end of the connecting segment (residues 1383-1436) and in the region containing the fourth FNIII repeat and the C-tail (residues 1570-1752). However, in cells, these additional binding sites cannot induce the assembly of hemidesmosomes without the interaction of the plectin-ABD with beta4. Because the additional plectin binding sites overlap with sequences that mediate an intramolecular association of the beta4 cytoplasmic domain, we propose that they are not accessible for binding and need to become exposed as the result of the binding of the plectin-ABD to beta4. Furthermore, these additional binding sites might be necessary to position the beta4 cytoplasmic domain for an optimal interaction with other hemidesmosomal components, thereby increasing the efficiency of hemidesmosome assembly.

Amino Acid Sequence↗
PubMed2001

Mutations in the 3beta-hydroxysterol Delta24-reductase gene cause desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis.

Desmosterolosis is a rare autosomal recessive disorder characterized by multiple congenital anomalies. Patients with desmosterolosis have elevated levels of the cholesterol precursor desmosterol, in plasma, tissue, and cultured cells; this abnormality suggests a deficiency of the enzyme 3beta-hydroxysterol Delta24-reductase (DHCR24), which, in cholesterol biosynthesis, catalyzes the reduction of the Delta24 double bond of sterol intermediates. We identified the human DHCR24 cDNA, by the similarity between the encoded protein and a recently characterized plant enzyme--DWF1/DIM, from Arabidopsis thaliana--catalyzing a different but partially similar reaction in steroid/sterol biosynthesis in plants. Heterologous expression, in the yeast Saccharomyces cerevisiae, of the DHCR24 cDNA, followed by enzyme-activity measurements, confirmed that it encodes DHCR24. The encoded DHCR24 protein has a calculated molecular weight of 60.1 kD, contains a potential N-terminal secretory-signal sequence as well as at least one putative transmembrane helix, and is a member of a recently defined family of flavin adenine dinucleotide (FAD)-dependent oxidoreductases. Conversion of desmosterol to cholesterol by DHCR24 in vitro is strictly dependent on reduced nicotinamide adenine dinucleotide phosphate and is increased twofold by the addition of FAD to the assay. The corresponding gene, DHCR24, was identified by database searching, spans approximately 46.4 kb, is localized to chromosome 1p31.1-p33, and comprises nine exons and eight introns. Sequence analysis of DHCR24 in two patients with desmosterolosis revealed four different missense mutations, which were shown, by functional expression, in yeast, of the patient alleles, to be disease causing. Our data demonstrate that desmosterolosis is a cholesterol-biosynthesis disorder caused by mutations in DHCR24.

Amino Acid Sequence↗
PubMed2001

The hemidesmosomal protein bullous pemphigoid antigen 1 and the integrin beta 4 subunit bind to ERBIN. Molecular cloning of multiple alternative splice variants of ERBIN and analysis of their tissue expression.

The bullous pemphigoid antigen 1 (eBPAG1) is a constituent of hemidesmosomes (HDs), cell-substrate adhesion complexes in stratified epithelia. Although its COOH terminus interacts with intermediate filaments, its NH(2) terminus is important for its recruitment into HDs. To identify proteins that interact with the NH(2) terminus of human eBPAG1, we performed a yeast two-hybrid screen, which uncovered a protein belonging to the LAP/LERP (for LRR and PDZ domain) protein family with 16 NH(2)-terminal leucine-rich repeats and a COOH-terminal PDZ domain. The gene for this LAP/LERP protein comprises at least 26 exons located on the long arm of chromosome 5. In most human tissues, several transcripts were detected differing in the coding region situated upstream of or within the PDZ domain. One of the encoded variants was found to correspond to the recently described protein ERBIN. In yeast and in vitro binding experiments, ERBIN was shown to interact not only with eBPAG1 but also with the COOH-terminal region of the cytoplasmic domain of the integrin beta4 subunit, another component of HDs. Antibodies raised against the COOH terminus showed that ERBIN is expressed in keratinocytes. In transfected epithelial cells the protein, however, was not localized in HDs but was either diffusely distributed over the cytoplasm or concentrated at the basolateral plasma membrane. Because ERBIN had been shown previously to interact with the transmembrane tyrosine kinase receptor Erb-B2, which in turn associates with the integrin beta4 subunit, we suggest that ERBIN provides a link between HD assembly and Erb-B2 receptor signaling.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome.

Mevalonic aciduria (MA) and hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) are two autosomal recessive inherited disorders both caused by a deficient activity of the enzyme mevalonate kinase (MK) resulting from mutations in the encoding MVK gene. Thus far, disease-causing mutations only could be detected by analysis of MVK cDNA. We now describe the genomic organization of the human MVK gene. It is 22 kb long and contains 11 exons of 46 to 837 bp and 10 introns of 379 bp to 4.2 kb. Three intron-exon boundaries were confirmed from natural splice variants, indicating the occurrence of exon skipping. Sequence analysis of 27 HIDS and MA patients confirmed all previously reported genotypes based on cDNA analysis and identified six novel nucleotide substitutions resulting in missense or nonsense mutations, providing new insights in the genotype/phenotype relation between HIDS and MA.

Alternative Splicing↗
PubMed2001

Two different mutations in the cytoplasmic domain of the integrin beta 4 subunit in nonlethal forms of epidermolysis bullosa prevent interaction of beta 4 with plectin.

The integrin alpha 6 beta 4 plays a crucial role in the assembly and maintenance of hemidesmosomes. Previous work has shown that the recruitment of plectin into hemidesmosomes is dependent on beta 4 and involves a region of the beta 4 cytoplasmic domain, which contains the first two fibronectin (FNIII) repeats and a short region of the connecting segment. Two missense mutations (R1225H and R1281W) in beta 4 that are responsible for nonlethal forms of epidermolysis bullosa are located in the second FNIII repeat. One of them is confined to a loop region that connects two beta strands (EC') whereas the other is located at the N-terminal end of the second FNIII repeat. We here report that these mutations render beta 4 unable to interact with plectin and prevent the localization of plectin in hemidesmosomes. Substitution of a lysine residue (K1279W) that forms part of the same loop as R1281 had no effect on the ability of beta 4 to recruit plectin. Furthermore, we show that an extended loop structure in beta 4, composed of the amino acids DDN (1262--1264), which resembles the RGD integrin-binding loop in fibronectin, is not involved in the binding to plectin. These results further demonstrate that binding of beta 4 to plectin is essential for the proper formation and function of hemidesmosomes and that loss of the interaction between beta 4 and plectin is associated with a mild form of epidermolysis bullosa.

Animals↗
PubMed2001

The interaction of plectin with actin: evidence for cross-linking of actin filaments by dimerization of the actin-binding domain of plectin.

Plectin is a major component of the cytoskeleton and is expressed in a wide variety of cell types. It plays an important role in the integrity of the cytoskeleton by cross-linking the three filamentous networks and stabilizing cell-matrix and cell-cell contacts. Sequence analysis showed that plectin contains a highly conserved actin-binding domain, consisting of a pair of calponin-like subdomains. Using yeast two-hybrid assays in combination with in vitro binding experiments, we demonstrate that the actin-binding domain of plectin is fully functional and preferentially binds to polymeric actin. The sequences required for actin binding were identified at the C-terminal end of the first calponin homology domain within the actin-binding domain of plectin. We found that the actin-binding domain of plectin is able to bundle actin filaments and we present evidence that this is mediated by the dimerization of this domain. In addition we also show that plectin and another member of the plakin family, dystonin, can heterodimerize by their actin-binding domains. We propose a new mechanism by which plectin and possibly also other actin-binding proteins can regulate the organization of the F-actin network in the cell.

Actins↗
PubMed1999

Characterization of the KNOX class homeobox genes Oskn2 and Oskn3 identified in a collection of cDNA libraries covering the early stages of rice embryogenesis.

For identification of genes involved in embryogenesis in the model cereal rice, we have constructed a collection of cDNA libraries of well-defined stages of embryo development before, during and after organ differentiation. Here, we focus on the possible role of KNOX (maize Knotted1-like) class homeobox genes in regulation of rice embryogenesis. Three types of KNOX clones were identified in libraries of early zygotic embryos. Two of these, Oskn2 and Oskn3, encode newly described KNOX genes, whereas the third (Oskn1) corresponds to the previously described OSH1 gene. In situ hybridizations showed that during the early stages of embryo development, all three KNOX genes are expressed in the region where the shoot apical meristem (SAM) is organizing, suggesting that these genes are involved in regulating SAM formation. Whereas OSH1 was previously proposed to function also in SAM maintenance, Oskn3 may be involved in patterning organ positions, as its expression was found to mark the boundaries of different embryonic organs following SAM formation. The expression pattern of Oskn2 suggested an additional role in scutellum and epiblast development. Transgenic expression of Oskn2 and Oskn3 in tobacco further supported their involvement in cell fate determination, like previously reported for Knotted1 and OSH1 ectopic expression. Whereas Oskn3 transformants showed the most pronounced phenotypic effects during vegetative development, Oskn2 transformants showed relatively mild alterations in the vegetative phase but a more severely affected flower morphology. The observation that the KNOX genes produce similar though distinct phenotypic reponses in tobacco, indicates that their gene products act on overlapping but different sets of target genes, or that cell-type specific factors determine their precise action.

Amino Acid Sequence↗
PubMed1999

Identification and characterization of three novel missense mutations in mevalonate kinase cDNA causing mevalonic aciduria, a disorder of isoprene biosynthesis.

Mevalonic aciduria is a rare autosomal recessive metabolic disorder, characterized by psychomotor retardation, failure to thrive, hepatosplenomegaly, anemia and recurrent febrile crises. The disorder is caused by a deficient activity of mevalonate kinase due to mutations in the encoding gene. Thus far, only two disease-causing mutations have been identified. We now report four different missense mutations including three novel ones, which were identified by sequence analysis of mevalonate kinase cDNA from three mevalonic aciduria patients. All mutations affect conserved amino acids. Heterologous expression of the corresponding mutant mevalonate kinases as fusion proteins with glutathione S -transferase in Escherichia coli showed a profound effect of each of the mutations on enzyme activity. In addition, immunoblot analysis of fibroblast lysates from patients using specific antibodies against mevalonate kinase identified virtually no protein. These results demonstrate that the mutations affect not only the activity but also the stability of the mutant proteins.

Adolescent↗
PubMed1997

Incentives and the management of physician behavior in health service organizations.

The performance of a health services organization is affected by the cumulative behavior of physicians out of proportion to their numbers or the economic value of their services. Managers are challenged to optimize physician behavior and to change it in concert with the evolving expectations of health service customers. Incentives are the tools available for this effort. This article discusses the interrelation of physician behavior, physician needs, and the major classes of incentives: economic, noneconomic, and rules. While most organizations recognize and use financial incentives, few utilize noneconomic incentives systematically. Given the financial restrictions of advanced markets, managers should understand the role of rules and the value of noneconomic issues to physicians when developing incentive programs.

Behavior↗
PubMed1995

[Hair analysis in the diagnosis of toxic hepatitis after Ecstasy abuse].

HISTORY AND CLINICAL FINDINGS: A young man, aged 18 years, was admitted to hospital for suspected hepatitis, having developed increasing jaundice without any pain. His urine was light brown in colour and the stools often liquid and pale. Every 14 days for the last 4 months he had been taking 2 tablets of "ecstasy" (methylenedioxyamphetamine; MDMA). Physical examination was unremarkable and the patient was in good general condition. TESTS: The activities of GOT, GPT and alkaline phosphatase were raised (to 903, 744 and 270 U/l, respectively) as was the bilirubin concentration (16.8 mg/dl). Tests were negative for: leptospira and the viruses of mumps, HI, varicella zoster, picornavirus, cytomegaly, Coxsackie and hepatitis, A, B and C. Ultrasound revealed hepatomegaly, with a normal echo pattern. Hair analysis demonstrated, in two different hair segments (0-2 cm and 2-4 cm, respectively) both MDMA (6.4 and 4.3 micrograms/g hair) and its metabolite MDA (0.7 and 5.0 micrograms/g hair). TREATMENT AND COURSE: No specific treatment was required. After intake of the drug had been stopped the transferase activities and bilirubin concentration became essentially normal. CONCLUSION: Hair analysis can be valuable in confirming "ecstasy" abuse, especially when it is denied, and thus contribute to clarifying the cause of toxic hepatitis.

Adolescent↗
PubMed1995

Evidence for gammacerane as an indicator of water column stratification.

A new route for the formation of gammacerane from tetrahymanol is proposed; in addition to dehydration and hydrogenation, sulphurisation and early C-S cleavage are shown to be important in the pathway of formation, especially in marine sediments. Evidence is twofold. First, relatively large amounts of the gammacerane skeleton are sequestered in S-rich macromolecular aggregates formed by natural sulphurisation of functionalised lipids. Selective cleavage of polysulphide linkages with MeLi/MeI led to formation of 3-methylthiogammacerane, indicating that the gammacerane skeleton is primarily bound via sulphur at position 3, consistent with the idea that tetrahymanol (or the corresponding ketone) is the precursor for gammacerane. Second, upon mild artificial maturation of two sediments using hydrous pyrolysis, gammacerane is released from S-rich macromolecular aggregates by cleavage of the relatively weak C-S bonds. The stable carbon isotopic compositions of gammacerane and lipids derived from primary producers and green sulphur bacteria in both the Miocene Gessoso-solfifera and Upper Jurassic Allgau Formations indicate that gammacerane is derived from bacterivorous ciliates which were partially feeding on green sulphur bacteria. This demonstrates that anaerobic ciliates living at or below the chemocline are important sources for gammacerane, consistent with the fact that ciliates only biosynthesize tetrahymanol if their diet is deprived of sterols. This leads to the conclusion that gammacerane is an indicator for water column stratification, which solves two current enigmas in gammacerane geochemistry. Firstly, it explains why gammacerane is often found in sediments deposited under hypersaline conditions but is not necessarily restricted to this type of deposits. Secondly, it explains why lacustrine deposits may contain abundant gammacerane since most lakes in the temperate climatic zones are stratified during summer.

Animals↗
PubMed1995

Prognostic significance of cellular proliferation in renal cell carcinoma: a comparison of synthesis-phase fraction and proliferating cell nuclear antigen index.

DNA aneuploidy has repeatedly been shown to be a significant prognostic indicator in renal cell carcinoma; however, few studies have emphasized the importance of measurements of cellular proliferation. This study evaluated 55 patients treated by radical nephrectomy and for whom clinical follow-up was available. There were 36 men and 19 women with a mean age of 61 yr. Robson stage distribution was I, 38 cases; II, five cases; and III, 12 cases. Flow cytometric analysis in 44 cases revealed 29 DNA diploid and 15 DNA aneuploid tumors with a median synthesis-phase fraction (SPF) of 4.4% (range 1.0 to 31.4%). The median proliferating cell nuclear antigen index was 3.9% (range 0.1 to 58.0%). There was a significant correlation between SPF and proliferating cell nuclear antigen index (R = 0.769) in the 33 cases in which both were available. Cellular proliferation, as determined by SPF, was a significant prognostic indicator (P < 0.02), but proliferating cell nuclear antigen index did not correlate with outcome (P > 0.05). Other significant predictors in this study were Robson stage (P = 0.03) and nuclear grade (P = 0.0003). DNA ploidy did not correlate with outcome (P > 0.05). We conclude that cellular proliferation, as measured by SPF analysis, is a significant predictor of outcome for renal cell carcinoma. Although the proliferating cell nuclear antigen index correlated with SPF, it did not achieve statistical significance as a prognostic indicator.

Adult↗
PubMed1994

The alpha-subunit of the Na,K-ATPase has catalytic activity independent of the beta-subunit.

All catalytic activities of the Na,K-ATPase have been ascribed to the alpha-subunit; however, normal activity requires the presence of the beta-subunit. Using recombinant baculoviruses to infect insect cells, we demonstrate that the alpha-subunit, without the beta-subunit, has catalytic activity. During the normal catalytic cycle of the Na,K-ATPase, the alpha-subunit is transiently phosphorylated by ATP at an aspartate residue. This phosphorylation requires Na+, in the presence of K+ the enzyme undergoes rapid dephosphorylation. In contrast, phosphorylation of the independent alpha-subunit by ATP occurs in the presence of Mg2+, does not require Na+ or K+, and is not affected by ouabain. The phosphorylation is, however, inhibited by EGTA and increasing ionic strength. Chemical properties of the alpha-subunit phosphointermediate are consistent with phosphorylation at the normal aspartyl residue. Membranes from cells infected with the recombinant alpha baculovirus exhibit an EGTA-sensitive Mg(2+)-ATPase activity that is not present in the uninfected cells. The Mg(2+)-ATPase of the alpha-infected cells is reduced under conditions of high ionic strength and completely inhibited by EGTA. Thus the phosphorylation of the unassociated alpha-subunit is representative of the ATPase activity of the enzyme. These results suggest that the alpha-subunit of the Na,K-ATPase can catalyze an activity not normally associated with the enzyme and demonstrate that the bea-subunit plays an important role in conferring normal activity to the enzyme complex.

Animals↗