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Biomedical subjects

C Jansen

Publications and source records attributed to C Jansen.

At least 19 recordsLinked to original sources

Surgical repair of aortopulmonary window: thirty-seven years of experience.

An aortopulmonary window (APW) is a communication between the ascending aorta and the pulmonary trunk in the presence of two separate semilunar valves. In order to increase our understanding about the surgical management of this rare lesion and its long-term results, we describe our experience over a 37-year period. Between 1968 and 2005, 18 patients were diagnosed with APW. Seventeen underwent surgical correction. Age at operation ranged from 22 days to 22 years (median, 0.20 years). Follow-up ranged from 2 weeks to 28.6 years (median, 11.0 years). Surgical closure was achieved using a single patch in 7 patients (41.2%) double patch in 4 (23.5%), primary closure in 3 (17.6%), clip in 2 (11.8%), and ligation in 1 (5.9%). Complex APW was present in 8 patients (44.4%). One patient was treated nonsurgically. There were no early or late deaths after surgery. Both primary closure and patch closure gave excellent long-term results. Sporadic postoperative complications were only associated with complex lesions. One patient who was treated conservatively died (of pulmonary hypertension) 21 years after diagnosis. Repair of APW is ideally performed in the first months of life, before irreversible PHT has developed. Various surgical repair techniques in this series of patients gave excellent short-term and long-term results, without significant hemodynamic sequelae.

Adolescent↗

[Angiographic follow-up after carotid artery stenting of bifurcation stenosis].

PURPOSE: The purpose of this prospective study was to determine the restenosis grade, the intima hyperplasia and the stent expansion via angiographic follow-up six months after carotid artery stenting. MATERIALS AND METHODS: In 100 patients, angiographic follow-up was performed 5.9 months (range: 2.9-11.4 months) after carotid artery stenting. The restenosis grade, the intima hyperplasia and the stent expansion were measured by selective angiography of the treated carotid artery. RESULTS: The mean restenosis grade was 16 % (range: 0-78 %). In 6 of 100 patients (6 %), a restenosis grade of > 50 % was measured. In 4 patients the restenosis grade was 50-70 %. In 2 patients the restenosis grade was > 70 %. In 91 of 100 patients (91 %), the restenosis was localized in the former area of stenosis of the carotid artery, and in 9 of 100 patients (9 %), the restenosis was localized in the cranial stent end. The mean grade of intima hyperplasia was 31 % (range: 2-70 %). The mean increase in stent expansion at the time of follow-up was 10 % (range: 0-59 %). No correlation was able to be determined between the grade of stenosis and the grade of restenosis (rho = 0.017, range: - 0.180-0.213), between the grade of residual stenosis and the grade of restenosis (rho = 0.257, range: 0.064-0.431) and between intima hyperplasia and the grade of restenosis (rho = 0.476, range: 0.309-0.615). CONCLUSIONS: Carotid artery stenting is associated with a low incidence of high-grade restenosis 6 months after an intervention. The intima hyperplasia, which can be observed in each Wallstent, is partly compensated by the expansion of the self-expandable stent. Without a correlation between the grade of residual stenosis and the grade of restenosis, low-grade residual stenosis can be accepted. Therefore, we recommend undersized postdilation of the Wallstent.

Aged↗

Limited costs of wrong root placement in Rumex palustris in heterogeneous soils.

Nutrient hot spots in the soil have a limited life span, but the costs and benefits for root foraging are still underexposed. We assessed short-term costs that may arise when a nutrient-rich patch induces root proliferation, but then rapidly disappears. Rumex palustris plants were grown with a homogeneous or a heterogeneous nutrient application. After root proliferation in a nutrient-rich patch, nutrient supply was switched from homogeneous to heterogeneous, and vice versa, or the patch location was changed. R. palustris proliferated its roots in the rich patch. After switching, the relative growth rates of the roots were adjusted to the novel pattern of nutrient availability. However, the changes in local root biomass lagged behind the rapid shift in nutrient supply, because the root mass realized in specific sectors could not be rapidly relocated. Despite this, R. palustris did not exhibit costs of switching in terms of biomass or nitrogen uptake. Our data suggest that rapid shifts in uptake rate and redistribution of nitrogen within the plant may have lowered the costs of incorrect root placement.

Biomass↗

[The first patient with the new variant of Creutzfeldt-Jakob's disease in The Netherlands].

A Dutch woman died at the age of 26 years, after a disease duration of 18 months, due to the new variant of Creutzfeldt-Jakob's disease (vCJD). She had never travelled to the United Kingdom and there was no history of potential iatrogenic exposure. However, she had worked in the catering and food production industry for the previous 6 years and had frequently consumed raw meat. The disease course showed the classical clinical picture of vCJD, which was confirmed by post-mortem examination of the brain. Contrary to classical sporadic CJD, patients with the variant disease are usually younger and present predominantly with psychiatric symptoms. Sensory complaints like pain and dysaesthesiae usually follow soon. Only later are these symptoms followed by rapidly progressive neurological symptoms and signs. All patients genotyped so far are homozygous for methionine on codon 129 of the prion protein gene. Recognition of the disease is of particular importance because of possible transmission via blood and tissues. In patients with rapidly progressive psychiatric symptoms and unexplained neurological signs, particularly sensory complaints, one must consider the possibility of vCJD.

Adult↗

Two cases of fatal necrosis of the lesser pelvis in patients treated with combined radiotherapy and hyperthermia for cervical carcinoma.

This study reports two cases of fatal necrosis of the lesser pelvis in patients with advanced cervical carcinoma, who had received combined radiotherapy and hyperthermia. The necrosis reached far from the high dose area, in one of the cases even outside the radiation portals. Both patients initially had treatment-related morbidity which responded well to surgical treatment. After a disease-free interval, a rapidly progressive necrosis developed. Necrosis to this extent after combined modality treatment has, to the authors' knowledge, not been described.

Adult↗

Ultraviolet B-induced phosphorylation of histone H3 at serine 28 is mediated by MSK1.

N-terminal tail phosphorylation of histone H3 plays an important role in gene expression, chromatin remodeling, and chromosome condensation. Phosphorylation of histone H3 at serine 10 was shown to be mediated by RSK2, mitogen- and stress-activated protein kinase-1 (MSK1), and mitogen-activated protein kinases depending on the specific stimulation or stress. Our previous study showed that mitogen-activated protein kinases MAP kinases are involved in ultraviolet B-induced phosphorylation of histone H3 at serine 28 (Zhong, S., Zhong, Z., Jansen, J., Goto, H., Inagaki, M., and Dong, Z., J. Biol. Chem. 276, 12932-12937). However, downstream effectors of MAP kinases remain to be identified. Here, we report that H89, a selective inhibitor of the nucleosomal response, totally inhibits ultraviolet B-induced phosphorylation of histone H3 at serine 28. H89 blocks MSK1 activity but does not inhibit ultraviolet B-induced activation of MAP kinases p70/85(S6K), p90(RSK), Akt, and protein kinase A. Furthermore, MSK1 markedly phosphorylated serine 28 of histone H3 and chromatin in vitro. Transfection experiments showed that an N-terminal mutant MSK1 or a C-terminal mutant MSK1 markedly blocked MSK1 activity. Compared with wild-type MSK1, cells transfected with N-terminal or C-terminal mutant MSK1 strongly blocked ultraviolet B-induced phosphorylation of histone H3 at serine 28 in vivo. These data illustrate that MSK1 mediates ultraviolet B-induced phosphorylation of histone H3 at serine 28.

Animals↗

MAP kinases mediate UVB-induced phosphorylation of histone H3 at serine 28.

Histone H3 phosphorylation is related closely to chromatin remodeling and chromosome condensation. H3 phosphorylation at serine 28 is coupled with mitotic chromosome condensation in diverse mammalian cell lines. However, the pathway that mediates phosphorylation of H3 at serine 28 is unknown. In the present study, ERK1, ERK2, or p38 kinase strongly phosphorylated H3 at serine 28 in vitro. JNK1 or JNK2 was able also to phosphorylate H3 at serine 28 in vitro but to a lesser degree. UVB irradiation markedly induced phosphorylation of H3 at serine 28 in JB6 Cl 41 cells. PD 98059, a MEK1 inhibitor, and SB 202190, a p38 kinase inhibitor, efficiently repressed UVB-induced H3 phosphorylation at serine 28. Expression of dominant negative mutant (DNM) ERK2 in JB6 Cl 41 cells totally blocked UVB-induced phosphorylation of H3 at serine 28. Additionally, DNM p38 kinase or DNM JNK1 partially blocked UVB-induced H3 phosphorylation at serine 28. Furthermore, UVB-induced H3 phosphorylation at serine 28 was inhibited in Jnk1(-/-) cells but not in Jnk2(-/-) cells. These results suggest that UVB-induced H3 phosphorylation at serine 28 may be mediated by mitogen-activated protein kinases.

Animals↗

Multijoint grasping movements. Simulated and observed effects of object location, object size, and initial aperture.

Studies of human prehension have revealed characteristic patterns of grasping kinematics. We sought to gain insight into the determinants of those patterns by means of a computer simulation and accompanying behavioral experiment concerning multijoint, planar grasping behavior. The simulation was based on a recent theory of posture-based motion planning which hypothesizes that movement preparation entails time-limited, multiple task-constraint satisfaction. Prehension was modeled with a stick-figure animation involving 12 series of 81 grasping movements. Circular objects to be grasped were located at three angles (45 degrees, 90 degrees, and 135 degrees) and at three distances (20 cm, 30 cm, and 40 cm) relative to the initial location of the hand in the workplane. Additionally, three object sizes (2 cm, 4 cm, and 6 cm in diameter) and three initial aperture sizes (0.3 cm, 3.3 cm, and 7.0 cm) were used. Analyses of the simulated grasping movements focused on the time course of the hand opening, the tangential velocity of the wrist, and the rotations of the joints in the arm, hand, and fingers. The results showed that the model accurately mimicked detailed kinematics of prehension observed in earlier studies. With respect to the frequently reported relationship between object size and hand opening, the simulations further revealed an effect of initial aperture. This predicted effect was confirmed in an experiment in which four participants performed analogous planar grasping tasks. An analysis of the time course of the opening of the hand showed that maximum aperture covaried with initial aperture. A conclusion of this work is that a major determinant of grasping kinematics is avoidance of collisions with objects that are to be grasped.

Adult↗

Posture-based motion planning: applications to grasping.

This article describes a model of motion planning instantiated for grasping. According to the model, one of the most important aspects of motion planning is establishing a constraint hierarchy--a set of prioritized requirements defining the task to be performed. For grasping, constraints include avoiding collisions with to-be-grasped objects and minimizing movement-related effort. These and other constraints are combined with instance retrieval (recall of stored postures) and instance generation (generation of new postures and movements to them) to simulate flexible prehension. Dynamic deadline setting is used to regulate termination of instance generation, and performance of more than one movement at a time with a single effector is used to permit obstacle avoidance. Old and new data are accounted for with the model.

Attention↗

Stent design related neointimal tissue proliferation in human coronary arteries; an intravascular ultrasound study.

AIMS: Histological restenosis models in animals have indicated that stent design has a significant impact on vessel trauma during stent implantation and on the amount of subsequent neointimal tissue proliferation. The impact of different stent designs on intimal hyperplasia in human atherosclerotic coronary arteries has not been determined. METHODS AND RESULTS: Angiographic and intravascular ultrasound studies were performed at the 6 month follow-up in 131 consecutive native coronary lesions of 131 patients treated with 50 Multi-Link stents, 40 InFlow stents and 41 Palmaz-Schatz stents. Lumen and stent cross-sectional areas (CSA) were measured at 1 mm axial increments. Mean intimal hyperplasia cross-sectional area (stent CSA-lumen CSA) and mean intimal hyperplasia thickness were calculated. Intravascular ultrasound demonstrated different levels of intimal hyperplasia proliferation for the three stents. Mean intimal hyperplasia thickness was 0.16+/-0.08 mm for Multi-Link stents, 0.26+/-0.19 mm for Palmaz-Schatz stents and 0.39+/-0.14 mm for Inflow stents (P<0.001). Multivariate analysis proved that stent type was the only independent predictor of intimal hyperplasia thickness at follow-up (P<0.001). CONCLUSION: Coronary stent design has a significant impact on subsequent intimal hyperplasia after implantation into atherosclerotic human coronary arteries. The corrugated ring design of the Multi-Link stent proved to result in less tissue proliferation at 6-month follow-up than the tubular slotted design of Palmaz-Schatz and InFlow stents.

Coronary Disease↗

[Effect of optimized integrated management on long-term effectiveness of cardiologic rehabilitation].

BACKGROUND AND OBJECTIVE: Long-term risk factor (RF) modification after cardiac rehabilitation (CR) is less than satisfactory. Problems of communication between the CR centre and the practising physician (GP) are one potential source of sub-optimal management. The goal of the PROTECT-study was to evaluate the influence of improved communication between rehabilitation centres and the GP on the quality of RF-modification. PATIENTS AND METHODS: In 50 specialized CR centres 882 patients in the group with intensified communication were compared to 160 patients in the usual care group. All patients underwent a course of residential CR. Intensified communication was attempted by a total of four phone calls to the GP, a RF booklet in which the RF profile, the individual RF treatment goals and the current RF status were delineated. Main treatment goals with respect to RF-modification after 6 months were: Blood pressure < 140/90 mmHg, LDL-Cholesterol < 100 mg/dl or at least 115 mg/dl and a body mass index of < 25 or at least < 30. RESULTS: The percentage of of patients with adequate blood pressure control (< 140/90 mmHg) was 85.1% vs. 85%, with LDL-cholesterol < 100 mg/dl 27.2% vs. 23.9%, with good body-mass index (< 25) 32.4% vs. 28.2% (intensified communication vs. control group; p = ns). The treatment initiated by the CR centres was continued in about 90% of patients. CONCLUSION: The study has shown that improved communication between the CR centres and the GP's after CR had only a marginal effect on the quality of RF-management. One key element of secondary prevention could be to get the patient more strongly involved in reaching the targets of therapy.

Aged↗

Biochemical and biophysical characterization of in vitro folded outer membrane porin PorA of Neisseria meningitidis.

Two subtypes of the outer membrane porin PorA of Neisseria meningitidis, P1.6 and P1.7,16, were folded in vitro after overexpression in, and isolation from Escherichia coli. The PorA porins could be folded efficiently by quick dilution in an appropriate buffer containing the detergent n-dodecyl-N, N-dimethyl-1-ammonio-3-propanesulphonate. Although the two PorA porins are highly homologous, they required different acidities for optimal folding, that is, a pH above the pI was needed for efficient folding. Furthermore, whereas trimers of PorA P1.7,16 were almost completely stable in 2% sodium dodecyl sulphate (SDS), those of P1.6 dissociated in the presence of SDS. The higher electrophoretic mobility of the in vitro folded porins could be explained by the stable association of the RmpM protein to the porins in vivo. This association of RmpM contributes to the stability of the porins. The P1.6 pores were moderately cation-selective and displayed a single-channel conductance of 2.8 nS in 1 M KCl. The PorA P1.6 pores, but not the PorA P1.7,16 pores, showed an unusual non-linear dependence of the single-channel conductance on the salt concentration of the subphase. We hypothesize that a cluster of three negatively charged residues in L5 of P1.6 is responsible for the higher conductance at low salt concentrations.

Escherichia coli↗

The assembly pathway of outer membrane protein PhoE of Escherichia coli.

The assembly of the wild-type and several mutant forms of the trimeric outer membrane porin PhoE of Escherichia coli was investigated in vitro and in vivo. In in vivo pulse-chase experiments, approximately half of the wild-type PhoE molecules assembled within the 30-s pulse in the native conformation in the cell envelope. The other half of the molecules followed slower kinetics, and three intermediates in this multistep assembly process were detected: a soluble trypsin-sensitive monomer, a trypsin-sensitive monomeric form that was loosely associated with the cell envelope and a metastable trimer, which was integrated into the membranes and converted to the stable trimeric configuration within minutes. The metastable trimers disassembled during sample preparation for standard SDS/PAGE into folded monomers. In vitro, the isolated PhoE protein could efficiently be folded in the presence of N,N-dimethyldodecylamine-N-oxide (LDAO). A mutant PhoE protein, DeltaF330, which lacks the C-terminal phenylalanine residue, mainly followed the slower kinetic pathway observed in vivo, resulting in increased amounts of the various assembly intermediates. It appears that the DeltaF330 mutant protein is intrinsically able to fold, because it was able to fold in vitro with LDAO with similar efficiencies as the wild-type protein. Therefore, we propose that the conserved C-terminal Phe is (part of) a sorting signal, directing the protein efficiently to the outer membrane. Furthermore, we analysed a mutant protein with a hydrophilic residue introduced at the hydrophobic side of one of the membrane-spanning amphipathic beta strands. The assembly of this mutant protein was not affected in vivo or in vitro in the presence of LDAO. However, it was not able to form folded monomers in a previously established in vitro folding system, which requires the presence of lipopolysaccharides and Triton. Hence, a folded monomer might not be a true assembly intermediate of PhoE in vivo.

Biochemistry↗

Immunogenicity of in vitro folded outer membrane protein PorA of Neisseria meningitidis.

In vitro folded and the denatured form of PorA P1.6 from Neisseria meningitidis strain M990 were used for immunization studies in mice. Previously, the antigen was isolated from cytoplasmic inclusion bodies, folded and purified. Its immunogenicity without adjuvant appeared to be low. The addition of the adjuvant QuilA, but not of galE lipooligosaccharide, considerably enhanced the immunogenicity. Moreover, when immunized with folded PorA P1.6 plus QuilA, a clear switch towards the IgG2a subclass of antibodies and concomitantly, the appearance of serum bactericidal activity, which is believed to be important for protective immunity, was observed. Hence, a tool for preparing vaccines against serogroup B meningococci devoid of endotoxin is available.

Adjuvants, Immunologic↗

A novel nonsense mutation of the KAL gene in two brothers with Kallmann syndrome.

Kallmann syndrome (KS), defined by the association of hypogonadotropic hypogonadism and anosmia or hyposmia, can be caused by mutations in the KAL gene on Xp 22.3. This gene encodes an extracellular matrix glycoprotein called anosmin-1, which belongs to the class of cell adhesion molecules. In the absence of a functional KAL protein, migration of both olfactory and gonadotropin-releasing hormone neurons is arrested. A defective anosmin-1 molecule may also play a role in the development of synkinesia and renal agenesis, which are exclusively seen in the X-linked form of KS. We describe the clinical presentation and molecular diagnosis of the defect in two brothers with KS. An X-linked mode of transmission was assumed on the basis of synkinesia and the presence of oligomenorrhoea in the mother. A novel nonsense mutation was found in exon 13 of the KAL gene, encoding the region of the fourth fibronectin type III repeat of anosmin-1, which results in an apparently nonfunctional truncated protein.

Adolescent↗

Transforming growth factor alpha (TGF-alpha) increases cell number in a human pancreatic cancer cell line but not in normal mouse pancreas.

BACKGROUND: The pancreas harbors growth factors such as the epidermal growth factor (EGF) family. The physiological and pathophysiological roles of growth factors in normal pancreas remain unsettled. Human pancreatic cancer overexpresses the EGF receptor, and the ligands EGF and transforming growth factor alpha (TGF-alpha). The aim of the present experiments was to study the effect of TGF-alpha in a pancreatic cancer cell line and in normal mouse pancreas. METHOD: The LN-36 cell line, established from a pancreatic duct cell adenocarcinoma, was incubated with TGF-alpha or EGF. The effect of an EGF receptor-specific, tyrosine kinase inhibitor (tyrphostin B56) with or without growth factors was also studied. The cell number was measured with the XTT-colorimetric method. TGF-alpha, the tyrphostins A25, B48, and B56, were in separate experiments infused during 1 wk to normal female mice by subcutaneous (sc) minipumps. RESULTS: The LN-36 cell line responded to TGF-alpha and EGF with increased cell number; +61% with 10(-10) M TGF-alpha and +34% with 10(-9) M EGF. Tyrphostin B56 at a concentration of 10(-5) M reduced the cell number by 76%, but when incubated together with growth factors the reduction was only 44% with TGF-alpha, and 39% with EGF. Infusion of TGF-alpha increased mouse pancreatic wet weight and protein content but was without effect on DNA synthesis, measured as incorporation of tritiated thymidine. Infusion of three different tyrphostins did not influence mice pancreas. CONCLUSION: The results support the role of TGF-alpha to maintain growth of pancreatic cancer cells by the EGF receptor. Infusion of TGF-alpha induced hypertrophy in normal mouse pancreas.

Animals↗

[Legal problems in the allocation of naturally limited resources].

Problems with regard to the allocation of naturally resources frequently arise in the field of the transplantation of organs. Section 12 of the German Transplant Act (TPG) lays down as a rule, that all transplant organs shall be allocated to suitable patients according to rules which comply with the level of research of medical science and especially with regard to prospects of success and priority. This basic rule for the allocation of naturally limited resources may not only be applied to the allocation of transplants but also to comparable cases (e.g. to new medical methods, which cannot be made available to all patients due to limited possibilities). In case of disaster, when the doctor has to select from a number of persons to be treated or rescued, jurisdiction leaves the decision to the discretion of the acting doctor assuming, in case of doubt, justification due to clash of responsibilities.

Ethics, Medical↗

[Rehabilitation treatment after stroke. An assessment of current status].

A standardized postacute inpatient rehabilitation program (Anschlussheilbehandlung) after stroke is well established in Germany. Yet the needs of patients being admitted to an Anschlussheilbehandlung (AHB) are not completely known. Therefore sociodemographic data, handicap, impairment and neuropsychologic deficits in 200 stroke patients were evaluated before admission to an AHB with different scores (Barthel, modified Rankin Score, NIHSS, HAWIE-R, Wilde, etc.). About half of the patients were still working prestroke. Most patients suffered from several vascular risk factors, which were insufficiently treated, and about a third of the patients had cerebrovascular disease prior to this stroke. At admission to the rehabilitation program the group of patients with severe neurological deficits was small. In average the disability was rather moderate (Rankin = 2.6). Mainly gait and finger dexterity were handicapped. Functional impairment was outweighed by neuropsychological deficits.

Adult↗