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Biomedical subjects

C Schulz

Publications and source records attributed to C Schulz.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Enhanced liposomal transfection through the application of sex steroids in gynecological cancer cells].

OBJECTIVE: Liposomal transfection in gene therapeutic application against gynecological malignoma does not reach satisfying efficacy. A desirable goal would be the specific intensification of transfection in these kind of cells. Steroids have successfully been used in other systems to increase liposomal transfection and hopefully there might be a specific impact of sexual steroids in cells from high sex steroid receptor expressing malignoma, like some mamma- and endometrium cancer. MATERIAL AND METHODS: The mamma carcinoma cell line T-47D was transfected with the transfection agent DOTAP and cyclodextrin solubilized steroids and cholesterol were co-applied. The efficiency of transfection was followed by luciferase activity resulting from the transfected reporter gene. RESULTS: Like cholesterol, which is already established as transfection co-agent, also the steroids progesterone, estrogen, testosterone and hydrocortisone provoked a clear increase in transfection efficiency shown in a dose dependent manner. CONCLUSIONS: These results indicate the usefulness of steroids as additives for liposomal transfection procedures in gene therapeutic application. As sexual steroid receptors migrate into the nucleus of a cell after binding its specific ligand a targeted enhancement of transfection is supposable in malignoma overexpressing steroid receptors. There is evidence that plasmid DNA can be co-transported with nuclear proteins into the nucleus.

Breast Neoplasms↗
PubMed2003

Upregulation of MCAM in primary bronchial epithelial cells from patients with COPD.

An increasing body of evidence indicates that the bronchial epithelium plays a crucial role in the pathophysiology of chronic obstructive pulmonary disease (COPD). The aim of this study was to identify new genes whose bronchoepithelial expression is specifically altered in COPD patients. Primary bronchial epithelial cell (PBEC) cultures were established from exsmokers with stable airflow limitation and never smokers. Complementary deoxyribonucleic acid array technology was used to investigate the differential expression of 847 cytokine and cytokine-related genes between the two groups. Statistical analysis was performed by means of significance analysis of microarrays and Bonferroni-corrected analysis of variance on ranks. Discriminant analysis and light cycler measurements as well as flow cytometry and Western blotting were used to confirm the significance of the array results at both the messenger ribonucleic acid (mRNA) and protein expression levels. With respect to array experiments, melanoma cell adhesion molecule (MCAM) was identified as the sole gene showing highly significant upregulation in PBECs from COPD patients compared to never smokers. Light cycler measurements confirmed these results, revealing a 2.9-fold and 2.0-fold increase in MCAM mRNA expression in COPD patients compared to nonsmokers and smokers, respectively. In addition, these differences are associated with higher median protein expression levels. These results strongly suggest involvement of melanoma cell adhesion molecule in the pathophysiology of the chronic airway inflammation seen in patients with chronic obstructive pulmonary disease.

Antigens, CD↗
PubMed2002

Differences in LPS-induced activation of bronchial epithelial cells (BEAS-2B) and type II-like pneumocytes (A-549).

Lipopolysaccharide (LPS) as a major component of the outer membrane of gram-negative bacteria stimulates various cells to initiate a signalling cascade which ultimately leads to cell activation and expression of immunoregulatory or inflammatory cytokines. The human respiratory epithelium is an important environmental interface, but differences in LPS-induced cell activation between bronchial and alveolar epithelial cells have not yet been investigated in detail. First, the expression of Toll-like receptors (TLRs), as pattern-recognition receptors, was investigated for the bronchial epithelial cells and type II-like pneumocytes, demonstrating that they fulfil the prerequisites for LPS signalling. Thereafter, the effects of LPS, soluble CD14 (sCD14) and LPS-binding protein (LBP) on the release of interleukin-6 (IL-6) and IL-8 were studied. In the presence of LPS, sCD14 induced a significant and concentration-dependent cytokine release in type II-like pneumocytes, whereas the response of bronchial epithelial cells to sCD14 stimulation was low, implicating sCD14-independent activation mechanisms. Furthermore, LBP revealed inhibitory effects on the activation of alveolar epithelial cells, which may represent a novel local defence mechanism during gram-negative infection. We conclude that distinct pathways exist for LPS-induced activation of bronchial and alveolar epithelial cells.

Acute-Phase Proteins↗
PubMed2002

[The Child Environment Survey].

The German Environmental Survey (GerES) is a representative population study conducted in Germany since the mid-1980s. GerES IV is the first survey for children only; it will be conducted in close connection with the Health Survey for Children and Adolescents on a random sample of 1,800 children (3 to 14 years of age) taken from the study population of the Health Survey for Children and Adolescents. Various parameters will be analysed in blood, urine, house dust, indoor air and tap water. They include neurotoxins (PCBs, Pb, Hg), carcinogenic/cocarcinogenic substances (PAHs, benzene, halocarbons, Cd, As), substances that may cause irritation of the respiratory tract, allergies and asthma (VOC, formaldehyde, house dust mite, mould fungi, pet allergens) and substances that may have an effect on metabolism with potentially long-term consequences (such as DEHP). An additional part was devoted to the link between hearing ability, noise and stress. A one-year pilot study on 550 children and adolescents was conducted in 2001 to 2002 to collect information on parameters influencing the response rate and to test the suitability of the different instruments intended to be used for the main study.

Adolescent↗
PubMed2002

Subchondral mineralization patterns of the glenoid after tear of the supraspinatus.

Clinical experience has shown that in many cases of rupture of the supraspinatus tendon the head of the humerus shifts upward against the acromion. This implicates alterations in the stress acting on the joint surface. Accordingly, this should be reflected by changes in the distribution of the subchondral mineralization on the glenoid. Computed tomography osteoabsorptiometry was used to evaluate the distribution patterns on the subchondral bone plate of the glenoid in 67 human shoulders. The position of the two most frequent density maxima was determined by a standard procedure. In macroscopically normal specimens (n = 24) every case had an anterosuperior density maximum and the majority (75%) also had a posterior positioned maximum. In some instances a third maximum, placed centrally (17%) or in an anteroinferior position (4%) was seen. In shoulders with a torn supraspinatus tendon (n = 43) a third density maximum frequently appeared in the center of the glenoid (42%); however, most notable was a significant change of the posterior maximum position toward central and superior. With increasing size of the tendon defect an extension of the shift of the posterior maximum (superiorly and centrally) was observed in contrast to the constant anterior maximum. The changes in the distribution of glenoid subchondral bone mineralization in shoulders with a supraspinatus tear must be regarded as a morphologic parameter for the altered long-term stress acting on the joint surface.

Aged↗
PubMed2002

Tumour necrosis factor-alpha induced CD70 and interleukin-7R mRNA expression in BEAS-2B cells.

Over the past few years, evidence has emerged for the potential role of the human bronchial epithelial cell in the initiation and progress of inflammation of the airway. Thus, the aim of this study was to investigate the expression pattern of cytokines and immunomodulatory factors in the human bronchial epithelial cell. To elucidate this highly complex expression and regulation pattern, the simian virus-40 transformed human bronchial-epithelial cell line BEAS-2B was stimulated with human recombinant tumour necrosis factor (hrTNF)-alpha (10 ng x mL(-1) (specific activity, 2.86 x 10(7) U x mg(-1))) and messenger ribonucleic acid (mRNA) expression pattern was analysed by complementary deoxyribonucleic acid (cDNA) array analysis. Among 375 arrayed cDNA clones, 173 (46%) were detected in BEAS-2B cells. The levels of expression of 17 genes, including those of monocyte chemoattractant protein (MCP)-1, intercellular adhesion molecule (ICAM)-1, growth-related oncogene (GRO) alpha, beta, gamma, interleukin (IL)-7 receptor, CD70, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and regulated in activation, normal T-cell expressed and secreted (RANTES) were elevated after TNF-alpha stimulation. The differential character of 12 clones was further characterised and verified by real time polymerase chain reaction (PCR) analysis of total ribonucleic acid (RNA) isolated from BEAS-2B cells after 4 or 16 h incubation with increasing TNF-alpha concentrations (1 pg-10 ng x mL(-1)). The authors semiquantified concentration-dependent mRNA upregulation of cytokines and immunology factors identified in the array and could determine threshold values of mRNA increases at 10 pg x mL(-1)-1 ng x mL(-1) TNF-alpha by real-time PCR. For CD70 (CD27 ligand) and interleukin-7 receptor, which to the best of the author's knowledge have not yet been described in the human bronchial epithelial cell, a rapid and continuous messenger ribonucleic acid increase induced by 100 pg x mL(-1) tumour necrosis factor-alpha after only 60-90 min was shown. A potential role for these genes in the inflammatory process in the human bronchial epithelial cell is proposed.

Antigens, CD↗
PubMed2001

Stem cell self-renewal specified by JAK-STAT activation in response to a support cell cue.

Stem cells generate many differentiated, short-lived cell types, such as blood, skin, and sperm, throughout adult life. Stem cells maintain a long-term capacity to divide, producing daughter cells that either self-renew or initiate differentiation. Although the surrounding microenvironment or "niche" influences stem cell fate decisions, few signals that emanate from the niche to specify stem cell self-renewal have been identified. Here we demonstrate that the apical hub cells in the Drosophila testis act as a cellular niche that supports stem cell self-renewal. Hub cells express the ligand Unpaired (Upd), which activates the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in adjacent germ cells to specify self-renewal and continual maintenance of the germ line stem cell population.

Animals↗
PubMed2001

Genetic analysis of dPsa, the Drosophila orthologue of puromycin-sensitive aminopeptidase, suggests redundancy of aminopeptidases.

Abstract. The Drosophila genome contains a single orthologue of mammalian puromycin-sensitive aminopeptidases, dPsa. Even though dPsa was expressed in many tissues during development, animals lacking dPsa activity were viable. Ubiquitous overexpression of dPsa during embryonic or larval development resulted in lethality and overexpression in isolated tissues during development resulted in localized lesions. These results suggest that even though dPsa function was not essential for viability, dPsa expression must be tightly regulated for normal development. By screening the Drosophila genome we found 43 predicted aminopeptidases and generated a phylogenetic tree of aminopeptidases related to dPsa by sequence. We discuss possible functions of dPsa and the idea that other Drosophila aminopeptidases might perform redundant functions with dPsa for regulating protein turnover.

Amino Acid Sequence↗
PubMed2001

[Correlation between histopathology and epiluminescent microscopy in nonmelanocytic skin lesions].

Epiluminescence microscopy techniques make surface and subsurface structures accessible to visual examination in vivo. The visualization of a multitude of special morphological features, such as blood vessels, adnexa and deposits of pigments in normal and pathologically changed skin allows a reproducible and topographical stratification. There is a chance of identifying the architecture of the stratum corneum, the epidermis and the papillary bodies. Changes in the amount of melanin can be individually assessed in the stratum corneum and the deeper layers extending into the upper dermis. It is possible to differentiate the orientation, size and color of the blood vessels of the cutaneous vascular plexus, involving the capillaries of the stratum papillare and the subpapillary plexus.

Equipment Design↗
PubMed2001

The effects of the selective serotonin reuptake-inhibitor fluvoxamine on body weight in Zucker rats are mediated by corticotropin-releasing hormone.

Brain serotonin plays a crucial role in the regulation of food intake and body weight homeostasis. Previous data suggest an interaction with corticotropin-releasing hormone (CRH). To further examine the interaction between these neurotransmitters, the selective serotonin reuptake-inhibitor (SSRI) fluvoxamine was given intraperitoneally in fa/fa Zucker rats with and without the CRH-receptor-antagonist alpha-helical CRH administered intracerebroventricularly (i.c.v.). The saline treated animals gained weight. Fluvoxamine led to a significant weight loss while not affecting food intake. Furthermore, insulin levels in this animal model were reduced following fluvoxamine administration. These effects were antagonized by alpha-helical CRH and are thus most likely mediated via CRH or CRH-like peptides.

Animals↗
PubMed2001

The surgical treatment of Kienböck's disease by radius and ulna metaphyseal core decompression.

We present a new surgical procedure, metaphyseal core decompression, to treat Kienböck's disease. Twenty-two patients were treated between 1976 and 1988 and were retrospectively reviewed. Sixteen were male and 6 female with an average age of 36 years (range, 18-64 years). The surgical technique involved curettage of the distal radius and ulna metaphyseal bone through small cortical windows. The average follow-up period was 10 years (range, 6-16 years). No postoperative complications were noted and no patient underwent additional surgical procedure. Sixteen patients were pain-free; 4 noted occasional pain. Twenty returned to their prior occupation. One patient had moderate pain and altered his occupation. Another had increasing pain and had x-ray evidence of advanced intercarpal arthritis. The average arc of wrist extension and flexion was 77% of the opposite wrist and the average grip strength was 75%. Long-term follow-up monitoring indicates that the metaphyseal core decompression produces results at least as good as other surgical procedures without any postoperative complications.

Adult↗
PubMed2001

[Heparin-induced type II thrombocytopenia as the etiology of severe recurrent pulmonary embolism].

Heparin-induced thrombocytopenia (HIT) is a rare complication of anticoagulative heparin therapy. The more severe HIT type II is defined by peripheral thrombocytopenia combined with thrombotic and thromboembolic events. We report the case of a 24 year old male patient who was admitted to our ICU with thromboembolic obstruction of the right central pulmonary artery, and deep venous thrombosis (DVT) of the right superficial femoral vein. Systemic thrombolytic therapy with urokinase for seven days resulted in nearly complete resolution of the thromboembolic material in the pulmonary arteries. Antithrombotic therapy with intravenous heparin and overlapping oral phenoprocoumon was continued on the regular ward. Six days later, the patient had to be readmitted to the ICU with evidence of hemodynamic compromise due to massive bilateral pulmonary thromboembolism that could be confirmed by CT scan--DVT had extended to the right iliacal vein. Additionally, peripheral thrombocyte counts had markedly declined from 112.000 to 35.000/microliter within 3 days, indicating the presence of a Hit type II. This was verified by positive ELISA testing for antibodies against platelet factor 4 (PF4)-heparin-complex. A filter device was temporarily implanted into the inferior vena cava. The patients condition stabilized upon reinitiated systemic thrombolysis and replacement of heparin therapy against recombinant hirudin. Pulmonary artery pressures normalized. Peripheral thrombocytopenia diminished within three days. HIT type II is a severe complication of anticoagulative therapy with heparin. Here we report a case, and discuss diagnostic procedures as well as differential diagnosis to HIT type I.

Adult↗
PubMed2001

Plasma free amino acid concentrations in healthy Guatemalan adults and in patients with classic dengue.

BACKGROUND: Plasma free amino acid patterns in health and disease have been reported. However, amino acid concentrations in adult populations in developing countries and in patients with dengue, as a model for an acute infectious viral disease endemic to the tropics, have not been reported. OBJECTIVE: The purpose of this study was to determine the amino acid profile in both healthy Guatemalan adults from different socioeconomic backgrounds and at 3 time points during the course of classic dengue. DESIGN: The study was carried out in Guatemala and included measurement of plasma free amino acids in 22 healthy control subjects (14 low income, 8 middle class) and 17 febrile patients. Measurements of amino acids were repeated within a 48-h interval in 20 of the healthy Guatemalans. In 9 patients with dengue, amino acids were assayed 3 times: on admission to a local hospital in the coastal plain of Guatemala, on hospital discharge, and 7 d after hospital discharge. RESULTS: Branched-chain amino acid concentrations in healthy adults and dengue patients in Guatemala were lower than normal values reported in the literature for healthy Swedish adults. With the exception of increased phenylalanine concentrations and an increased ratio of phenylalanine to tyrosine, all amino acids as well as the Fischer molar ratio were decreased in the acute phase of dengue. CONCLUSIONS: Healthy Guatemalans have different amino acid patterns than do Swedish subjects independent of socioeconomic status. The systemic viral disease dengue is associated with changes in the plasma free amino acid pattern, reflecting infection-related alterations in amino acid metabolism.

Adult↗
PubMed2001

Reduction of systemic and cardiac adhesion molecule expression after off-pump versus conventional coronary artery bypass grafting.

Cardiopulmonary bypass (CPB) and operative trauma are associated with increased expression of proinflammatory mediators. We determined the relative contribution of CPB on activation of cytokines and adhesion molecules in patients undergoing coronary revascularization by comparing them with patients receiving off-pump coronary artery bypass grafting (OPCAB). Twenty-six patients were assigned to either the OPCAB procedure using a suction device and regular sternotomy (n = 13), or were treated conventionally using extracorporeal circulation, blood cardioplegia, and hypothermic arrest (29 degrees C-31 degrees C; n = 13). Systemic levels of TNF-alpha and the soluble adhesion molecules P-selectin and intracellular adhesion molecule 1 (ICAM-1) were assayed. Immunohistochemistry was used to account for cardiac-specific expression of adhesion molecules in interventricular endomyocardial sections. Both systemic and endomyocardial expression of adhesion molecules were lower in the OPCAB group. Coronary revascularization with CPB resulted in a significant higher expression of TNF-alpha, which was associated with P-selectin and ICAM-1 expression. This was accompanied with higher catecholamine requirement in the CPB group in the early postoperative period. Despite comparable surgical trauma, the OPCAB procedure without the use of CPB and cardioplegic arrest significantly reduces systemic and cardiac adhesion molecule expression and catecholamine requirement. Since the clinical course in the early postoperative period was comparable, larger trials are required to select the appropriate patient who benefits most from one or the other treatment regime.

Adult↗
PubMed2001

Effects of corticotropin-releasing hormone on locus coeruleus neurons in vivo: a microdialysis study using a novel bilateral approach.

OBJECTIVE: Stress-induced release of noradrenaline (NA) from locus coeruleus (LC) neurons is mainly regulated by corticotropin-releasing hormone (CRH). Tyrosine is a precursor of NA and plays an intriguing role in the regulation of NA release. DESIGN: We studied the effects of injecting CRH into the LC using a novel bilateral approach which relies on the mainly ipsilateral projections of LC neurons allowing stimulation of one hemisphere while using the other as control. To analyze the modification of the CRH effect, tyrosine was given intraperitoneally. A combination of CRH and its antagonist d-Phe was administered for validation of the specificity of CRH effects. METHODS: Wistar rats were used in all experiments. Injections were made through fused silica capillaries implanted into both LCs and microdialysis samples were collected bilaterally from the prefrontal cortex (PFM) every 20 min for 1 h before and 3 h after injections. The effects of LC stimulation were investigated by determining 3-methoxy-4-hydroxyphenylglycol (MHPG) in the dialysates. RESULTS: Following CRH injection into one LC and contralateral infusion of artificial cerebrospinal fluid (aCSF), MHPG levels, which are indicative of NA release, increased only in the ipsilateral PFM. These effects were blocked by d-Phe. Simultaneous administration of tyrosine i.p. led to a significant prolongation of MHPG release. CONCLUSIONS: These data provide the first physiological evidence of unilateral LC projections with the bilateral stimulation design proving to be a very valuable tool for the study of LC firing rate, to decrease number of animals and time expenditure. Prolongation of MHPG release after tyrosine supplementation is most likely due to increased NA synthesis.

Animals↗
PubMed2000

Endovascular irradiation from beta-particle-emitting gold stents results in increased neointima formation in a porcine restenosis model.

BACKGROUND: Recent studies have shown that ionizing radiation reduces neointima formation after balloon angioplasty and stent implantation in experimental models of restenosis and first clinical trials. The objective of this study was to determine the dose distribution of a new beta-particle-emitting radioactive gold stent and to evaluate the dose-dependent vascular response in the coronary overstretch pig model. METHODS AND RESULTS: Sixteen Göttinger minipigs underwent placement of 11 nonradioactive and 36 beta-particle-emitting stents with activity levels of 10.4+/-0.6, 14.9+/-2.4, 22.8+/-1.3, 35.8+/-2. 8, and 55.4+/-5.3 microCi of (198)Au. Three months after implantation, the percent area stenosis, neointimal thickness, neointimal area, and vessel injury were analyzed by quantitative histomorphometry. The lifetime radiation doses at a depth of 1 mm were 3.3+/-0.2, 4.7+/-0.5, 7.2+/-0.4, 11.4+/-0.9, and 17.6+/-1.7 Gy for the different activity groups. No dose-response relationship was observed in the radioactive stents with respect to percent area stenosis (P=0.297), mean neointimal thickness (P=0.82), or mean neointimal area (P=0.65). Significantly lower neointima formation and less luminal narrowing was seen in the control group than in the beta-particle-emitting stents (P<0.001). Multilinear regression analysis revealed that only radioactivity made a significant independent contribution to the degree of percent area stenosis (P<0. 001). CONCLUSIONS: Neointima formation in pigs is markedly increased by beta-particle-emitting stents with (198)Au as the radioisotope. This study provides evidence that dosages of 3 to 18 Gy of low-dose-rate beta-particle irradiation via endovascular stents cause pronounced luminal narrowing in the animal model at 3 months.

Animals↗
PubMed2000

RANTES in the postoperative course after liver transplantation.

RANTES (regulated upon activation, normal T-cell expressed and secreted), an inflammatory cytokine, promotes accumulation and activation of leukocytes. In 67 liver transplantations, systemic concentrations of RANTES were correlated to graft survival and incidence of rejection. RANTES levels either increased to highly elevated levels at day 14 (84 +/- 64 ng/ml; group 1; n = 43) or remained within the limit of healthy controls (19 +/- 11 ng/ml at day 14; group 2; n = 24). The 100-day graft function rate was 0.91 in group 1 and 0.63 in group 2 (P = 0.002). The risk ratio for rejection during the first 100 days was increased 2.2-fold in group 2 compared to group 1 (P = 0.02). High postoperative release of RANTES after liver transplantation, a beneficial factor, may reflect a general systemic immunological activation. It can be concluded that high early systemic RANTES levels may play a role in immunological recognition leading to a tolerance of the liver graft.

Adolescent↗