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Biomedical subjects

T Hofer

Publications and source records attributed to T Hofer.

At least 19 recordsLinked to original sources
PubMed2006

Dose-controlled exposure of A549 epithelial cells at the air-liquid interface to airborne ultrafine carbonaceous particles.

The geometry of commercially available perfusion chambers designed for harbouring three membrane-based cell cultures was modified for reliable and dose-controlled air-liquid interface (ALI) exposures. Confluent A549 epithelial cells grown on membranes were integrated in the chamber system and supplied with medium from the chamber bottom. Cell viability was not impaired by the conditions of ALI exposure without particles. Expression of the inflammatory cytokines interleukin 6 and interleukin 8 by A549 cells during ALI exposure to filtered air for 6h and subsequent stimulation with tumor necrosis factor was not altered compared to submersed controls, indicating that the cells maintained their functional integrity. Ultrafine carbonaceous model particles with a count median mobility diameter of about 95+/-5 nm were produced by spark discharge at a stable concentration of about 2 x 10(6) cm(-3) and continuously monitored for accurate determination of the exposure dose. Delivery to the ALI exposure system yielded a homogeneous particle deposition over the membranes with a deposition efficiency of 2%. Mid dose exposure of A549 cells to this aerosol for 6h yielded a total particle deposition of (2.6+/-0.4) x 10(8) cm(-2) corresponding to (87+/-23) ng cm(-2). The 2.7-fold (p < or = 0.05) increased transcription of heme oxygenase-1 indicated a sensitive antioxidant and stress response, while cell viability did not reveal a toxic mechanism.

Aerosols↗
PubMed2005

Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging.

Mutations in mitochondrial DNA (mtDNA) accumulate in tissues of mammalian species and have been hypothesized to contribute to aging. We show that mice expressing a proofreading-deficient version of the mitochondrial DNA polymerase g (POLG) accumulate mtDNA mutations and display features of accelerated aging. Accumulation of mtDNA mutations was not associated with increased markers of oxidative stress or a defect in cellular proliferation, but was correlated with the induction of apoptotic markers, particularly in tissues characterized by rapid cellular turnover. The levels of apoptotic markers were also found to increase during aging in normal mice. Thus, accumulation of mtDNA mutations that promote apoptosis may be a central mechanism driving mammalian aging.

Aging↗
PubMed2004

[The incompetent perforators in the development of varicose veins].

AIM: Does it make sense to dissect any incompetent perforator which is found with the color duplex sonography during the preoperative mapping of varicose veins? PATIENTS AND METHODS: 221 patients with recurrent varicose veins were examined by color duplex sonography for new transfascial insufficiencies. RESULTS: Among 371 transfascial insufficiencies there were 61 (16.4%) incompetent perforators. 31 isolated perforators (25 (9.4%) of 266 legs isolated perforators of the thigh,6 (2.3%) isolated perforators of the calf) were exclusively responsible for the recurrence of varicose veins. 13 incompetent perforators of the calf were associated with additional transfascial insufficiencies,as well as superficial and in 3 cases even deep varicose veins, resulting at an advanced clinical stage (CEAP-classification C3-CS). CONCLUSION: The dissection of the thigh perforators and the rare isolated perforators of the calf may help to protect from possible and early recurrence.

Humans↗
PubMed2002

[Malignant skin tumours in a private dermatology practice. A quality control study].

BACKGROUND AND OBJECTIVE: The campaign for early detection of malignant melanoma and the increase in people with photodamaged skin have a remarkable influence on the daily dermatological routine. Could these factors lead to the introduction of quality control in a private dermatology practice? PATIENTS AND METHODS: Over a period of one year the diagnoses of all patients were registered. The clinical diagnosis of any skin tumour undergoing surgical removal was compared with the final histopathological diagnosis. RESULTS: 56% of 3004 diagnoses involved females; 44%, males. In 40.5%, the possibility of a pigmented or non-pigmented skin tumour was raised. 49% of the 291 tumours removed were malignant (107 basal cell carcinoma, 20 squamous cell carcinoma, 16 melanoma) while 11.7% were malignant precursor lesions. 48% of 44 melanocytic naevi with clinical atypia showed histopathological dysplasia but none were a malignant melanoma. No cancers were detected among 59 clinically benign tumors. In 71.8% of cases, the clinical diagnosis agreed with the result of the histopathological examination. CONCLUSIONS: This study shows, in concordance with literature, that a dermatologist can provide high quality treatment and prophylaxis of malignant skin tumours. With an optimal cost-performance ratio, he or she is the most competent partner for patients and health insurance companies.

Basal Cell Carcinoma↗
PubMed2002

[Myerson nevus as a primary patch of Gibert pityriasis rosea. A case report].

UNLABELLED: There are only few articles in literature which discuss the association between Meyerson's naevi and Pityriasis rosea. And when so, the discussion is done in a controversial way. Here an 18 year old man is presented who visits the outpatient clinic. He has a ten day history of a solitary Meyerson's naevus on his back. Over the next three weeks this naevus will develop to the typical herold patch followed by the classical exantheme of Pityriasis rosea. CONCLUSION: Halo dermatitis associated with Pityriasis rosea don't represent Meyerson's naevi. But they reflect the rare "nevocentric" property of a not so rare dermatose.

Adolescent↗
PubMed2002

The effectiveness of budesonide therapy for Crohn's disease.

AIM: To assess the effectiveness and safety of budesonide in comparison to corticosteroids, 5-aminosalicylic acid (5-ASA), or placebo for inducing remission of active Crohn's disease and for maintaining remission. STUDY SELECTION CRITERIA: Randomized controlled trials comparing budesonide to corticosteroids, 5-ASA products or placebo were included. Trials had to report on the effectiveness of treatment (defined as decreasing or maintaining Crohn's Disease Activity Index, CDAI, scores < or = 150) or adverse events. DATA ANALYSIS: After assessing the validity of study design and independent, duplicate data extraction from selected trials, summary relative risks (RR) were calculated for each outcome. A test of heterogeneity was also calculated for each outcome using a random effects model. RESULTS: Budesonide was more likely to induce remission than placebo (RR=1.82, 95% CI: 1.15-2.88) or 5-ASA (RR=1.73, 95% CI: 1.26-2.39), although only one trial compared budesonide to 5-ASA products. Although budesonide induced remission less frequently than conventional corticosteroids (RR=0.87, 95% CI: 0.76-0.995), there was no significant difference between conventional corticosteroids and budesonide for inducing remission among patients with a low disease activity (initial CDAI=200-300). Budesonide was significantly less likely to cause corticosteroid-associated adverse events than conventional corticosteroids (RR=0.65, 95% CI: 0.53-0.80). No significant difference in total adverse events or corticosteroid-associated adverse events was demonstrated between budesonide and 5-ASA or placebo. CONCLUSION: Budesonide is significantly more effective than placebo or 5-ASA for inducing remission of active Crohn's disease. Although budesonide is 13% less effective for the induction of remission in active Crohn's disease than conventional corticosteroids, it is less likely to cause corticosteroid-related adverse effects. Budesonide is ineffective in maintaining remission.

Anti-Inflammatory Agents↗
PubMed2002

Palmar digital vein thromboses: their different expressions.

There have only been a few reports about thrombotic events in the volar digital veins. The observation of 2 such cases gives reason to discuss this rare symptomatology. Thrombosis of the digital veins can be categorised into three subtypes: the first shows clinical similarity to thrombotic events in veins or varicose veins of the limbs and may be related to a hypercoagulable state; the second group develops in a pre-existing normal vein or an acquired venous cavernoma and does not show clinical or histological signs of inflammation; the third category resembles Mondor's disease and may be named Mondor's phlebitis of the finger; histopathological examination has yet to be done. In any case of thrombosis of the volar digital veins, an inherited or acquired hypercoagulable state must be ruled out.

Adult↗
PubMed2001

Mammalian PASKIN, a PAS-serine/threonine kinase related to bacterial oxygen sensors.

The PAS domain is a versatile protein fold found in many archaeal, bacterial, and plant proteins capable of sensing environmental changes in light intensity, oxygen concentration, and redox potentials. The oxygen sensor FixL from Rhizobium species contains a heme-bearing PAS domain and a histidine kinase domain that couples sensing to signaling. We identified a novel mammalian PAS protein (PASKIN) containing a domain architecture resembling FixL. PASKIN is encoded by an evolutionarily conserved single-copy gene which is ubiquitously expressed. The human PASKIN and mouse Paskin genes show a conserved intron-exon structure and share their promoter regions with another ubiquitously expressed gene that encodes a regulator of protein phosphatase-1. The 144-kDa PASKIN protein contains a PAS region homologous to the FixL PAS domain and a serine/threonine kinase domain which might be involved in signaling. Thus, PASKIN is likely to function as a mammalian PAS sensor protein.

Amino Acid Sequence↗
PubMed2001

Dissecting hypoxia-dependent and hypoxia-independent steps in the HIF-1alpha activation cascade: implications for HIF-1alpha gene therapy.

The heterodimeric hypoxia-inducible factor (HIF)-1 is a master transcriptional regulator of oxygen homeostasis and a possible target for gene therapy of ischemic disease. Although the role of oxygen concentration in HIF-1a protein stabilization is well established, it is less clear whether and how oxygen-regulated mechanisms contribute to HIF-1a protein modifications, nuclear translocation, heterodimerization with the b-subunit, recruitment of cofactors, and gene trans-activation. Because the HIF-1a protein is proteolytically degraded under normoxic conditions, we established two HeLa Tet-Off cell lines (HT42 and HT43), which inducibly overexpress high levels of HIF-1a under normoxic conditions, allowing to distinguish hypoxia-dependent from hypoxia-independent activation mechanisms. Using these cells, we found that normoxically induced HIF-1a is localized to the nucleus, binds DNA, and trans-activates reporter and endogenous target genes. The levels of p53 expression remained unaffected. The MAP kinase inhibitor PD98059 attenuated HIF-1a protein modifications and trans-activation ability but not protein stabilization and DNA-binding activity. Because overexpressed HIF-1a is fully localized to the nucleus but displays only partial DNA-binding and trans-activation activity, mitogen-activated protein kinase-dependent phosphorylation might be required for full HIF-1 activation. HIF-1a protein was also overexpressed in vivo, following the transplantation of HT42 cells into nude mice, demonstrating the feasibility of HIF-1a gene transfer.

Animals↗
PubMed2001

[Acne inversa: a dapsone-sensitive dermatosis].

Acne inversa is a chronic disease with a major impact on the quality of life. Therapeutic options were long restricted to local disinfectants and systemic antibiotics, as well as repeated incision and drainage which produce only short term benefits. Retinoids, antiandrogens and radiation therapy are only partially successful. The best approach appears to be surgical removal of the entire apocrine sweat gland apparatus. Dapsone is used in dermatology to treat inflammatory dermatoses such as dermatitis herpetiformis and pyoderma gangrenosum, and was formerly the treatment of choice for acne conglobata. We report its successful use in acne inversa. Five female patients aged 23-40 years with acne inversa for a mean of 9.6 years were included. All patients showed an almost complete resolution of their symptoms within 2-4 weeks. All patients rated the treatment results with dapsone as good or very good. The treatment was well tolerated and no important side effects occurred. Because of its lack of teratogenicity, dapsone may be the most favorable treatment option in young women with acne inversa.

Acne Vulgaris↗
PubMed2001

Hypoxia affects expression of circadian genes PER1 and CLOCK in mouse brain.

The key elements of circadian clockwork and oxygen homeostasis are the PAS protein family members PER and CLOCK and hypoxia-inducible factor 1alpha (HIF-1alpha). The PAS domain serves as an interface for protein-protein interactions. We asked whether a cross-talk exists between the PAS components of hypoxic and circadian pathways. We found several isoforms of PER1 protein that exhibit tissue-specific size differences. In the mouse brain, a predominantly nuclear 48 kDa isoform that followed a daily rhythm was observed. The 48 kDa form was found in the nuclear fractions derived from mouse liver, Swiss3T3 fibroblasts, and N2A neuroblastoma cells. In mouse kidney and human 293 kidney cells, a 55 kDa PER1 form was detected. CLOCK was observed as a predicted 100 kDa protein in rat-1 cells and in all analyzed mouse tissues including brain, liver, kidney, and spleen. In contrast to PER1, CLOCK protein expression was not rhythmic. Exposure to hypoxia led to increased PER1 and CLOCK protein levels in mice. Based on coimmunoprecipitation experiments that showed protein-protein interaction between PER1 and the alpha subunit of HIF-1, we suggest that these hypoxic effects may be modulated by HIF-1alpha.-Chilov, D., Hofer, T., Bauer, C., Wenger, R. H., Gassmann, M. Hypoxia affects expression of circadian genes PER1 and CLOCK in mouse brain.

3T3 Cells↗
PubMed2000

Chirality and circular dichroism of oriented molecules and anisotropic phases

The results of the "Chirality measurement" circular dichroism along different viewing directions within molecules and phases-the anisotropy of circular dichroism can give suitable information in order to check helicity rules or to analyze the suprastructural chirality of films of organic materials, respectively. These results of the ACD spectroscopy (the CD of anisotropic phases and oriented molecules) show that in an oriented state different information about "chirality" will be gained from different viewing directions. ACD measurements of alpha,beta-unsaturated ketosteroids, TADDOLes and binaphthol derivatives were analyzed. The chiral induction of cholesteric phases, the helical twisting power, is introduced as another chirality measurement which may possibly be a new relative method for the determination of the absolute configuration. Copyright 2000 Wiley-Liss, Inc.

Journal Article↗
PubMed2000

Magnetic phagosome motion in J774A.1 macrophages: influence of cytoskeletal drugs.

The role of the different cytoskeletal structures like microfilaments (MF), microtubuli (MT), and intermediate filaments (IF) in phagosome motion is unclear. These cytoskeletal units play an important role in macrophage function (migration, phagocytosis, phagosome transport). We investigated ferromagnetic phagosome motions by cell magnetometry. J774A.1 macrophages were incubated with 1.3-microm spherical magnetite particles for 24 h, after which more than 90% of the particles had been phagocytized. Phagosome motions can be caused either by the cell itself (relaxation) or by applying magnetic twisting forces, yielding cell stiffness and viscoelastic properties of the cytoskeleton. Apparent viscosity of the cytoplasm was non-Newtonian and showed a shear-rate-dependent power law behavior. Elastically stored energy does not force the magnetic phagosomes back to their initial orientation: 57% of the twisting shear was not recoverable. Cytoskeletal drugs, like Cytochalasin D (CyD, 2 - 4 microM), Colchicine (CoL, 10 microM), or Acrylamide (AcL, 40 mM) were added in order to disturb the different cytoskeletal structures. AcL disintegrates IF, but affected neither stochastic (relaxation) nor directed phagosome motions. CyD disrupts MF, resulting in a retarded stochastic phagosome motion (relative decay 0.53 +/- 0.01 after 5 min versus 0.34 +/- 0.01 in control), whereas phagosome twisting shows only a small response with a 9% increase of stiffness and a small reduction of recoverable strain. CoL depolymerizes the MT, inducing a moderately accelerated relaxation (relative decay 0.28 +/- 0.01 after 5 min) and a 10% increase of cell stiffness, where the pure viscous shear is increased and the viscoelastic recoil is inhibited by 40%. Combining the two drugs conserves both effects. After disintegrating either MF or MT, phagosome motion and cytoskeletal stiffness reflect the behavior of either MT or MF, respectively. The results verify that the dominant phagosome transport mechanism is MF-associated. MT depolymerization by CoL induces an activation of the F-actin synthesis, which may induce an accelerated relaxation and an increase of stiffness. Cell mechanical properties are not modulated by MF depolymerization, whereas MT depolymerization causes a loss of viscous resistance and a loss of cell elasticity. The mean energy for stochastic phagosome transport is 5*10(-18) Joules and corresponds to a force of 7 pN on a single 1.3-microm phagosome.

Acrylamide↗
PubMed2000

Immunologic characterization of normal human pleural macrophages.

Human pleural macrophages (PLM) have been studied in effusions, but little is known about normal human PLM. We therefore analyzed resting human PLM recovered by lavage before lobe resection from patients with a central bronchial tumor, not involving the pleura, and from patients with pulmonary chondroma, intrapulmonary hemorrhage, and pneumothorax. Analysis of surface antigens, phagocytosis capacity, and cytokine production was done in comparison to the regular CD14(++) blood monocytes and the recently described blood monocyte subset CD14(+)CD16(+) monocytes. When defining fluorescence intensity for the various markers on CD14(++) monocytes as 100%, the PLM gave the following pattern: CD14, 45%; CD32, 200%; CD64, 72%; CD11b, 128%; CD33, 74%; CD54, 299%; and HLA-DR, 1,906%. When CD16 on the CD14(+)CD16(+) monocytes was set as 100%, the level of CD16 expression on PLM was 7.7%. Taken together, when compared to blood monocytes, PLM appear to represent a cell-type intermediate of regular CD14(++) monocytes and the CD14(+)CD16(+) subset. In functional studies, we demonstrate that PLM can perform efficient Fc-receptor-mediated phagocytosis of antibody-coated sheep red blood cells. Compared with blood monocytes, the capacity of PLM to produce tumor necrosis factor is similar, but a striking finding in PLM was the constitutive interleukin-10 messenger RNA expression that could not be substantially increased by lipopolysaccharide stimulation. This first characterization of normal, noneffusion human PLM can form the basis for a better interpretation of findings in malignant and inflammatory exudates.

Animals↗
PubMed1999

Characterization of the Escherichia coli CcmH protein reveals new insights into the redox pathway required for cytochrome c maturation.

The CcmH protein of Escherichia coli is encoded by the last gene of the ccm gene cluster required for cytochrome c maturation. A mutant in which the entire ccmH gene was deleted failed to synthesize both indigenous and foreign c-type cytochromes. However, deletion of the C-terminal hydrophilic domain homologous to CycH of other gram-negative bacteria affected neither the biogenesis of indigenous c-type cytochromes nor that of the Bradyrhizobium japonicum cytochrome c550. This confirmed that only the N-terminal domain containing a conserved CXXC motif is required in E. coli. PhoA fusion analysis showed that this domain is periplasmic. Site-directed mutagenesis of the cysteines of the CXXC motif revealed that both cysteines are required for cytochrome c maturation during aerobic growth, whereas only the second cysteine is required for cytochrome c maturation during anaerobic growth. The deficiency of the point mutants was complemented when 2-mercapto-ethanesulfonic acid was added to growing cells; other thiol compounds did not stimulate cytochrome c formation in these strains. We propose a model for the reaction sequence in which CcmH keeps the heme binding site of apocytochrome c in a reduced form for subsequent heme ligation.

Bacterial Proteins↗
PubMed1999

32P-postlabeling high-performance liquid chromatography (32P-HPLC) adapted for analysis of 8-hydroxy-2'-deoxyguanosine.

8-Hydroxy-2'-deoxyguanosine (8-OH-dG) is a promutagenic lesion in DNA caused by reactive oxygen species. It normally exists at a level of 0.1-1 per 10(5) 2'-deoxyguanosines (dG). To analyze the lesion in easily obtainable biological samples, a very sensitive analytical method is required. The method should also handle the problem with potential oxidation of dG to 8-OH-dG during workup and analysis. 32P-postlabeling high-performance liquid chromatography (32P-HPLC) is an analytical method previously used to analyze lipophilic DNA adducts at levels as low as 1 per 10(9) normal nucleotides when analyzing microgram amounts of DNA. This method was adapted for analysis of 8-OH-dG. The aim was to develop an analytical method that provided a high sensitivity and good reproducibility, prevented oxidation of dG present in samples to 8-OH-dG, was capable of analyzing DNA from very small samples and still offered high sample throughput and ease of use. In analysis of calf thymus DNA, the method had a detection limit of 0.1 8-OH-dG per 10(5) dG when 1 microgram of DNA was used. The standard deviation of repeated analyses of the same sample was +/-10% and the result corresponded well with the established analytical method using HPLC with electrochemical detection. 32P-HPLC is sensitive enough to enable analysis of low levels of 8-OH-dG in biological samples such as small volumes of blood, needle biopsies and tissue swabs. It also substantially reduces oxidation of dG to 8-OH-dG during sample workup and analysis.

8-Hydroxy-2'-Deoxyguanosine↗