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Biomedical subjects

W Hoffmann

Publications and source records attributed to W Hoffmann.

At least 55 records · Page 3Linked to original sources
PubMed2001

Trefoil factor family-peptides promote migration of human bronchial epithelial cells: synergistic effect with epidermal growth factor.

A process termed "restitution" enables rapid repair of the respiratory epithelium by migration of neighbouring cells. Mucin-associated TFF-peptides (formerly P-domain peptides or trefoil factors) are typical motogens enhancing migration of cells in various in vitro models mimicking restitution of the intestine. The human bronchial epithelial cell line BEAS-2B was used as a model system of airway restitution. The motogenic activities of recombinant human TFF2 as well as porcine TFF2 were demonstrated by in vitro wound healing assays of BEAS-2B cells. TFF2 did not induce phosphorylation of the epidermal growth factor (EGF) receptor. EGF was capable of enhancing the motogenic effect of human TFF2 at a concentration of 3 x 10(-10) M whereas EGF itself (i.e., in the absence of TFF2) did not stimulate migration at this low concentration. Furthermore, TFF2 as well as monomeric and dimeric forms of TFF3 enhanced migration of BEAS-2B cells in Boyden chambers. Motogenic activity of TFF2 was also shown for normal human bronchial epithelial (NHBE) cells in Boyden chambers. These results suggest that TFF-peptides act as motogens in the human respiratory epithelium triggering rapid repair of damaged mucosa in the course of airway diseases such as asthma.

Bronchi↗
PubMed2001

Molecular medicine of TFF-peptides: from gut to brain.

TFF-peptides (i.e. TFF1, TFF2, TFF3; formerly P-domain peptides, trefoil factors) have been established as secretory products typical of the gastrointestinal tract. Their synthesis has recently been recognized in a number of mucin-producing epithelial cells, for example, of the respiratory tract, the salivary glands, the uterus and of the conjunctiva. They have a pivotal role in maintaining the surface integrity of these delicate epithelia as constituents of mucus gels as well as by their anti-apoptotic properties and their motogenic activity modulating cell migratory processes. The latter is important for rapid healing in particular of gastrointestinal and respiratory epithelia by a process termed "restitution". On the other hand, one of these peptides--namely TFF3--has been detected as a new neuropeptide of the human hypothalamo-pituitary axis where it is synthesized in oxytocinergic neurons of the paraventricular and supraoptic nuclei. From there it is transported to the posterior pituitary where it is released into the blood stream. Synthesis of TFF-peptides also occurs pathologically as result to chronic inflammatory diseases, for example of the gastrointestinal tract. Aberrant synthesis of TFF-peptides is observed in many tumors.

Animals↗
PubMed2001

[Radiation exposure in diagnostic radiation: a quantification model for analytic epidemiological studies].

The present paper introduces a model for retrospective assessment of radiation exposure to patients undergoing conventional diagnostic radiography. The model allows for the quantification of relevant organ doses as well as the effective dose from exposures in the time period between 1946 and 1995. The assessment procedure consists of three consecutive steps. The first step uses a set of ideal doses that were measured under optimum conditions. In the second step, we account for the state of radiological technology available at the time of a given exposure. The third step, finally, considers the prevailing standard of radiological practice. Model parameters are derived from a compilation of data from the contemporary radiologic literature as well as from a multitude of historic sources. The three-dimensional matrix of ideal doses and respective correction factors presented here can be readily implemented in the context of analytic epidemiological studies.

Humans↗
PubMed2000

CT-based virtual simulation using the AdvantageSim 4.1. system. Description of reliability and accuracy.

BACKGROUND: CT simulation systems provide integration of CT-based planning target volumes, which allows to operate without the conventional simulator. The aim of our study was the quantitative assessment of the accuracy of field alignment and isocenter position using the new virtual simulation system AdvantageSim 4.1. for different treatment regions. PATIENTS AND METHODS: Twenty-seven patients with prostate cancer, 23 patients with head and neck cancer and 30 lung cancer patients were included in this prospective trial. CT-based virtual simulation was performed to define treatment isocenter position. The linear discrepancies of the digitally reconstructed beam's eye views were compared with the conventional simulation and first treatment verification images. RESULTS: Among all patients the mean difference of isocenter position between conventional and virtual simulation was 3.5 mm. The isocenter displacements ranged from 0 to 6 mm. There was no significant difference in isocenter accuracy between the different treatment regions. CONCLUSIONS: Virtual simulation with AdvantageSim 4.1. is feasible in daily routine and allows to replace conventional simulation for different target volumes with a reliable accuracy of isocenter and field alignment. The beam's eye views allow the precise evaluation of the coverage of the planning target volume and the shielding of organs at risk.

Feasibility Studies↗
PubMed2000

Biological effects of ionizing radiation on human blood compounds ex vivo.

PURPOSE: Blood compounds are irradiated ex vivo to prevent transfusion-associated graft-versus-host-disease. Recently, ex vivo irradiation of re-transfused wound blood has been proposed to prevent metastatic spread in patients with malignant tumors, an issue requiring different dose concepts. To determine effects on blood cells we examined the impact of various doses of ionizing radiation. METHODS: Full blood was irradiated with doses of 10-150 Gy. Potassium, LDH and hemoglobin levels were determined 2 h-96 h after irradiation. The lymphocyte proliferation after irradiation was measured by means of a lymphocyte-transformation assay. The impact of irradiation on mitogen-induced secretion of cytokines was determined by the ELISA technique, and P-selectin expression as an indicator of platelet activation was analyzed by flow-cytometry. RESULTS: Potassium levels increase with aging and irradiation dose. Mitogenic capacity is reduced by over 90% with moderate doses of 10-20 Gy, but a residual proliferation is still detectable up to 50 Gy. No enhancement of extracellular cytokine levels is detectable, but the cytokine release is reduced by radiation. Neither induction of platelet activation nor abrogation of activation has been detected. CONCLUSIONS: Doses of 30-50 Gy abrogate lymphocyte proliferation almost completely. In this range we did not observe severe adverse effects on blood transfusions. Hemolysis might be enhanced when the samples are stored for a longer period after irradiation.

Blood Platelets↗
PubMed2000

Analysis of illicit drugs by nonaqueous capillary electrophoresis and electrochemical detection.

Nonaqueous capillary electrophoresis (NACE) was applied to the determination of illicit drugs. The complete separation of amphetamine, methamphetamine, 3,4-methylene dioxy amphetamine (MDA), 3,4-methylene dioxy methamphetamine (MDMA), mescaline, cocaine and benzoylecgonine was obtained using an acetonitrile based buffer solution containing 10 mM sodium acetate and 1 M acetic acid. Electrochemical detection using a Pt microdisk electrode set to a potential of +1.8 V was found to be selective for MDA, MDMA and mescaline. The detection limits for these compounds were in the low ng/mL range which is between 2 and 3 orders of magnitude lower compared to UV-detection.

3,4-Methylenedioxyamphetamine↗
PubMed2000

Safety and efficacy of interventional occlusion of patent ductus arteriosus with detachable coils: a multicentre experience.

UNLABELLED: In order to define the safety and efficacy of Cook detachable coils for interventional closure of patent ductus arteriosus, we performed a retrospective analysis of all patients who underwent cardiac catheterization in seven centres for intended interventional occlusion of patent arterial duct. From January 1995 until March 1998, cardiac catheterization for intended interventional occlusion of patent arterial duct was performed in 317 consecutive children. Successful placement of at least one coil was achieved in 282 children (89%). The mean diameter of the ductus in children treated with Cook detachable coils was 1.65 mm, mean fluoroscopy time was 10.7 min. Occlusion rates were 62% 10 min after the procedure, 82% at the time of discharge, 91% at 4 months and 95% at late follow-up (2 years). In children with a ductus diameter of < or = 2.5 mm the rate of successful coil deployment was 94% with a 98% occlusion rate at late follow-up. Complications occurred in 11 procedures (3.5%) including haemolysis (3 patients), embolization of a coil to the pulmonary artery (7 patients, 2.3%) and inability to release a coil (1 patient). CONCLUSION: In our opinion, Cook detachable coils are safe and effective especially in the treatment of persistent ductus arteriosus with a diameter < or = 2.5 mm. Due to the low costs these coils appear to be superior to other devices in this subgroup of patients.

Adolescent↗
PubMed2000

Litomosoides sigmodontis in mice: reappraisal of an old model for filarial research.

Onchocerciasis and lymphatic filariasis (LF) are major causes of severe morbidity and considerable socio-economic problems throughout the tropics. Vector control and mass chemotherapy have helped to control these infections in some regions, but the temporary success of such measures argues strongly for the development of vaccines. Success in such a venture will require detailed knowledge of protective immune responses in conjunction with the identification of target antigens. By comparison with other important parasitic infections, such as schistosomiasis and leishmaniasis, work on the development of vaccines for onchocerciasis and LF has been constrained because of the difficulties of producing cyclical and patent filarial infection in laboratory mice. Wolfgang Hoffmann and colleagues here outline the opportunities presented by the rodent filaria Litomosoides sigmodontis for filarial research.

Animals↗
PubMed2000

Analysis of mdm2 and p53 gene alterations in glioblastomas and its correlation with clinical factors.

Malignant gliomas are the most frequent primary brain tumors. Recent studies defined several genetic markers, which might characterize molecular-biological subsets of glioblastomas with probably prognostic implications. To elucidate the involvement of murine-double-minute (mdm)2 gene amplifications and mutations of the tumor suppressor gene p53 in the tumorigenesis of malignant gliomas we analyzed a series of 75 glioblastomas. The p53 mutations occur in one-third of glioblastomas, mdm2 amplifications were found in 13% of cases. Our analysis revealed a hot spot in the p53 gene locus in codon 156, the same point mutation was detected in 4 tumor samples. None of the mdm2 amplified tumors had p53 mutations, supporting the hypothesis, that mdm2 amplifications are alternative mechanisms for p53 inactivation. Patients with p53 mutated tumors were significantly younger characterized by a mean age of 44 years. Additionally association with longer overall survival could be detected for this subgroup of patients. In our study, survival estimation revealed a significant correlation of mdm2 gene amplification with shorter survival time, and support the hypothesis, that mdm2 oncogene activation appears to occur late in tumor progression and may be characteristic as negative prognostic marker.

Adult↗
PubMed2000

Long-term outcome in patients with advanced hilar bile duct tumors undergoing palliative endoscopic or percutaneous drainage.

OBJECTIVE: Advanced tumors of the hepatic duct bifurcation (Klatskin tumors) present problems to the endoscopist in deciding which procedure to use for palliative treatment of the resulting cholestasis--endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD), or both. There are technical difficulties with all forms of treatment for stenoses in the hilar region and intrahepatic bile ducts, and there are as yet no clear data on which type of drainage is feasible or preferable. SUBJECTS: 59 consecutive patients (30 men, 29 women; mean age 71 years) underwent palliative treatment for malignant hilar bile duct tumors of Bismuth stages II-IV during a three-year period (1992-94). METHOD: A retrospective analysis was carried out, and long-term follow-up data were obtained from telephone interviews with the patients, relatives, or referring physicians. RESULTS: The 59 patients were treated using ERCP (n = 20) or PTBD (n = 39). Three died within 30 days, and six were lost to follow-up. Clinically adequate drainage was achieved in 78% (n = 46) of the total patient group. Patient survival was a median of six months (range 0.5-38), and was slightly longer when the primary drainage procedure was successful (7.5 months). Initial complications occurred in 11% after ERCP and in 33% after PTBD, with a 30-day mortality of 5%. After the initial intervention, five patients who received ERCP treatment had to be switched to PTBD during the longer-term course. Three of these five patients died within 30 days of the PTBD insertion. CONCLUSIONS: Palliative treatment in patients with advanced Klatskin tumors is still suboptimal, even when combined endoscopic and percutaneous techniques are used in the same institution, allowing treatment to be tailored to the individual patient's needs. There is therefore a need for improvements in existing forms of treatment, as well as for the development of new forms of treatment.

Adult↗
PubMed2000

Co-localization of TFF3 peptide and oxytocin in the human hypothalamus.

TFF-peptides (formerly P domain peptides, trefoil factors) are typical secretory products of many mucous epithelial cells. TFF3 is also synthesized in the hypothalamus and has anxiolytic or anxiogenic activities when injected into the rat amygdala. Here we show by immunohistochemistry that TFF3 is localized to a distinct population of neurons of the human hypothalamic paraventricular and supraoptic nuclei. Generally, TFF3-positive cells are co-localized in oxytocin-producing cells and not in vasopressin-producing cells. Relatively large amounts of TFF3-but not TFF1 and TFF2-are present in the posterior lobe of the human pituitary, where it is probably released into the bloodstream. Furthermore, TFF3 was also detectable in human postmortem cerebrospinal fluid.

Blotting, Western↗
PubMed2000

Measurement of the dose components of fast and thermal neutrons and photons from a 0.1 mg 252Cf source in water for brachytherapy treatment planning.

The use of 252Cf in brachytherapy is expected to be more effective with the therapy of bulky tumors than the conventional therapy with photons. For treatment planning a code developed for calculation of gamma dose was used to generate the dose distributions of fast and 10B enhanced thermal neutrons and photons. Dose distributions of these components measured with ionization chambers and a GM counter were fitted to analytical functions as required by the modified treatment planning program. A comparison of these experimental results and the treatment planning output indicate good agreement. Therefore, the program may be used to optimize the brachytherapy procedure considering all three dose components. A realistic case of a patient being treated with conventional brachytherapy has been used to calculate the dose distribution that would be obtained by use of the 252Cf source.

Brachytherapy↗
PubMed2000

Electric field distributions in a phased-array applicator with 12 channels: measurements and numerical simulations.

In this paper we examine the SIGMA-Eye hyperthermia applicator (BSD Medical Corp., Salt Lake City, Utah 84119) with respect to the control of electric field distributions. This applicator is equipped with 12 pairs of antennas fed by 12 amplifiers, allowing the individual adjustment of phase and power for each of them. Measurements were conducted using phantoms with well-defined electrical properties. Specific electro-optical sensors, capable of measuring both electric field amplitudes and phases, have been developed, and a system for data acquisition and analysis has been set up. In its initial state the applicator appeared not to be satisfactorily matched at 100 MHz for the phantom used, with return losses up to 20% in power. By tuner readjustments we achieved values below 5%. For various settings of the amplifiers' control parameters we measured field distributions, both in the phantom and in the surrounding water bolus. The experimental results were compared with numerical simulations based on finite difference and finite element methods. Measured and calculated electric fields exhibit deviations of 10% on average, allowing, in principle, a satisfactory prediction of fields by numerical simulations or as well by on-line measurements at selected locations of the applicator at antenna proximity. However, to obtain this satisfactory agreement a modification of the control parameters in the calculations (phases and amplitudes in the feed points of the antennas) was necessary. The origin of these problems is mainly attributed to cross-talk phenomena and other characteristics of the transforming network, which need to be scrutinized further for a full understanding.

Computer Simulation↗
PubMed1999

Structure of the Xenopus laevis TFF-gene xP4.1, differentially expressed to its duplicated homolog xP4.2.

TFF-peptides (formerly P-domain peptides, trefoil factors) represent major secretory products of mucous epithelia in mammals and amphibia. The nucleotide sequence of a large portion of a gene encoding the TFF-peptide xP4.1 from Xenopus laevis and its genomic organization were determined in the present study. The peptide xP4.1 containing four TFF-domains is thought to represent the functional frog homolog of human TFF2 (formerly hSP). The xP4.1 gene analyzed spans a region of about 7 kb and consists of six exons. Each TFF-domain is encoded by a single exon flanked by type 1 introns typical of shuffled modules. The 5'-upstream region contains a TATA-box, and potential binding sites for hepatocyte nuclear factor 3 and AP-1. Furthermore, the cDNA sequence of a transcript named xP4.2 with 91% similarity to xP4.1 is presented. RT-PCR analysis revealed that xP4.1 and xP4.2 genes are differentially expressed. xP4.1 transcripts are detectable only in the stomach, but not in the esophagus, whereas xP4.2 transcripts are found both in the esophagus and in the stomach with a descending gradient from fundus to antrum.

Amino Acid Sequence↗
PubMed1999

Radiation sensitivity of human squamous cell carcinoma cells in vitro is modulated by all-trans and 13-cis-retinoic acid in combination with interferon-alpha.

PURPOSE: Retinoids and interferon-alpha (IFN-alpha) have been shown to exert antiproliferative and radiosensitizing effects. The present study was designed to determine differential effects of retinoids in combination with IFN-alpha on radiation toxicity of 5 human squamous cell carcinoma (SCC) cell lines. METHODS AND MATERIALS: Using clonogenic assays, the effects of all-trans (ATRA), 13-cis-retinoic acid (13cRA), and IFN-alpha on radiation toxicity were analyzed. Basal mRNA expression of the cytoplasmic retinoic acid binding protein, CRABP I, was determined in retinoid-sensitive and -insensitive cell lines by reverse transcriptase/polymerase chain reaction (RT-PCR). RESULTS: Treatment with ATRA, 13cRA, or IFN-alpha resulted in a cell line-specific inhibition of clonogenic survival. A comparison of retinoid-sensitive and insensitive cells revealed that retinoid sensitivity seems to be dependent on the basal expression level of CRABP I. ATRA, 13cRA, and IFN-alpha alone or in combination altered radiation sensitivity by affecting predominantly the alpha-component of the linear-quadratic dose-response curve. Likewise, depending upon the treatment condition the surviving fraction at 2 Gy (SF2) was decreased cell line-specifically. Combined treatment with ATRA or 13cRA and IFN-alpha markedly enhanced radiation cytotoxicity. CONCLUSION: These in vitro data indicate that the combined treatment with retinoids, IFN-alpha, and ionizing radiation could be beneficial for patients presenting with SCC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

The chromosome-based challenge assay using fluorescence in situ hybridization: a possible test for increased cancer susceptibility.

UNLABELLED: The challenge assay is a cytogenetic approach to measure the repair competence of cells. For in vitro studies, human lymphocytes are exposed to different substances and are irradiated simultaneously. To investigate subjects exposed occupationally or environmentally, untreated blood samples are directly irradiated without any further treatment. Certain substances like heavy metals reveal carcinogenic potential without well defined mechanism of action. While they are not mutagenic they may have an effect on DNA repair capacity. The challenge assay was successfully applied in vitro experiments with cadmium to detect an interaction of this heavy metal with the repair of X-ray-induced chromosome breaks. CdCl(2) alone had no effect on the formation of chromosome aberrations (CA), not even in the cytotoxic concentration (50 microM). However, cadmium showed an effect on the number of chromosomal rearrangements (CR) after X-ray challenge. For 0.5 microM CdCl(2), CA frequencies were significantly elevated compared to the rates for X-rays alone. For the two higher concentrations the rates showed a slight additional increase. Hence, the challenge assay appears suitable to test for chromosomal sensitivity induced by toxicants. Subsequently, a study of styrene exposed workers was initiated to address the question whether styrene exposure has an influence on the DNA repair. In addition, we investigated whether a polymorphism of genes coding for phase II detoxifying enzymes glutathione-S-transferases GSTM1 and GSTT1 had an influence on chromosomal sensitivity. First and preliminary data are presented. While there is a correlation of the rate of CR with cumulative lifetime exposure of styrene, the most recent styrene exposure had no effect. 'At risk' genotypes with higher incidence of CA could not be identified at this stage of the ongoing study. CONCLUSION: the challenge assay is able to detect enhanced susceptibility for CR caused by genetic predisposition for DNA repair deficiency. Our data indicate that environmental or occupational exposure to certain substances can interfere with DNA repair processes. As the process of induction of CR is associated with carcinogenesis, the challenge assay may provide a valuable biomarker for cancer epidemiology studies.

Cadmium↗