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Biomedical subjects

T Herrmann

Publications and source records attributed to T Herrmann.

At least 19 recordsLinked to original sources

[Positron emission tomography (PET) in oncology: a part of medical therapeutic expertise].

Early inclusion of positron emission tomography (PET) in the stepwise oncological diagnosis improves tumor staging and can make further costly diagnostic and inadequate therapeutic measures superfluous. The advantage of this method, in answering the many questions that arise, has been supported by an extensive literature and analysis of interdisciplinary data. Its use is therefore demanded by doctors working in oncology. Surgeons and radiotherapists demand PET studies before local treatment is started so that patients with advanced-stage cancer are spared invasive local therapeutic measures. Oncologists take advantage of PET"s potential to administer stage-related chemotherapy and provide evidence of its efficacy. Expensive treatment regimens can be immediately tested for their efficacy and, if ineffective, can be replaced by a more suitable combination of chemotherapeutic agents. For this purpose combined PET and CT can be considered the (future) standard for oncological diagnosis. Manufacturers have already positioned themselves to provide PET only as part of combined PET/CT equipment. If these advances are not used, patients are deprived of optimal treatment. Furthermore, PET provides considerable potential for cost savings by avoiding expensive measures that do not prolong life. Responsible use of these resources within the health service system requires the early use of PET in the staging of diagnostic methods so that therapeutic options can be weighed through interdisciplinary consultation. The patient can thus be given optimal information and included in therapeutic decisions. It is our obligation as doctors to demand from the decision makers that PET equipment be provided for use in accordance with correct indications and to reimburse the costs as is already the case in other parts of Europe.

Cross-Cultural Comparison↗

Status of the PCDD and PCDF contamination of commercial milk caused by milk cartons.

Within the scope of this study, possible migration of polychlorinated dibenzodioxins and -furans (PCDDs/PCDFs) from cartons (produced using bleached cardboard) into cow's milk was investigated. Three different types of carton were examined. The milk samples were taken at different times of storage and analysed for PCDDs/PCDFs. In contrast to a similar study carried out in 1990, the I-TEQ-results of all cartons analysed may be considered very low. No significant migration of toxic (2,3,7,8-chlorine-substituted) PCDDs/PCDFs could be observed. This is due to the very low PCDD/PCDF concentrations in modern cardboards as a result of the elemental chlorine-free (ECF) bleaching processes used. As far as the milk samples are concerned, no influence of the cardboards (according to the I-TEQ data) could be ascertained. I-TEQ concentrations in milk did not noticeably change during storage times of three, six and eight days. The I-TEQ-data obtained for all milk samples was found to be in the range typical of background concentrations in cow's milk in Germany. Although 1,2,7,8-TCDF is not included in the calculation of the TEQ (no 2,3,7,8-chlorine-substitution), analysis of this congener in cardboard samples was also carried out as a matter of general interest for cardboard investigations and an indicator of pulp bleaching with free chlorine.

Animals↗

Contamination of the alluvial plain, feeding-stuffs and foodstuffs with polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (DL-PCBs) and mercury from the River Elbe in the light of the flood event in August 2002.

Meadow soils, feeding-stuffs and foodstuffs from the alluvial plain of the river Elbe were analyzed in respect of PCDD/Fs, DL-PCBs and mercury with a view to assessing the consequences of the extreme flood of August 2002. The PCDD/F concentrations in the soils range from 3 to 2100 ng WHO-TEQ/kg dm, and for the DL-PCBs the range was 0.32 to 28 ng WHO-TEQ/kg dm. On the basis of established threshold values >40% of the areas are only fit for restricted usage. Mercury concentrations range from 0.11 to 17 mg/kg dm, whereby the action value of 2 mg/kg dm is exceeded in about 50% of the soil samples. A cumulative memory effect from past floods rather than a recent contamination from August 2002 is documented. Soils taken from behind broken dykes showed significantly lower concentrations. Grass, hay and grass silage originating from pasture land in Lower Saxony were taken before and immediately after the flooding. PCDD/Fs range from 0.29 to 16 ng WHO-TEQ/kg, the maximum permitted value of 0.75 ng WHO-TEQ/kg was exceeded in about 50% of the samples. Muscle-tissue from cattle, sheep, lamb and a roe deer as well as untreated milk from individual cows returned values ranging from 0.76 to 5.9 pg WHO-PCDD/F-TEQ/g fat, and 10% of the samples returned values higher than the permitted maximum of 3 pg WHO-PCDD/F-TEQ/g fat. The action value of 2 pg WHO-PCDD/F-TEQ/g fat was exceeded in 33% of the samples. No direct connection between these results and the effects of the flood could be established. A major input path for PCDD/Fs is the tributary Mulde, which discharges contaminated sediments from its catchment area into the Elbe.

Animal Feed↗

Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma -- CapRI: study protocol [ISRCTN62866759].

UNLABELLED: After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation. DESIGN: The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrollment. DISCUSSION: The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers.

Adenocarcinoma↗

[Human biomonitoring investigations of organochlorine compounds -- PCB, DDE, HCB, beta- and gamma-HCH, PCDD/PCDF, Dioxin-like PCB's and polybrominated biphenyl ethers].

Although PCB and PCB-containing materials are not processed for a long time, PCB is under discussion again and again caused by the pollution of indoor environments. To objectify the discussion, the dates of the PCB-biomonitoring, the organochlorine-compounds (DDE, HCB, beta-/gamma -HCH, PCDD/PCDF) and the polybrominated biphenyl ethers concerning the investigations within the project "Sentinel Health Departments" in Baden-Wurttemberg are represented. Additionally results from children from Kazakhstan (Aral-Sea area) and from teachers which are working in PCB polluted schools as well as from a long term investigated test person are reported. Blood concentrations of the following compounds decreased from 1996/97 to 2002/03: the sum of the concentration of PCB 138,153 and 180 decreased from 0.46 microg/L to 0.20 microg/L, DDE from 0.32 microg/L to 0.17 microg/, HCB from 0.20 microg/L to 0.08 microg/L, beta-HCH below the level of detection, I-TEQ NATO to 4.8 pg/g blood fat, TEQ WHO (without PCB) to 5.5 pg/g blood fat, PCB 126 to 18,8,pg/g blood fat and PCB 169 to 12.8 pg/g blood fat. The influence of breast feeding and the gender on the level of the pollution is conspicious. No local correlations were found in Baden-Wurttemberg, but they were found in comparison with the results of Kazakhstan (Aral-Sea area). The difficulty to produce time series while the analyzing pollutants are more and more decreasing, as well as the change of the calculation base of the summation of parameters like I-TEQ NATO to TEQ WHO are discussed.

Adult↗

HJV gene mutations in European patients with juvenile hemochromatosis.

A large variety of mutations within the genes encoding hepcidin (HAMP) and hemojuvelin (HJV) have been identified in patients with the severe iron overload disorder juvenile hemochromatosis (JH). The aim of the present study was to evaluate the molecular background of JH in patients from central parts of Europe. Sequence analyses of HAMP and HJV were performed in seven JH patients from six families from Germany, Slovakia, and Croatia. For detection of the G320V mutation in HJV, a rapid polymerase chain reaction-based assay was developed. No mutations were found within the HAMP gene. Six of seven (86%) JH patients carried at least one copy of the G320V mutation within the HJV gene. Four of these patients were homozygous for the G320V mutation. In addition, two novel HJV mutations were identified (C119F and S328fsX337). Taken together, the present study demonstrates that molecular analysis of the HJV gene is a powerful tool for an early and reliable diagnosis of JH. As in affected patients from Greece, the G320V mutation seems to be widely distributed among JH patients from central parts of Europe. Therefore, detection of the G320V mutation could identify the majority of JH cases from these regions non-invasively.

Adolescent↗

Does long term residency near industry have an impact on the body burden of polychlorinated dibenzo-p-dioxins, furans, and polychlorinated biphenyls in older women?

BACKGROUND: For the retrospective study of environment and health linkages biomarkers of exposure are required. Polychlorinated dibenzo-dioxins and furans (PCDD/F) and polychlorinated biphenyls (PCBs) have been useful markers in some settings. This is the first study of PCDD/F body burden in a population based sample from the UK. AIMS AND METHODS: The authors aimed to investigate whether long term residents close to a heavy chemical industrial complex (Teesside, UK) had a higher body burden and distinct pattern of PCDD/F and PCBs. We measured current levels of PCDD/F and PCBs in a population based sample of older women (mean 64 years, range 42-79 years). Forty women were recruited, 20 living near (zone A: 0.1-2.7 km) and 20 distant (zone C: 5-40 km) from industry during 2000-03. The authors ascertained occupational exposure to lung carcinogens, residential history, consumption of local produce, breast feeding, diet, and height and weight. RESULTS: The mean body burden measured on lipid basis in ng/kg for the whole sample was: WHO-TEQ (PCDD/Fs): 29.9, 2378TCDD: 4.0, PCB 118:16200, PCB156: 13100. Body burdens were similar to others reported from industrialised countries, except that mean 2378TCDD was slightly higher. Mean ages, body mass index, and lifelong dietary patterns were similar in both zones. The authors found no significant difference in mean body burden levels between zones A and C before or after adjustment for covariates. All congener patterns were consistent with an urban background pattern, and there was no significant difference between congener compositions in the two zones. The TCDD body burden increased with age with accelerated increments above age 70. CONCLUSION: Long term residency near heavy and chemical industry did not have an effect on women's body burden of PCDD/Fs and PCBs on Teesside, UK. The body burden of PCDD/F and PCBs was not a suitable biomarker for chronic, non-occupational exposure to industrial air pollution.

Aged↗

The Elbe flood in August 2002--occurrence of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans (PCDD/F) and dioxin-like PCB in suspended particulate matter (SPM), sediment and fish.

As a result of extreme precipitation in August 2002 major flooding occurred in the catchment area of the rivers Elbe, Vltava (Moldau) and Mulde. Pollutants from industrial sites and from municipal sewage treatment works (STW) entered the Elbe and led to a serious pollution problem in the river. PCDD/F concentrations (in pg WHO-TEQ/g dw) in SPM ranged from 7-150, in sediments from 3-140; the "safe sediment value" of 20 was exceeded in 46% of the samples. 24 eels showed a wide concentration variation for these contaminants. The WHO-PCDD/F+PCB-TEQ values lay in the range from 11-56 pg/g ww, whereby the WHO-PCB-TEQ values were several times higher than the WHO-PCDD/F-TEQ values. The maximum permitted value of 4 pg WHO-PCDD/F/g ww (EU Directive No. 2375/2001) was reached or exceeded in 54% of the individuals. A statistical analysis using data from SPM and sediment samples showed that in the Czech river section the flooding activated a contamination source in the vicinity of the Spolana works. The influence of the tributary Mulde could be clearly demonstrated. Only a major clean-up of the contaminated sites in Bitterfeld can lead to a mid to long term improvement in respect of PCDD/F and dioxin-like PCB input into the Elbe.

Animals↗

Effect of dose and dose-distribution in damage to the kidney following abdominal radiotherapy.

PURPOSE: To define the effects of abdominal radiotherapy on the kidney with regard to dose-distribution parameters. MATERIALS AND METHODS: Ninety-one patients with abdominal radiotherapy were included in the study, and the minimum follow-up was 1 year. Conventional fractionation, 5 x 1.8-2.0 Gy week(-1) to total doses of 30.6-62.5 Gy, was employed. Assessment of organ function was performed before, immediately after, and at 6 months and 1 year after radiotherapy. In cases with a significant radiation response at 1 year, subsequent follow-ups were done at 6-month intervals. Documented parameters included clinical examination, static and sequential scintigraphy of the kidneys, abdominal computed tomography, and sonography. RESULTS: Twenty-one patients (23%) developed a reduction in kidney function detected by static scintigraphy. Only in 15 of these patients was impairment of renal function observed by sequential scintigraphy. The contribution of the irradiated kidney to overall renal function decreased progressively to 34-40% by the third year after treatment. Hypertension was seen in two patients. No changes were found in laboratory parameters. ED(50) for scintigraphic changes decreased from 27 Gy for 10% of the volume to 7.6 Gy for 100%. ED(5) were in the range of 3-6 Gy, and this was independent of volume. CONCLUSIONS: Sophisticated imaging techniques allow the identification of radiation effects in partial volumes of the kidneys. A dose-response relationship in relation to the volume of kidney irradiated can thus be established for scintigraphic changes. As in a number of other organs, such changes do not relate directly to loss of renal function due to the reserve capacity of unirradiated kidney tissue.

Blood Pressure↗

Wastewater recycling concept for an urban multi-storey building.

An innovative system for blackwater recycling is described. An existing building comprising of 32 flats built in 1962 was renovated and equipped with vacuum toilets to collect blackwater separately. The energy and water consumption was determined. The flushing water consumption decreased from 40 l/p/d to 9 l/p/d.

Conservation of Natural Resources↗

Mouse fatty acid transport protein 4 (FATP4): characterization of the gene and functional assessment as a very long chain acyl-CoA synthetase.

FATP4 (SLC27A4) is a member of the fatty acid transport protein (FATP) family, a group of evolutionarily conserved proteins that are involved in cellular uptake and metabolism of long and very long chain fatty acids. We cloned and characterized the murine FATP4 gene and its cDNA. From database analysis we identified the human FATP4 genomic sequence. The FATP4 gene was assigned to mouse chromosome 2 band B, syntenic to the region 9q34 encompassing the human gene. The open reading frame was determined to be 1929 bp in length, encoding a polypeptide of 643 amino acids. Within the coding region, the exon-intron structures of the murine FATP4 gene and its human counterpart are identical, revealing a high similarity to the FATP1 gene. The overall amino acid identity between the deduced murine and human FATP4 polypeptides is 92.2%, and between the murine FATP1 and FATP4 polypeptides is 60.3%. Northern analysis showed that FATP4 mRNA was expressed most abundantly in small intestine, brain, kidney, liver, skin and heart. Transfection of FATP4 cDNA into COS1 cells resulted in a 2-fold increase in palmitoyl-CoA synthetase (C16:0) and a 5-fold increase in lignoceroyl-CoA synthetase (C24:0) activity from membrane extracts, indicating that the FATP4 gene encodes an acyl-CoA synthetase with substrate specificity biased towards very long chain fatty acids.

Amino Acid Sequence↗

Exploratory patterns of rats on a complex maze provide evidence for topological coding.

Rats' exploratory patterns on a complex elevated maze were analyzed in both light and dark conditions. Rats were less active in the light than in the dark. In the light, they spent more time exploring the outer areas of the maze than the inner areas whereas exploration of both regions was similar in the dark. In both light and dark, rats spent more time investigating choice points (which provided multiple directions for movements) than runways that allowed only simple movements. In addition, choice points that provided more connections with other distant places were associated with more exploration. While such effects might be the result of stimulus-seeking of distant information in the light, increased exploration times in the dark presumably reflect the processing of local information associated with the maze connectivity. These results suggest that exploratory patterns in the dark reflect processing of the topological structure of the maze.

Journal Article↗

NMR structure of the calreticulin P-domain.

The NMR structure of the rat calreticulin P-domain, comprising residues 189-288, CRT(189-288), shows a hairpin fold that involves the entire polypeptide chain, has the two chain ends in close spatial proximity, and does not fold back on itself. This globally extended structure is stabilized by three antiparallel beta-sheets, with the beta-strands comprising the residues 189-192 and 276-279, 206-209 and 262-265, and 223-226 and 248-251, respectively. The hairpin loop of residues 227-247 and the two connecting regions between the beta-sheets contain a hydrophobic cluster, where each of the three clusters includes two highly conserved tryptophyl residues, one from each strand of the hairpin. The three beta-sheets and the three hydrophobic clusters form a repeating pattern of interactions across the hairpin that reflects the periodicity of the amino acid sequence, which consists of three 17-residue repeats followed by three 14-residue repeats. Within the global hairpin fold there are two well-ordered subdomains comprising the residues 219-258, and 189-209 and 262-284, respectively. These are separated by a poorly ordered linker region, so that the relative orientation of the two subdomains cannot be precisely described. The structure type observed for CRT(189-288) provides an additional basis for functional studies of the abundant endoplasmic reticulum chaperone calreticulin.

Amino Acid Sequence↗

Three-dimensional structure topology of the calreticulin P-domain based on NMR assignment.

Calreticulin (CRT) is an abundant molecular chaperone of the endoplasmic reticulum. Its central, proline-rich P-domain, comprising residues 189-288, contains three copies of each of two repeat sequences (types 1 and 2), which are arranged in a characteristic '111222' pattern. Here we show that the three-dimensional structure of CRT(189-288) contains a single hairpin fold formed by the entire polypeptide chain. The loop at the bottom of the hairpin consists of residues 227-247, and is closed by an anti-parallel beta-sheet of residues 224-226 and 248-250. Two additional beta-sheets contain residues 207-209 and 262-264, and 190-192 and 276-278. The 17-residue spacing of the beta-strands in the N-terminal part of the hairpin and the 14-residue spacing in the C-terminal part reflect the length of the type 1 and type 2 sequence repeats. As a consequence of this topology the peptide segments separating the beta-strands in the N-terminal part of the hairpin are likely to form bulges to accommodate the extra residues. These results are based on nearly complete sequence-specific NMR assignments for CRT(189-288), which were obtained using standard NMR techniques with the (13)C/(15)N-labeled protein, and collection of nuclear Overhauser enhancement upper distance constraints.

Amino Acid Sequence↗