Biomedical subjects
Publications and source records attributed to B Köhler.
A longitudinally fiber-pumped, passively Q-switched Nd:YAG laser oscillator-power amplifier system is reported with which a maximum pulse energy of 68 mJ was achieved at high pulse stability, beam quality, and efficiency. Therefore, a compact fiber-coupling interface was developed for stacked arrays of quasi-cw diode lasers, providing a pump power of 1 kW at the fiber end.
BACKGROUND: Basal cell carcinoma (BCC) of the skin is the most common human cancer. The genetic alterations underlying BCC development are only partly understood. OBJECTIVES: To investigate further the molecular genetics of sporadic BCCs, we performed mutation analyses of 10 skin cancer-associated genes in 42 tumours. METHODS: Single-strand conformational polymorphism analysis followed by DNA sequencing was used to screen for mutations in the sonic hedgehog pathway genes PTCH, SMOH, SUFUH and GLI1, in the TP53 tumour suppressor gene, and in the proto-oncogenes NRAS, KRAS, HRAS, BRAF and CTNNB1. Microsatellite markers flanking the PTCH, SUFUH and TP53 loci at 9q22, 10q24 and 17p13, respectively, were studied for loss of heterozygosity (LOH). RESULTS: PTCH mutations were found in 28 of 42 tumours (67%). Microsatellite analysis revealed LOH on 9q22 in 20 of 38 tumours investigated (53%), including 14 tumours with and six tumours without PTCH mutations. SMOH mutations were identified in four of the 42 BCCs (10%) while two tumours demonstrated mutations in SUFUH, including one missense mutation and one silent mutation. None of the BCCs showed LOH at markers flanking the SUFUH locus. Seventeen BCCs (40%) carried TP53 mutations, with only three tumours showing evidence of biallelic TP53 inactivation. TP53 mutations were present in BCCs with and without mutations in PTCH, SMOH or SUFUH. Interestingly, 72% of the TP53 alterations were presumably ultraviolet (UV)-induced transition mutations. In contrast, only 40% of the PTCH and SMOH alterations corresponded to UV signature mutations. No mutations were identified in GLI1, NRAS, KRAS, HRAS, BRAF or CTNNB1. CONCLUSIONS: Our data confirm the importance of PTCH, SMOH and TP53 mutations in the pathogenesis of sporadic BCCs. SUFUH alterations are restricted to individual cases while the other investigated genes do not appear to be important targets for mutations in BCCs.
The effect of 2 different blends of essential oils on Clostridium perfringens (Cp) in the intestine and feces of broiler chickens was tested in 6 field trials for each blend. One hundred parts per million of the blends were mixed in a commercial corn-based diet throughout the entire growing period for experimental flocks. Samples from the jejunum, cecum, cloaca, and feces were taken on d 14, 21, and 30 from experimental and control flocks and tested quantitatively for Cp via blood agar plate, litmus milk medium, and ELISA. Blend A reduced (P < or = 0.05) the average Cp concentration in the feces on all sampling days, in the jejunum and cecum on d 14 and 21, and in the cloaca on d 14. Blend B effected a significant reduction of Cp concentration in the jejunum on d 14 and 30 and in the cloaca on d 14. The percentages of specimens from the control group that tested positive for Cp were 83.3% for feces, 88.0% for jejunum and cloaca, and 82.6% for cecum. Specimens from the feces and 3 sections of the intestine were Cp positive in groups treated with blend A (60.8, 64.6, 47.9, and 70.8%) and with blend B (65.9, 63.6, 63.6, and 72.7%). Our results indicate that specific blends of essential oil components can control Cp colonization and proliferation in the gut of broilers and therefore may be of help to prevent problems with Cp and necrotic enteritis.
Cynomolgus macaques are frequently used in biomedical research. However, in contrast to their closest relative, the rhesus macaque, little is known about their Mhc genes except for the DQB1 locus. In this study, 33 DRB-sequences belonging to 17 allelic lineages were detected in a total of 68 macaques, 58 originating from Mauritius and 10 from China. The majority of the sequences were detected in the few macaques from China, confirming the low degree of genetic variation in macaques from Mauritius. In summary, the DRB region in cynomolgus macaques is polymorphic. The sequences belong in general to the same allelic lineages as in their closest relative, the rhesus macaque. Two exon 2 DNA sequences were identical in both species and may represent a trans-species origin. In addition, protein sequences of members of the DRB*W1 lineage seem to be rather conserved in the three macaque species examined so far. Six DRB-haplotypes were detected in the macaques from Mauritius. While single DRB-alleles or some protein sequences seemed to be conserved among macaque species, we could not detect any evidence for a trans-species conservation of a complete DRB region. Overall, the data indicate that reorganization of the DRB region by recombination is a major force in creating diversity in cynomolgus macaques as it is in rhesus macaques.
A quality assurance system (OPTIDOS, PTW-Freiburg) developed for dose rate verification of 90Sr/90Y radiation source trains (RSTs) was calibrated and validated. These source trains are used in the 5-F-BetaCath system (Novoste Corp.) for the treatment of endovascular diseases. The calibration factor of the OPTIDOS system was obtained empirically and is valid for 90Sr/90Y dose rate measurements at the specification point which is located at 2 mm distance from the source axis. A total of 187 OPTIDOS dose rate verifications of the 5-F-BetaCath system were performed in different hospitals. The histogram of the deviation between the manufacturer's dose rate specification and the dose rate measured using the OPTIDOS dosimetry system is Gaussian shaped with +/- 3% relative width and a mean shift of about +2% with respect to the corresponding dose rate specification. Additionally, 128 OPTIDOS dose rate verifications of the new jacketed RST (3.5-F-BetaCath, Novoste Corp.) were performed using the same calibration factor as derived for the 5-F-BetaCath system. Distribution of the deviation between the certified and the measured dose rate is nearly identical in comparison to the histogram of the 5-F-BetaCath system. The mean value of the deviations is shifted by -1.5% with respect to the certified dose rate. In order to compare the results of the calibrated OPTIDOS dosimetry system with a standard measuring method, separate dose rate measurements were performed using electron accelerator calibrated radiochromic films in which calibration is traceable to PTB (Physikalisch Technische Bundesanstalt, Germany). Deviation between both the methods is less than 3.1%. These results confirm that the calibrated OPTIDOS dosimetry system can be considered suitable for quality assurance of both types of RST used in the BetaCath systems.
BACKGROUND: Malaria plays an important role as a dangerous imported infection in Europe. In addition, the number of elderly travellers is increasing. We examined the hypothesis, whether age can be considered as a risk factor for the development of complications in malaria. PATIENTS AND METHODS: We examined retrospectively 134 case records of patients of all age groups with a plasmodial infection. We analysed personal data, travel details and patient histories, the neurological status, respiratory function, as well as haematological, biochemical and parasitological parameters. RESULTS: There is significant evidence for a correlation between age and the frequency of complications in malaria like cerebral involvement, respiratory failure, renal failure, anaemia, and hyperparasitaemia. Out of 132 patients over 15 years of age, 49 (37.1 %) developed a severe course of malaria. In the age group of 60 years and above this percentage increased to 61.5 %. The age distribution in the group with severe malaria was significantly shifted towards the elderly (p = 0.016 in Mann-Whitney test). The duration of hospitalisation also increased with age from an average of five days for the group below 45 years to 21 days for the elderly of 60 years and above. CONCLUSION: Our findings suggest a higher risk for a severe course of malaria in the elderly. For this reason, extensive advice on the correct use of exposure- and chemoprophylaxis of malaria is especially important for travellers above the age of 60.
PURPOSE: Conversion coefficients are commonly used to estimate the radiation dose in projectional radiography from the dose-area product (DAP). This study investigates whether conversion coefficients can also be used for dosimetry in fluoroscopic procedures. MATERIALS AND METHODS: Thermoluminescence dosimeters (TLD) were placed into an anthropomorphic phantom (Alderson Rando Phantom) to measure the dose absorbed by the gonads and uterus. A standardized enteroclysis in double contrast technique (Sellink/Herlinger) was simulated and the DAP was measured. Three examinations with 70, 80 and 90 kV were carried out with a fluoroscopy time of 15 minutes each. The relations between the DAP and the organ dose were analyzed and a linear regression was performed to determine the conversion coefficients [mSv/cGycm (2)]. RESULTS: The DAP and the organ dose measured by TLD were strongly correlated (r > 0.95) for all examined organs. CONCLUSION: The strong correlations between TLD-measured organ doses and DAP recommend the use of conversion coefficients for the dosimetry of fluoroscopic procedures.
By applying diffraction grids to the detection surface the full vector content of the elastic wave field of ultrasonic transducers can be measured using common heterodyne interferometers. The signal to noise ratio is good enough to detect even small edge wave contributions to the elastic wave field. Numerical simulation of the elastic wave propagation by the elastodynamic finite integration technique helps to understand the origin of several field components observed in the measurements.
In this study, we determined the sequences of four intimin variant genes detected in attaching and effacing Escherichia coli isolates of human origin. Three of them were novel and were designated eae-eta (eta), eae-iota (iota), and eae-kappa (kappa). The fourth was identical to the recently described eae-zeta (zeta), isolated from a bovine E. coli O84:NM isolate. We compared these sequences with those of published intimin-alpha, intimin-beta, intimin-gamma1, intimin-gamma2, intimin- epsilon, and intimin-theta alleles. Sequence analysis of these 10 intimin alleles confirmed extensive genetic diversity within the intimin gene family in E. coli. The genetic diversity was more prominent in the 3' region (starting at bp 2,112), which encodes the binding domain of intimin. Phylogenetic analyses revealed four groups of closely related intimin genes: alpha and zeta; beta and kappa; gamma1 and gamma2/theta; and epsilon and eta. Calculation of homoplasy ratios of sequences of the 5' region of eae (positions 1 to 2,111) revealed evidence for intragenic recombination. Split decomposition analysis also indicates that recombination events have played a role in the evolutionary history of eae. In conclusion, we recommend an eae nomenclature system based on the Greek alphabet and provide an updated PCR scheme for amplification and typing of E. coli eae.
Novel chiral macrocycles consisting of two rigid oligoarylene rods and two chiral spiroindane clips have been synthesized by condensation of spiroindane diols and CF3-activated alpha-omega-difluorooligoaryls. Since a broad variety of planar aromatic macrocycles is known, our non-planar, chiral rings represent a new class of macrocyclic compounds. The first two examples, which contain quaterphenylene and diphenylbithiophene rods, are presented in this communication; for one of them a crystal structure is given. The chiroptical properties of the macrocycles can be interpreted as an interplay of the "intra-rod" helicity of individual oligoarylene rods and the "inter-rod" helicity between both chromophores of the macrocycle. The macrocycles can act as chiral dopands of commercially available, and novel, polymeric nematic liquid crystals (emissive polyfluorenes). The "intra-rod" helicity of individual oligoarylene rods is the main feature in determining the resulting helical twisting power (HTP). The cholestric induction in mesogenic, emissive polyfluorenes is of special interest for a realization of electronic devices that have a circularly polarized electroluminescence. The results are also important for an understanding of larger ensembles of chiral rodlike molecules, especially their pi-pi interactions.
SNARE proteins are required for fusion of transport vesicles with target membranes. Previously, we found that the yeast Q-SNARE Vti1p is involved in transport to the cis-Golgi, to the prevacuole/late endosome, and to the vacuole. Here we identified a previously uncharacterized gene, VTS1, and the R-SNARE YKT6 both as multicopy and as low copy suppressors of the growth and vacuolar transport defect in vti1-2 cells. Ykt6p was known to function in retrograde traffic to the cis-Golgi and homotypic vacuolar fusion. We found that VTI1 and YKT6 also interacted in traffic to the prevacuole and vacuole, indicating that these SNARE complexes contain Ykt6p, Vti1p, plus Pep12p and Ykt6p, Vti1p, Vam3p, plus Vam7p, respectively. As Ykt6p was required for several transport steps, R-SNAREs cannot be the sole determinants of specificity. To study the role of the 0 layer in the SNARE motif, we introduced the mutations vti1-Q158R and ykt6-R165Q. SNARE complexes to which Ykt6p contributed a fourth glutamine residue in the 0 layer were nonfunctional, suggesting an essential function for arginine in the 0 layer of these complexes. vti1-Q158R cells had severe defects in several transport steps, indicating that the second arginine in the 0 layer interfered with function.
PURPOSE: To investigate whether the standardized helmet technique adequately covers the cribriform plate. METHODS AND MATERIALS: For 11 patients with acute leukemia or primary intracerebral neoplasms undergoing irradiation with the standardized helmet technique, three-dimensional isodose distributions were evaluated with special respect to the dose to the cribriform plate and the ocular lenses. RESULTS: The average dose received by 95% of the cribriform plate with the standardized helmet technique was 85% of the prescribed dose. To enclose the cribriform plate by the 95% isodose (according to the ICRU 50 report) with a 10-mm safety margin allowing for deviations during treatment planning and delivery, the eye block had to be moved in the ventrocaudal direction with an average vector length of 13.6 mm. Consequently, the mean dose received by 5% of the lenses rose from 18% to 91% of the prescribed total dose. CONCLUSION: Sufficient lens shielding is usually not compatible with safe irradiation of the frontobasis by the standardized helmet technique.
Organometallic polymers were prepared by acyclic diyne metathesis (ADIMET) or by Pd-catalyzed coupling of 1,3-diethynylcyclobutadiene(cyclopentadienyl)cobalt with a suitably substituted diiodobenzene. The polymers obtained by Heck coupling show a degree of polymerization (Pn) of 20-60. The monomers for ADIMET were made by the Pd-catalyzed coupling of [1,3-bis(trimethylsilylethynyl)-2,4-bis(trimethylsilyl)cyclobutadiene](cyclopentadienyl)cobalt to 1-bromo-2,5-dialkyl-4-propynylbenzenes in the presence of KOH in yields of 40-48%. The monomers carry hexyl, ethylhexyl, and (S)-3,7-dimethyloctyl side chains. Polymerization of the propynylated monomers furnishes organometallic polymers with a Pn of up to 230 arylene-ethynylene units. The polymers were fully characterized by polarizing microscopy, transmission electron microscopy, circular dichroism, differential scanning calorimetry, and X-ray diffraction (XRD). They show nematic, lyotropic liquid crystalline phases as well as chiroptical properties from which aggregation in poor solvents and in the solid state can be concluded. Lamellar or irregular honeycomb-shaped morphologies in these organometallic polymers can be detected by electron microscopy.
A total of 44 bacterial strains obtained from 49 clinically healthy ducklings of different ages originating from four different farms were identified as members of the species Riemerella anatipestifer (RA) using conventional biochemical test methods. Numerical analysis of the whole-cell fatty acid patterns of these isolates resulted in two different clusters, one of which showed a similar pattern to that of the type strain of RA. Strains having a different fatty acid methyl esters (FAME)-profile (cluster II) were designated R. anatipestifer-like (RA-like). Sequencing of 16S rRNA genes of RA-like field isolates revealed 99% identity to RA. The significance of these observations are discussed. The present findings document for the first time that RA seems to represent a normal part of the pharyngeal flora of healthy Pekin ducks.
Mutations of the Wilms tumor suppressor gene (WT1 ) have been described only in patients with syndromes associated with urogenital malformation and Wilms tumor or nephropathy. We present a male patient with an isolated genital malformation caused by a WT1 mutation.
UNLABELLED: A 22-year-old female German student was admitted with fever of unknown origin for 5 days to the hospital of her hometown immediately after returning from a 7-week journey under simple conditions through 4 West African countries. After exclusion of malaria and typhoid and nonrespondence to antibiosis, she was transferred on the 4th day to the Department of Tropical Medicine in Würzburg. After the clinical assumption of Lassa fever, the virus was confirmed by PCR within 3 hours (Bernhard Nocht Institute, Hamburg) on the 10th day of her illness. The assumption was based on travel history, continuous fever, cough, pharyngitis, thoracic pain, and exclusion of other acute infections. From the beginning, the patient was cared for with barrier nursing and after diagnosis under strict isolation in an intensive care unit reserved for her alone by a team of doctors and nurses specialized in tropical medicine and intensive care. The staff was protected through isolation suits with filters. Monitoring and therapy entailed all methods of intensive care and intravenous administration of ribavirin 16 mg/kg body weight = 900 mg every 6 hours. The patient died on the 14th day of her illness in a volume deficiency shock due to uncontrollable heavy hemorrhage from all organs including the skin, a so-called "leakage syndrome". CONCLUSION: Conclusions are drawn regarding training in tropical medicine, diagnostics of highly contagious infections, intensive care of patients affected with them under isolation, contact tracing, psychological crisis intervention for personnel, media information, care of the infectious corpse and disposal of infectious waste.
OBJECTIVE: The purpose of our study was to measure and compare patient exposure by direct digital and conventional panoramic radiography. MATERIAL AND METHODS: Dose measurements were carried out on an anthropomorphic phantom, which was specially developed for dental radiography. Panoramic radiographs were taken with three different conventional devices (Orthopantomograph 10E, Orth Oralix FD, Siemens Orthophos) and two direct digital devices (Orthopantomograph 100 Digipan, Siemens Orthophos DS Ceph). The exposure conditions were according to clinical routine. The energy dose was measured at 28 places inside and on the surface of the phantom by using a set of 108 thermoluminescence detectors. Additionally, exposure time, tube voltage, central-beam dose, and dose-area products were measured. The effective doses were calculated on the basis of the absorbed doses. RESULTS: In each case, the highest energy doses were recorded at the parotid gland, the mandibular angle, the submandibular gland, and the skin in the neck. Panoramic radiographs taken with the conventional units yielded in effective doses in the range of 16-21 microSv, the digital units caused 5 or 14 microSv. CONCLUSION: In comparison with conventional techniques, patient exposure can be reduced by direct digital panoramic radiography. The extent of dose reduction depends on the device employed and is generally smaller than the dose reduction that can be achieved by digital imaging devices in intraoral radiography.
OBJECTIVES: To study the clinical efficacy of posterior composite resin restorations placed in general practice after five years. METHODS: Two commercial composite resin systems were used. Three general practitioners placed the restorations at a Public Dental Health Service Office. The patients were not selected specifically for this study. Class II cavities were restored with Superlux Molar and P-50 APC composite systems on an alternate basis. At baseline, 63 restorations were placed in molars and premolars in 45 patients. For primary caries, generally a conservative cavity design was used (n = 23), while replacements of amalgams resulted in the larger conventional Class II design (n = 40). The restorations were assessed using a modified USPHS criteria. Wear measurements were determined by the Leinfelder method. Photographs and bite-wing radiographs were taken to supplement the clinical evaluation of colour match, marginal adaptation and recurrent caries. Saliva sampling was performed to determine the rate of secretion and the level of mutans streptococci and lactobacilli. RESULTS: At the five-year review 51 restorations were available for examination, of which nine restorations were rated clinically unacceptable. Including the failed restorations (n = 7), at the three-year review, a total of 16 restorations had failed (27.6%) over a five-year period. The most common reasons for failure were recurrent caries (n = 7) and marginal defects (n = 4). The mean wear of Superlux Molar was 167 microns and of P-50 APC 158 microns. Eight of the 11 patients with failed restorations due to caries and marginal defects had high counts of mutans streptococci at baseline. CONCLUSIONS: The failures in the present group of patients did not specifically relate to material, tooth type or cavity design. However, it is suggested that patient factors such as caries activity should be monitored and managed.