Biomedical subjects
Publications and source records attributed to D Berg.
The changing conditions of the German medical system has strongly influenced the updating of the perinatal quality assurance project. Instead of controversial aims by the different sides the modified German Perinatal Quality Assurance Project will be able to guarantee high level perinatal quality in our obstetrical departments.
Oligonucleotides containing the modified bases 5-methylcytosine and 2-aminoadenine in place of cytosine and adenine, respectively, have higher than normal affinity for complementary sequences The strong binding oligonucleotides (SBO) are much better than their normal counterparts in PCR amplification: they yield significantly more product per cycle, allow amplification at annealing temperatures as high as 72 degrees C and, unlike their normal counterparts, allow efficient priming from within a palindromic sequence. We propose that such strong binding oligonucleotides will be valuable in numerous PCR applications, including: (i) minimization of the frequency of mutants among PCR products; (ii) when only short specific primers can be designed based on available sequence information; (iii) when the material available for the analysis is limited in quantity; and (iv) when primer binding is blocked by DNA secondary structure involving a primer binding site, or chain extension is impeded by secondary structure in downstream sequences.
There have been reports of an association between Darier's disease, an autosomal dominant genodermatosis, and psychiatric illness. Recently the gene causing Darier's disease has been mapped to an area on 12q, between D12S58 and D12S84. The findings of linkage analysis of 4 markers in the Darier's disease region on 12q in five families segregating schizophrenia are presented. They fail to support close linkage between schizophrenia and the Darier's disease region on 12q.
Positional cloning with microsatellite markers allowed further localization of the Darier disease gene to a 2-cM interval of chromosome 12, 12q23-24.1, between the polymorphic loci D12S234 and D12S129. A region this size is suitable for construction of a contig to identify the Darier disease gene. Use of a polymorphic intronic marker for nitric oxide synthetase 1 gene, which maps to the same chromosomal area as the Darier gene, allowed exclusion of that gene as the Darier disease gene.
Resistance of Helicobacter pylori to metronidazole often causes failure of commonly used combination drug treatment regimens. We determined the MICs of metronidazole and clarithromycin against 18 H. pylori strains from Peru using tetrazolium egg yolk (TEY) agar. The MIC results obtained by agar dilution with petri dishes were compared with the results found through a miniwell format. The results of the two protocols for measuring drug susceptibility differed by no more than 1 dilution in all cases. On TEY agar, bright-red H. pylori colonies were easy to identify against a yellow background. Sixty-one percent (11 of 18) of the strains were resistant to metronidazole (MIC, > or = 4 micrograms/ml) and 50% (9 of 18) were resistant to clarithromycin (MIC, > or = 0.125 micrograms/ml), whereas none (0 of 5) of the strains tested were resistant to tetracycline (MIC, > or = 1 micrograms/ml). Thus, the prevalence of metronidazole and clarithromycin resistance in Peru is higher than that in developed regions of the world. The miniwell plate with TEY agar allows easy H. pylori colony identification, requires about one-third less of the costly medium necessary for petri dish assaying, conserves space, and yields MICs equivalent to those with agar dilution in petri dishes.
We use modified oligonucleotides with enhanced strength of complementary DNA binding for primer walking DNA sequencing with strings of short contiguous oligonucleotides as primers. Such an approach allows us to reduce the probability of primer failures due to unstable binding of oligos with templates. In this paper the factors affecting the priming efficiency of segmented primers (strings composed of several short oligonucleotides contiguously juxtaposed on the template) used for DNA sequencing were investigated. Modified oligonucleotides were used to discriminate the effects caused by intrinsic properties of the oligonucleotides and by template features. It was shown that the most crucial factor is the stability of the duplex formed by the template with the 3'-outermost oligonucleotide of a string. The data were obtained with a model M13 template and in the process of sequencing the region flanking a long terminal repeat of human endogenous retrovirus HERVK mapped on chromosome 19. The sequencing was done by primer walking with strings of contiguous modified hexanucleotides. The effects revealed should be taken into consideration when choosing oligonucleotide units of segmented primers and for construction of minimised libraries composed of short unit oligonucleotides.
AIM: To demonstrate changes in gastric mucosal blood flow caused by intraoperative radiotherapy of the celiac artery combined with external radiotherapy of the upper abdomen in a rabbit model. The study was designed to identify a possible correlation between a radiation-induced reduction in mucosal blood flow and the induction of gastric ulcer. MATERIAL AND METHOD: Intraoperative radiation doses of 0 or 30 Gy were given to the celiac artery in rabbits. After a delay of 14 days external radiotherapy of the upper abdomen with 3 x 4 Gy/week to a maximum total dose of 40 Gy was initiated. Gastric mucosal blood flow was assessed by intraventricular injection of radioactively-labelled microspheres (15 microns) followed by measurement of radioactivity in the mucosa. The injections were performed at various time intervals between 2 and 63 days after intraoperative radiation. RESULTS: Intraoperative radiotherapy, including sham-intraoperative radiation, resulted in a transitory reduction of mucosal blood flow by about 50% of the control value on day 7 (Figure 3). After a temporary recovery by day 14, a marked and permanent reduction in blood flow was assessed after week 6. This time corresponds to the time of development of gastric ulcer. CONCLUSIONS: A relationship between the time of ulcer development and of reduced gastric mucosal blood flow was observed after combined intraoperative and external radiotherapy. The mechanical component of intraoperative treatment has to be emphasized. Reduced blood flow was also seen after intraoperative radiotherapy alone, without an induction of ulcer by this treatment. Hence additional mucosal damage by external radiation must be present for the induction of gastric ulcer.
Darier disease is an autosomal dominant skin disorder characterized by abnormal keratinocyte adhesion. Recent data have provided evidence for linkage of the Darier disease locus to 12q23-24.1 in British families. We have carried out linkage analysis using the 12q markers D12S58, D12S84, D12S79, D12S86, PLA2, and D12S63 in 6 Canadian families. Pairwise linkage analysis generated positive lod scores at all 6 markers at various recombination fractions, and each family showed positive lod scores with more than one marker. The peak lod score in the multipoint analysis (Zmax) was 5.5 in the interval between markers D12S58 and D12S84. These positive lod scores in North American families of varied European ancestry confirm the location of the Darier disease gene, and suggest genetic homogeneity. The future identification and sequencing of the gene responsible for Darier disease should lead to improved understanding of the disease and of keratinocyte adhesion in general.
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A 75-year-old woman being treated with prednisone and methotrexate had a 5.5 x 2.2 cm ulcer on the leg. A biopsy specimen revealed suppurative, granulomatous dermal inflammation with necrotic areas of septate, branching hyphae containing brown pigment. Cultures grew Curvularia pallescens. Oral ketoconazole therapy was started and the lesion was excised. The site healed after multiple excisions and grafts, and ketoconazole therapy was stopped after 7 months. This is the first reported case of invasive cutaneous infection by C. pallescens.
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Large deviations, regional differences and the decline in hysterectomy frequencies suggest that the indication for hysterectomy has not always been based on well defined medical standards. Paramedical factors also have an influence on the indication. The patient has to decide in many cases whether she would like to tolerate the clinical symptoms, which could have been improved or healed by hysterectomy, or not. New endoscopic techniques as alternative to or support of the classical hysterectomy procedure have not yet been sufficiently proved. Influences on the costs of operations, the rate of complications and above all the setting of indications need further careful observation and analyses. It is difficult to establish quality assessment procedures in hysterectomy, because controlling the indication by histopathological examination of the exstirpated uterus cannot regard the variety of indications.
3-Hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase) plays a rate-limiting role in isoprenoid biosynthesis and is associated with cell proliferation and transformation. Although an elevated level of HMG-CoA reductase activity is consistently detected in cancer cell lines and tumors, the question remains whether HMG-CoA reductase activity may have a causative role in cell transformation. We have stably transfected the A549 human adenocarcinoma cells with both bicistronic and retroviral expression vectors, including the whole cDNA of human HMG-CoA reductase. Stably transfected cells showed strong morphological changes and disorganization in the filamentous actin architecture, became contact inhibited, and had a lower doubling time. Moreover, they exhibited anchorage-independent growth reduction and lost their capability to induce tumors in nude mice. Surprisingly, no quantitative modification of enzyme activity was observed following transfection, although expression of HMG-CoA reductase cDNA was shown by Northern blot analysis. When endogenous and transfected reductase activity was bypassed by the addition of mevalonate and compactin, a competitive inhibitor, the filamentous actin distribution in HMG-CoA reductase-transfected cells became very similar to that of control cells, demonstrating the role of exogenous HMG-CoA reductase activity in this process. All of our data together strongly suggest that phenotype reversion is dependent on exogenous HMG-CoA reductase expression and that enzymatic activity is implied in this mechanism. HMG-CoA reductase cDNA expression, by expression of a particular form of reductase, might be a negative regulator of cell growth and thus reverse the phenotype of tumor cells.
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BACKGROUND: Darier's disease (keratosis follicularis) is known to have a genetic cause as evidenced by its autosomal dominant transmission in families. The gene causing this disease has not been discovered. OBJECTIVE: During an ongoing linkage study of schizophrenia, a family segregating Darier's disease was found. This family is being studied in an attempt to locate prospective regions that may contain the Darier's disease gene. METHODS: Two genetic strategies are being employed: (1) testing candidate genes for the disorder and (2) scanning the entire genome with polymerase chain reaction-based microsatellite markers. RESULTS: Thirty-nine marker systems located on chromosomes 1, 2, 4, 5, 6, 9, 11, 12, 16, 17, 22, X, and Y have been genotyped. Slightly positive lod scores were achieved between six markers and Darier's disease. The remaining 33 markers were nonsegregating or indeterminate, or revealed an obligate recombinant. CONCLUSION: Linkage analysis can lead to localization of the gene causing Darier's disease. In these preliminary studies low positive lod scores were obtained, potentially pointing to the chromosomal location of the Darier's disease gene.
103 current publications on perinatal mortality of home delivery (HD) have been investigated concerning their possible usage for statistics. Only few could meet the necessary statistical requirements. All publications which were in favour of home delivery showed statistical faults; therefore, they cannot give clear evidence of advantages and disadvantages of HD. The group of the described HD (approximately 85,000 home deliveries) were compared with a statistically comparable group of hospital deliveries. The risk for children to die during or after birth is between 3 and 23 times higher for home-born children than for those born in hospitals. The rate of unexpected incidents during delivery, where transport to hospital was required, is about 11%; this corresponds to the rate of unexpected incidents in hospitals. In home delivery, it is not possible to provide obstetrical operative interventions. The frequency of operatively terminated deliveries is about 40% in the group of secondarily transferred patients. The Netherlands have about 30% home deliveries; their perinatal mortality rate (0.96%) is the highest of all comparable high-developed countries (Germany: 0.6%). Considering the necessary safety of the child, home delivery is irresponsible.