[Development of public health as a university discipline in Dresden].
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Biomedical subjects
Publications and source records attributed to G Burger.
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From 923 breast cancers sent in for hormone receptor determination, 745 diagnostically utilizable Pappenheim-stained biopsy smears at 500-fold magnification were classified into eight atypia groups (1-4 without nucleoli, 5-8 with nucleoli) visually in terms of the severity of the cellular malignancy criteria. The hormone receptor status was determined with the dextran-coated charcoal method. Values from 10 fmol/mg estrogen receptor (ER) and (or) progesterone receptor (PR) content were designated as receptor-positive. There was a decrease in the proportion of receptor-positive results with increasing degree of atypia from 97% in group 2 (cases with only small nuclei without nucleoli) to 37% in group 7 (cases with multiple prominent nucleoli). When the average atypia values of subgroups were compared, the highest values were found for the 222 receptor-negative carcinomas. The marginally receptor-positive values were on average between the receptor-negative and the receptor-positive cases with high values. Both the low-ER and the low-PR have more pronounced criteria of malignancy compared to the respective high-receptor reference group.
The mitochondrial DNA of Neurospora crassa contains a long potential gene, designated URFN, which is located immediately downstream from the CO1 gene. These two genes are encoded in different reading frames and overlap by 13 codons. URFN is 633 triplets long and terminates at a UAG stop codon. Its codon usage is atypical for N. crassa mitochondrial exons and introns, and resembles that of the long open reading frame (ORF) of the mitochondrial plasmid present in N. crassa strain Mauriceville. Multiple sequence repetitions occur in the presumptive URFN polypeptide, most notably a seven-times reiterated motif of 16 to 18 amino acid residues length. The hydropathy pattern shows that the N-terminal third of the URFN polypeptide is predominantly apolar and includes several potentially membrane-spanning stretches; the remaining part is hydrophilic. Calculation of the secondary structure predicts a high proportion (47%) of alpha-helix conformation. The longest alpha-helix contains 40 residues. No similarities to other mitochondrial genes or reading frames have been found, except a significant homology over a stretch of 16 amino acid residues between the N-terminal part of URFN and a well-conserved sequence in the C-terminal region of CO1. The repetitive region in URFN resembles a similarly repetitive stretch in an unassigned reading frame from bacteriophage lambda. Three arguments support the view that URFN is translated. The open reading frame has a considerable length; URFN is transcribed into a mRNA including the overlapping CO1 gene; URFN is most probably conserved among all the various Neurospora species examined thus far, strongly suggesting that it codes for an essential protein.
We have developed a collection of programs for manipulation and analysis of nucleotide and protein sequences. The package was written in Fortran 77 on a Sirius1/Victor microcomputer which can be easily implemented on a large variety of other computers. Some of the programs have already been adapted for use on a Vax 11. Our aim was to develop programs consisting of small, comprehensible and well documented units that have very fast execution times and are comfortably interactive. The package is therefore suitable for individual modifications, even with little understanding of computer languages.
Late damage in the rectum of rats was studied after local irradiation with 2 MeV fast fission neutrons and the results were compared with those for 300 kV X-rays. A similarity between latency times, and between clinical, gross pathological and histological appearances of the rectal obstruction after the two types of radiation was observed. The r.b.e. evaluated from ED 50/200 days values was 1.8 for single doses, 2.1 for two fractions and 3 for five fractions and these are similar to r.b.e.s from other investigations of chronic intestinal radiation damage. Using linear quadratic analysis, a limiting r.b.e. of 5 was obtained. The beta-values are similar for both radiation qualities. Because of the high gamma-contamination (25 per cent) in the RENT I beam a possible correction of the r.b.e. for neutrons only, assuming interaction, is discussed.
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In Neurospora crassa, a 2670 base-pair segment of the mitochondrial DNA was sequenced including a gene homologous to the mammalian URF1 that was recently shown to encode a subunit of the respiratory chain NADH dehydrogenase complex. URF1 of N. crassa is interrupted by an intron of 1118 base-pairs that divides the protein-coding sequence into two exons of 636 and 480 base-pairs length, respectively. The deduced URF1 polypeptide of 371 residues was aligned with that of other eukaryotes, revealing a degree of conservation similar to that of ubiquitous mitochondrial genes. The two highly conserved stretches coincide with the most polar regions of the otherwise hydrophobic URF1 polypeptides and may constitute functional domains of the complex I subunit. In the exon sequences of URF1, 17 codons occur that are infrequently utilized in other mitochondrial genes of N. crassa, indicating a low translational efficiency or a foreign origin of URF1. The URF1 intron is inserted in the most conserved region. It belongs to group I and contains an open reading frame of 305 codons not continuous with the upstream exon. Sequences convincingly homologous to conserved group I decapeptide motifs were not found in the URF1 intronic unassigned reading frame (URF). However, significant homology was detected to intronic URFs of the respective gene from Podospora anserina, suggesting that these reading frames constitute a novel type of group I intronic URFs. Three species of URF1 transcripts were identified. They arise most probably by subsequent removal of the intron and leader sequences from an URF1 precursor transcript.
A compound consisting of a beta-stimulant, salbutamol (Ventolin; Allen & Hanburys) (100 micrograms/puff), and a steroid, beclomethasone dipropionate (Becotide; Allen & Hanburys) (50 micrograms/puff), was studied to test the hypothesis that the corticosteroid could enhance the bronchodilator properties of the beta-stimulant during chronic asthma and simulated acute attacks (antigen challenge). Conventional doses (200 micrograms and 100 micrograms of salbutamol and beclomethasone respectively) were compared using a schedule which included a second administration 1 hour later. The results obtained on the baseline bronchial responsiveness of chronic asthmatics and during the delayed asthmatic response (simulated acute asthma) were similar. The compound was as effective as salbutamol alone but not more so. A significantly greater bronchodilator response was recorded in all patients after the second administration of both the compound and salbutamol alone. The practical advantages of having one rather than two inhalers are evident, but the appropriate application of this compound agent, probably in a prophylactic role, must be defined.
The pattern of transcripts arising from a large contiguous portion of the Neurospora crassa mitochondrial genome and the processing of these transcripts have been investigated. Evidence is presented for the transcription of a single, at least 12.5 kb, precursor RNA that contains sequences corresponding to the apocytochrome b (cob), tRNACys, cytochrome oxidase subunit 1 (CO I), tRNAArg and unidentified reading frame (URF) 1 genes. The two tRNA sequences serve as punctuation signals for the cleavage of this large transcript. Processing at the tRNACys and tRNAArg sequences directly generates the proposed CO I mRNA, as well as the mature 3' end of the cob transcripts. Moreover, three other sites have been identified that are specifically involved in further 5' end processing events. One of the two 5' end processing sites of the cob transcript shares homology with the 5' end processing sites of the mitochondrial 19S and 25S rRNA precursors. PstI palindromes do not act as processing signals because six of these palindromic sequences are present in the cob and CO I mRNAs.
It is possible to predict to some extent the hormone receptor status of carcinomas of the breast via cytomorphology of fine needle biopsy specimens. In most cases the cytologically highly differentiated carcinomas are receptor-positive and the poorly differentiated ones receptor-negative if the cases are arranged in the sequence of increasing conspicuousness of cellular criteria of malignancy. Since visual microscopic examination is subjective by nature, quantification was carried out by means of high-resolution image analysis using Pappenheim stained slides. The quantitative image analysis grading system basing on this method proved to be even more efficient than visual diagnosis.
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Spastic contractures are a common problem which frequently requires the use of splinting or casting. Customized adjustable orthoses can reduce contractures without the problems often associated with these procedures. These devices reduced contractures in a head-injured patient's severely spastic wrist and ankles. As a wrist contracture decreased, the patient increasingly used her arm and hand for feeding, grooming, and leisure activities. The plastic orthoses, molded to the individual limb, incorporate Klenzak or Lehrman fracture brace joints. Custom fit positions spastic limbs and promotes improved range of motion. Small brace joint adjustments are done at intervals to promote slow stretch of spastic limbs; since the device remains on during the adjustment, there is no loss of range of motion. The device may be removed for skin monitoring. The patient maintains joint range, as the orthosis becomes a permanent part of the home program. High cost of the device is potentially offset by the advantages of decreased skin morbidity, reduced therapist time in making adjustment, and maintenance of gains in range of motion. Such orthoses also have been used for elbow contractures.
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22 revertants of Saccharomyces cerevisiae with intragenic suppressors (supa) of cob exon mutations (G. Burger, Mol. Gen. Genet., in the press) were analyzed. They display either a reduced amount of cytochrome b, or a shifted maximum absorption wavelength of total cytochrome b or a reduced growth rate on glycerol. The relationship of physico-chemical properties (content, light absorption and midpoint potential of cytochromes bK and bT) and functional properties (electron transport and energy yield) has been examined. In seven of eight revertants with a shifted maximum absorption wavelength of cytochrome b neither growth rate nor electron transfer activity was affected. In 13 of 14 revertants, reduced content of cytochrome b corresponds to a reduced electron transport rate through the cytochrome bc1 segment. A lower enzymatic activity, which is not due to a quantitative but to a qualitative alteration of cytochrome b was found in two revertants. Two revertants show electron transport rates of wild-type level concomitant with a reduced growth rate on glycerol, obviously due to a less efficient energy coupling. All revertants were shown to contain a high and a low potential cytochrome b, referred to as bK and bT. Those cob-/supa mutations which shift the maximum absorption wavelength or diminish the content of cytochrome b affect both b cytochromes in all cases. The results support that electron transport and energy conservation are catalyzed by the unity of cytochrome bK and bT and that both heme centers are bound to an identical apoenzyme. Comparing electron flow rates of succinate:cytochrome c oxidoreductase and NADH:cytochrome c oxidoreductase in cob- mutants and two revertants provides evidence that ubiquinone does not constitute a homogeneous pool, suggested by the dissimilar interaction of both dehydrogenases with the bc1 segment.
About 300 revertants were derived from 44 cob- mutants, mapping in the structure coding regions (exon 1, 3, 4, 5, or 6) of the mitochondrial apocytochrome b gene in Saccharomyces cerevisiae, strain 777-3A. Most of the revertants could not be distinguished from the wild-type by means of physiological properties. Twenty-two revertants different in phenotype are described here in more detail. The suppressor mutations (supa) that compensate the primary cob- mutations (i.e., restore growth on glycerol) are mitochondrially inherited. They were localized in the same cob exon regions as the respective primary mutations, except for one revertant with a primary mutation in exon 6 and a suppressor, 4.2 map units distant, which may be located either in intron 5 or downstream in exon 6. Of 21 suppressors 17 are closely coupled to the primary mutation with recombination frequencies of less than or equal to 0.1%-0.3%. An estimate predicts that in more than 80% of these revertants only one amino acid is altered at that point of the polypeptide corresponding to the cob- site in the gene. The most interesting revertant phenotypes are: reduced growth rate on glycerol. The respective cob-/supa mutations are scattered over the whole cob region and cannot be correlated exclusively with special gene regions. decreased cytochrome b content. The most extreme reductions (28% and 30% of wild-type level) were observed to be due to mutations located in the 5' proximal part of exon 1. The highest percentage of revertants with decreased cytochrome b content was predominantly found mapping in exon 3.(ABSTRACT TRUNCATED AT 250 WORDS)
Seven hydatid cysts of the liver were detected by ultrasound and confirmed surgically. On ultrasound scans they were mimicked tumors (Type IV according to the classification established by W. Hassine) and there was a high level of echoes. Two masses were surrounded by a spiral completely free of echoes. Five masses were limited by a border completely free of echoes.
Analytical and quantitative cytology is based upon photometric and morphometric measurements of single cells in stained cytological specimens. It analyzes the features of single cells and cell populations with respect to their cytodiagnostic relevance. One way to do this is the establishment of learning sets of visually selected cells, and the intercomparison of unknown cells with these data sets. Difficulties arise with the visual classification of single cells from PAP-stained gynecological smears and the pooling into classes due to the considerable photometric variation from specimen to specimen. It is demonstrated, that neither for a cancer prescreening apparatus nor an interactive diagnostic machine, highly differentiated learning sets can be dispensed with. The build-up of the TUDAB learning sets and results of single cell classification, visual reclassification, as well as population analysis and specimen classification are shown.
Prevalences of neoplastic and nonneoplastic lesions were reported for 3,000 virgin and 800 retired breeder BALB/c and C57BL/6 mice, untreated and of both sexes. The most common nonneoplastic lesions in the BALB/c mice were: hepatic fatty metamorphosis, uterine hemosiderosis and mineralization, testicular atrophy, ovarian cysts, and adrenal subcapsular spindle cell hyperplasia. The most common neoplasms in the BALB/c mice were: pulmonary tumors, hepatocellular neoplasms, Harderian adenomas, and uterine polyps. Common nonneoplastic lesions in the C57BL/6 mice were: pulmonary lymphoid accumulations, hepatic fatty metamorphosis, multifocal aggregates of mononuclear cells in the liver, proteinaceous renal casts, uterine hemosiderosis, endometrial cystic hyperplasia, ovarian atrophy, ovarian cysts, and pituitary cysts. The most common neoplasms in the C57BL/6 mice were angiosarcomas and pituitary adenomas. Hematopoietic tumors were common in both strains.