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Biomedical subjects

I Bauer

Publications and source records attributed to I Bauer.

At least 19 recordsLinked to original sources

Prevalence of cystic fibrosis mutations in the East German population.

A representative multicenter cystic fibrosis (CF) mutation analysis on about half of all known cystic fibrosis patients of the 5 East German Länder is reported. Analyses for 17 mutations, among them Delta F508, R553X, G542X, S549R,N,I, G551D, S1255X, R347P,H, and Y122X, were performed. As expected, the delta F508 mutation in exon 10 of the CFTR gene is the major gene alteration causing CF in our patients. However, in comparison to studies from Western Germany, a significantly lower percentage of just over 60% is found in our patients, resembling data obtained from slavonic populations. The severe phenotype of cystic fibrosis is most frequently associated with homozygosity for the delta F508 mutation. No particular allele association could be found with the intermediate and mild phenotypes of this disease. The next most frequent of the investigated mutations is R553X (13.3% of non-delta F chromosomes) followed by R347P (9.2%) and G542X (4.4%).

Cystic Fibrosis

Hypomagnesaemia in type 2 (non-insulin-dependent) diabetes mellitus is not corrected by improvement of long-term metabolic control.

Low levels of magnesium have frequently been reported in diabetes mellitus especially in poorly controlled Type 1 (insulin-dependent) diabetic patients. Furthermore hypomagnesaemia might contribute to insulin resistance in Type 2 (non-insulin-dependent) diabetes. As the influence of improved metabolic control on plasma magnesium levels is unknown in Type 2 diabetic patients we studied magnesium plasma levels in 50 patients 1) before, 2) one and 3) three months after the initiation of insulin therapy or intensified treatment with oral hypoglycaemic agents. Magnesium plasma levels were measured by a colorimetric method and were significantly reduced in diabetic patients compared to healthy control subjects (0.79 +/- 0.01 mmol/l vs 0.88 +/- 0.01 mmol/l; p less than 0.0001). Metabolic control was significantly improved as documented by reduced HbA1C levels in both insulin-treated patients or the patients on oral hypoglycaemic agents (p less than 0.003). However, plasma magnesium levels remained unchanged during the follow-up in the insulin-treated group (1: 0.79 +/- 0.02 mmol/l; 2: 0.81 +/- 0.02 mmol/l; 3: 0.79 +/- 0.01 mmol/l) as well as in the patients on oral hypoglycaemic agents (1: 0.79 +/- 0.03 mmol/l; 2: 0.78 +/- 0.02 mmol/l; 3: 0.84 +/- 0.04 mmol/l). This study shows that even marked improvement of glycaemic control does not correct hypomagnesaemia in Type 2 diabetes. We conclude that hypomagnesaemia might be related to the insulin-resistant state and that possible beneficial effect of chronic magnesium administration should be evaluated in these patients.

Blood Glucose

[Detection of human papillomaviruses (HPV) in laryngeal papilloma. An in situ hybridization study].

Together 35 papillomas of the larynx (8 juveniles, 27 adults) were studied for the presence of HPV-DNA by means of nucleic acid hybridization. The hybridization procedure was carried out "in situ" with biotinylated probes of HPV 6/11 and 16/18 under stringent conditions. The results are shown in Table 1. In all juvenile papillomas we detected HPV 6/11, but we did not find positive signals after hybridization with HPV 16/18, 25 (92.6%) of the examinated adult papillomas were HPV 6/11 positive. The detection procedure of HPV 16/18 was positive twice (11.8%). The results of our studies support the hypothesis of HPV 6/11 in development of larynxpapillomas.

Adult

[Type 6/11 and 16/18 squamous epithelial cancers of the upper respiratory tract and digestive system. An in situ hybridization study].

61 squamous cell cancers (27 laryngeal, 12 hypopharyngeal, 14 tonsillary, 8 tongue) with different keratinization and grading and seven lymph node metastases of HPV 16/18 positive carcinomas were analysed for the presence of HPV-DNA by in situ hybridisation. 65.5% of them were found to be positive. Twelve laryngeal carcinomas (44%), five tonsillary tumours (35.7%), eight tumours of the hypopharynx (66.6%) and three tongue carcinomas (37.5%) were shown to contain HPV 16/18 DNA. The detection rates of HPV 6/11 were lower. 44 of the analysed tumours (72.1%) had a grading G2. 29 of these tumours (65.9%) were HPV positive. Only eight of the patients were no heavy smokers or alcoholic drinkers. One of the lymph node metastases was positive for HPV 16/18. The results indicate that HPV may be involved in the pathogenesis of squamous cell carcinomas of head and neck tumours.

Biopsy

[Use of the Dot-Blot technique in the detection of human papillomavirus(HPV) deoxyribonucleic acid (DNA) in malignant tumors of the oropharynx].

A total of 23 malignant oropharyngeal tumours (palate, tongue, tonsils, pharynx) and two lymph node metastases were analysed for presence of papilloma virus DNA. Thirteen (54.5%) of 22 squamous cell cancers of different koilocytosis and grading were found to contain HPV 16/18 DNA. Only 16.6% (4 cases) were positive for HPV 6/11 DNA. There was no detectable HPV-DNA in the lymph node metastases (Table 1). The control biopsies (19) were negative after hybridisation.

Aged

[Bronchoalveolar lavage--a diagnostic method in chronic nonspecific bronchopulmonary diseases in childhood? 2. Studies of cellular and humoral parameters in BAL irrigation fluid].

With a view of the pathogenesis of chronic bronchopulmonary diseases the interrelations between infections and evolving defense system are of interest, they are perhaps detectable by means of diagnostic bronchoalveolar lavage. We carried out cytodifferentiation, investigated adenosine deaminase activities and interleukin 1 formation of macrophages, determined immunoglobulin concentrations (secretory IgA), lysozyme, alpha 2-macroglobulin, alpha 1-antitrypsin, albumin. Because the cytodifferentiation yields insight into topical inflammatory reactions, shows diagnostic useful informations in single cases and because it is simple to carry out we can recommend it for each bronchological examination. There were no results specific for any disease group for parameters mentioned above.

Adenosine Deaminase

First analysis of the F508 deletion in cystic fibrosis patients from the GDR.

Cystic fibrosis (CF) patients (n = 157) from the GDR were analysed for the occurrence of the recently discovered 3bp deletion causing CF. About 50% of all investigated patients were homozygotes and about 30% heterozygotes for this deletion. Of the analysed CF chromosomes from these patients, 62% carry the deletion, which is in strong linkage disequilibrium with the KM19 restriction fragment length polymorphism allele 2 and the 1/2 XV2c/KM19 haplotype.

Chromosome Deletion

Diagnosis of cystic fibrosis by means of particle electrophoresis test.

Incubation of polystyrene latex particles with CF serum leads to reduced electrophoretic mobility (EPM) measured by a particle electrophoresis device. About 85% of 50 CF patients, 60 CF heterozygotes and 190 controls (healthy subjects and patients with different disorders) could be identified correctly.

Adsorption

Pharmacodynamics, pharmacokinetics and metabolism of digitoxin and derivatives in cats.

Derivatives of dihydro-digitoxin (DHD) were studied in the search for a glycoside with a primarily extrarenal clearance and a faster elimination rate than digitoxin. The positive inotropic doses of the derivatives of DHD were higher than those of digitoxin and digoxin. There was no significant difference in the therapeutic margin. After injection of 3H-digoxin in unaesthetized cats, no metabolites were found in the serum which did not bind with the antibody used for the RIA. After injection of 3H-digitoxin and its derivatives, the radioactivity was cleared from the serum at a much lower rate than the concentrations assayed by RIA. The metabolites which did not bind to the digitoxin antibody were hydrophilic and had a low protein binding. Digitoxin-bisdigitoxoside (Dt-2) determined by RIA rapidly disappeared from the serum. The radioactivity remaining after 24 h was eliminated with a half-life of 219 h. Ten min after injection of DHD the serum contained no unchanged DHD, but 36% digitoxin suggesting that the reduction of digitoxin to DHD is reversible and that the conversion of DHD to Dt-2 is the rate limiting step in the metabolism of digitoxin. The total body clearance of digitoxin, its metabolites and derivatives determined by RIA increased in the order DHD-oxime less than or equal to digitoxin less than DHD less than or equal to DHD-acetyloxime less than DHD-methyloxime. The clearance and the elimination rate of DHD-methyloxime were significantly higher than those of digitoxin (P = 0.05).

Animals

Crossovers in two German cystic fibrosis families determine probe order for MET, 7C22 and XV-2c/CS.7.

We have followed the segregation of the probes pJ3.11, 7C22, pB79a, and MET through cystic fibrosis families in the German Democratic Republic with two affected sibs. Two families with a crossover between MET and the CF phenotype were detected. In one of these families recombination was also observed between the DNA probe 7C22 and CF, and between the markers XV-2c and CF, which suggests that XV-2c, MET and 7C22 are all on the same side of CF. The other MET recombinant family is informative with XV-2c and does not recombine, which excludes the genetic order XV-2c--MET--CF if multiple recombinant events are disregarded. These two families together demonstrate that recombinations may occur in a very small genetic interval, which has important implications for prenatal diagnosis based on data from linked markers.

Crossing Over, Genetic

[Microbiologic and clinical significance of cefotiam].

Modern cephalosporins are of considerable importance for the therapy of severe infections by multiresistant organisms. According to in-vitro-findings on ampicillin-resistant E. coli as well as Klebsiella spp., Proteus spp., and serratia spp., altogether 159 strains, instead of cefotaxime nearly always also cefotiam can be used. The two remedies are clearly superior to cephalothin. cefotiam is ineffective to Pseudomonas aeruginosa. But in this case also cefotaxime is clearly inferior to azlocillin. In 6 of 7 casuistic instances the clinical effectiveness of cefotiam could be confirmed with good tolerability. The contemporary establishment of staph. aureus in mixed infections of serratiastaphylococci proved as as particular advantage. A primary therapeutic failure referred to a necrotizing pancreatitis, when no causative organism was proved, in which case also cefotaxime remained without any effect. Despite the improved individual medical possibilities the control of the infectious hospitalism by critical administration of antibiotics and improved hospital hygiene, particularly strict non-infection, must remain the pre-eminent task.

Adult

Structure of nonintegrated, circular Herpesvirus saimiri and Herpesvirus ateles genomes in tumor cell lines and in vitro-transformed cells.

Nonintegrated, circular DNA molecules of Herpesvirus saimiri and Herpesvirus ateles were found in five lymphoid cell lines originating from tumor tissues or established by in vitro immortalization of T lymphocytes. The arrangement of unique (L) and repetitive (H) DNA sequences in circular viral genomes was analyzed by partial denaturation mapping followed by visualization with an electron microscope. Three types of circular viral DNA structures were found. (i) The virus-producing cell line RLC, which is derived from an H. ateles-induced rabbit lymphoma, contains circular viral genomes which consist of a single L-DNA and a single H-DNA region, both the same length as in virion DNA. (ii) The circular viral genomes of the nonproducer cell lines H1591 and A1601, in vitro transformed by H. saimiri and H. ateles, respectively, have deletions in the unique L-DNA region and larger H-DNA regions. Cell line A1601 lacks about 8% of virion L-DNA, and H1591 cells lack about 40% of viral L-DNA information. (iii) The nonproducing H. saimiri tumor cell lines 1670 and 70N2 harbor viral genomes with two L-DNA and two H-DNA regions, respectively. Both types of circular molecules have a long and a short L-segment. The sequence arrangements of circular DNA molecules from H. saimiri-transformed cell lines were compared with those of linear virion DNA by computer alignment of partial denaturation histograms. The L-DNA deletion in cell line H1591 was found to map in the right half of the virion DNA. Comparison of the denaturation patterns of both L regions of cell lines 1670 and 70N2 identified the short L regions as subsets of the long L regions. Thus, circular viral DNA molecules of all four nonproducer cell lines represent defective genomes.

Animals

Episomal and nonepisomal herpesvirus DNA in lymphoid tumor cell lines.

Tumor cell lines derived from Herpesvirus saimiri (H. saimiri)- and Herpesvirus ateles (H. ateles)-induced lymphomas of New World primates and rabbits contain multiple copies of viral genomes. Partial denaturation mapping and blot hybridizations of episomal DNA from lymphoid tumor cell line No. 1670 showed that a 12.5md-fragment is missing which represents the EcoRI D- and H-fragments of virion L-DNA. However, the missing piece can be demonstrated in total cellular DNA by reassociation kinetics, possibly because it persists in integrated form. Both episomal and nonepisomal H-DNA are heavily methylated in a number of the lymphoid cell lines, and methylation may be reduced by conventional methylation inhibitors (S-adenosyl homocystein, SIBA) as well as by the tumor promoting phorbol ester TPA.

Animals