Biomedical subjects
Publications and source records attributed to S Köhler.
This paper presents an information system for the support of clinical research in reproductive medicine (ISRA/R). The system is established on a database approach--all data arising at our center is instantly recorded on-line into the database. Thus a mighty tool has been established to aid us considerably in our daily work as well as in clinical studies.
In the present paper we examined, whether the combined GnRH-agonist/hMG therapy implies an increased risk of the ovarian hyperstimulation syndrome (OHS). In a retrospective analysis, 525 GnRH-a/hMG cycles were compared with 643 cycles of hMG stimulation, which were simultaneously performed at the Department of Gynecology and Obstetrics of the University of Hamburg. Two different GnRH-agonists were used: Buserelin (Hoechst) given intranasally (410 cycles) and Triptorelin (Ferring) intramuscularly (115 cycles). The clinical results of hMG "only"-therapy revealed an OHS incidence of 7% for grade II and 0.2% for grade III. In contrast, significantly higher incidences were observed after GnRH-a/hMG treatment. In Buserelin/hMG cycles in 23% OHS grade II and in 1.0% OHS grade III occurred, in Triptorelin/hMG cycles in 40% OHS II and in 5.2% OHS III, respectively. The increased incidence of OHS correlated with higher ovarian estrogen production as well as a higher number of follicles following the GnRH-a/hMG stimulation. Furthermore, in GnRH-a/hMG cycles a prolonged duration of follicular maturation occurred due to an increase of the active phase; in addition the amount of hMG-ampoules needed for ovarian stimulation was higher. After GnRH-a/hMG treatment, an endogenous LH-surge was not detected, whereas in 34% of hMG stimulated cycles irregular LH-fluctuations were observed. There was a higher pregnancy rate in GnRH-a/hMG cycles (15%/525 cycles), as compared to hMG stimulation (8%/643 cycles), but the abortion rate was similar (23%, GnRH-a/hMG, versus 13%, hMG). The demonstration of an increased ovarian response leading to better pregnancy rates but also higher risks of OHS is well known from earlier data of hMG stimulation in patients with hypogonadotropic amenorrhoea (WHO group I). This implies that GnRH-agonist pre-treatment shows similar endocrine conditions in normogonadotropic patients.
Both the androgen-induced decline in serum sex hormone-binding globulin (SHBG) levels during puberty and the anabolic effect of exogenous testosterone are absent in patients with androgen insensitivity (testicular feminization). To determine whether the androgen-induced decline in serum SHBG could be used as a test of androgen sensitivity, we studied the effect of the anabolic-androgenic steroid stanozolol (17 beta-hydroxy-17 alpha-methyl-5 alpha-androstano-[3,2-c]pyrazol) on serum SHBG in 25 control subjects, 3 patients with complete androgen insensitivity, and 4 patients with partial androgen insensitivity. Stanozolol was administered orally for 3 days (0.2 mg/kg.day); blood samples were taken before and 5, 6, 7, and 8 days after the beginning of the test for measurements of serum SHBG. The lowest value (i.e. the peak response) in each subject was used as the measure of the response to stanozolol. In the control subjects the mean nadir serum SHBG level was 51.6 +/- 5.9% (+/- SD) of the initial value (P less than 0.001). In the 4 patients with partial androgen insensitivity the nadir serum SHBG ranged from 73-89%, and in the 3 patients with complete androgen insensitivity it ranged from 93-97% of the initial value. Thus, the decrease in serum SHBG after short term administration of stanozolol reflects androgen responsiveness and, thus, may be used to differentiate patients with androgen insensitivity syndromes from those with other causes of male pseudohermaphroditism.
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This paper for the first time presents the results of extensive histological and histomorphometric studies investigating the tensile strength of tissue adhesives in model experiments on animals. The material used in comparative studies were TISSEEL, a human adhesive based on fibrinogen, HISTOACRYL-blue, a cyanoacrylate, and KL-3, a type of urethane adhesive. All the materials used in these studies were shown to be principally suitable as tissue adhesives. TISSEEL, the biological adhesive, was obviously superior to all the other adhesives whereas the two synthetic adhesives HISTOACRYL-blue and KL-3 were found to be roughly equal in their properties. The animal model described in the present paper is recommended for use as a standard technique for testing the suitability of new tissue adhesives.
The kinetics of complex formation between recombinant hirudin or recombinant hirudin mutants with thrombin were analyzed. In order to elucidate the inhibitor's reactive site peptide bond predetermined amino acid substitutions were introduced at positions of basic amino acid residues by means of site-directed mutagenesis of a hirudin gene. In comparison to recombinant hirudin (Ki = 19 pM) only those mutant inhibitors which were modified at amino acid position Lys47 showed a higher Ki value for their complexes with thrombin. The observed effects are mainly due to increased koff rate constants.
Thiol-activated hemolysins (listeriolysins) from Listeria monocytogenes (Sv4b) and Listeria ivanovii were purified to homogeneity. The N-terminal amino acid sequences of the 58 kDa listeriolysin of L. ivanovii and of a 24 kDa protein which may represent the CAMP-factor of L. ivanovii were determined. Antibodies raised against the L. ivanovii listeriolysin and anti-streptolysin O antibodies were used in Western blot analyses to detect listeriolysin(s) in virulent and avirulent Listeria strains. It was found that all virulent strains of L. monocytogenes synthesize and secrete listeriolysin (Mr 58-59 kDa), albeit in significantly variable quantities. No protein cross-reaction with anti-listeriolysin antibodies or anti-streptolysin O-antibodies was present in the supernatant of Listeria innocua, Listeria welshimeri, Listeria grayi and Listeria murrayi strains. Furthermore, the avirulent but hemolytic Listeria seeligeri did not cross-react with these antibodies. In a L. monocytogenes (strain EGD) gene bank constructed in Escherichia coli two types of hemolytic clones were identified. The first type carried recombinant plasmids with a common 2.0 kb fragment coding for a 23 kDa protein. This hemolytic activity was not activated by DTT and the 23 kDa protein did not cross react with anti-listeriolysin or anti-streptolysin antibodies. The other type of hemolytic clones was detected by using anti-streptolysin O antibodies to screen the gene bank. Some of these clones synthesized a protein of 61 kDa which cross reacted with anti-streptolysin O (or anti-listeriolysin) antibodies. By transposon Tn916 mutagenesis of L. monocytogenes two types of nonhemolytic mutants were obtained. Type I produced no extracellular protein that cross reacted with anti-listeriolysin (or anti SLO) antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
For the identification of the primary binding site of hirudin for thrombin we generated hirudin mutants with site directed amino acid substitutions with the help of recombinant DNA technology. Preliminary results indicate, that lys (47) may be directly involved in the hirudin-thrombin interaction: 1. The mutant glu (47) shows a Ki-value which is increased by two orders of magnitude (1.6.10(-9) M); 2. Incubation of mutant ala(48) with endoproteinase lys-C results in proteolysis of the newly formed peptide bond lys(47)-ala(48), whereas all other peptide bonds (lys-X) are not accessible.
Submitted is the revised version of a proposal for a guideline for biological testing of materials (biomaterials) which remain temporarily or permanently, resp., at or in the human body or have contact with drugs or body fluids outside the human body.
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The activities of the alkaline and the acid bone phosphatases as well as the concentrations of calcium and phosphorus were measured in the periimplantal tissue of the rat femur bone after implantation of the vitroceramic Ap 40, the metal oxide stabilized vitroceramics Ap 40 A and Ap 40 Z, as well titanium after 2, 10, and 15 weeks. The incorporation of the vitroceramic Ap 40 turns out like a primary bone fracture healing. The implants Ap 40 A and Ap 40 Z are a compromise with a higher stability and the osteogenesis induced effect is preserved, but is belated in contrast to Ap 40.
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A method for testing the bioactivity of hard tissue implants is described by analysis of the periimplantary enzyme activities of the alkaline and the acid phosphatase in the femur of rats. Bioactive materials cause an increase of the activity of the alkaline phosphatase in the periimplantal bone tissue. An increase of the activity of the acid phosphatase is a measure for the biodepressive effect of the implant material.
A DNA containing the coding sequence for the proteinase inhibitor protein hirudin from the leech Hirudo medicinalis has been obtained by enzymic ligation of chemically synthesized deoxyoligonucleotides. The 226 bp synthetic gene carries signals for the translation initiation and termination. Fragment synthesis was performed by the Khorana ligation method as well as by the fill-in method. Efficiencies of these two methods are compared. The synthetic gene was expressed in E. coli as a fusion protein with beta-galactosidase under the control of the lac-promoter as well as a non-hybrid protein under the control of the lambda PL-promoter. The non-hybrid expression product was shown to have similar biological properties as the authentic protein isolated from the leech.
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