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Biomedical subjects

M Köhler

Publications and source records attributed to M Köhler.

At least 181 records · Page 10Linked to original sources
PubMed1989

Protein-DNA conjugates produced by UV irradiation and their use as probes for hybridization.

Several proteins have been crosslinked to DNA by low dose uv irradiation. The principle of the method is based on an efficient and fast radiation induced reaction of amino acid residues with DNA at low pH. The method seems to be of general applicability for crosslinking proteins to DNA in a very simple one step procedure. Some of such DNA-protein conjugates have been used as probes for hybridization experiments. DNA-protein A probes were found to be most useful.

Blotting, Southern↗
PubMed1989

GABAA receptor beta subunit heterogeneity: functional expression of cloned cDNAs.

Cloned cDNAs encoding two new beta subunits of the rat and bovine GABAA receptor have been isolated using a degenerate oligonucleotide probe based on a highly conserved peptide sequence in the second transmembrane domain of GABAA receptor subunits. The beta 2 and beta 3 subunits share approximately 72% sequence identity with the previously characterized beta 1 polypeptide. Northern analysis showed that both beta 2 and beta 3 mRNAs are more abundant in the brain than beta 1 mRNA. All three beta subunit encoding cDNAs were also identified in a library constructed from adrenal medulla RNA. Each beta subunit, when co-expressed in Xenopus oocytes with an alpha subunit, forms functional GABAA receptors. These results, together with the known alpha subunit heterogeneity, suggest that a variety of related but functionally distinct GABAA receptor subtypes are generated by different subunit combinations.

Adrenal Medulla↗
PubMed1989

Two novel GABAA receptor subunits exist in distinct neuronal subpopulations.

Two cDNAs encoding novel GABAA receptor subunits were isolated from a rat brain library. These subunits, gamma 2 and delta, share approximately 35% sequence identity with alpha and beta subunits and form functional GABA-gated chloride channels when expressed alone in vitro. The gamma 2 subunit is the rat homolog of the human gamma 2 subunit recently shown to be important for benzodiazepine pharmacology. Cellular localization of the mRNAs encoding the gamma 2 and delta subunits in rat brain revealed that largely distinct neuronal subpopulations express the two subunits. The delta subunit distribution resembles that of the high affinity GABAA receptor labeled with [3H]muscimol; the gamma 2 subunit distribution resembles that of GABAA/benzodiazepine receptors labeled with [3H]flunitrazepam. These findings have implications for the composition of two different GABAA receptor subtypes and for information processing in networks using GABA for signaling.

Animals↗
PubMed1989

Subcutaneous injection of desmopressin (DDAVP): evaluation of a new, more concentrated preparation.

A more concentrated desmopressin (DDAVP) preparation (40 micrograms/ml), which required small injection volumes (less than 1 ml), was studied in a double-blind trial in 10 healthy volunteers, 12 patients with haemophilia A, and 8 patients with uraemic bleeding. DDAVP was administered by subcutaneous injection at a dose of 0.4 micrograms/kg body weight. In healthy subjects, peak levels of DDAVP ranging from 480 to 638 pg/ml were reached 1 h after the subcutaneous injection and DDAVP was eliminated with a mean half-life of 3.1 h. DDAVP produced a 2.5-fold (3.0-fold) increase of factor VIII:C (factor VIII:Ag) and a 1.9-fold (2.2-fold) increase of von Willebrand factor:Ag (ristocetin cofactor) over baseline levels. Additionally, a 2.1-fold increase of tissue-type plasminogen activator antigen was observed. Factor VIII and von Willebrand factor were rapidly eliminated with a half-life ranging from 1.3 to 5.7 h and from 1.1 to 11.4 h, respectively. In haemophilia A patients, DDAVP produced a 2.3-fold increase of factor VIII:C 1 h after the injection. DDAVP was given on 8 occasions for management of bleeding, and only in 1 patient did a wound haematoma (after herniotomia) occur. In 7 of the 8 patients with uraemia the bleeding time shortened, and in all patients an increase of platelet retention and a decrease of platelet count was observed (p less than 0.05). No serious local or systemic untoward side effects were observed.

Adult↗
PubMed1989

Study of a new low molecular weight heparin (LU 47311) administered to healthy volunteers.

A newly developed low molecular weight heparin (LU 47311) was given to 6 healthy volunteers (males, mean age: 30.5 years, range: 20-39 years). They obtained a single dose of 40 and 60 anti FXaU per kg body weight, respectively, by subcutaneous administration. The anti FXa elimination half-life was close to 3 hours. The APTT showed slight response following high dose. No significant influence on fibrinolysis as measured by t-PA and PAI assays was noticed. There was no clear evidence of enhancement of platelet function when detected by Born's method and platelet factor 4 and beta-thromboglobulin assays. However, a moderate but significant increase of thromboxane B2 was noticed in the group obtaining an elevated dose of LMW heparin. Serum levels of triglycerides and cholesterol remained unaltered. The aminotransferases, electrolytes, renal function parameters and cell counts of the peripheral blood were not influenced by LMW heparin.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

[The use of the determination of the immune competence of patients with malignant tumors of the maxillofacial area for making a diagnosis and prognosis].

The value of evidence of pretherapeutic investigations with the leucocyte adherence inhibition assay (LAI) for 5-year prognosis we examined in 42 patients with malignant tumors of the maxillo-facial region. We found a tendency of higher frequency of recurrence in patients with preoperative positive LAI, but this was not statistically significant. In 19 patients we accomplished follow-up studies until 20 months after operation. Here we found no false-positive LAI, so that a positive LAI indicated always a tumor recurrence (33% of patients with recurrence), but two thirds of patients with recurrence reacted negative. In conclusion the LAI is of too small sensitivity and of too high expense.

Diagnosis, Differential↗
PubMed1988

Structural and functional basis for GABAA receptor heterogeneity.

When gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in vertebrate brain, binds to its receptor it activates a chloride channel. Neurotransmitter action at the GABAA receptor is potentiated by both benzodiazepines and barbiturates which are therapeutically useful drugs (reviewed in ref. 1). There is strong evidence that this receptor is heterogeneous. We have previously isolated complementary DNAs encoding an alpha- and a beta-subunit and shown that both are needed for expression of a functional GABAA receptor. We have now isolated cDNAs encoding two additional GABAA receptor alpha-subunits, confirming the heterogeneous nature of the receptor/chloride channel complex and demonstrating a molecular basis for it. These alpha-subunits are differentially expressed within the CNS and produce, when expressed with the beta-subunit in Xenopus oocytes, receptor subtypes which can be distinguished by their apparent sensitivity to GABA. Highly homologous receptor subtypes which differ functionally seem to be a common feature of brain receptors.

Amino Acid Sequence↗
PubMed1988

In vivo recovery and half-life time of a steam-treated factor IX concentrate in hemophilia B patients. The influence of reagents and standards.

Factor IX (FIX) recovery and half-life was measured in ten hemophilia B patients under standardized conditions. Each patient received a steam-treated high-purity factor IX concentrate at a dose of 19-39 U/kg body weight. FIX activity was determined using a one-stage assay, which was calibrated against the international concentrate standard (reagents from Immuno, Heidelberg). The in vivo recovery ranged from 24% to 53% (mean value 37.7%) and the half-disappearance time (HDT) from 8-30 h (mean 16.7 h). In four of the ten patients, the distribution and elimination half-lives were estimated and ranged from 0.3 h to 3.9 h (mean 1.4 h) and from 28.6 h to 39.7 h (mean 33.1 h), respectively. In six patients FIX was redetermined using a different FIX deficient plasma and a plasma standard (reagents from Merz & Dade, Munich, FRG). Recoveries and HDT based on the results obtained with this method were significantly higher (68.2% vs 39.7%; p less than 0.05), and longer (14.8 h vs 10.6 h; p less than 0.05), respectively. FIX activity was also measured by both assay systems in 100 healthy subjects (50 males, 50 females). The reagents from Immuno yielded a mean value of 0.77 U/ml, while the mean FIX activity utilizing standards and reagents from Merz & Dade was 1.11 U/ml (p less than 0.000001). The coefficient of correlation between the FIX activity measurements, as determined in 100 healthy subjects and 6 hemophilia B patients using the different test systems, was r = 0.9 (N = 159; y = 0.08 +/- 1.3* chi; p less than 0.001). Our data suggest that recovery and HDT of factor IX concentrate strongly depend on the assay and calibration conditions and that an international FIX activity plasma standard is urgently required.

Adolescent↗
PubMed1988

Pharmacokinetics and haematological effects of desmopressin.

The pharmacokinetics and haematological effects of 1-deamino-8-D-arginine vasopressin (desmopressin, DDAVP) after intravenous, subcutaneous and intranasal administration has been studied in man. Using a sensitive, specific radioimmunoassay for DDAVP, the AUC was determined for each route of administration. It was not significantly different for the i.v. and s.c. routes. There was no effect of the route on the plasma half-life of DDAVP which ranged from 2.7 to 4.6 h. Absorption of DDAVP after intranasal (i.n.) administration was poor. Based on AUC data, bioavailability via the two s.c. methods and the i.n. route was 112%, 94% and 2%, respectively. DDAVP has a pronounced effect on coagulation and fibrinolytic parameters, causing a 4.0- (i.v.), 2.9- (s.c.), 3.1- (s.c.; 40 micrograms/ml) and 1.2- (i.n.) fold increase in factor VIII: Ag. The corresponding effect on tissue-type plasminogen activator (t-PA) was 1.9- (i.v.), 1.3- (s.c.), 2.2- (s.c.; 40 micrograms/ml) and 1.0- (i.n.) increase over the basal value. There was also a 1.4- to 1.6-fold increase in leukocyte count 4 h after s.c. and i.v. DDAVP. At plasma DDAVP levels greater than 300 pg/ml no correlation was found between the AUC and the maximum plasma DDAVP and biological response, which indicates a ceiling limit for exogenous stimulation of the coagulation and fibrinolytic systems.

Administration, Intranasal↗
PubMed1988

Experimental confirmation of the change of water structure in the critical range of micelle formation: a new method of critical micelle concentration (CMC) determination.

The decrease in the water structure in the critical range of micelle formation, which had been deduced theoretically, was confirmed by means of a new determination method. The method was based upon the dependence of the gelatin helicity on the water structure and the correlation between the helix-coil equilibrium and the disintegration of gelatin microcapsules. The significant rise in the disintegration rate, indicating a decay of water structure, represents also a new method of critical micelle concentration (CMC) determination.

Capsules↗
PubMed1988

Reference values and variability of plasminogen in healthy blood donors and its relation to parameters of the fibrinolytic system.

During a survey of four month's duration the following parameters were determined in 43 healthy blood donors (22 males, 21 females; mean age 29 years/20-49/): plasminogen activity, plasminogen concentration, alpha 2-antiplasmin (alpha 2-AP) activity, alpha 2-AP concentration, tissue type plasminogen activator (t-PA) activity, t-PA concentration, plasminogen activator inhibitor--I (PAI-I) activity, AT III activity, AT III concentration and heparin cofactor II (HC II) activity. Normal values including standard deviation (x +/- 2s) were: plasminogen activity: 96.3% (65.9-126.8), plasminogen concentration: 12.2 mg/dl (7.7-16.8), alpha 2-AP activity: 99.9% (83.8-116), alpha 2-AP concentration: 108.1% (84.5-131.8), t-PA activity: 0.85 IU/l (0.0-1.92), t-PA concentration: 10.3 ng/ml (2.5-18.1), PAI-I activity: 15.2 AU/ml, AT III activity: 111.4% (87.8-134.9), AT III concentration: 31.6 mg/dl (24.2-39.1) and HC II activity: 110.7% (81.4-140.0). Concerning plasminogen values no sex related difference could be stated. Women who were smokers and used oral contraceptives tended to present elevated t-PA activity levels due to a lower activity of PAI-I, although this tendency was not significant. Determining concentration and activity of components in the fibrinolytic system plays an important part in the diagnosis, therapy and prognosis of thrombophilic disorders.

Adult↗
PubMed1988

The clinical significance of different routes of desmopressin (DDAVP) administration in various bleeding disorders.

In our study, we wanted to evaluate the clinical effect of s.c. DDAVP on haemostasis in different kinds of bleeding disorders. A total of 109 patients was treated with DDAVP s.c. at a dose of 0.4 microgram/Kg body weight. An effect of DDAVP on F VIII modalities was found after s.c. injection in all patients, but in comparison to i.v. DDAVP, the effect seems to be somewhat less. From our data, the patients blood groups do not influence the amount of F VIII modalities. Furthermore, the s.c. injection of DDAVP was found to be effective in patients with disorders of primary haemostasis. A number of operations was performed under the use of s.c. DDAVP in 24 patients with different kinds of bleeding disorders, in none of them, bleeding complications occurred.

Administration, Intranasal↗
PubMed1988

[Problems in measuring parameters of the fibrinolytic system: circadian rhythm of tissue-type plasminogen activator and plasminogen activator inhibitor].

Reference values of tissue-type plasminogen activator (t-PA) antigen, t-PA activity, and plasminogen activator inhibitor (PAI) were established in healthy blood donors using different assay systems. Significant differences between male and female donors were found, due to the intake of oral contraceptives. PAI-activity determinations, using the method described by Chmielewska et al. (1983) or the modification by KabiVitrum, were only poorly correlated (r = 0.53; N = 98; p greater than 0.0001). PAI-activity (Chmielewska et al. 1983) determinations and t-PA antigen measurements were also significantly correlated (r = 0.52; N = 96), which may be a consequence of a joint regulation. In a second series, the diurnal variations of t-PA and PAI were investigated in blood donors (N = 83). PAI-activity and t-PA antigen were about 30 to 40 percent decreased in the evening hours, when compared with the morning values. In two controlled studies, the acute effects of heparins and desmopressin (DDAVP) on the fibrinolytic system were investigated in healthy individuals (N = 10). Again, a pronounced diurnal variation of t-PA and PAI was found. PAI and t-PA were significantly higher in the morning when compared with the evening. However, t-PA activity (Verheijen et al. 1982) showed a reversed pattern, low levels were found in the morning and increased levels in the evening. Our studies clearly show that when determining parameters of the fibrinolytic system, the diurnal variations have to be taken into account.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

[Administration of terfenadine in a single dose: comparison to standard treatment, as a double blind study, in patients presenting with allergic rhinitis].

This double-blind, randomized multicentre study was designed to compare efficacy and tolerability of 120 mg terfenadine taken once daily (in the morning) with the established regimen of 60 mg terfenadine taken twice daily in the treatment of seasonal rhinitis. Two comparable groups, a total of 191 hay fever patients, were treated for 1 week. Symptom severity was assessed by the investigators before and at the end of the treatment (visual analogue scale), and daily by the patient (four-point rating scale). All symptoms improved to a similar degree in both groups. Differences between the two groups were not statistically significant, except for nasal symptoms in three cases as assessed by the visual analogue scale in one centre (better relief in the group given 120 mg terfenadine once daily). Tolerability was good and similar in both groups. The data presented show that in the treatment of hay fever 120 mg terfenadine given once daily is an effective, convenient and well tolerated alternative to the regimen of 60 mg terfenadine given twice daily.

Benzhydryl Compounds↗