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G Baumann

Publications and source records attributed to G Baumann.

At least 217 records · Page 12Linked to original sources
PubMed1994

Serum growth hormone-binding protein is unchanged in adult panhypopituitarism.

The role of GH in regulating GH-binding protein (GHBP) and GH receptor concentrations in humans is not clear. Studies performed mostly in children and on a minor scale in adults are somewhat controversial. The key question as to whether GHBP levels are altered in hypopituitarism before GH treatment is instituted remains unanswered. In this study, we have selected a severely GH-deficient group of adult patients with panhypopituitarism, acquired as a result of surgery and irradiation of hypothalamic-pituitary tumors, to evaluate the GHBP/receptor status by measuring GHBP activity in plasma. Twenty panhypopituitary patients (8 males and 12 females; age range, 20-74 yr) and 20 age (22-68 yr)- and sex-matched normal subjects were studied. GH deficiency was confirmed by insulin-induced hypoglycemia and arginine infusion tests; the peak GH response was less than 2 micrograms/L. Plasma insulin-like growth factor-I levels were below or in the low normal range (mean +/- SD, 88.3 +/- 53.6 micrograms/L) and were significantly different from insulin-like growth factor-I (IGF-I) levels in the normal group (mean +/- SD, 189 +/- 49.8 micrograms/L; P < 0.01). Plasma GHBP activity, measured using a GH-binding/gel chromatography assay, showed similar values in the GH-deficient group (mean +/- SD, 14.1 +/- 3.83%) and the control group (mean +/- SD, 13.7 +/- 3.79%), with no statistically significant difference. Neither the intra- nor intergroup comparison of GHBP levels according to age and sex showed statistically significant differences or age trends. In the light of these data and considering that GHBP activity in plasma probably reflects the GH receptor status in tissues, we may assume that the GH receptor was unaffected by chronic GH deficiency. These findings also support the previously reported concept that the GHBP/receptor level is a relatively fixed determinant of growth, established individually and independently of GH secretory status in early life, perhaps on a genetic basis.

Adult↗
PubMed1994

A growth hormone/prolactin-binding protein in human milk.

In the course of studies of the distribution of GH-binding proteins (GHBP) in biological fluids, we identified a human (h) GH/hPRL-binding component in human milk. To characterize its nature, 16 human milk samples were analyzed by molecular exclusion chromatography after incubation with monomeric [125I]hGH. All samples showed a peak indicative of a hGH-containing complex with a mol wt of 52 kilodaltons (kDa)--considerably smaller than the high affinity GH-binding protein complex in plasma (80-85 kDa). Binding of [125I]hGH was inhibited in a dose-dependent fashion by unlabeled hGH and to a lesser extent by hPRL, but not by oGH. Scatchard analysis yielded a Ka of 2.1 x 10(8) M-1 and a maximum binding capacity of 5.1 micrograms/L for hGH, and a Ka of 0.5 x 10(8) M-1 for hPRL. The derived molecular size of the milk GH/PRL-binding protein (BP) is 30 kDa, assuming 1:1 binding stoichiometry. The milk BP was not immunoprecipitable with any of 4 monoclonal antibodies directed against the hGH receptor or with a polyclonal antiserum directed against the hPRL receptor. The milk BP bound to hGH affinity columns, but unlike the GHBP in human plasma, did not bind to wheat germ lectin columns, suggesting different or no glycosylation. We conclude that human milk contains a high affinity GH/PRLBP that differs from the serum GHBP in its ligand specificity (binding both hGH and hPRL), molecular size, immunological, and glycosylation characteristics. Based on its immunochemical and ligand-binding characteristics, it does not appear to be a truncated GH receptor such as the plasma GHBP. Its lack of immunoreactivity with the one available antiserum also does not support its identity with a truncated PRL receptor. However, it cannot be excluded that the milk BP may represent a proteolytically or otherwise altered truncated form of the PRL receptor (or, less likely, the GH receptor) that maintains some binding activity, but has its immunological epitope(s) disabled. The precise nature and function of this protein remain to be defined.

Binding, Competitive↗
PubMed1994

Assay systems for the growth hormone-binding protein.

The first method used for detection of growth hormone-binding protein (GHBP) in biological fluids was based on the incubation of the sample with radiolabeled GH followed by separation of bound and free GH by gel exclusion chromatography. Recently, other methods have been developed which are faster and easier to use. These methods include variants of the original binding/column assay (e.g., separation of bound and free GH is obtained by immunoprecipitation, charcoal adsorption, ion exchange chromatography, or HPLC), and a ligand-mediated immunofunctional assay (LIFA), in which a monoclonal antibody is used to capture the GHBP on a microtiter plate; all binding sites are saturated with GH and an anti-GH antibody is used to detect the amount of GH (endogenous and exogenous) bound to the GHBP. To permit comparison of results obtained by different methods we have cross-validated the LIFA with two different binding assays: (i) the original long column assay (column assay), and (ii) an assay based on immunoprecipitation (RIPA) of the GH/GHBP complex with an anti-GHBP antibody.

Adolescent↗
PubMed1994

Molecular mechanisms of immunosuppressive agents.

Recent data on the molecular mechanism of some immunosuppressive drugs provide strong support for the fascinating postulate that CSA and FK506 work by binding to immunophilins and then, as a drug-immunophilin complex, inhibiting the calcium-activated protein phosphatase, calcineurin. This inhibition could result in an altered modification pattern of the cytoplasmic components of transcription factors, thereby disturbing their nuclear translocation, which is a prerequisite for proper IL-2 transcription. It looks as if, with the immunosuppressive microbial metabolites as molecular probes, the pieces of this complex signal transduction puzzle are starting to fit together! Once the details of the chain of events along the T-cell signaling pathways are known, the molecular structures involved will provide new tools to be used in the search for and the rational design of new and improved therapeutic agents.

Amino Acid Isomerases↗
PubMed1994

[Viability of corneal endothelium after long-term storage at +4 degrees C in Optisol].

For successful corneal transplantation endothelial cell function of at least 50% is considered necessary. Corneal grafts are often evaluated by morphological criteria, such as endothelial cell size or density. Donor corneas with a storage time longer than 10 days are usually excluded from transplantation. The viability of the endothelium of 35 human donor corneas was evaluated after storage for up to 27 days at +4 degrees C in Optisol storage medium by using the Janus green photometry technique. The results were compared with the endothelial cell density counted. We demonstrated that the human corneal endothelium remains satisfactorily viable (minimum 68% viable cells) for a period of at least 27 days and that morphological changes do not sufficiently reflect the functional intactness of the cornea. Morphological irregularities should be interpreted as a form of compensation by a viable endothelial cell layer.

Aged↗
PubMed1994

[Therapy of cardiogenic shock].

Cardiogenic shock is a syndrome of different etiologies resulting in the inability of the heart to provide adequate O2 delivery to peripheral organs and tissues with or without signs of severe pulmonary congestion or pulmonary edema. Clarification of the underlying etiologies is essential for prognosis and therapy. Depending on the various etiologies, the therapeutic procedure may be totally different. Furthermore, it is decisive to differentiate between an acute shock (e.g., acute myocardial infarction) and the development of a cardiogenic shock state on the basis of preexisting chronic congestive heart failure (e.g., congestive cardiomyopathy). Whenever possible the underlying disease should be treated causally (e.g., PTCA or thrombolytic therapy in AM, lysis in acute pulmonary embolism) in addition to symptomatic pharmacologic treatment with vasodilators and/or inodilators. In myogenic cardiogenic shock, the treatment with inotropic drugs (with and without vasodilatory potency) and, if necessary, in combination with additional vasodilators may be life-saving. At present, there is no alternative to catecholamines in the acute state with apparent hemodynamic instability. Catecholamines still represent the initial first line treatment. A Swan-Ganz catheter is mandatory in such situations. In view of the rapid beta 1-receptor down-regulation induced by endogenous catecholamines, long-term administration of exogenous catecholamines (adrenalin, dopamine, dobutamine), seems essentially problematic, since these compounds intensify and accelerate this process.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1994

[Value of color duplex ultrasound in diagnosis of insufficiency of perforant veins. A prospective study of 94 patients].

Using colour coded duplex sonography in pre-operative diagnosis of insufficient perforant veins we succeeded in accomplishing a close correspondence between diagnostic methods and intraoperative findings. We examined 94 patients suffering from primary varicosis by duplex sonography and found 334 perforant veins in total, i.e. 2.4 per leg, which we marked with special ink. Nearly 50% of the patients had also been examined by phlebography, which was evaluated by the vascular surgeons only. One third of the phlebographies were not satisfactory. The vascular surgeon evaluated the accuracy of perforant veins marked by duplex sonography with 95.8%, whereas the sufficient phlebographies only reached an accuracy of 65%. The insufficient phlebographies showed only 16% of the duplex-sonographically marked perforant veins. The confluence of the insufficient minor saphenous vein with the popliteal vein corresponded in all of the 22 cases with the sonographic findings. The colour coded duplex sonography enables the vascular surgeon to localize the insufficient perforant veins exactly and also provides for minimal tissue damage, which means a relevant decrease of postoperative pain.

Blood Flow Velocity↗
PubMed1993

Cyclosporins. Structure-activity relationships.

Cyclosporin A (Sandimmun) achieves immunosuppressive activity by complex formation with cyclophilin and subsequent binding of the binary complex to and inhibiting protein phosphatase 2B (calcineurin). Complexes of nonimmunosuppressive cyclophilin binding cyclosporin analogues do not inhibit protein phosphatase 2B, suggesting a crucial role for this enzyme in T cell activation. Binding of cyclosporin A to cyclophilins A, B, and C, respectively, results in complexes of significantly different inhibitory potency. The cyclosporin molecule thus has two functional domains, one mediating cyclophilin binding and a second one endowing affinity of the complex to calcineurin, thereby inhibiting its enzyme activity. Structure-activity studies and x-ray crystallography of cyclosporin-cyclophilin complexes indicate a crucial role of leucine side chains in positions 4 and 6 of the cyclosporin macrocycle for the calcineurin interaction.

Amino Acid Sequence↗
PubMed1993

Molecular mechanisms of immunosuppression by cyclosporins.

Despite the successful clinical application of the immunosuppressive drug cyclosporin A (CsA, Sandimmun), its precise mechanism of action in the process of T cell activation remains elusive. CsA binds to the high-affinity cytosolic receptor cyclophilin whose peptidyl-prolyl cis-trans isomerase activity is inhibited upon binding. The linkage of this effect with the inhibition of the T cell receptor-mediated signal transduction pathway, which leads to a suppression of lymphokine gene transcription, is still unclear. We analyzed the relationship between cyclophilin-binding and immunosuppressive activity (e.g., effect on IL-2 transcription) of cyclosporin derivatives in vitro. The results show that binding to cyclophilin is required, but not sufficient for immunosuppression. Cyclosporin analogues which completely lack immunosuppressive activity but fully retained their cyclophilin-binding capacity antagonize the immunosuppressive activity of CsA. These derivatives inhibit the isomerase activity of cyclophilin, which clearly demonstrates that inhibition of the cyclophilin isomerase activity does not lead to immunosuppression. In analogy to the other immunosuppressants of microbial origin, FK-506 and rapamycin, a specific structure of the "effector" domain of CsA, which is unrelated to the cyclophilin-binding domain, determines the biological activity. In the nucleus, CsA interferes with the DNA-binding of inducible transcription factors to their respective DNA motifs within lymphokine promoters by affecting intracellular translocation of transcription factor subunits.

Amino Acid Isomerases↗
PubMed1993

Effect of growth hormone administration frequency on 24-hour growth hormone profiles and levels of other growth related parameters in girls with Turner's syndrome. Dutch Working Group on Growth Hormone.

OBJECTIVE: The optimal dose and frequency of GH administration in Turner's syndrome is unknown. There is some evidence that a schedule which mimics normal pulsatile GH secretion may be more effective than a single daily dose. We therefore wished to study the influence of the frequency of GH administration on 24-hour GH profiles and levels of other growth-related factors in Turner's syndrome. DESIGN: Four weeks after initiation of 0.05 microgram/kg/day ethinyl oestradiol, we compared twice daily (b.i.d.-fractionated dose) with once daily (o.d.) s.c. injections of 6 IU GH/m2/day in a 2-week cross-over design with a 2-week washout interval. Each treatment period was concluded with 24-hour GH profile tests. Pretreatment plasma/serum levels of GH, IGF-I, binding proteins for GH (GHBP) and IGF-I (IGFBP-3) were used as a basis for comparison of the levels found after each regimen. A one-compartment open model was used for estimation of pharmacokinetic parameters. SUBJECTS: Ten previously untreated girls with Turner's syndrome aged > or = 11 years. MEASUREMENTS: Plasma levels of GHBP by standardized binding assay; GH, IGF-I, and IGFBP-3 serum/plasma levels by radioimmunoassay. RESULTS: There were significantly higher maximum GH levels and a greater area under the curve with o.d. than with b.i.d. GH, while GH clearance was greater with b.i.d. The pharmacokinetic values with o.d. injections were in conformity with values for healthy and GH-deficient children. Pretreatment GHBP levels tended to be high compared with values in healthy prepubertal children. These levels decreased with GH therapy, significantly so with b.i.d. GH only. There was a significant increase in levels of IGF-I and IGFBP-3, irrespective of regimen. The IGF-I to IGFBP-3 ratio, a possible indicator of the growth response, rose significantly and comparably with both regimens. There was no consistent diurnal variation with either regimen in GHBP, IGF-I or IGFBP-3 levels. Four-hourly levels of GH, GHBP, IGF-I and IGFBP-3 were not correlated. CONCLUSIONS: Although the 24-hour profiles differed during once or twice daily administration of the same total growth hormone dose, the diurnal pattern and mean levels of factors involved in the biological effects of GH are comparable for both regimens.

Adolescent↗
PubMed1993

Influence of the high-affinity growth hormone (GH)-binding protein on plasma profiles of free and bound GH and on the apparent half-life of GH. Modeling analysis and clinical applications.

The discovery of a specific high-affinity growth hormone (GH) binding protein (GH-BP) in plasma adds complexity to the dynamics of GH secretion and clearance. Intuitive predictions are that such a protein would damp sharp oscillations in GH concentrations otherwise caused by bursts of GH secretion into the blood volume, prolong the apparent half-life of circulating GH, and contribute a reservoir function. To test these implicit considerations, we formulated an explicit mathematical model of pulsatile GH secretion and clearance in the presence of absence of a specific high-affinity GH-BP. Simulation experiments revealed that the pulsatile mode of physiological GH secretion creates a highly dynamic (nonequilibrium) system, in which the half-life of free GH, its instantaneous secretion rate, and the GH-BP affinity and capacity all contribute to defining momentary levels of free, bound, and total GH, the percentage of GH bound to protein, and the percentage occupancy of GH-BP [corrected]. In contrast, the amount of free GH at equilibrium is specified only by the GH distribution volume and secretion rate and the half-life of free hormone. We conclude that the in vivo dynamics of GH secretion, trapping, and clearance from the circulation offer a variety of regulatory loci at which the time structure of free, bound, and total GH delivery to target tissues can be controlled physiologically.

Carrier Proteins↗
PubMed1993

Growth hormone-binding protein determination in plasma: a comparison of immunofunctional and growth hormone-binding assays.

The recent development of an immunofunctional assay for GH-binding protein (GHBP) facilitates measurement of GHBP in biological fluids. Previous methods employed GH binding followed by size exclusion chromatography to determine GHBP levels (GH binding assay), and a considerable body of information exists based on data obtained with that type of assay. To cross-validate the two methods and permit comparison of results obtained in the two assays, we measured GHBP by both methods in 61 plasma samples from normal adults (aged 19-69), 10 patients with acromegaly, 2 patients with Laron dwarfism, and in a normal adult plasma pool. The results show a good overall correlation between the two methods (r = 0.669). However, for individual observations, the coefficient of determination was not high enough to permit interconversion of data with high precision. There is both biological and methodological variation in GHBP levels, rendering the interpretation of a single observation difficult except in the extreme range. The range of values was wider in the immunoassay (56-1187 pmol/L) than in the GH-binding assay (12.1-36.1% GH bound/400 microL). There was no significant sex difference in plasma GHBP levels, nor was there an age-dependent trend in adult subjects as assessed by both assays. Patients with acromegaly had significantly decreased GHBP levels in both assays, but the majority of the values were within the low normal range. The two patients with Laron dwarfism had undetectable GHBP in both assays. The previously defined unit of GHBP (i.e. the amount contained in 1 ml pooled adult plasma) corresponds to 256 fmol GHBP as determined by immunofunctional assay.

Adult↗
PubMed1993

[Significance of treatment of early forms and prevention of heart failure. Value of ACE inhibitors in therapy after myocardial infarct].

Myocardial infarction has become the most important condition causing congestive heart failure. Several treatment regimens compete with each other in the early and later post myocardial infarction phase focussing on different pathophysiologic mechanisms. In this review emphasis is put on absolute risks and absolute risk reductions in patients with left ventricular dysfunction after myocardial infarction. In the first year mortality is still as high as 10% and the major risks are sudden unexpected death, reinfarction, and congestive heart failure. In the following years sudden death and development of congestive heart failure become less prominent, while a considerable risk of reinfarction persists. Thrombolysis and beta-blockade are the most important drugs in the acute infarction phase leading to a marked reduction in one year mortality. In the first year after infarction beta-blockade has an established place in the prevention of sudden death; revascularization and aspirin are established in reinfarction prophylaxis. However, since most drugs lower 1 year mortality by 0.5 to 2% only, drugs like ACE inhibitors that influence more than one risk, i.e. sudden death and reinfarction as well as deterioration of pump dysfunction might play a more important role in the therapeutic strategy after myocardial infarction. A supplementation by one or two drugs aiming at the individually estimated leading risks might be the best choice in patients with left ventricular dysfunction today.

Angiotensin-Converting Enzyme Inhibitors↗