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Biomedical subjects

G Baumann

Publications and source records attributed to G Baumann.

At least 307 records · Page 17Linked to original sources
PubMed1987

Circulating molecular variants of growth hormone in childhood.

Human growth hormone (hGH) is known to consist of several molecular forms. We examined the molecular nature of circulating hGH in 18 normal children and compared the resulting patterns to those previously obtained in adults. hGH secretion was stimulated with L-dopa, the hormonal forms were extracted from plasma by immunoadsorbent chromatography, and their molecular nature was analyzed by polyacrylamide gel electrophoresis. Circulating monomeric hGH consisted of 73% hGH22K, 16% hGH20K, and 10% of an acidic hGH from (N alpha-acylated or deamidated hGH). These relative proportions are indistinguishable from those found in the plasma of adults. No age or sex differences in the circulating hGH pattern were found. We conclude that the types and proportions of hGH forms in the blood of normal children are the same as those previously established in adults. These data provide a framework against which children with postulated structurally abnormal ("bioinactive") hGH can be compared.

Adolescent↗
PubMed1987

The effect of circulating growth hormone-binding protein on metabolic clearance, distribution, and degradation of human growth hormone.

We recently described a specific binding protein for human GH (hGH) in human plasma, with which a substantial portion of circulating hGH is complexed. The biological function of the complexed fraction is unknown. To test the hypothesis that complexed hGH may have different in vivo kinetics than free hGH, we compared the MCRs, distribution volumes (Vd), and degradation rates of complexed and free [125I] hGH in the rat. A partially purified GH-binding protein preparation, generated by affinity chromatography on a hGH column, was used for this purpose. A mixture of hGH with binding protein (equivalent to the amount contained in 0.9 mL human plasma) was injected iv as a single dose. Parallel experiments were conducted with hGH in the absence of binding protein. Disappearance of total, immunoprecipitable, and trichloroacetic acid-precipitable radioactivity from rat plasma was followed, and MCR, Vd, and degradation rates were derived by standard mathematical techniques. The MCR was 6-fold slower for complexed than for free hGH (2.3 vs. 14 mL/min X kg), Vd was 4-fold smaller for complexed hGH than for free hGH (71 vs. 256 mL/kg), and initial degradation rate was 4.5-fold lower for complexed than for free hGH (13.2% vs. 59.9%/15 min). The Vd of complexed hGH was close to the intravascular volume, while the Vd for free hGH corresponded to the extracellular volume. We conclude that one function of the hGH-binding protein is relative confinement of hGH to the vascular compartment, thereby protecting it from degradation and prolonging its biological half-life.

Animals↗
PubMed1987

Pharmacokinetic studies of highly purified human prolactin in normal human subjects.

Previous estimates of PRL pharmacokinetics have been made using radioiodinated human PRL (hPRL) infusions or by measuring serum PRL disappearance following prolactinoma resection. The recent purification of hPRL in significant quantities made it possible to measure the clearance and volume of distribution directly. Studies were also carried out to determine absorption and clearance after im injection. In five normal men whose endogenous PRL secretion was suppressed by dopamine, a loading dose of hPRL (70-90 micrograms) followed by a constant infusion (1.39-2.9 ng/min) produced steady state serum PRL levels of 15.2-25.4 ng/mL by 30-60 min. The calculated mean volume of distribution was 7.3 +/- 2.9 (+/- SD) L. The calculated MCR was 71 +/- 19 mL/min X m2, and the calculated production rate was 802 +/- 377 micrograms/24 h X m2. The plasma disappearance half-life following discontinuation of the infusion was 37 +/- 10 min. The PRL infusate consisted primarily (75.6%) of a 22.5 K dalton species, probably PRL monomer, a component eluting at 45K daltons (16.1% of the total radioimmunoreactivity), probably dimer, and a small amount of a larger mol wt species. Serum obtained during dopamine infusion but before hPRL infusion contained 68.1% of the 22.5K, 7.2% of the 45K, and 24.7% of the larger mol wt moieties. During hPRL infusion in two men there was a relative decrease in the proportion of PRL monomer to 55% and 69% and a relative increase in the PRL dimer to 33% and 18%, respectively. hPRL was injected im in doses of 1, 2, 4, and 8 micrograms/kg without prior dopamine infusion. No significant changes in serum PRL levels occurred after the 1 and 2 micrograms/kg doses (n = 5). After the 4 micrograms/kg dose (n = 8), mean serum PRL levels rose from 10.0 +/- 1.8 (+/- SEM) ng/mL to peak levels of 13.1 +/- 1.8 ng/mL (P less than 0.01). After the 8 micrograms/kg dose (n = 7), PRL levels rose from 9.3 +/- 1.6 to 16.5 +/- 1.8 ng/mL (P less than 0.01). The PRL rise began between 60 and 80 min after injection; peak levels occurred at 160-180 min. In two men given 8 micrograms/kg who were sampled for an additional 3 h, PRL levels peaked at 200-220 min and began to fall by 220-240 min, but had not returned to baseline by 6 h. There were no side-effects of PRL administration, although the 8 micrograms/kg dose caused transient local discomfort.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Absence of the plasma growth hormone-binding protein in Laron-type dwarfism.

We recently described a specific, high affinity binding protein (BP) for growth hormone (GH) in normal human plasma. Little is known about the source, regulation and biological role of this BP. Because its specificity is similar to that of the GH receptor, we considered the possibility that it represented a circulating receptor subunit or fragment. Laron-type dwarfism is a rare disorder characterized by severe growth failure, resistance to GH, and GH receptor deficiency. To probe the relationship between the receptor and the circulating binding protein, we measured the binding of GH to plasma from a child with Laron-type dwarfism and compared it with that in plasma of normal children and adults. Normal plasma samples were supplemented with unlabeled GH to the endogenous GH level in the plasma of the Laron patient to yield comparable saturation of the BP. After incubation of plasma with radiolabeled GH, bound GH was separated from free GH by gel filtration on Sephadex G-100. There was no detectable binding (less than 1.5%) of GH in the plasma of the Laron-type dwarf, whereas in normal children the bound GH fraction averaged 24.0 +/- 6.1% (mean +/- SD). Thus, the GH-BP is either absent or functionally abnormal in Laron-type dwarfism. This finding suggests that the circulating GH-BP is related to and/or may be derived from the GH receptor. Alternatively, it is possible that the BP plays an as yet poorly understood pivotal role in the promotion of somatic growth.

Carrier Proteins↗
PubMed1987

Acromegaly.

Acromegaly is caused by GH-secreting pituitary adenomas and, in rare cases, by ectopic production of GRH with resultant hypersecretion of GH. Important systemic manifestations include acral enlargement, swelling, disfigurement, glucose intolerance and diabetes, hypertension, nerve entrapment, arthropathy, and cardiac disease. Tumor-related major manifestations are visual impairment, oculomotor paralysis, and hypopituitarism. Morbidity is substantial, and mortality is increased. Diagnosis should be made as early as possible by measuring plasma GH after an oral glucose load and plasma somatomedin C levels. Assessment of a pituitary lesion is best made by CT scanning in the coronal plane. Therapy is mandatory and consists of surgical removal of the pituitary adenoma (usually by the transsphenoidal route) or of the ectopic source of GRH (carcinoids or islet cell tumors). Adjunctive radiation and/or drug therapy is often necessary if complete surgical ablation of the adenoma is not possible. Radiation therapy can be administered as conventional supervoltage x-ray treatment or in the form of heavy particle beams. Drugs effective in partially lowering GH levels are bromocriptine and (not yet released) somatostatin analogues. Long-term follow-up of treated patients is important to guard against recurrence, progression, or development of hypopituitarism.

Acromegaly↗
PubMed1986

Big growth hormone forms in human plasma: immunochemical evidence for their pituitary origin.

Large molecular weight (oligomeric) forms of human growth hormone (hGH) are present in both pituitary extracts and plasma, but the origin of the plasma forms is not known. We used a monoclonal anti-hGH antibody (No. NA-71), previously employed to characterize hGH oligomers in pituitary extracts, to examine circulating hGH oligomers. This monoclonal antibody discriminated between monomeric and polymeric hGH forms in the pituitary. Plasma from normal subjects and acromegalic patients was fractionated by Sephadex G-100 chromatography and fractions were assayed by a monoclonal radioimmunoassay (RIA) using antibody NA-71 and by a polyclonal RIA. The oligomeric plasma hGH fraction showed decreased immunoreactivity in the monoclonal RIA, similar to that observed with pituitary oligomers. The immunopotency ratios of the various plasma hGH size isomers, as determined in the two RIAs, were virtually identical to those of pituitary hGH size isomers. We conclude that circulating hGH oligomers are immunochemically indistinguishable from pituitary hGH oligomers, and thus are most likely derived from pituitary stores.

Antibodies, Monoclonal↗
PubMed1986

Secretory patterns of growth hormone during basal periods in man.

Human growth hormone (hGH) concentrations in plasma often fall to levels not detectable by RIA. These so-called basal levels prevail during the greater part of the day. Since hGH is involved in the homeostasis of several metabolic processes, it is important to examine its exact plasma concentration and secretory pattern during basal periods. We used an immunoadsorbent technique to extract hGH from large plasma samples to precisely measure basal hGH concentrations and their variation with time. Blood samples (20 mL) were drawn from 12 normal subjects in the fasted and rested state every 15 minutes over a three-hour period. Plasma hGH levels varied over three orders of magnitude (range, 34 to 60,000 pg/mL). During basal periods, episodes of secretory pulses, of moderate sustained secretion, and of complete secretory inactivity occurred. Women had significantly higher overall hGH levels as well as basal hGH levels than men, but no significant sex difference in the pulse frequency during basal periods could be detected in the limited time allotted for study. No convincing relationship was noted between variations in plasma glucose and the secretory pattern of hGH, or vice versa. We conclude that hGH is secreted in an episodic fashion during basal periods. Conceptually, basal and stimulated hGH secretion may be viewed as extremes of a continuous spectrum of pituitary activity, basal hGH levels are lower than heretofore appreciated, the known tendency of women to higher hGH levels is also evident in the basal range, and oscillations in plasma glucose do not affect the microsecretory pattern of hGH, nor are endogenous hGH pulses followed by acute changes in glycemia.

Adult↗
PubMed1986

The autodecomposition of radiolabeled human growth hormone.

Human growth hormone (hGH) was radiolabeled with 125I, using a gentle lactoperoxidase technique. The stability and decomposition products of this tracer were studied by frequent periodic analysis by Sephadex G-100 chromatography on a long column. Monomeric 125I-hGH showed an exponential decline, with a half-life of 61 days. The main radioactive degradation product was iodide, which appeared with a fractional appearance rate of 0.01136 per day. Secondary degradation products were a series of radioactive oligomers of hGH, which appeared with an overall fractional rate of 0.00525 per day. The kinetic data obtained should provide guidelines for the shelf-life and repurification schedule of radioiodinated polypeptides.

Drug Stability↗
PubMed1986

The metabolic clearance, distribution, and degradation of dimeric and monomeric growth hormone (GH): implications for the pattern of circulating GH forms.

The ratio of oligomeric (big) to monomeric (little) human (h)GH forms in plasma exceeds that in the pituitary gland severalfold. To investigate whether delayed metabolic clearance of oligomers could explain this discrepancy, we measured MCR, distribution volumes, and degradation rates of radio-labeled hGH22K dimer, hGH20K dimer, hGH22K monomer, and hGH20K monomer in the rat. Hormones were injected as a bolus, and disappearance from plasma was followed by immunoprecipitation and trichloroacetic acid precipitation. MCRs of the dimers were significantly lower than those of the corresponding monomers (5-fold in the case of hGH22K, and 2-fold in the case of hGH20K). Both dimers were also degraded at slower rates than the monomers. Distribution volumes for the dimers, although somewhat smaller, were not statistically different from those for the monomers and were consistent with distribution in the extracellular space. We conclude that hGH dimers are relatively protected from degradation and hence cleared more slowly from the blood than hGH monomers. This may lead to their accumulation in the circulation relative to their monomeric counterparts, which may explain their high proportion in plasma as compared to pituitary.

Animals↗
PubMed1986

A specific growth hormone-binding protein in human plasma: initial characterization.

Human (h) GH in plasma exists as a series of size isomers, which are in part explained by the presence of hGH oligomers. However, certain aspects of circulating large mol wt hGH, such as its high relative proportion compared to that in the pituitary, are poorly understood. To explore whether binding of hGH to plasma protein(s) could contribute to the phenomenon of large mol wt hGH, we incubated freshly prepared monomeric [125I]hGH or biosynthesized [3H]hGH with normal human plasma or serum at pH 7.4 for various time periods at 22 and 37 C. Plasma radioactive hGH patterns were then analyzed simultaneously with unincubated tracer hGH by Sephadex G-100 and G-200 chromatography. We found that part of the radioactivity was converted to a component with an apparent mol wt of 85,000, suggesting binding to a plasma protein(s). This phenomenon was inhibited in a dose-dependent fashion by unlabeled hGH. Saturation/Scatchard analysis indicated an association constant (Ka) of 2-3 X 10(8) M-1 and a maximum binding capacity of 20 ng hGH/ml plasma. Binding was rapid, reversible, and specific. A number of polypeptide hormones, including human placental lactogen, hPRL and rat GH, did not inhibit hGH binding. However, the 20K variant of hGH interacted weakly with the plasma binding component (Ka, 1.2 X 10(7) M-1; maximum binding capacity, 450 ng/ml). The binding component was heat labile and could be partially purified by gel permeation chromatography and affinity chromatography on a hGH-Sepharose column. Its estimated mol wt is 60,000-65,000, and it appears to bind one molecule of hGH to form a complex of 80,000-85,000 mol wt. The binding component is neither albumin nor an immunoglobulin. Under physiological conditions, a minimum of 15-18% of circulating hGH is presumably bound to this plasma component. We conclude that a specific, high affinity, low capacity binding protein for hGH with mol wt of 60,000-65,000 exists in normal and hypopituitary human plasma. hGH complexed with this protein forms part of big-big hGH. The biological significance of this binding protein remains to be investigated.

Binding, Competitive↗
PubMed1986

Molecular forms of human growth hormone secreted in vivo: nonspecificity of secretory stimuli.

Several molecular forms of human GH (hGH) are present in blood, but their individual regulation is largely unknown. To examine the factors controlling the secretion of individual hGH variants, the relationship between the mixture of circulating hGH forms and the type of preceding secretory stimulus was studied in 18 normal subjects and 5 acromegalic patients. The stimuli employed were L-dopa, GH-releasing hormone-(1-40), exercise, spontaneous sleep-related and daytime secretory bursts, estrogens, and TRH in the acromegalic patients. Three monomeric hGH forms (22K, 20K, and acidic hGH) were identified in all samples; their mean relative proportions were 76.4%, 15.8%, and 7.9%, respectively. These proportions were similar in all subjects, regardless of stimulus, sex, or presence of acromegaly (P greater than 0.25). We conclude that the release of individual hGH forms is not stimulus specific, but, rather, that the secretory granule contents are released in toto upon somatotroph stimulation.

Acromegaly↗
PubMed1986

Insulin receptors in embryo and extraembryonic membranes of early somite rat conceptus.

Intact rat conceptuses were cultured from day 9.5 of gestation on. Individual components of the conceptus, including the embryo and the extraembryonic membranes (consisting of yolk sac, amnion, and allantoic placenta), were isolated and examined for insulin receptors at two time points during organogenesis: day 10.4 of gestation (approximately 10-12 somites) when the yolk sac had become vascularized and just before closure of the anterior neuropore and day 11.6 (approximately 27-31 somites) when vascularization of the chorioallantoic placenta had been established and the neural tube was closed completely. The studies were designed to provide inferential insights about the possible role of insulin in embryogenesis during different phases of nutrient delivery. Active insulin degradation occurred with embryo as well as membrane homogenates during incubation at 37 degrees C. Degradation was markedly reduced at 4 degrees C, and binding of 125I-labeled insulin by embryo or membrane homogenates prepared on day 10.4 or 11.6, respectively, of gestation approached equilibrium after a 20-h incubation at this temperature. Values for the specific binding of tracer (0.4 ng/ml) or carrier (10.4 ng/ml) insulin by embryo and membrane homogenates were the same on days 10.4 and 11.6; specific binding was significantly greater with preparations of membranes than embryo at both time points. Full binding curves on day 11.6 showed similar affinities for insulin by embryo and membranes (Ke = 1.2 X 10(8)/M and 4.6 X 10(8)/M, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Allantois↗
PubMed1985

Thermo-induced transcripts of a soybean heat shock gene after transfer into sunflower using a Ti plasmid vector.

A genomic DNA fragment containing a soybean heat shock gene (hs6871) was inserted into the T-DNA region of the Agrobacterium tumefaciens pTiC58 plasmid. A strain carrying the modified Ti plasmid was used to incite tumors in sunflower hypocotyls. The expression of the heat shock gene was investigated by Northern blot analysis of RNA and S1 nuclease mapping of the transcriptional start site. Heat shock-induced poly(A) mRNA was detected in tumor tissue only after incubation at 40 degrees C (heat shock) not at the normal growth temperature (28 degrees C). Transcripts from hs6871 are faithfully initiated in sunflower, starting at the same site on the DNA as in soybean. The low level of transcripts initiating correctly on hs6871 in sunflower is consistent with a general tissue-specific reduction in the expression of partially homologous native heat shock genes in sunflower tumors.

Journal Article↗
PubMed1985

Effects of three histaminergic compounds on function and oxygen consumption of isolated guinea-pig hearts.

First experiences in man indicate, that even in catecholamine-insensitive congestive cardiomyopathy a considerable improvement of myocardial function can be attained by the H2-receptor agonist impromidine. In an isolated, pressure-volume work performing guinea-pig heart preparation cardiac effects of three histaminergic compounds (Na,5-dimethylhistamine (HC1)2, 5-ethyl-Na-methyl-histamine (HC1)2, Na,Na-dimethyl-histamine (HC1)2) were examined. Influences on function and myocardial oxygen consumption were compared to those obtained by impromidine. Dose-response curves for the histamine derivatives were 1.7-2.5 orders of magnitude right of the impromidine curves. Maximal inotropic stimulation was greater for Na,5-dimethyl-histamine (HC1)2 than for impromidine. All compounds exhibited a high chronotropic effect and, at high concentrations, a net coronary dilating effect.

Animals↗
PubMed1985

Slow metabolic clearance rate of the 20,000-dalton variant of human growth hormone: implications for biological activity.

The 20,000-dalton variant of human GH (hGH) (20 K) exhibits full growth-promoting bioactivity in the rat despite its poor interaction with GH receptors, as compared to the principal 22,000-dalton form of hGH (22 K). To test the possibility that prolonged survival time of 20 K in vivo may contribute to this apparent discrepancy, we compared the MCRs of 22 K and 20 K in the rat by the single injection technique. Both radiolabeled and native 22 K and 20 K were examined in this regard. The MCR of 20 K was 2- to 3-fold lower than that of 22 K, a statistically significant difference (P less than 0.05). The distribution volumes were similar for the two hGH forms and corresponded approximately to the extracellular fluid space. We conclude that the prolonged persistence of 20 K in the circulation may contribute to its higher than expected bioactivity in vivo in the rat.

Animals↗
PubMed1985

Molecular forms of circulating growth hormone during spontaneous secretory episodes and in the basal state.

After pharmacological stimulation of the pituitary gland, human GH (hGH) in plasma consists of three or more monomeric molecular forms and several corresponding oligomers. However, the chemical nature of hGH circulating under physiological (stimulated or basal) conditions is not known. In particular, the molecular basis for the GH-like bioactivity of plasma is poorly understood. To gain information on the type(s) of hGH normally found in blood, we extracted hGH from plasma obtained at the time of spontaneous secretory episodes (nocturnal and random release) and during basal periods in 15 normal subjects. Appropriate plasma volumes (30 or 300 ml) were extracted by immunoadsorbent chromatography, and the extracts were analyzed by native polyacrylamide gel electrophoresis at pH 7.5 and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis at pH 10. The plasma hGH pattern at the time of spontaneous secretion was similar to that after pharmacological stimulation and consisted of 22K (principal), 20K, and acidic hGH as well as hGH dimer. In contrast, plasma hGH patterns during basal periods were highly variable and included immunoreactive hGH fragments in addition to the known hGH forms. Components with mol wt of 30K, 16K, and 12K were consistently identified. We conclude that 1) endogenously stimulated hGH secretion results in the same plasma hormone patterns as pharmacological stimuli; 2) several immunoreactive hGH fragments contribute to the heterogeneity of plasma hGH; and 3) hGH fragments may become a dominant part of total immunoreactivity in the basal state.

Adult↗