Growth hormone-binding protein activity is inversely related to 24-hour growth hormone release in normal boys.

To investigate the physiological relationship between serum GH-binding proteins and 24-h GH release, we compared the 24-h GH pulse attributes in serum samples obtained at 20-min intervals to the serum GH-binding protein activity (GH-BP) from 38 normal boys between 7 5/12 and 18 4/12 yr of age. GH-BP was determined in a serum sample from each study (containing less than 1.0 micrograms/L GH) using a standardized GH-BP assay.

Effects of histamine H1-receptor blockade on respiratory and cardiac manifestation of systemic anaphylaxis.

In vivo anaphylaxis is associated with respiratory distress and cardiovascular failure. The present investigation was designed to further characterize respiratory and cardiac anaphylactic events. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin together with Freund's adjuvant.

Short stature and decreased serum growth hormone-binding protein in the Mountain Ok people of Papua New Guinea.

Two circulating GH-binding proteins (GH-BP), one of which is related to the GH receptor, have been described. To assess their possible role in or link with determining statural growth, we measured their activity/level in the serum of 25 adult subjects from a short-statured population from the highlands of Papua New Guinea (Mountain Ok people, similar in stature to African pygmies) and in 25 normal-statured North American control subjects. The Mountain Ok people have normal levels of GH, insulin-like growth factor-I (IGF-I), IGF-II, and serum albumin and prealbumin in association with short stature, making them a unique study population.

Piroximone, dobutamine and nitroprusside: comparative effects on haemodynamics in patients with congestive heart failure.

Four intravenous doses of piroximone, an imidazolone derivative, were administered to 12 patients with congestive heart failure to produce a four-point dose-response curve. The haemodynamic effects were compared with those of dobutamine and nitroprusside, the substances being given sequentially and in randomized order. Piroximone and dobutamine significantly and similarly increased cardiac index (CI) and stroke volume index (SVI).

Cyclosporin A and FK-506 both affect DNA binding of regulatory nuclear proteins to the human interleukin-2 promoter.

The structurally unrelated immunosuppressive drugs cyclosporin A (Sandimmun) and FK-506 both interfere with the process of T-cell proliferation by blocking the transcription of the T-cell growth factor interleukin-2 (IL-2). Here we demonstrate that the transcriptional activation of this gene requires the binding of regulatory nuclear proteins to a promoter element with sequence similarity to the consensus binding site for NF-kappa B-related transcription factors. We present evidence that the binding by regulatory nuclear proteins to the kappa B element of the IL-2 promoter is affected negatively by cyclosporin A and FK-506 at concentrations paralleling their immunosuppressive activity in vivo.

Effects of histamine H1- and H2-receptor antagonists on cardiovascular function during systemic anaphylaxis in guinea pigs.

The heart is a target organ of anaphylaxis. In isolated perfused hearts, an anaphylactic reaction is characterized by arrhythmias, coronary constriction and severe impairment of ventricular contractile force. Various mediators such as PAF, thromboxane A2 and leukotrienes are responsible for anaphylactic coronary constriction and negative inotropic effects.

Effects of growth hormone-binding proteins on serum growth hormone measurements.

GH-binding proteins (GH-BPs) in human blood theoretically may interfere with measurements of immunoreactive GH by forming complexes with GH and competing with antibody reagents for ligand. Indeed, results of serum GH obtained by immunoassays are known to differ markedly depending on the assay employed. To assess the potential role of circulating GH-BPs in this phenomenon, we systematically examined their effect on GH measurement in four RIAs and two immunoradiometric assays.

Growth hormone binding proteins: biochemical characterization and assays.

Circulating growth hormone binding proteins have recently been recognized in man and certain animals. In man, two specific growth hormone binding proteins have been described, one with high affinity and another with low affinity. The high affinity binding protein corresponds to the extracellular portion of the hepatic growth hormone receptor, whereas the low affinity binding protein appears unrelated to the receptor.

Effects of platelet-activating factor on beta- and H2-receptor-mediated increase of myocardial contractile force in isolated perfused guinea pig hearts.

Platelet-activating factor (PAF) has been termed an important mediator of cardiovascular shock due to immunological reactions, including anaphylaxis and endotoxic reactions. Previous studies have shown that PAF is a potent cardiodepressive agent inducing a drastic coronary constriction and a sustained impairment of myocardial contractility. In this study, an attempt was made to further characterize the prolonged PAF effects on coronary circulation and myocardial contractile force in the isolated guinea pig heart perfused at constant pressure.

Therapeutic value of H2-receptor stimulation in congestive heart failure. Hemodynamic effects of BU-E-76, BU-E-75 and arpromidine (BU-E-50) in comparison to impromidine.

Previous studies from our department revealed that congestive heart failure (CHF) is paralleled by a decrease in number of sarcolemmal beta-receptors due to excessive levels of circulating endogenous catecholamines. In contrast, the myocardial H2-receptor system proved to be not affected (Am. Heart J.

Structure-activity relationships of histamine H2-agonists, a new class of positive inotropic drugs.

The cimetidine-like moiety in impromidine was replaced by either alternative partial structures known from H2-antagonists or by H2-nonspecific lipophilic groups. The most potent H2-agonists were found in a series of compounds structurally derived from the H1-antagonist pheniramine. Arpromidine (N1-[3-(4-fluorophenyl)-3-(2-pyridinyl)propyl]-N2-[3-(1H-imidazol-4- yl)propyl]guanidine) may be considered a new lead for the development of "cardiohistaminergics".

Metabolism of growth hormone (GH) and different molecular forms of GH in biological fluids.

Human growth hormone (GH) consists of a number of molecular variants which derive from 2 genes, several alternative mRNA splicing mechanisms, and post-translational modifications such as deamidation, acylation, glycosylation, and oligomerization. After secretion, GH binds to two (or possibly more) circulating GH-binding proteins, one of which is a truncated GH receptor. The resulting mixture of GH moieties in plasma is enormously complex, consisting of over 100 molecular states.

Long-term treatment with piroximone in patients with chronic heart failure.

The safety and efficacy of long-term oral piroximone therapy was assessed in 12 patients with chronic heart failure. Of these 12 patients, two died suddenly, and a further two were withdrawn because of worsening heart failure within 6 months while 8 completed the 1-year follow-up period. In 7 of these 8 patients, clinical evaluations showed sustained benefit, as demonstrated by significant increases in exercise tolerance.

Plasma transport of the 20,000-dalton variant of human growth hormone (20K): evidence for a 20K-specific binding site.

The 20,000-dalton variant of human GH (20K) is known to circulate in blood, but few details are known about its plasma transport. A substantial portion of 20K appears to be protein bound despite its low affinity for the receptor-related GH-binding protein (BP). We, therefore, investigated the binding pattern of 20K in human plasma.

Effects of platelet-activating factor on myocardial contraction and myocardial relaxation of isolated perfused guinea pig hearts.

Platelet-activating factor (PAF) is an important mediator of cardiovascular shock owing to immunologic reactions, including anaphylaxis and endotoxaemia. Previous studies have shown that PAF is a potent cardio-depressive agent causing a marked coronary constriction and a sustained impairment of myocardial contractility. In this study, we attempted to characterize further the prolonged PAF effects on coronary circulation and myocardial contractile force in isolated guinea pig hearts perfused at constant pressure (60 cm H2O) or constant flow which was adjusted to a level of 100% above basal flow.

Growth hormone-binding protein: II. Studies in pygmies and normal statured subjects.

The serum concentrations of a specific GH-binding protein, derived from the GH receptor, were assayed in sera from 62 African pygmies and 101 normal statured controls. Samples were assayed in the absence and presence of excess GH using 2 separatory procedures. Interassay variability for samples was corrected by a standard reference pool of sera from adults assayed with all unknown samples.

The 20,000 Da variant of human growth hormone does not bind to growth hormone receptors in human liver.

The 20,000 Da variant of human growth hormone (hGH) (20K) exhibited no specific binding to hGH receptors in human liver plasma membranes. This contrasts with the 22,000 Da form of human growth hormone (22K), which bound with high affinity to the same hepatic receptor preparation. Since the liver is considered a major target organ for the somatogenic pathway of growth hormone action, this finding implies that in humans the 20K form plays little role in that pathway.

Growth hormone-binding proteins.

Two growth hormone-binding proteins (GH-BPs) have recently been discovered in human plasma. Both are specific for human GH; one has high affinity and the other has low affinity. The high-affinity BP corresponds to the extracellular portion of the GH receptor, whereas the low-affinity BP does not appear to be related to the receptor.

Plasma transport of human growth hormone in vivo.

We have previously shown that a substantial part of human GH is complexed with GH-binding proteins (BPs) when GH is incubated with plasma in vitro. The proportion of GH bound in vivo, however, is unknown and may differ because of factors that cannot be assessed in vitro, such as binding to tissue receptors, distribution of GH outside the vascular compartment, and fluctuating GH and possibly BP levels. Accordingly, we studied the plasma transport characteristics of GH in vivo in six normal men.

Cardiovascular effects of forskolin (HL 362) in patients with idiopathic congestive cardiomyopathy--a comparative study with dobutamine and sodium nitroprusside.

Forskolin, a diterpene derivative of the Indian plant Coleus forskhohlii, proved to be a marked positive inotropic and vasodilatory compound in animal experiments with a mechanism of action distinct from catecholamines, cardiac glycosides, and phosphodiesterase-inhibiting compounds. The cardiovascular effects of forskolin seem to be mediated by a direct stimulatory action at the catalytic unit of sarcolemmal adenylate cyclase. The aim of the present study was to clarify the cardiovascular profile of this compound in 12 patients with stage III (NYHA) congestive cardiomyopathy.

Basal plasma growth hormone levels in man: new evidence for rhythmicity of growth hormone secretion.

Circulating GH levels in man fluctuate widely due to pulsatile GH secretion by the pituitary gland. During much of the time, plasma GH is undetectable by current assays. This is punctuated by occasional secretory episodes, resulting in plasma GH peaks of varying height.

[Acute reduction of increased atrial natriuretic peptide level and cyclic guanosine monophosphate in patients with chronic heart failure caused by beta-adrenergic stimulation with dopexamine hydrochloride. Correlation with hemodynamic parameters].

In eight patients (63 +/- 8 years) with dilated cardiomyopathy, the acute effects of positive inotropic stimulation with dopexamine hydrochloride, a beta-2-agonistic and DA1-dopaminergic catecholamine, on the plasma levels of ANP and cGMP were tested. A four-point dose-response curve was prepared for dopexamine from 1 microgram/kg/min to 4 micrograms/kg/min. Each infusion stage lasted 15 min; ANP and cGMP were taken from the mixed venous blood.