In this report we describe a newly developed radioimmunoassay (RIA) for the determination of the high-affinity growth hormone-binding protein (GHBP) in human blood. Using this RIA for the measurement of GHBP in serum of 29 patients with acromegaly, decreased concentrations were found compared to the normal range, depending on the activity of the disease. Growth hormone-binding protein was correlated inversely to log GH (r = -0.7, p < 0.001). A weaker relationship was shown between the GHBP activity determined in a functional assay based on charcoal separation and log GH (r = -0.51, p < 0.01). While insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) were correlated directly to log GH (r = 0.77 and r = 0.66, p < 0.001), an inverse and weaker relationship was evident between GHBP measured by RIA and IGF-I or IGFBP-3 (r = -0.61 and r = -0.57, p < 0.01). In contrast, no correlation could be detected between data of the functional GHBP assay and IGF-I or IGFBP-3.(ABSTRACT TRUNCATED AT 250 WORDS)
We have found that the human GH forms complexes with the purified proteinase inhibitor, alpha 2-macroglobulin. This inhibitor occurs in two different forms in human blood, known as native and transformed alpha 2-macroglobulin. It could be clearly demonstrated by chromatography and electrophoresis combined with autoradiography that the GH binds specifically to the transformed inhibitor, but not to the native protein. The binding was characterized as being mainly noncovalent to specific binding sites present only in the transformed inhibitor molecule. Binding analysis using antibody precipitation technique revealed two different classes of binding sites with dissociation constants of 0.49 +/- 0.12 and 61 +/- 8 mumol/L for high and low affinity binding sites, respectively. Distribution analysis of 125I-labeled GH in whole plasma suggested that the hormone is bound to different proteins: 1) to the high affinity GH-binding protein, and 2) to the low affinity GH-binding protein identified as transformed alpha 2-macroglobulin.
Peripheral arterial disease is more aggressive in concomitant diabetes posing an increased risk for critical limb ischemia and subsequent limb loss. The majority of therapies available are not effective to prevent amputation in patients with severe disease. The current observational study reports the effect of the heparin-induced extracorporal LDL-precipitation (H.E.L.P.) as a novel therapeutic approach in patients with severe diabetic foot syndrome. Seventeen diabetic patients with septic foot lesions recruited from the diabetic outpatient clinic underwent H.E.L.P. apheresis regularly until fibrinogen levels were stabilized at 3 g/l or infection was controllable as evidenced by alleviation of necrosis. Patients were subsequently followed up for 2 to 73 months. Fibrinogen levels were reduced by 68% after H.E.L.P. treatment. No severe complications were noted. Necrosis could be confined in sixteen patients. Minor amputations were indicated in twelve patients. Three patients underwent major amputations of the lower limb and two patients received surgical reconstruction. In conclusion, H.E.L.P. apheresis may offer an alternative therapeutic option to diabetic patients with critically ischemic feet and appears to have a beneficial major/minor amputation ratio.
Decreased GHBP levels in IDDM as well as in NIDDM correlate with insulinopenia. Since the degree of insulinopenia depends on the capability of the beta-cells to secrete proinsulin, C-peptide and insulin, we hypothesize that these hormones at least partially influence the serum level of GHBP. Low GHBP levels may reflect a reduced GH receptor density and a concomitant GH insensitivity, which leads to an impaired IGF generation in insulin-deficient patients.
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