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Biomedical subjects

R D Hesch

Publications and source records attributed to R D Hesch.

237 records · Page 14Linked to original sources

Homologous radioimmunoassay for human mid-regional parathyroid hormone.

A radioimmunoassay, selective for the clinically important mid region of human parathyroid hormone (hPTH), is reported. The synthetic 44-68 amino acid sequence (h44-68PTH) was used as both the standard and tracer material. This eliminated many of the undesirable characteristics associated with PTH assays the employ hormone of biological origin. These components allowed the detection of mid regional fragments present in both intact and fragmented hPTH, with a working range between 50 and 2500 pg/ml h44-68PTH. There was no interference from serum proteins and no significant cross reactivity to a range of N-terminal, C-terminal and other mid regional hPTH peptides. The assay proved to be rapid (total time 24 h) and was extremely reproducible, with an intraassay and interassay variation of 2.8% and 5.6% respectively (expressed as percentage SE in mean). The plasma concentration of normal subjects was established as 129 +/- 6 pg/ml (h44-68PTH) with a range of 50-300 pg/ml (n = 42). This assay, using fully synthetic hPTH peptides, was able to distinguish between euparathyroid and hyperparathyroid subjects, which suggests that the assay is of diagnostic value.

Amino Acid Sequence↗

Inhibition of renal adenylate cyclase by plasma from uremic patients.

The native plasma of patients suffering from renal insufficiency inhibited the parathyroid hormone (PTH), the vasopressin (VP) and the NaF-activated adenylate cyclase (AC) in bovine renal plasma membranes. A crude immunoglobulin fraction, prepared by (NH4)2SO4 precipitation, decreased only the hormone, but not the NaF activated AC. Chromatography of the native plasma on a AcA 34 column revealed two peaks inhibiting the PTH and to a lesser extent the VP dependent AC. Only the second peak reduced the NaF stimulated cAMP production. None of the column samples inhibited the isoproterenol stimulated adenylate cyclase in turkey red blood cells. Further purification of the first peak on a Sepharose 6B column confirmed previous results that immunoglobulins may block the PTH receptor in the kidney. Repurification of the second peak of inhibition on a Bio-Gel P10 column suggested that small peptides crossreacting in the radioimmunoassay for PTH may desensitize the hormonal receptor.

Adenylyl Cyclase Inhibitors↗

[Morphologic study of iliac crest spongiosa in patients with osteoporosis treated according to the ADFR (activation, depression of resorption, formation, repeat the cycle) with parathyroid hormone and diphosphonates (Hannover PTH I study)].

Treatment of osteoporosis with a complete reconstruction of the normal three dimensional architecture of trabecular bone is an unsolved problem. In addition to the well established fluoride therapy new concepts in the treatment of osteoporosis were developed. There is growing interest in the so called ADFR concept (activation, depression of resorption, formation, repeat the cycle) as a physiological stimulation of osteoblastic bone formation. The histological results following ADFR treatment in 8 patients are reported. After 12 months of treatment with parathyroid hormone [1-38)hPTH) (stimulation of the basic metabolic units) and the diphosphonate EHDP (depression of osteoclastic resorption) no change of remodelling processes at the trabecular bone surface could be observed. The results demonstrate many doubts in the importance of the ADFR concept for the treatment of osteoporosis.

Adult↗