“Classical” neuroendocrine peptide hormones produced by cells of the immune system

Cells of the immune system are shown to produce peptide hormones whose production was once thought to be restricted to neuroendocrine tissue. Interestingly, in some cases, very specific stimuli elicit the production of one species of neuropeptide hormone. In other instances, it appears that some peptide hormones are constitutively produced. In either situation, the various immunocyte-derived hormones have biological activity in endocrinological assays. In the present report, a review of the various neuroendocrine hormones produced by cells of the immune system is discussed.     

A peptide mimetic of calcium.

Proteins of the troponin superfamily use homologous amino acid sequences as binding sites for Ca2+ and seem to have evolved from an ancestral Ca2+ binding site. We have utilized this ancestral sequence to construct a peptide (Ca(2+)-like peptide) with inverted hydropathy to the calcium-coordinating region of this protein. This synthetic peptide acted like Ca2+ in that (i) it increased the calmodulin-dependent hydrolysis of cAMP by phosphodiesterase, (ii) it interacted with EDTA, and (iii) it enhanced contraction of urinary bladder smooth muscle in vitro. Unlike Ca2+, the peptide's effects were destroyed by acid hydrolysis. These findings demonstrate the synthesis of a peptide that can substitute for Ca2+ and may have considerable utility for the study of Ca(2+)-regulated pathways and possible therapeutic value as a pharmacologic agent.     

Subunit structure of the variable V-1 antigen of Mycoplasma pulmonis.

It was previously shown that multiple structural variants of the V-1 antigen (variable antigen 1) of Mycoplasma pulmonis could be found within a single strain. This antigen is unusual in that it produces a ladder pattern after sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The present study showed that some variants of V-1 could be extracted into the aqueous phase of a phenol-H2O system. Analysis with anti-V-1 monoclonal antibodies showed that the phenol-H2O-extracted V-1 had a regular spacing of 3.1 kilodaltons (kDa) between bands and trypsinization of this extracted V-1 resulted in the gradual symmetrical collapse (2.9-kDa increments) of the ladder into a single band, suggesting the presence of multiple identical subunits within the V-1 structure. The upper band from the phenol-H2O-extracted V-1 was isolated and analyzed by SDS-polyacrylamide gel electrophoresis immunoblotting, resulting in the regeneration of the original ladder pattern with 3.1-kDa spacing between bands. When V-1 was boiled for increasing times in the presence of SDS, the staining intensity of the upper band decreased with the concurrent appearance of additional lower-molecular-weight bands. Finally, by using whole cells, it was found that the lower-molecular-weight species of the ladder pattern selectively partitioned into the hydrophobic phase of a Triton X-114 phase partitioning system, and the higher-molecular-weight bands were found in the aqueous phase. These data indicate that the V-1 bands are composed of subunits which may aggregate via hydrophobic interactions and that these aggregates at least partially dissociate when exposed to harsh denaturing conditions, resulting in the characteristic ladder pattern of V-1.     

The changing face of reoperative parathyroidectomy: a single-centre comparison of 147 parathyroid reoperations

IntroductionReoperative parathyroidectomy for persistent and recurrent primary hyperparathyroidism is dependent on radiology. This study aimed to compare outcomes in reoperative parathyroidectomy at a single centre using a combination of traditional and newer imaging studies.Materials and methodsRetrospective case note review of all reoperative parathyroidectomies for persistent and recurrent primary hyperparathyroidism over five years (June 2014 to June 2019; group A). Imaging modalities used and their positive predictive value, complications and cure rates were compared with a published dataset spanning the preceding nine years (group B).ResultsFrom over 2000 parathyroidectomies, 147 were reoperations (101 in group A and 46 in group B). Age and sex ratios were similar (56 vs 62 years; 77% vs 72% female). Ultrasound use remains high and shows better positive predictive value (76% vs 57 %). 99mTc-sestamibi use has declined (79% vs 91%) but the positive predictive value has improved (74% vs 53%). 4DCT use has almost doubled (61% vs 37%) with better positive predictive value (88% vs 75%). 18F-fluorocholine positron emission tomography-computed tomography and ultrasound-guided fine-needle aspiration for parathyroid hormone are novel modalities only available for group A. Both carried a positive predictive value of 100%. Venous sampling with or without angiography use has decreased (35% vs 39%) but maintains a high positive predictive value (86% vs 91%). Cure rates were similar (96% vs 100%). Group A had 5% permanent hypoparathyroidism, 1% permanent vocal cord palsy and 1% haematoma requiring reoperation. No complications for group B.ConclusionOptimal imaging is key to good cure rates in reoperative parathyroidectomy. High-quality, non-interventional imaging techniques have produced a shift in the preoperative algorithm without compromising outcomes.