Human transfer factor. I. Production by the great pool technic and the biochemical and immunological characteristics of the preparation

A great pool procedure for producing human transfer factor preparations from buffy-coats of stored whole blood which has not been used up till now is described. From an initial tool size of about 1,500 units of whole blood the procedure represented makes it possible to gain higher amounts of uniform and in their immunological efficacy in vitro standardizable preparations for controlled long-term therapy studies. By means of various immunological in vitro tests, stimulating as well as suppressing activities of the charges obtained could be identified. Starting from the differentiated immunological effects of various charges of the transfer factor on T-cell populations in vitro, the possibility of influencing T-cell subpopulations through well-conceived therapeutic measures by a transfer factor is discussed.     

Cell-Penetrating Mimics of Agonist-Activated G-Protein Coupled Receptors

Cell-penetrating peptides have proven themselves as valuable vectors for intracellular delivery. Relatively little is known about the frequency of cell-penetrating sequences in native proteins and their functional role. By computational comparison of peptide sequences, we recently predicted that intracellular loops of G-protein coupled receptors (GPCR) have high probability for occurrence of cell-penetrating motifs. Since the loops are also receptor and G-protein interaction sites, we postulated that the short cell-penetrating peptides, derived from GPCR, when applied extracellularly can pass the membrane and modulate G-protein activity similarly to parent receptor proteins. Two model systems were analyzed as proofs of the principle. A peptide based on the C-terminal intracellular sequence of the rat angiotensin receptor (AT1AR) is shown to internalize into live cells and elicit blood vessel contraction even in the presence of AT1AR antagonist Sar¹-Thr⁸-angiotensin II. The peptide interacts with the same selectivity towards G-protein subtypes as agonist-activated AT1AR and blockade of phospholipase C abolishes its effect. Another cell-penetrating peptide, G53-2 derived from human glucagon-like peptide receptor (GLP-1R) is shown to induce insulin release from isolated pancreatic islets. The mechanism was again found to be shared with the original GLP-1R, namely G₁₁-mediated inositol 1,4,5-triphosphate release pathway. These data reveal a novel possibility to mimic the effects of signalling transmembrane proteins by application of shorter peptide fragments.     

The frequency of adverse drug reaction related admissions according to method of detection, admission urgency and medical department specialty

Background  

Adverse Drug Reactions (ADRs) have been regarded as a major public health problem since they represent a sizable percentage of admissions. Unfortunately, there is a wide variation of ADR related admissions among different studies. The aim of this study was to evaluate the frequency of ADR related admissions and its dependency on reporting and method of detection, urgency of admissions and included medical departments reflecting department/hospital type within one study.     

On interleukins 4, 6 and 10 and their interrelationship with immunoglobulins G and M in common variable immunodeficiency.

Following culture of human peripheral blood mononuclear cells (PBMNC) from 25 normal donors and 15 patients with common variable immunodeficiencv (CVID), we were unable to identify any IL10-defective patients. Clear-cut effects of IL4 could be demonstrated in controls, while in CVID all effects are less pronounced. While in both controls and CVID baseline levels of 1L6, IgG and IgM were found to be correlated, this was altered by the addition of either IL4 or Poke Weed Mitogen (PWM). We therefore conclude that the inability of PBMNC to produce IL10 is not the cause of CVID in our patients. In CVID, the regulating circuitry triggered by IL4 remains principally intact, however, some subgroups of CVID behave significantly differently.