Carl Peter J. Maury

Elevated levels of circulating cachectin/tumor necrosis factor in patients with acquired immunodeficiency syndrome☆

PURPOSE In order to evaluate the relationship between cachectin/tumor necrosis factor (TNF) and cachexia in the acquired immunodeficiency syndrome (AIDS), we studied the serum levels of endogenous cachectin/TNF in subjects with human immunodeficiency virus (HIV) infection. PATIENTS AND METHODS Fifty-three serum samples were obtained from 39 HIV-seropositive patients. The condition of each patient was clinically classified as either asymptomatic, lymphadenopathy syndrome (LAS), AIDS-related complex (ARC), or AIDS. Control sera were obtained from 29 healthy male blood donors. A double antibody radioimmunoassay was used to measure the serum levels of cachectin/TNF. RESULTS Cachectin/TNF levels were within the reference range of the control values in all (eight of eight) asymptomatic HIV-infected subjects and in 11 of 13 of the patients with LAS. In contrast, all patients with AIDS (nine of nine) and five of nine of the patients with ARC had raised levels of cachectin/TNF. Fluctuation of the levels of cachectin/TNF occurred during follow-up, but initially raised levels remained elevated. CONCLUSION Since cachectin/TNF suppresses lipoprotein lipase in adipocytes in vitro, and causes weight loss under experimental conditions, the findings of raised levels of cachectin/TNF in patients with AIDS may have relevance to the pathogenesis of cachexia.

Origin of life. Primordial genetics: Information transfer in a pre-RNA world based on self-replicating beta-sheet amyloid conformers

The question of the origin of life on Earth can largely be reduced to the question of what was the first molecular replicator system that was able to replicate and evolve under the presumably very harsh conditions on the early Earth. It is unlikely that a functional RNA could have existed under such conditions and it is generally assumed that some other kind of information system preceded the RNA world. Here, I present an informational molecular system that is stable, self-replicative, environmentally responsive, and evolvable under conditions characterized by high temperatures, ultraviolet and cosmic radiation. This postulated pregenetic system is based on the amyloid fold, a functionally unique polypeptide fold characterized by a cross beta-sheet structure in which the beta strands are arranged perpendicular to the fiber axis. Beside an extraordinary structural robustness, the amyloid fold possesses a unique ability to transmit information by a three-dimensional templating mechanism. In amyloidogenesis short peptide monomers are added one by one to the growing end of the fiber. From the same monomeric subunits several structural variants of amyloid may be formed. Then, in a self-replicative mode, a specific amyloid conformer can act as a template and confer its spatially encoded information to daughter molecular entities in a repetitive way. In this process, the specific conformational information, the spatially changed organization, is transmitted; the coding element is the steric zipper structure, and recognition occurs by amino acid side chain complementarity. The amyloid information system fulfills several basic requirements of a primordial evolvable replicator system: (i) it is stable under the presumed primitive Earth conditions, (ii) the monomeric building blocks of the informational polymer can be formed from available prebiotic compounds, (iii) the system is self-assembling and self-replicative and (iv) it is adaptive to changes in the environment and evolvable.

Enzyme immunoassay of antibodies to epithelial glycoprotein: Increased level of antibodies in coeliac disease

From the papules of a patient with massive cutaneous hyalinosis, we earlier isolated a mannose-rich glycoprotein that, by immunohistochemical methods, was also shown to be present in epithelial cells of small intestine and normal skin. A solid-phase enzyme immunoassay of IgG and IgM antibodies to this epithelial glycoprotein is described, in which polystyrene tubes are coated with the purified antigen. The antibodies are allowed to bind, and are detected with alkaline phosphatase-conjugated anti-human IgG and IgM. IgG, IgA and IgM antibodies were determined in the sera of patients with pemphigus, pemphigoid, dermatitis herpetiformis, several autoimmune diseases, in a patient with massive cutaneous hyalinosis, in coeliac disease, and in control subjects. Very high values were found in the patient with massive cutaneous hyalinosis, and significantly elevated values in coeliac disease. In the other patient groups values were equal to or only slightly higher than in controls.

Amyloid and the origin of life: self-replicating catalytic amyloids as prebiotic informational and protometabolic entities

A crucial stage in the origin of life was the emergence of the first molecular entity that was able to replicate, transmit information, and evolve on the early Earth. The amyloid world hypothesis posits that in the pre-RNA era, information processing was based on catalytic amyloids. The self-assembly of short peptides into β-sheet amyloid conformers leads to extraordinary structural stability and novel multifunctionality that cannot be achieved by the corresponding nonaggregated peptides. The new functions include self-replication, catalytic activities, and information transfer. The environmentally sensitive template-assisted replication cycles generate a variety of amyloid polymorphs on which evolutive forces can act, and the fibrillar assemblies can serve as scaffolds for the amyloids themselves and for ribonucleotides proteins and lipids. The role of amyloid in the putative transition process from an amyloid world to an amyloid–RNA–protein world is not limited to scaffolding and protection: the interactions between amyloid, RNA, and protein are both complex and cooperative, and the amyloid assemblages can function as protometabolic entities catalyzing the formation of simple metabolite precursors. The emergence of a pristine amyloid-based in-put sensitive, chiroselective, and error correcting information-processing system, and the evolvement of mutualistic networks were, arguably, of essential importance in the dynamic processes that led to increased complexity, organization, compartmentalization, and, eventually, the origin of life.

Glycosylation pattern of kappa light chains in massive cutaneous hyalinosis

In the light of the hypothesis that the kappa light chain accumulation in massive cutaneous hyalinosis (MCH) is related to an abnormal glycosylation pattern, we analyzed the oligosaccharide structures of the cold precipitable kappa light chains excreted in the urine of an MCH patient.The MCH kappa chains contain about 25% carbohydate. Concanavalin A-Sepharose affinity chromatography of the glycopeptides obtained from pronase digests showed that the bulk of the glycopeptides (82%) did not bind to the column; 16% had a weak affinity, and 2% a strong affinity. Methylation analyses indicated that the unbound fraction consisted mainly of tetra-antennary glycopeptides, but tri-antennary and bisecting structures were also found. Most of the weakly-bound glycopeptides had a biantennary carbohydrate structure.

Serum amyloid A levels in acute graft-versus-host disease in bone marrow transplant recipients

We studied serum amyloid A levels of 31 bone marrow transplant recipients with and without acute graft‐versus‐host disease. Before transplantation the mean SAA concentration was 5.1±0.8 mg/1 (mean ± SEM). It remained low in patients with no signs of aGVHD but increased significantly during aGVHD to 54.0 ± 8.2 mg/l (p < 0.001 compared to pre‐BMT value). Severe infections also induced high SAA levels.