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Biomedical subjects

A Frey

Publications and source records attributed to A Frey.

85 records · Page 5Linked to original sources
PubMed1986

Two human 35 kd inhibitors of phospholipase A2 are related to substrates of pp60v-src and of the epidermal growth factor receptor/kinase.

We have purified two 35 kd phospholipase A2 inhibitors from human placenta, which we refer to as lipocortin I and II. Both proteins exhibit similar biochemical properties and occur in placenta at about 0.2% of the total protein. By peptide mapping, sequence, and immunological analyses, we show that lipocortin I and the 35 kd substrate for the EGF-receptor/kinase from A431 cells are the same protein. By similar criteria, we determine that lipocortin II is the human analogue of pp36, a major substrate for pp60src, which has been characterized in chicken embryo fibroblasts and in bovine brush border preparations. The amino acid sequences of lipocortin I and II that we deduced from cDNA clones share 50% homology, indicating that they probably evolved from a common gene.

Amino Acid Sequence↗
PubMed1984

[Heberden arthroses in judo athletes].

Increased occurrence of Heberden nodes has been observed in judo practitioners. Nine out of 30 members of the Swiss national team showed such nodes clinically on several fingers, whereas sportsmen in other disciplines did not. X-ray showed that all judokas examined have more or less severe osteoarthrosis of the distal interphalangeal joints (DIP), whether Heberden nodes were present or not. At the same time, in most cases osteoarthrosis of the proximal interphalangeal joints (PIP) was found by X-ray and clinical examination. Osteoarthrosis of DIP and PIP in this young age group is due to overstress and injury to the joints involved. Acute injuries to the finger joints evidently cause Heberden nodes with, in some instances, only minor osteoarthrotic lesions visible by X-ray, while overstress of DIP and PIP is the cause of osteoarthrosis in these joints, which is only detectable by X-ray.

Adolescent↗
PubMed1982

Glucocorticoids directly affect the synthesis of ribosomal RNA in rat-liver cells.

Administration of the glucocorticoid dexamethasone to rats significantly stimulated the synthesis of ribosomal RNA by hepatic nuclei in vitro, as determined by hybridization to plasmid DNA containing the appropriate gene from X. laevis. This effect was also seen in rats in which RNA polymerase B had previously been blocked by the administration of alpha-amanitin. RNA synthesized in response to the hormone hybridized to both the 5' and 3' end of the gene for the precursor to ribosomal RNA. We conclude from these data that the steroid directly affects transcription of the ribosomal gene without obligatory participation of RNA polymerase B and hence the intermittent production of mRNA or its translation products.

Amanitins↗
PubMedDate not supplied

Gram-positive bacterial sepsis in rat and tissue lipolytic activity on commercial parenteral fat emulsions.

To study the influence of a gram-positive sepsis on the metabolism of circulating lipids, fasted rats were injected with saline (control group) or with a suspension of heat-killed or live Staphylococcus aureus. 18 h later, body temperature was increased, while albuminemia and ketonemia were decreased in the group injected with heat-killed bacteria, as opposed to the control group. Passing from these groups to the group injected with live bacteria, more differences appeared: increase of triglyceridemia and free cholesterolemia; decrease of esterified cholesterol levels and especially of the in vitro activity of diaphragm, heart and adipose tissue lipoprotein lipase and of hepatic lipase. The decrease of lipolytic activities occurred whether they were measured on a fat emulsion containing long-chain or medium- and long-chain triglycerides. The fact that for the latter the activity was always higher than for the former suggests that the host infected with gram-positive bacteria would clear exogenous fat more easily in the case of medium-chain triglycerides.

Animals↗
PubMedDate not supplied

Peptomer aluminum oxide nanoparticle conjugates as systemic and mucosal vaccine candidates: synthesis and characterization of a conjugate derived from the C4 domain of HIV-1MN gp120.

Peptomers are polymers composed of peptides that are specifically cross-linked in a head-to-tail fashion. Recently, a peptomer composed of an amphipathic peptide from the C4 domain of HIV-1MN gp120 was shown to display a prominent alpha-helical conformation that, as an immunogen, elicited rabbit antibodies recognizing native and recombinant gp120 [Robey et al. (1995) J. Biol. Chem. 270, 23918-23921]. For the present study, we synthesized a conjugate composed of the C4 peptomer covalently linked to calcinated aluminum oxide nanoparticles. The nanoparticles were first reacted with (3-aminopropy])-triethoxysilane to provide an amine load of 15.9 mmol of R-NH2/g of solid. The amine-modified aluminum oxide nanoparticles then were reacted with N-acetylhomocysteine thiolactone at pH 10 to place a reactive thiol on the nanoparticles. A bromoacetylated C4 peptomer, modified at the epsilon-amines of lysine residues, then was reacted with the thiolated nanoparticles to give the peptomer covalently linked to aluminum oxide via a thioether bond. The peptomer load was determined to be 16 mg of peptomer/g of particles, a 55% theoretical yield. Particle shape and size of the peptomer-conjugated alumina were analyzed by electron microscopy and displayed a mean maximum diameter of 355 nm and a mean minimum diameter of 113 nm, well within the desired size range of 300 nm believed to be optimal for mucosal immunization purposes. Experimentally determined values of mean particle diameters, specific surface area, and specific peptomer load provided the information necessary to calculate the mean antigen load, which was determined to be 53000 +/- 42000 peptomer epitopes per particle. Peptomer-alumina conjugates, such as that described here, could form the basis of a new class of biomaterial that combines a chemically defined organic immunogen with a nontoxic chemically defined inorganic adjuvant.

AIDS Vaccines↗
PubMedDate not supplied

Grafting protein ligand monolayers onto the surface of microparticles for probing the accessibility of cell surface receptors.

Coupling of a specific ligand to vaccines or drugs can be a powerful aid to route these compounds to a certain target cell population. However, if the targeted receptor is buried in a glycocalyx, binding of the ligand may be sterically hindered or even abolished, especially when the ligand is attached to bulky payloads. The antigen-transporting M cells that cover the gut-associated lymphoid tissue have a less pronounced glycocalyx than neighboring enterocytes. Such architectural differences might provide a possibility for targeting micro- or nanoparticulate vaccines to the mucosal immune system. To investigate the influence of the glycocalyx on the accessibility of cell surface receptors, we developed a system where a monolayer of ligand molecules is coupled in spatially aligned manner onto the surface of microparticles. On the basis of fluorescent carboxylate-modified particles of 1 micron diameter, different synthetic strategies were tested. Particles were first modified to display aldehyde functions on their surface, then protein ligands were coupled via Schiff base formation. The performance of the particles was tested on cultured mouse fibroblasts using the B subunit of cholera toxin as ligand and the plasma membrane glycolipid ganglioside G(M1) as receptor. Cholera toxin B subunit-coated microparticles generated by one of our synthetic pathways exhibited specific binding to fibroblasts which could be blocked with soluble cholera toxin B subunit. As particles as small as 50 nm and any proteinaceous ligand may be used, this system provides a versatile means for monitoring receptor accessibilities in vitro and in vivo.

3T3 Cells↗
PubMedDate not supplied

Studies on the tolerance of medium chain triglycerides in dogs.

Two groups of five conscious dogs received total parenteral nutrition (about 100 kcal/kg body weight per 24 hr) continuously for 96 hr (0.28 g triglycerides/kg body weight per hr, constituting more than 55% of the energy supply). The only difference between the two groups was the nature of the 20% lipid emulsion. In one group, this emulsion contained only long-chain triglycerides (LCTs), and in the other it contained a mixture (vol/vol) of medium chain triglycerides (MCTs) and LCTs. MCTs thus were given in an amount of about 30% of the total energy supplied. During infusion with the MCT/LCT mixture, C8, C10, and C12 fatty acids appeared in the total plasma fatty acids. When the infusion was stopped, the medium-chain fatty acids disappeared; those with shorter chains did so more rapidly. The plasma triglyceride clearance was faster for the MCT/LCT mixture than for the LCTs, whereas phospholipid and cholesterol clearance seemed slower for the MCT/LCT mixture. With this mixture, there was a slight increase in the plasma concentrations of ketone bodies, lactate, and pyruvate, and a slight decrease in plasma glucose. The MCT/LCT mixture was well tolerated, causing no discernible problems, and, in particular, no signs of narcosis or encephalopathy.

Animals↗
PubMedDate not supplied

Effects of L-carnitine infusion on intralipid clearance and utilization. Study carried out in septic patients of an intensive care unit.

Endogenous and exogenous supplies of carnitine are decreased in septic patients under total parenteral nutrition, while carnitine urinary elimination is increased. But the increase of lipid role in the energetic cover requires a greater intervening role of tissue carnitine. So one may hope that in septic patients additional supply of L-carnitine would increase the catabolism of infused lipids. Twenty-eight septic patients, admitted in an intensive care unit were given parenteral nutrition (200 g of glucose, 12.5 g of N/24 hr). On the day of the study, 250 ml of Intralipid 20% (Kabi Vitrum) were administered in 4 hr. During the same period 13 patients were infused with 2 g of L-carnitine (Sigma-Tau). The remaining 15 patients constituted the control group. Basic plasma levels of triglycerides, nonesterified fatty acids, free glycerol, phospholipids, and ketone bodies remained within physiological limits. They increased during the lipid infusion and returned to initial values, 4 hr after the end of the infusion. Free and total carnitine levels and free/total carnitine ratio were comparable to healthy subjects' reference values. These parameters increased during L-carnitine infusion. This infusion had no effect on exogenous lipid clearance. However, it seemed to increase the uptake and the hepatic oxidation of circulating fatty acids. It invalidated the increase of lactate and pyruvate that had been noticed when lipids were solely infused.

Adult↗
PubMedDate not supplied

Adult croup--a case report.

A case of a female adult patient with croup is described. Inflammation, as well as pseudomembranes, restricting the patency of trachea, developed within several hours after the first symptoms of infection were observed. Tracheostomy was performed Bronchofiberoscopies were repeated on a regular basis several times a day over a period of two weeks, with the removal of fibrinous casts and dense secretion being the only way to save the patient's life.

Croup↗
PubMedDate not supplied

Decreased lipolytic activity in tissues during infectious and inflammatory stress.

The clearance rate of endogenous and exogenous circulating lipids during the septic or inflammatory state remains a controversial subject. Thus, we have developed rat models of gram-negative and gram-positive sepsis and of sterile inflammation to study this problem. In addition to the febrile response, these stresses induced some of the following metabolic changes in the blood: decreased total protein, albumin, and ketone body levels and increased lactate, pyruvate, alanine, cholesterol, and triacylglycerol levels. The activities of heart, diaphragm, and adipose tissue lipoprotein lipase and of hepatic lipase decreased to differing extents depending on whether the enzyme substrate was a long-chain or a medium- and long-chain triglyceride-based emulsion. However, the latter emulsion was always hydrolyzed faster than the former. This observation suggests that, during infection/inflammation, the medium- and long-chain triglyceride-based emulsion would be cleared more quickly, would induce less hypertriglyceridemia, and would thus deliver lipid energy more rapidly than a traditional long-chain triglyceride-based emulsion.

Alanine↗
PubMedDate not supplied

In vivo and in vitro release of lipoprotein lipase and hepatic lipase by low molecular weight heparins.

The purpose of this study was to compare lipoprotein lipase (LPL) and hepatic lipase (HL) releasing activities of different low molecular weight heparins (LMWH) and of a standard heparin. In vivo, the injection of most LMWH led to a LPL and HL releasing activity inferior to that obtained with a standard heparin. The releasing of LPL by muscle in vitro and of HL by perfused liver was identical with both types of heparins, but in epididymal adipose tissue, LPL activity released by LMWH was generally higher than the activity released by unfractionated heparin. We have no explanation for this apparent contradiction between the in vivo and in vitro results.

Adipose Tissue↗