[High-density lipoproteins, total cholesterol, triglycerides and serum trypsin activity. Study in chronic alcoholic and withdrawn subjects]. / Lipoprotéines de haute densité, cholestérol total, triglycérides et activité trypsique sérique. Etude chez l'homme alcoolisé chronique et sevré d'alcool.

Apolipoprotein is controlled by proteolytic processus and serum trypsin-like activity (STA) may be elevated in some chronic alcoholic subjects. STA, apoA lipoprotein, HDL-cholesterol, total cholesterol and triglycerides were tested in 44 men dealt in 4 groups (subjects with normal or elevated STA, alcoholic or withdrawn). Significantly lower apoA lipoprotein (p less than 0,02) and HDL-cholesterol (p less than 0,001) levels as well as significantly higher triglyceride levels (p less than 0,01) were evidenced in the group with elevated STA compared to the group with normal STA. In another way, a negative correlation between HDL-cholesterol and STA (p less than 0,01) and a positive correlation between triglycerides and STA (p less than 0,001) were noted. The different factors known to modify these lipidic parameters cannot account for such disturbances. The role of elevated STA is evoked.

The effects of 17 alpha-ethynyloestradiol and of acute inflammation on the plasma concentration of rat alpha 1-acid glycoprotein and on the induction of its hepatic mRNA.

We measured the serum concentration of alpha 1-acid glycoprotein (alpha 1-AGP) and we evaluated the content of its hepatic mRNA in rats after 17 alpha-ethynyloestradiol treatment or after turpentine-induced acute inflammation, or after both treatments performed simultaneously. We have also studied the affinity of serum alpha 1-AGP for concanavalin A under these conditions. Both types of stimuli induce a marked retention of the glycoprotein on free concanavalin A. The serum concentration of alpha 1-AGP is increased about 14-fold compared with that in control rats when a single pharmacological dose (50 micrograms) or multiple injections of 17 alpha-ethynyloestradiol are administered. This increase is greater in turpentine-oil-injected rats (about 21-fold) and reaches a maximum (about 32-fold) in rats injected with 17 alpha-ethynyloestradiol plus turpentine oil; this increase in alpha 1-AGP corresponds to the addition of the effects of the two inducing agents. Similar changes are also observed either in the alpha 1-AGP mRNA content as estimated by using an alpha 1-AGP-specific cDNA probe, or in the amount of translatable alpha 1-AGP mRNA. The results indicate that: after a high dose of 17 alpha-ethynyloestradiol and after acute inflammation, the increase of the alpha 1-AGP serum concentration is due to an accumulation of the alpha 1-AGP mRNA; different mechanisms and/or pathways are probably involved in regulating the synthesis of alpha 1-AGP under various stimuli; 17 alpha-ethynyloestradiol as well as acute inflammation seem to control the glycosylation process of alpha 1-AGP in an identical manner.

Human alpha 1-antitrypsin genetic polymorphism: PI N subtypes.

Three new genetic variants (PI types) of alpha 1-antitrypsin are described. They have been compared to previously described phenotypes by several techniques including narrow pH range isoelectric focusing in ultrathin polyacrylamide gels. In this system, the relevant alpha 1-antitrypsin gel bands, identified by crossed immunoelectrophoresis, focused between PI M2, the most cathodal PI M subtype, and PI P BUD, the most anodal PI P subtype. They were therefore considered to be PI N subtypes. Two of them, PI N GRO and PI N YER, could not be separated by isoelectric focusing, but gave a different pattern in agarose gel electrophoresis. None of the new alleles seemed to be associated with disease. The high resolving power of isoelectric focusing is emphasized with respect to the information it may provide concerning amino acid substitutions, while the use of other techniques proved to be of utmost importance in the differentiation of other variants showing similar isoelectric points.

Inter-alpha-trypsin-inhibitor (ITI): two distinct mRNAs in baboon liver argue for a discrete synthesis of ITI and ITI derivatives.

Human serum inter-alpha-trypsin-inhibitor (ITI) has so far been assumed to be comprised of a single polypeptide chain which can undergo fragmentation, whereby inhibitory ITI derivatives are released into the blood stream. In contrast, the analysis of the baboon liver mRNA translation products showed that ITI is made up of heavy and light chain(s). The latter may be excreted independently and very likely corresponds to the so-called ITI derivatives.

Inter-alpha-trypsin inhibitor (ITI): use of new antisera for qualitative studies and discrete quantitation of ITI and its derivatives.

Inter-alpha-trypsin inhibitor (ITI) is a human protease inhibitor characterized by its coexistence with several physiological derivatives displaying immunological cross-reactivity when analyzed in plasma with usual anti-ITI antisera. Taking advantage of the presence in urine of a particular ITI derivative, antisera with restricted specificity for either ITI or its derivatives could be prepared. Some applications of these new reagents are given, including qualitative studies and discrete quantitation--by electroimmunoassay--of ITI and ITI derivatives. The procedures herein described should prove useful for qualitative and quantitative analysis to investigators dealing with mixtures of antigenically related proteins.

Inter-alpha-trypsin-inhibitor (ITI): use of immunoadsorbents for preparation of anti-ITI antiserum, ITI-free human serum and purified ITI.

Immunoaffinity chromatography was used to prepare various reagents required for studies of inter-alpha-trypsin-inhibitor (ITI), a human protease inhibitor. To absorb an initially polyspecific anti-ITI antiserum, a mixture of all serum proteins except ITI was prepared as follows: normal human serum was gel filtered (Sephacryl S-300) and the part of peak II containing normal ITI was removed; another aliquot of serum was heated, gel filtered, and peak I which contained all ITI molecules in aggregated form was discarded. The remaining fractions from both gel filtrations were immobilized on gel and used as an immunoadsorbent. The monospecific anti-ITI antiserum thus obtained was immobilized on gel and could bind ITI from human serum. Under conditions chosen to weaken non-specific adsorptions and desorb ITI without denaturation, this immunoadsorbent made it possible to prepare ITI-free serum and purified ITI with biological activity.

"Tryptic-like" activity in sera of patients with pancreatitis.

Serum trypsin esterolytic activity was measured in 106 sera from 61 controls and 45 patients with pancreatitis. A trypsin specific synthetic substrate, N-alpha-benzoyl-L-arginine-paranitroanilide, was used. High levels of enzymatically active trypsin were shown to be present in serum of patients with pancreatitis. No difference between the two samples was noticed for the serum concentrations of alpha-1-antitrypsin and alpha-2-macroglobulin (the two main serum trypsin inhibitors). Active trypsin was contained in the high molecular weight fraction of plasma proteins, corresponding to a complex with alpha-2-macroglobulin. The determination of serum typsin activity as a sensitive test for detection of pancreatitis was demonstrated to be statistically significant.

Tryptic and elastolytic inhibitory capacities of serum from various Pi phenotypes.

Alpha-1-antitrypsin deficiency is responsible for emphysema in adults. The genetic polymorphism of this protein (Pi system) is used to detect these deficiencies. The relationship between the serum protease inhibitory capacities and M, MZ and Z Pi phenotypes was investigated. 120 sera including 31 M, 33 MZ and 56 Z were studied. The alpha-1-antitrypsin concentration varied according to the Pi phenotype, the sex and the health of the subject. The alpha-2-macroglobulin level did not depend on the Pi phenotype. The trypsin inhibitory capacity fluctuated with the age and the health of the subject, but did not faithfully represent the Pi phenotype. In contrast, the elastase inhibitory capacity depended only on the Pi phenotype. The relationship between alpha-1-antitrypsin levels and the serum elastase inhibitory capacities was linear. Canonical analysis was employed to determine the relative contributions of each antiprotease to the two inhibitory capacities. It appeared that the elastase inhibitory capacity was influenced more by the alpha-1-antitrypsin level while the trypsin inhibitory capacity was more sensitive to alpha-2-macroglobulin.

[Pan-lobular emphysema: relationship with serum alpha-1-antitrypsin levels, Pi phenotype and the HLA system (author's transl)]. / Emphysème pan-lobulaire: relations avec le taux d'alpha 1-antitrypsine sérique, le phénotype Pi et le système H.L.A.

Pi phenotypes have been studied in a group of 433 patients. Patients with panacinar emphysema and/or bullae were identified from careful analysis of their clinical, physiological, radiological and anatomical characteristics. Twenty-five p.cent of the emphysematous patients were MZ; there was no significant difference in the alpha-1-antitrypsin plasmatic levels between the groups. The HLA antigens were studied in order to try to identify the possible cofactors in the development of emphysema. The role of occupational pollutants and/or of tobacco is discussed. The frequency of the MZ phenotype in our series differs from previous publications. This discrepancy is discussed on the basis of the criterious used to identify the emphysematous patients.

Genetic variants of serum alpha-1-antitrypsin (Pi types) in Bretons.

The results of Pi typing on 280 Bretons from Morbihan (Southern Brittany) are reported. 6 phenotypes and 5 alleles have been found in this study. Pi M is the most frequent as in other populations. Pi S and Pi F apears as the two main variants in population genetics.