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Each albumin variant, its source, and ethnic origin are listed in the Appendix. Many of the new variants were found in several individuals in a single family. In other cases the variants were found in one or more individuals in a single village. The electrophoretic comparisons were made in the three starch-gel systems, acetate-EDTA at pH 5.0, tris-lithium-succinate-citrate at pH 6.0 and tris-EDTA-borate at pH 6.9, used previously (Weitkamp et al. 1973). RESULTS The results of the comparison of 30 new or recently described serum albumin variants with 20 variants previously distinguished using three starch-gel electrophoretic systems are presented in Table 1. Although the amount of separation reported here for the 20 variants previously described differs slightly from the earlier results, due to minor variations in electrophoretic conditions, the conclusions regarding their mobility relative to normal albumin and to each other remain the same. Three new variants, RS I, Xavante, and Yanomama-2, all slowly migrating, have been identified. Electropherograms showing these variants adjacent

Summary In the serum of vipers several heteroagglutinins active against the red cells of many animal species can be distinguished. These agglutinins represent mixtures of antibodies of more or less strict specificity. Some are specific for human or equine blood groups, others are only species-specific, and still others are specific for antigenic patterns common to several species. It is interesting to note that, among the antibodies reacting with several antigens, some, such as those reacting with the human A and B antigens, are found in the serum of a wide variety of species (fish, reptiles, birds, domestic mammals such as rabbits, dogs, cattle, or wild mammals, such as monkeys). It has thus been shown that the serum protein molecules which have been the object of the present immunological studies possess at least one property in common, namely that of agglutinating certain red cell antigens. Resume On peut denombrer, dans le serum de vipere, un certain nombre d'heteroagglutinines actives sur les hematies de nombreuses especes animales. Ces agglutinines sont un melange d'anticorps de specificite plus oumoins etroite. Les unes sont specifiques d'antigees definissant des groupes sanguins chez l'homme ou le cheval, d'autres ne reconnaissent que «l'espece», d'autres enfin ne decelent que des motifs antigeniques communs a plusieurs especes. Parmi cette diversite des structures proteiques capables de reagir avec de nombreux antigenes, il est interessant de noter que certains motifs, tels que ceux reagissant avec les antigenes A et B humains, se rencontrent dans le serum d'especes les plus variees (poissons, reptiles, oiseaux, mammifees domestiques: lapin, chien, baeufs ou sauvages: singes). Les etudes immunologiques permettent dans ce cas de reconnaitre des molecules proteiques presentant au moins entre elles un caractere commun, a savoir l'agglutination de certains antigenes erythrocytaires. Zusammenfassung Das Serum von Vipern enthalt eine Reihe von Heteroagglutininen gegen Erythrozyten verschiedener Tierarten. Bei diesen Agglutininen handelt es sich urn ein Antikorpergemisch mit mehr oder minder ahnlicher Spezifitat. Die einen Antikorper reagieren mit BhtgruppenMerkmalen des Menschen und des Pferdes. Andere reagieren artspezifisch; wiederum andere reagieren mit Antigenen, die bei mehreren Tierarten vorkommen. Daruber hinaus wird darauf hingewiesen, das die Seren zahlreicher verschiedener Tiere (Fische, Reptilien, Vogel, Saugetiere (Kaninchen, Hund, Rind, Wildtiere, Affen) Antikorper enthalten, welche mit den A- und 3-Antigenen des menschlichen Serums reagieren. Auf Grund solcher Versuche ist es moglich, in den Seren der verschiedensten Tiere Proteine zu erfassen, welche das gemeinsame Merkmal der Heteroagglutination von Erythrozyten aufweisen.

Resume Dans des cas extremement rares, il est possible de mettre en evidence, dans les urines de sujets atteints de gammapathie « monoclonale , la presence, a cote de chaines legeres isolees, des molecules entieres d'immunoglobulines. L'auteur a ainsi demontre dans un cas la presence d'IgG urinaire, et dans deux cas celle d'IgA urinaire.

Resume L'activite anti-Gma, anti-Gmb et anti-Gmx, presente dans certains serums d'individus normaux, est de nature euglobulinique et en relation avec les fractions macroglobuliniques des γ-globulines (β2M). Cette activite parait etre supportee soit par la β2M seule, soit par l'association β2M-γ-globulines. Elle existe independamment du facteur rhumatoi'de. L'activite anti-Gm n'a pas ete rencontree dans des serums presentant une macroglobulinemie pathologique. Summary The anti-Gma, anti-Gmb and anti-Gmx activity present in the serum of certain normal individuals is a function of the euglobulin fraction and is related to the macroglobulin fraction of the γ-globulins (β2M). This activity appears to be exercised either by the β2M fraction alone or in association with the γ-globulins. It occurs independently of the rheumatoid arthritis factor. No anti-Gma activity was found in sera containing pathological macroglobulins. Zusammenfassung Die in den Seren gewisser gesunder Individuen gefundene Anti-Gma-, Anti-Gmb-und Anti-Gmx-Aktivitat ist an die Euglobulinfraktion gebunden und steht in Beziehung zur Makroglobulinfraktion der γ-Globuline (β2M). Diese Aktivitat scheint entweder an die s2M-Globuline oder an einen β2M-γ-Globulinkomplex gebunden zu sein. Sie existiert unabhangig vom Rheumafaktor. Seren mit pathologischer Makroglobulinamie zeigten keine Anti-Gm-Aktivitaten.

The frequency of isolated IgA deficiency was determined in a healthy population of 15,200 volunteer French blood donors. The screening was performed either by inhibition of passive haemagglutination or by double diffusion analysis in gel. The results obtained with the two methods were concordant. In the Parisian population, the incidence of selective IgA deficiency characterized by a serum level below 0.5 IU, was found to be 1/3,040. This index is lower than that reported by most other investigators: 1/300-1/3,000. These discrepancies depend on the type of population chosen for inquiry. In open and ethnically mixed populations, the incidence of IgA deficiency is lower than in more sedentary, rural, populations in which the probability of distant consanguinity is increased.

Moullec J., Fine J.-M., Linhard J. Les groupes d'haptoglobine, moyen d'étude des populations humaines.. In: Bulletins et Mémoires de la Société d'anthropologie de Paris, XI° Série. Tome 2 fascicule 1, 1961. pp. 109-124.

Resume A l'occasion d'une etude systematique, nous avons mis en evidence, chez quatre sujets, une dysglobulinemie « monoclonalede type γ G Kappa presentant tous les caracteres des dysglobulinemies « asymptomatiques dont nous avions deja presente une vingtaine d'observations chez des sujets âges de plus de 70 ans [6, 9] ainsi que d'autres cas de decouverte fortuite [10] . Ces caracteres peuvent se resumer ainsi : a) absence de toute symptomatologie clinique, radiologique ou cytologique evoquant le myelome, a l'exception, chez certains sujets, d'une legere anemie, d'une leucopenie moderee et d'une plasmocytose medullaire n'excedant pas 5 % ; b) vitesse de sedimentation normale ou peu elevee ; c) presence d'une paraproteine de type γ G monoclonale mais peu importante quantitativement ; d) absence de diminution des immunoglobulines normales ; e) absence de proteinurie de type Bence Jones. La mise en evidence d'anomalies proteiques, chez des sujets consideres comme en bonne sante et exempts de toute symptomatologie clinique, cytologique ou radiologique evoquant le myelome, revet une importance considerable car elle permet de suivre l'evolution dans le temps de cette dysglobulinemie. L'etude de cette evolution, ainsi que l'etude des familles de ces sujets, permettront une meilleure connaissance de ces formes particulieres de dysglobulinemies et jugeront de la benignite ou de la malignite de ces syndromes.

Resume La frequence des anomalies « monoclonalesa ete etudiee par l'electrophorese du serum dans deux populations de donneurs de sang. Cette frequence est de 0,1 % chez les donneurs de la cabine fixe du C.N.T.S. de Paris et 0,3 % chez les donneurs du C.T.S. de Saint-Nazaire. L'etude de 20 cas de sujets presentant une dysglobulinemie monoclonale, dont certains ont ete suivis pendant plusieurs annees, montre que 16 cas peuvent pour l'instant etre consideres comme des formes « essentielles benignes(ou asymptomatiques). Ces cas se distinguent du myelome par une absence totale de symptomatologie clinique, radiologique et cytologique, par un constituant monoclonal d'importance moyenne ou faible, une vitesse de sedimentation normale ou peu acceleree, l'absence de diminution des autres immunoglobulines et l'absence de proteine de Bence Jones urinaire. La frequence des IgG Kappa semble plus elevee dans les formes « essentiellesqu'au cours du myelome. Le depistage des dysglobulinemies monoclonales dans une population de sujets en bonne sante apparente permet de depister des stades infra-cliniques du myelome ou de la macroglobulinemie de Waldenstrom et dans le cas de formes « essentielles , de surveiller par des examens successifs l'evolution ou non de ces formes vers une affection maligne.

Resume Les auteurs rapportent un cas de dysproteinemie du type Ig A, pseudomyelomateuse, observee chez un malade ayant un cancer primitif du foie developpe sur une cirrhose post-hepatique et s'accompagnant de metastases osseuses multiples. L'association cancer visceral et dysproteinemie monoclonale et la pathogenie de l'anomalie proteique sont brievement discutees.

Zusammenfassung 1. 1. L'etude en electrophorese de zones sur differents supports (papier, gelose, gel d'amidon), en diffusion en gelose et en immunoelectrophorese de diverses albumines modifiees a ete pratiquee. 2. 2. L'albumine serique humaine a ete soumise aux traitements suivants: la desamination, l'acetviation, la carboxymethylation, le traitement par l'anhydride phtalique, la ninhydrine, la toluenesulfonation, la phosphorylation, le traitement par l'aldehyde formique, la performylation, la nitration, le methylation. Certaines preparations denaturees par la chaleur, l'uree ou la guanidine ont ete egalement etudiees. 3. 3. Les conclusions principales se degageant de ce travail sont les suivantes: (a) La substitution des groupements cationiques a entraine une acceleration clans le champ electrophoretique a pH 8.6, une diminution de colorabilite vis-a-vis des colorants anioniqucs usuels. Ces deux criteres constituent un controle rapide et aise pour apprecier le resultat de la modification chimique desiree. En immunoelectrophorese, ces memes albumines modifiees donnent une reaction normale en ce qui concerne la precipitation avec le serum anti-albumine native, ce qui souligne le peu d'importance des groupes amines de l'albumine dans la reaction antigene-anticorps.

Serum electrophoresis were performed in 13,400 healthy adult subjects (blood donors) and 20 cases of monoclonal gammapathy were detected: ten cases out of 10,300 blood donors from Paris and ten out of 3,100 blood donors from Saint-Nazaire. The frequency of ‘M Component’ was of 0.1 and 0.3%, respectively. Four cases were related to myeloma or Waldenstrom's macroglobulinaemia and the other 16 cases could be ascribed to a ‘benign essential monoclonal gammapathy’ (BEMG). The distribution of heavy and light chain classes in BEMG was 13 γ (11 K and 2 L) and 3 MK. This screening of a normal population allowed detection of either clinically premalignant states or the occurrence and evolution of benign essential forms of gammapathies.

Human plasma components, separated by starch gel electrophoresis, are eluted and concentrated by lyophilisation. Immuno-electrophoretic analysis shows that certain of these fractions are immunologically heterogenous.

BY immunological techniques, Darcy1 has shown, in rats bearing a Walker's tumour, the appearance of a serum protein absent in normal rat serum.

Immunological studies of the haptoglobin-hemoglobin complexes of different serum groups show different mobility by immuno-electrophoretic technique, and the antigenic relationship of these haptoglobins.

Inter-alpha-trypsin inhibitor (I alpha I) has been purified from C.N.T.S. fraction III as starting material. The purification procedure includes D.E.A.E. cellulose chromatography and gel filtration on G 150 Sephadex in the presence of EDTA. The purified protein gives one precipitation line in immunoelectrophoresis against anti-whole human sérum. It reacts only with an anti I alpha I immune serum and possesses a strong antitryptic activity. When studied in starch or polyacrylamide gel electrophoresis 2 components are observed, each of them having the same antigenic structure and the same antitryptic activity as the crude preparation. The slower and less important component is dissociated by 0,1% SDS. The molecular weight estimation of I alpha I BY PAA/SDS is about 180,000. This result is not modified by the presence of 1% beta mercaptoethanol indicating that I alpha I consists of one polypeptide chain. Crude preparation reveals under the same electrophoretical conditions small amounts of low molecular weight components (135,000 52,000 and 26,000) which can be due to a proteolytic action on I alpha I. Indeed plasmin is able to produce such fragments having an antitryptic activity as shown by fibrin/polyacrylamide gel electrophoresis. The relationship between small molecular weight inhibitors of human serum and bronchial secretions and those obtained after degradation of I alpha I by plasmin is discussed.

Pure alpha2M is prepared with fresh plasma as starting material, to prevent the interaction of alpha2M from proteolytic enzymes of plasma such as thrombin, plasmin and kallikrein. During the purification steps, polybrene and aprotin are used as inhibitors and plasminogen is absorbed onto bentonite. When alpha 2M is submitted to polyacrylamide gel electrophoresis (PAA) containing 0.1% SDS, a complete dissociation in two half-molecules of MW 380,000 occurs. When alpha2M is incubated in 1% SDS and 1% beta-mercaptoethanol as reducing agent, only one component of MW 190,000 is observed in PAA-SDS. This experiments show that the alpha2M molecule consist of two symetric halves of same MW (380,000) linked by non covalent bonds. Each two-half-molecules is made of two polypeptides chains MW 190,000 linked by disulfide bonds. Thus alpha2M molecule contains four polypeptides chains having a same MW. The same techniques were applied to the study of alaph2M proteinases complexes. Three different proteinases (plasmin, trypsin and papain) were used in these experiments. Trypsin and papain are commercialy available. Plasminogen was obtained by affinity chromatography and activated into plasmin by insoluble streptokinase fixed on PAB cellulose.

The distribution in heavy chain classes and light chain types of M components were studied in 757 cases of monoclonal gammapathies. These gammapathies were classified according to clinical and hematological data in 439 myeloma (MM), 165 Waldenström's macroglobulinemia (WM) and 152 monoclonal gammapathies occurring in other conditions. The IgG/IgA ratio differs in myeloma and in non-myelomatous gammapathies (64% IgG versus 33% IgA in myeloma and 95% IgG versus 5% in absence of myeloma). Presence of free light chains in patient's urines (Bence Jones proteinuria) was detected in about 72% of cases of MM, 48% of WM and only in 9% in others gammapathies. Concerning the sex of patients, an equal repartition between males and females is observed in MM, whereas males predominate in WM. The age distribution of the patients shows that 74% of myeloma and 79% of WM were above sixty. In addition to the 757 cases under study, 10 sera with two M Components were characterized.