Search

Twenty cases of “asymptomatic” monoclonal gammopathies were detected by routine electrophoresis in patient's sera or in blood donors and were followed over 3–14 years. Four cases have shown a malignant evolution—two evolved toward Waldenstrom's macroglobulinemia after 3 years and two could be classified as myeloma 3 and 7 years, respectively, after detection of the monoclonal protein. The remaining cases were still “asymptomatic” 4 years later (7 cases), 7–9 years later (8 cases) and 14 years later (1 case). A malignant evolution occurred in approximately 20% of cases.

This paper reports a rare familial occurrence of Waldenstrom's macroglobulinemia (WM) in siblings (two brothers and one sister). Examination of the siblings of a patient suffering from WM in 1965 showed that a brother and a sister had an “asymptomatic” monoclonal IgM in their sera without clinical or hematological features. Follow-up demonstrated a malignant transformation into WM after 7 years in the brother and after 15 years in the sister. This unusual incidence makes the true existence of asymptomatic gammopathies of IgM class questionable.

In order to investigate associations between summertime haze air pollution and asthma at an individual level, 52, 58, and 56 children (ages 7 to 13) attending a summer "asthma camp" were followed during the last week of June in 1991, 1992, and 1993, respectively. Most of the subjects had moderate to severe asthma. Daily records were kept of the environmental conditions, as well as of subject medication use, lung function, and medical symptoms. Air pollution was found to be significantly and consistently correlated with acute asthma exacerbations, chest symptoms, and lung function decrements. The pollutant most consistently associated with adverse health consequences was ozone (O3), although associations with sulfates and hydrogen ion suggest a possible role by fine particles as well. Effects were found to be roughly monotonic as a function of O3 concentration. Regression of morning (8:00 A.M.) to afternoon (5:00 P.M.) peak flow change on O3 indicated pulmonary function reductions similar to those previously reported for more active children without asthma. Moreover, analyses also indicated an increased risk of an asthma exacerbation and of experiencing chest symptoms of approximately 40% on the highest pollution day, relative to the mean. Based on these relative risk estimates, a rise in the 1-h daily maximal O3 from 84 ppb to 160 ppb was associated in this group with an increase from 20 to 28 (+/- 2) in the expected number of unscheduled medications administered/day, and from 29 to 41 (+/- 3) in the expected total number of chest symptoms/day. Thus, air pollution can be a major contributor to the respiratory problems experienced by children with asthma during the summer months.

Recombinant human deoxyribonuclease (rhDNase) is an agent which reduces the viscoelasticity of purulent sputum. Two cases are reported in which rhDNase was utilised for the management of lobar atelectasis due to retained purulent secretions.

Isolated albumin almost always contains polymerized forms which appear during preparation and storage of the protein. The proportion of polymerized forms reflects the degree of stability of the solution. The quantitative estimation of the polymers is usually performed by gel chromatography. In this work, the high resolution power of polyacrylamide gradient gel electrophoresis (Gradient PAGE) was used to separate the polymers present in the preparations of human serum albumin. The analysis of the different peaks obtained by gel chromatography allows to conclude that peak 1 contains aggregates and high polymers, peak 2 trimer and dimer and peak 3 the monomer of albumin. The aggregates of the peak 1 can be dissociated by SDS and correspond, in gradient PAGE, to the high polymers. By using gradient PAGE in the presence of SDS under the conditions described in this paper, it is possible to estimate the proportion of high polymers and aggregates present in albumin preparations. These results are similar to those obtained by chromatography followed by a protein assay but noticeably inferior to those resulting from measurements performed by absorbance at 280 nm.

Monoclonal gammopathies (M.G.) are a group of disorders characterized by the proliferation of a single clone of plasma-cells that produce a Monoclonal Immunoglobulin (M-Ig). The presence of M-Ig can be demonstrated by electrophoresis in the patient' serum and identified by immunoelectrophoresis as a molecule containing two heavy chains of a single class and two light chains of a single type. In M.G. of malignant origin, free light chains (Bence Jones Proteins) can be evidenced in the concentrated urines. The fact that M.G. may be more frequent in certain families show the existence of a familial predisposition of this disease whereas its origin is still unknown. M.G. are often associated with malignant proliferation of B lymphocytes such as multiple myeloma, Waldenstrom's macroglobulinemia, heavy chain disease as well as some other lymphoproliferative disorders. However, in a certain number of cases, the malignant origin of the M.G. was not proved, because M-Ig can occur in the serum of people apparently in good health and without clinical or hematological features (asymptomatic "benign" M.G.). Asymptomatic benign M.G. have been detected in increasing numbers during the last decade due to use of cellulose acetate electrophoresis for the routine examination of patients or in the course of systemic screening in normal populations such as blood donors. At the present time, a malignant origin of M.G. cannot be proved in more than thirty per cent of case and these "asymptomatic M.G." must be follow-up by a yearly clinical, hematological and electrophoretical check-up in order to detect a possible malignant evolution. In other cases, M.G. can be associated with neoplasms of cells types not known to produce M-Ig, in cold chronic agglutinin disease, and during the course of some auto-immune disorders.

Routine screening of monoclonal gammapathies (M.G.) was performed on the serum of 13,914 blood donors by cellulose acetate electrophoresis. Twenty-six cases of M.G. were detected corresponding to a frequency of 0.19 per cent. The incidence of the M.G. progresses with increasing age comparatively to the age distribution of the blood donors under investigation. Most of the M.G. detected can be classified as "asymptomatic" M.G. (23 of the 26) and heavy chain classes are only IgG or IgM with a large predominance of IgG class (about 90%). It is suggested that donors in whom M.G. have been detected should not be eligible for blood donation. A yearly clinical, hematologic and immunoglobulin checkup is recommended for these patients in order to detect a possible malignant transformation.

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

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.

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.

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.

Circulating proalbumin in humans has been described in two distinct events: genetic variants of proalbumin related to mutations at the cleavage site, and normal proalbumin related to an abnormal cleaving enzyme system. We report a case of acquired proalbuminemia that appeared after an acute episode of hepatitis related to the delta agent, in a chronic carrier of hepatitis B virus. This component, not present in normal plasma, was identified as proalbumin by immunological methods. It was indistinguishable from the molecule normally present in hepatocytes as judged by electrophoretic mobility, limited susceptibility to tryptic digestion, and its inability to bind labeled Ni. We suggest that this release of proalbumin is related to the concurrent presence of both hepatitis B and delta virus in some of the infected hepatocytes.

Bisalbuminaemia occurring together with paraproteinaemia in a case of proven myelomatosis is described. The albumin variant was investigated by dye-binding, electrophoresis at pH 5·0, 6·8, and 8·6, and by relative mobility studies compared with known genetically inherited variants. The present variant was indistinguishable from the previously described Pollibauer type.

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

In order to clarify the actual nomenclature of the albumin allotypes in French and Italian populations we compared the samples collected in our laboratory to those kindly supplied by Dr. Porta (Italy) with reference to albumin variants classified in starch gel electrophoresis using three buffer systems by Weitkamp. The inherited human albumin variants can be classified on the basis of their relative mobilities on cellulose acetate electrophoresis compatively to human transferrin mobility. The relative mobility of each variant can be expressed by the following ratio: migration distance of the variant versus migration distance of the normal albumin where zero represents the transferrin mobility. Using three buffers system at pH 8.6, 5.0 and 6.9, it is possible to distinguish some albumin variants having a same mobility at alkaline pH and different mobilities at acidic pH. In the european area, eleven albumin variants are distinguishable on the basis of their relative mobilities at different pH: four Fast moving variants: Gent, Vanves (a new variant described here), Reading and CN/BL, and seven Slow moving variants: MI/MI Slow, GE/CT, SO/BS (or D type), Pollibauer, Gainesville, Roma and B type. Thirty-six sera from unrelated subjects with genetic bisalbuminemia were analyzed in our laboratory. Their distribution was as follows: B type (22), Pollibauer (9), SO/BS (2), Gainesville (1), Gent (1) and Vanves type (1). The frequency of bisalbuminemia was 0.35 per 1,000 in a population of 19,949 blood donors.

Acquired Von Willebrand syndrome is reported in four patients with monoclonal lgG : benign gammapathy in three cases, multiple myeloma in one case ; to our knowledge, this last association has not been previously reported.Coagulation abnormalities included a borderline bleeding time, a low platelet retention on glass beads, decreased levels of factor VIII coagulant activity (VIII: c), factor VIII related-antigen (VIII R: Ag) and ristocetin-induced agglutination cofactor (VIII R: Cof).The late clinical onset, the negative family history and the immunological abnormality suggest an acquired Von Willebrand syndrome. After cryoprecipitate infusion the patients did not show the expected rise and there was no secondary increment in factor VIII: c.Time-dependent inhibition of factor VIII R: Cof was found in one case only and was associated with qualitative abnormality of factor VIII R: Ag demonstrated by crossed-immunoelectrophoresis. It was not possible to interpretate this last test in the other cases, due to the very low level of factor VIII R: Ag. The inhibitor activity was neither found in the IgG fraction nor in the monoclonal IgG but disappeared after IgG adsorption on staphylococcal protein A.The factor VIII abnormalities might be related to the binding and/or destruction of factor VIII by a circulating antibody, or to the adsorption of this factor on the malignant lymphocytes.

PRIMARY macroglobulinaemia (Waldenstrom's disease) has been observed in two brothers aged respectively 65 and 63 years. The clinical and haematological findings are summarized in Table 1. These two patients showed almost the same clinical picture : haemorrhagic disorders with frequent epistaxis, haematoma, melœna ; anaemia, increase of the lymphoid cells in the circulating blood, and in bone marrow. The eye grounds show a dysproteinaemic aspect and bilateral bleedings. Patient 1 (Louis D.) shows enlarged lymph nodes and splenomegaly.

In normal human serum IgA is present in a series of polymeric forms; the largely predominant monomeric 7S form coexists with components of increasing sedimentation coefficients (1,2). This size heterogeneity was also observed in serum of IgA myeloma (3,4). In 1964, studying 32 isolated IgA myeloma proteins, we reported that starch gel electrophoresis revealed 3 different types of polymerization — type I, II and III (5). More than 95% of 165 IgA M-components analyzed in this laboratory could be ascribed to one of these types. In our experience the type of polymerization remains stable for any given IgA myeloma. Taking advantage of a procedure for IgA purification which avoids the sieving effects or gel filtration (6), we confirmed and extended our previous findings (7). In this communication we present data concerning the types of size heterogeneity observed in monoclonal and polyclonal IgA preparations.

SummaryA familial occurrence of β 2 macroglobulinaemia has been found in 4 instances. The antigenic structure of the macroglobulins in members of a given family has been investigated with antisera specific to the patients' macroglobulins. In one family, the serum of the asymptomatic mother contained 2 distinct kinds of macroglobulins and each of her 2 sons (affected with Waldenstrom disease) had one of them and not the other. In 2 other families, the antigenic structure of the macroglobulin was different in each of the 2 relatives.

WE have investigated by starch gel electrophoresis1, using a technique described in a previous paper2, 28 sera from patients with multiple myeloma, 13 from patients with macroglobulinaemia, 4 sera from cases with atypical dysproteinaemia. In every case a characterization of abnormal serum components was carried out previously, using free-boundary electrophoresis3, analytical ultracentrifuging4, agar gel and immuno-electrophoresis5.