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A system of seric transferrin groups has been found in the newt, Pleurodeles waltlii Michahelles. The genetic transmission of this protein type is studied in this article. Polymorphism is based on the existence of 2 transferrins, TfA and TfB. Phenotypes B and AB were observed in a laboratory population, and the third phenotype, A, was obtained after crossing heterozygotes. Transferrin types were reproduced in clones of newts obtained by nuclear grafts.

High-altitude natives are challenged by hypoxia, and a potential compensatory mechanism could be reduced blood oxygen-binding affinity (P50), as seen in several high-altitude mammalian species. In 21 Qinghai Tibetan and nine Han Chinese men, all resident at 4200 m, standard P50 was calculated from measurements of arterial PO2 and forehead oximeter oxygen saturation, which was validated in a separate examination of 13 healthy subjects residing at sea level. In both Tibetans and Han Chinese, standard P50 was 24.5 ± 1.4 and 24.5 ± 2.0 mmHg, respectively, and was lower than in the sea-level subjects (26.2 ± 0.6 mmHg, P 0.01). There was no relationship between P50 and haemoglobin concentration (the latter ranging from 15.2 to 22.9 g dl(-1) in Tibetans). During peak exercise, P50 was not associated with alveolar-arterial PO2 difference or peak O2 uptake per kilogram. There appears to be no apparent benefit of a lower P50 in this adult high-altitude Tibetan population.

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.

Existing (5, 6) Nystrom pairs for the general second-order initial-value problem either control the local error in y only, or use more than eight stages. We develop a class of eight-stage (5, 6) Nystrom pairs that control the local error in y and y ′. We first give the derivation of the class. Then we discuss the selection of values for the free parameters in the class. Finally, we give numerical results to illustrate the possible gains in efficiency compared with existing eight-stage (5, 6) Nystrom and Runge-Kutta pairs.

The evolution of microstructure during a single pass of laboratory hot rolling (47% reduction) of a 5083 aluminium alloy has been investigated at different positions through the thickness of the plate. The thermomechanical histories of the subsurface and centre regions of the hot rolled slab were analysed using instrumented rolling blocks and finite element (FE) modelling; the pass history was then simulated physically using plane strain compression testing by deforming the test specimens to the appropriate equivalent strain at a representative equivalent strain rate and temperature associated with the rolling deformations. Microstructures formed by the plane strain compression simulations were then compared with the actual hot rolled microstructures. The main features of the microstructures, particularly the sizes and volume fractions of the recrystallised grains, were reproduced very well. Experimentally determined temperature profiles, mean strain rates, and strain accumulated at the centre of ...

The pneumococcal polysaccharide vaccine (PPV) is effective in preventing invasive pneumococcal disease, but remains underutilized. Prior surveys of physicians revealed concern regarding the safety and efficacy of the vaccine, but there has been little information published in the last 10 years that sheds light on why the vaccine remains underutilized. Although there is currently emphasis on providing PPV to hospitalized patients, there is even less known about what factors prevent PPV use in the hospital setting and chronic care setting. We performed a survey of physicians in Connecticut to determine what factors prevent utilization of the vaccine in three patient care settings.A survey of internists and family practitioners in Connecticut that ascertained their frequency of utilization of PPV and what factors inhibited utilization of PPV.Three hundred ninety-seven responses are included in the analysis. Forgetting to administer the vaccine (59% of respondents) and patient refusal (55% of respondents) were the factors most frequently noted as being important in preventing vaccination in the outpatient setting. In the inpatient and chronic care settings, difficulty in determining the patient's vaccine status was also noted. Concerns regarding the efficacy or safety of the vaccine did not seem to be important. The factor that correlated most closely with the respondents' reported frequency of vaccine use was forgetting to vaccinate.Physicians, although accepting the efficacy of PPV, are inhibited from its more frequent use by several factors.

Pneumonia is a frequent cause of hospitalization and death among elderly patients, but the relationships between processes of care for pneumonia and outcomes are uncertain, making quality improvement a challenge.To assess quality of care for Medicare patients hospitalized with pneumonia and to determine whether process of care performance is associated with lower 30-day mortality.Multicenter retrospective cohort study with medical record review.A total of 3555 acute care hospitals throughout the United States.A total of 14069 patients at least 65 years old hospitalized with pneumonia.Four processes of care: time from hospital arrival to initial antibiotic administration; blood culture collection before initial hospital antibiotics; blood culture collection within 24 hours of hospital arrival; and oxygenation assessment within 24 hours of hospital arrival. Associations between processes of care and 30-day mortality were determined with logistic regression analysis.National estimates of process-of-care performance were antibiotic administration within 8 hours of hospital arrival, 75.5% (95% confidence interval [CI], 73.1-77.9); blood cultures before antibiotics, 57.3% (95% CI, 54.5-60.1); initial blood culture collection, 68.7% (95% CI, 66.2-71.2); and initial oxygenation assessment, 89.3% (95% CI, 87.5-90.9). Lower 30-day mortality was associated with antibiotic administration within 8 hours of hospital arrival (odds ratio [OR], 0.85; 95% CI, 0.75-0.96) and blood culture collection within 24 hours of arrival (OR, 0.90; 95% CI, 0.81-1.00). State and territory performance estimates varied from 49.0% to 89.7% for antibiotics given within 8 hours and from 45.6% to 82.6% for blood cultures drawn within 24 hours.Administering antibiotics within 8 hours of hospital arrival and collecting blood cultures within 24 hours were associated with improved survival. The fact that states varied widely in the performance of these measures suggests that opportunities exist to improve hospital care of elderly patients with pneumonia.

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.

The effect of short term (8 weeks) sodium (Na+) depletion and its repletion on glomerular synthesis of heparan sulfate and urinary excretions of albumin, total protein, heparan sulfate, Na+ and potassium (K+) was studied in spontaneous hypertensive rats (SHR) and their control normotensive Wistar-Kyoto rats (WKY). Na+ depletion in SHRs significantly increased the synthesis of glomerular heparan sulfate and decreased urinary excretions of albumin, Na+ and heparan sulfate when compared with the Na+ repleted group. In WKY rats, Na+ depletion did not cause any of the above changes. These data suggest that Na+ depletion prevents the urinary loss of protein through preservation of glomerular heparan sulfate only in SHRs.

Metal fume fever is an acute self-limited illness induced most commonly by inhalation of zinc oxide fumes. The affected individual characteristically experiences the rapid onset of intense shaking chills, fever, and body aches a few hours after exposure, and symptoms dissipate spontaneously. While the occurrence of metal fume fever appears to be widespread and the current TLV/PEL of 5 mg/m3 and STEL of 10 mg/m3 may not be fully protective, no chronic health sequelae have been documented to date. Nonetheless, as any worker who has experienced a full-blown case will likely testify, metal fume fever remains one of the more noxious short-term illnesses contracted in the workplace, and its prevention deserves serious attention.

The diversity of a polyclonal anti-idiotypic response (Ab2) to a murine monoclonal anti-A (Ab1) was investigated after purification of two Ab2 populations. One was eluted from human polyclonal anti-A column and the other from Ab1. Analysis of the Ab specificity, as well as screening of the clonotypic distribution, were achieved after splitting Ab by IEF; this was followed by immunoblotting and probing with various anti-ABH mAb. The first population reacted with almost all the murine anti-ABH mAb, as well as with four human anti-A mAb, and consequently consisted of Ab2 beta. The second was composed of "true" Ab2 directed against Ab1. In the first population internal images mimicked either A Ag, or H Ag, or some epitopes common to both. This study demonstrates the plurality of internal images-bearing Ig molecules, some mimicking completely, and some only partially or even unfaithfully the nominal A determinant. The analysis of this idiotypic cascade proves the existence of a degeneracy of the initial restricted antigenic specificity. The consequences of such a process are discussed.

Normal human serum albumin and bisalbuminic fractions from genetic variants of european origin have been studied by ultrathin-layer isoelectric focusing performed on whole sera or after purification of albumin fractions by affinity chromatography on Blue-Trisacryl. Narrow range ampholytes giving pH gradient between 5 and 8, together with the use of 8 M urea, provided suitable patterns allowing to discriminate the various allotypes. In these conditions, both normal albumin and heterozygous variants were microheterogeneous with several main bands; in the case of normal albumin, four major bands were found, while variants exhibited additional bands differing in number and pI. The position of additional bands comparatively to that of normal albumin was consistent with the electrophoretic behavior of variants. Fast moving allotypes exhibited additional bands with more anodal pIs, whereas slow moving variants were characterized by cathodal additional bands. The number and position of these bands allowed to characterize some variants, when they failed to distinguish between some others, identical patterns being correlated to identical mutations arising at different locations on the albumin molecule. These observations indicate that isoelectric focusing could allow a clear distinction of albumin variants, provided that their mutation were different, or could confirm the occurrence of identical mutation when IEF patterns are indistinguishable. In addition to electrophoretic mobilities at various pH, analytical isoelectric focusing could be a useful technique employed as a second step in the identification of allotypes prior to the determination of the structural change characterizing the variant.

The evolution of microstructure during a single-pass of laboratory hot-rolling (47% reduction) of a 5083 aluminium alloy has been investigated at different positions through the thickness of the plate. The thermomechanical histories of the sub-surface and centre regions of the hot-rolled slab were analysed using instrumented rolling blocks and finite element modelling; the pass history was then simulated physically using plane-strain compression testing, by deforming the test specimens to the appropriate equivalent strain at a representative equivalent strain rate and temperature associated with the rolling deformations. Microstructures formed by the plane-strain compression simulations were then compared to the actual hot-rolled microstructures. The main features of the microstructures, particularly the sizes and volume fractions of the recrystallised grains, were reproduced very well. Experimentally-determined temperature profiles, mean strain -rates and strain accumulated at the centre of the slab during rolling were in reasonable agreement with the predictions of the finite element model; the measured strain immediately beneath the surface was however much higher. The implication of these results for the modelling of multi-pass hot-rolling are briefly discussed.

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.

Resume Un depistage systematique des gammapathies monoclonales (G.M.) a ete realise par electrophorese en acetate de cellulose sur 36.015 donneurs de sang. La frequence des G.M. est de 0,14 pour 100. La plupart des anomalies monoclonales des immunoglobulines ainsi detectees correspondent a des formes « asymptomatiques(86 pour 100) alors que les formes malignes d'emblee comme le myelome ou la maladie de Waldenstrom ne representent que 14 pour 100 des cas. Dans les formes asymptomatiques, seules les classes IgG et IgM sont observees, avec une tres large predominance des IgG (86,4 pour 100). La distribution des types de chaines legeres Kappa ou Lambda est la meme dans les formes asymptomatiques et dans les formes malignes. Les donneurs presentant une G.M. sont retires du don du sang et examines tous les ans (bilan clinique, hematologique et proteinologique) afin de suivre une eventuelle transformation maligne de la gammapathie.

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

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.

Explicit Nystrom pairs provide an efficient way to solve the general second-order initial-value problem when stability requirements do not determine the stepsize. The pairs can be derived by explicitly solving the order conditions for Nystrom pairs, or by applying a transformation to Runge-Kutta pairs. The two approaches lead to different classes of pairs. We refer to the two types of pairs as direct and transformed pairs, respectively. Even though transformed pairs are easier to derive, existing Nystrom pairs are direct pairs. In this paper we compare the properties of classes of direct and transformed ( p −1, p ) pairs, p = 4, 5, 6. The properties are the efficiency of the pair, the accuracy of the local error estimate and stepsize prediction, and the size of the stability region. We also investigate the existence of an interpolation scheme for the (3, 4) pairs.

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.

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.

Alpha-1 antitrypsin is the major component responsible for the normal alpha 1 band in human serum. Some genetic variants giving double alpha-1 band, may be associated with pathological process. In the course of a systematic screening of blood donors a double-band alpha-1 pattern was observed in a serum, due to the heterozygous expression of a genetic variant of the PI system. A possible clinical significance of the variant was investigated by characterizing it. The very rare allotype PI*X was identified and its frequency in the population of french blood donors was estimated around to one for 10,000.

Eight different types of genetic variants of albumin are observed in the French population. The analysis of electrophoretic patterns of sera containing these variants, performed a three different pHs (8.6, 5.0 and 6.9) after addition of a reference protein (transferrin), allows the identification each variant by a quantitative estimation of its relative mobilities. The accuracy and reproducibility of the technique make it a useful reference method, commonly employed for studying European variants. The samples used as references for five genetic variant types, proalbumins Christchurch and Lille, albumins Vanves, B and Reading, were subjected to sequence analysis to determine the nature and localization of their structural change. Together with the mutations of albumins Gent and Roma previously described, the data presented here make available seven reference specimens for which the structural changes are characterized out of the eight variants known to exist in France.

Total serum proteins were evaluated and serum protein electrophoresis performed on 3 500 blood donors after plasmapheresis. The results were standard for total serum proteins, serum albumin and immunoglobulin in 98% of the donors, whereas monoclonal immunoglobulin, immunodeficiencies or polyclonal hypergammaglobulinemia were detected in 2% of them. The frequency of monoclonal components is roughly 0.3%, corresponding to the frequency observed in normal adults of 40 to 60 years old. Donors found with monoclonal immunoglobulins or immunodeficiency should not be considered as eligible for blood donation.

Following transplant, circulating immunoglobulin levels fell moderately and remained depressed less than 2 months for IgG, and for variable and longer periods of time for IgM and IgA. Repeated quantitative determinations of antibodies against multiple antigens did not show any decrease in the pretransplant levels. Indeed some patients developed herpes and cytomegalovirus infections to which they responded by a sharp increase in antibody titers. In 2 cases, a primary immunization was demonstrated (against CMV and BK virus) with increasing levels of IgM and IgG antibodies. Lymphocyte counts in peripheral blood returned to 500 mm# between day 10 and 29 (median day 18) and to pretransplant values within 6 weeks. Non specific stimulation of lymphocytes by mitogens in the immediate post-transplant period showed a decreased response to PHA and Con A, whereas the responses to pokeweek mitogens and alloantigens were only slightly diminished. The degree of the responses was related to the dose of cryopreserved marrow infused. We conclude that:--although the minimum dose for autologous bone marrow transplantation in man is around 0,5 10(8) nucleated bone marrow cells/Kg, much higher doses should be used to ensure faster and better restoration of immune reactivity.--The similarity of the immunological dysfunction following autologous and allogeneous bone marrow transplantation suggest that, in the immediate post-transplant period, the role of GVHD in cellular immunity depression may be minimal.