Andreas Morell

A human myeloma protein with specificity against dinitrophenyl and nucleic acid derivatives

Abstract Immunochemical studies on a human IgG myeloma protein which precipitates with DNA-protein-conjugates are reported. This monoclonal immunoglobulin showed crossreactions with protein conjugates of a number of other compounds such as pyrimidines, purines, nucleotides and nucleosites. In addition it reacted with single stranded DNA and, to a much lesser extent, with native DNA. No reaction, however, was detectable with the free haptens DNA-lysine and 5-acetyluracil-1-caproic acid and with nucleotides and nucleosides. The binding activity could be localized in the Fab fragment of the immunoglobulin molecule.

Hypo‐β‐Lipoproteinaemia Associated with Auto‐Antibodies Against β‐Lipoproteins

Abstract In a 19 year old patient, presenting a severe hypo‐β‐lipoproteinaemia and a polyclonal IgG gammopathy, all known causes of hypo‐β‐lipoproteinaemia could be excluded. The patients IgG reacted with homologous and autologous low density lipoproteins like an antibody, the binding activity being localized in the Fab fragment of the IgG molecule. The reactive part of LDL appeared to be the protein moiety (apoprotein LDL). Turnover studies with radioiodinated LDL showed that the reduction of the LDL concentration in the patients serum was due to a decreased synthesis of LDL and also possibly to an immunelimination of LDL.

Serum β2-Microglobulin, Serum Creatinine and Bone Marrow Plasma Cells in Benign and Malignant Monoclonal Gammopathy

Serum beta 2-microglobulin concentrations were determined in samples of 65 patients with benign or malignant monoclonal gammopathy. In the group of patients suffering from multiple myeloma or Waldenströms macroglobulinemia the mean beta 2-microglobulin level was significantly higher than in the group with benign monoclonal gammopathy. Values above 3 mg/l were highly indicative of malignant disease and observed in 50% of the myeloma patients. Serum creatinine levels were significantly correlated to beta 2-microglobulin levels. However, mean creatinine concentrations did not significantly differ between the two groups of patients. Plasma cells and lymphoplasmocellular elements containing cytoplasmic immunoglobulin were counted in bone marrow samples of all patients. The counts, expressed in percent of nucleated bone marrow cells, allowed a good discrimination between the benign and the malignant group of patients. Bone marrow from patients with multiple myeloma or macroglobulinemia contained more, from patients with benign monoclonal gammopathy less than 17% plasma cells. No significant correlation was noticed between the extent of this plasmocytic bone marrow infiltration and serum beta 2-microglobulin or creatinine levels.

Differentiation Between Benign and Malignant Monoclonal Gammopathies by Discriminant Analysis on Serum and Bone Marrow Parameters

Bone marrow samples of 28 individuals with clinically benign and of 41 patients with malignant monoclonal gammopathy were analyzed for the total number of lymphoplasmocellular elements containing cytoplasmic immunoglobulins and for the monoclonal fraction of these cells. Monoclonal immunoglobulin components were determined in sera. A discriminant analysis was performed on the data: the variables were transformed and in a stepwise procedure used for the construction of a discriminant function which by adividing point allowed a good distinction between the two groups of patients. By use of this discriminant function, 91% of the patients in the sample were correctly classified.

Cytoplasmic immunoglobulins in bone marrow cells of polyclonal and of monoclonal origin.

Cytoplasmic immunoglobulins in human bone marrow plasma cells and lymphoid cells were characterized by direct immunofluorescence with fluorochrome-labelled reagents specific for immunoglobulin heavy and light chains. The percentage distribution of cells containing IgA, IgG or IgM and kappa- or lambda-immunoglobulins was determined in bone marrow samples from 168 immunologically normal individuals, in 11 patients with polyclonal increase of bone marrow plasma cells and in 80 patients with benign or malignant monoclonal gammopathies. A clear differentiation between monoclonal and polyclonal cell populations could be obtained in all cases.

Radial Segmentation of Nuclei (Rieder Cells): A Morphological Marker of T-Cell Neoplasms?

Pretreatment blood smears of adult patients with acute lymphoblastic leukemia were examined for neoplastic cells showing nuclear radial segmentation (RS). RS was present in 6 of 7 patients with immunologically proven T-cell leukemia, but not in 11 patients whose leukemic cells lacked T-cell markers. Electron microscopic studies of neoplastic cells showed multiple nuclear indentations and abundant cytoplasmic microfilaments and microtubuli in connection with pericentriolar dense material. RS formation was decreased in 1 patient after chemotherapy with a vincristine-containing regimen, while the white cell count remained unchanged. Radial segmentation (RS) of leukocyte nuclei is a well-known phenomenon, which is observed ex vivo (Rieder cells), and can be induced in vitro. Convoluted or multilobulated nuclei in lymphoid neoplasms are similar to RS nuclei both with regard to their structure and their sensitivity to spindle-blocking drugs. We propose that the nuclear alterations observed in a variety of different T-cell neoplasms are identical with RS, and suggest that RS might be a morphological marker for subsets of lymphoproliferative disorders of T-cell origin.

Terminal differentiation of PWM-stimulated human B lymphocytes.

Abstract Patterns of surface and cytoplasmic immunoglobulins were simultaneously studied on human B blast cells induced by pokeweed stimulation of peripheral blood lymphocytes. A double-staining immunofluorescent technique was used. After 4 and 7 days of culture, a gradual loss of surface IgD was observed on blast cells whereas numbers of plasmablasts with cytoplasmic immunoglobulin showed a marked increase. After 7 days, 92% of surface IgA positive blasts had passed terminal differentiation to cytoplasmic IgA-producing plasma-blasts. At the same time, 73% of surface IgM positive blasts were found to contain cytoplasmic IgM, and 30% of surface IgG positive cells had cytoplasmic IgG. Only a small fraction of blast cells with surface IgD was able to mature to IgD producing plasmablasts. In general, the class of surface and cytoplasmic immunoglobulin coincided in single blast cells, with the exception of surface IgD which was present on 10% of the cytoplasmic IgM-containing blasts.

Influence of exogenous interleukin-2 on the proliferation of lymphocytes from normal donors and from patients after autologous bone marrow transplantation

The influence of two interleukin-2 (IL-2) preparations on the proliferative response of normal lymphocytes to phytohemagglutinin (PHA) was examined. A recombinant IL-2 (rIL-2) and an IL-2 containing conditioned medium (LyIL-2) markedly enhanced 3H-thymidine incorporations at low PHA concentrations, whereas at optimal mitogen concentrations, this effect was marginal. In lymphocyte cultures of 3 patients after autologous bone marrow transplantation (ABMT), exogenous IL-2 augmented PHA-induced stimulations. Moreover, a dose-dependent increase of the 3H-thymidine uptake was observed in unstimulated cultures of all normal donors and patients. Combined autoradiography and surface marker analysis allowed to identify cells spontaneously proliferating in the presence of exogenous IL-2. Comparison of phenotypes of these cells revealed pronounced differences between a normal donor and a patient after ABMT.

Klinik und Therapie der primär benignen und Begleitparaproteinosen

Der Begriff „Paraproteinamie“ oder „Paraproteinose“ umschreibt keine Krankheit, sondern einen Serumeiweisbefund, der kennzeichnend fur eine homogene (monoklonale) Population Immunglobulin-(Ig-)produzierender und -sezer-nierender Zellen im Organismus ist. In einem Falle kann es sich dabei um einen klinisch vollig belanglosen Zufallsbefund, im anderen um das ominose Zeichen einer rasch progredienten lymphoretikularen Neoplasie handeln. Die das Schicksal des Patienten wie das Handeln des Arztes entscheidende Frage, welche Form der Storung im gegebenen Falle vorliegt, kann nur unter Berucksichtigung der klinischen Gesamtsituation, insbesondere des weiteren Verlaufes der Paraproteinamie beantwortet werden.

Hyperkatabole Hypo- β -Lipoproteinämie infolge Autoantikörper

Einer abnormen Verminderung der β-Lipoproteine im Serum konnen verschiedene Ursachen zugrunde liegen: primar ein autosomal dominant vererbter Synthesedefekt des Apoproteins B und sekundar eine Bildungsstorung der Lipoproteine infolge einer Erkrankung der Leber oder des Gastrointestinaltraktes. Ein gesteigerter Abbau der Lipoproteine wurde bei Schilddrusenerkrankungen beobachtet.