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Biomedical subjects

J Radl

Publications and source records attributed to J Radl.

At least 109 records · Page 6Linked to original sources
PubMed1984

Idiopathic paraproteinaemia. IV. The role of genetic factors in the development of monoclonal B cell proliferative disorders--a study in the ageing C57BL/KaLwRij and CBA/BrARij mouse radiation chimeras.

Mouse radiation chimeras, employing strains with a low (CBA/BrARij) and a high (C57BL/KaLwRij) frequency of idiopathic paraproteinaemia (IP), were used in a study on genetic influences in the development of IP, a benign B cell monoclonal proliferative disorder. Taking advantage of the different Igh1 allotypic markers between the two strains, the development of IP with increasing age was investigated by agar electrophoresis, immunoelectrophoresis and immunofixation. Four of 18 CBA recipients transplanted with C57BL bone marrow cells were shown to develop IP of the IgG2a isotype and the Igh1b (donor) allotype during their life. In contrast, none of the 23 C57BL recipients of CBA bone marrow developed an IgG2a paraprotein of the Igh1a allotype. However, in three of these 23 chimeras, an IgG2a and Igh1b (recipient) allotype paraprotein appeared with age; two of these mice proved to be reversals at 12 months and one at 15 months of age. The frequencies of homogeneous immunoglobulins of the donor type in the chimeras corresponded roughly to those of normal mice of the donor strain. Histopathological examination excluded a malignant origin of these monoclonal proliferations. These findings support the view that intrinsic cellular genetic factors are of major importance in the development of IP, a benign B cell neoplasia.

Aging↗
PubMed1983

Increased incidence of transient homogeneous immunoglobulins in irradiated and reconstituted C57BL/KaLwRij mice treated with 2'-deoxyguanosine.

Prolonged administration of micromolar amounts of 2'-deoxyguanosine (dGuo) to lethally irradiated and reconstituted mice led to an increased incidence of transient homogeneous immunoglobulins (H-Ig) in their sera. Analysis of the heavy and light chain isotype distribution among the H-Ig revealed more of the IgG2b and IgG3 isotypes and less of the IgM isotype and the lambda light chain containing H-Ig in the dGuo-treated group as compared to the control group. The increased incidence of H-Ig was preceded by a decreased suppressor T cell generation and activation in the dGuo treated group. These data indicate that deficient suppressor T cell activity plays an important role in the development of transient H-Ig.

Animals↗
PubMed1983

Low molecular weight IgM in sera of children following bone marrow transplantation for severe aplastic anaemia and acute leukaemia.

Serum samples of 16 children, treated with allogeneic bone marrow grafts for either aplastic anaemia or leukaemia, were investigated longitudinally for the presence of pentameric (19S) and low molecular weight (LMW) (7S) IgM. From 2 months following grafting, serum IgM increased in all patients, gradually in seven cases and with a transient overshoot in the other nine. In eight patients, LMW-IgM was detected transiently in the serum within the period when total IgM was increasing, either with (five patients) or without (three patients) overshoot. These data indicate that, at a certain stage of the immunological reconstitution after transplantation as in normal ontogeny, rather immature cells of the B cell lineage are able to produce and secrete LMW-IgM.

Adolescent↗
PubMed1983

Instability of the human immunoglobulin heavy chain constant region locus indicated by different inherited chromosomal deletions.

Previously we reported a gross genetic polymorphism of the human immunoglobulin heavy chain locus manifest by a large internal deletion within the constant region gene segment. We now describe a detailed serological and molecular genetic study of a Tunisian family in which members appear to carry two chromosomes 14 with different DNA deletions. The first is similar to that previously described encompassing three gamma subclass genes, a pseudo-epsilon gene and the alpha 1 subclass gene; the second deletion is less complex involving only the pseudo-epsilon gene and the alpha 1 gene.

Chromosome Deletion↗
PubMed1982

Increased levels of IgG4 subclass in 5 patients with acquired respiratory disease.

5 sera from a series of more than 1,000 serum samples from hospitalized patients tested by immunoelectrophoresis were selected for further examination because of a disproportional increase in the anodic part of IgG. A marked polyclonal increase in IgG4 subclass level was detected in each of these sera. While the patients suffered from a variety of diseases (e.g. Loeffler's syndrome, leiomyosarcoma, periarteritis nodosa, chronic bronchitis, and mycosis fungoides, respectively), they all had an acquired respiratory disease as the only common clinical denominator.

Adult↗
PubMed1980

Transient IgA-lambda paraproteinemia during treatment of acute myelomonoblastic leukemia.

Monoclonal plasma cell proliferation with secretion of IgA-lambda and free lambda light chains during a phase of bone marrow aplasia following intensive chemotherapy was observed in a patient suffering from acute myelomonoblastic leukemia. The clonal expansion and regression was investigated at the cellular level by immunofluorescence using an antiserum against the idiotype of the paraportein. Although a large panel of common antigens was used for testing, no antibody activity of the paraprotein could be demonstrated.

Aged↗
PubMed1980

Idiopathic paraproteinemia. III. Increased frequency of paraproteinemia in thymectomized aging C57BL/KaLwRij and CBA/BrARij mice.

The influence of thymectomy on the appearance of idiopathic paraproteinemia (IP) during aging was investigated in mice of the C57BL/KaLwRij and the CBA/BrARij strains, which under normal conditions develop IP in high and low frequency, respectively. Compared with sham-thymectomized mice, C57BL mice thymectomized at a young adult age showed a markedly increased frequency and an earlier onset of IP during aging; this was even more pronounced in neonatally thymectomized mice. A similar effect of thymectomy was also observed in mice of the CBA strain. Restriction in the heterogeneity of the serum immunoglobulins and the appearance of transient homogeneous Ig components was another frequent finding and this often preceded the appearance of IP in mice of both strains. Thymectomy did not substantially influence either the incidence of paraproteinemias due to a B cell malignancy or the isotype distribution among the paraproteins produced. The results are compatible with the hypothesis that IP develops in three stages as a consequence of an age-related immunnodeficiency that primarily affects the T immune system.

Aging↗
PubMed1980

Serum immunoglobulins in nude mice and their heterozygous littermates during ageing.

Serum immunoglobulin (Ig) levels were investigated in 6, 40 and 110 week old congenitally athymic (nude) mice and their heterozygous littermates. Concentrations of IgM, IgG1, IgG2a, IgG2b, IgG3 and IgA were determined by rocket electrophoresis. At 6 weeks of age, IgM was the most prominent serum Ig in both nude and heterozygous mice. Except for IgM and IgG3, some nude mice displayed unquantifiable levels of some of the other Ig classes or subclasses. At this age, the average levels of the various Ig classes and/or subclasses did not differ significantly between the two groups of mice. At the ages of 40 and 110 weeks, most nude mice showed serum Ig spectra in which all classes and subclasses were present. Young (6 week) and middle-aged (40 week) nude mice generally showed a wider variation in Ig levels than did their heterozygous littermates. The most striking differences between aged nude mice and aged heterozygous mice were: (a) the generally decreased levels of IgG2a, IgG2b and IgA; (b) the frequent occurrence of increased serum levels of IgG1; and (c) the increased incidence of homogeneous Ig components ('paraproteins') in the sera of nude mice.

Aging↗
PubMed1979

Regional deficiency of secretory IgA in a patient with combined immunodeficiency of the ADA deficient type.

The IgA system in a patient with SCID and ADA deficiency showed heterogeneity. Serum IgA and stool secretory IgA (SIgA) levels were normal, but with altered kappa/lambda and A1/A2 subclass ratios; IgA in saliva and urine was deficient. Amounts of secretory component were normal. Jejunal and rectal biopsies showed prominent lymphonodular hyperplasia, but no cells containing IgA. A normal serum IgA level therefore does not always predict an intact secretory IgA system.

Adenosine Deaminase↗
PubMed1979

Idiopathic paraproteinemia. II. Transplantation of the paraprotein-producing clone from old to young C57BL/KaLwRij mice.

Transplantation experiments in the C57BL/KaLwRij mouse model of idiopathic paraproteinemia (IP) showed that an IP-producing clone can be further propagated in young, lethally irradiated mice and also equally as well in nonirradiated recipients by a bone marrow and/or spleen cell transfer. The latency period before the original paraprotein was detected in the sera of recipients varied in different experiments between 1 and 9 months after transplantation. With subsequent transplantations, the "take" frequency gradually decreased. Propagation of IP for three to four generations seems to be the final limit. In comparison to age-matched seems to be the final limit. In comparison to age-matched control groups, no substantial influence of the transplanted IP on the survival of the recipients was observed. In contrast, transplantation of cells from mice with a B cell lymphoma or a myeloma led to continuous propagation of the malignancy, with a high "take" frequency, progressive development of the paraproteinemia, and a shortened survival time of the recipients. These findings indicate that IP represents in its final stage in the aging C57BL mice an intrinsic cellular defect within the affected B cell clone, which is, however, different from that found in B cell malignancies.

Aging↗
PubMed1979

Homogeneous immunoglobulins in the serum of irradiated and bone marrow reconstituted mice: the role of thymus and spleen.

The influence of thymectomy and splenectomy on the frequency and class distribution of homogeneous immunoglobulins (H-Ig) in serum was studied in lethally irradiated (DBA/2 x C57Bl/Rij)F1 mice reconstituted with syngeneic bone marrow. During four follow-up periods in the first 9 months after transplantation, the sham-operated controls and splenectomized animals developed transient H-Ig in an average frequency of 14.2 and 15.7% respectively. There were no marked differences in the incidence of H-Ig within these two groups. In contrast, thymectomized mice and mice both thymectomized and splenectomized showed H-Ig in much higher frequencies (average percentages 31.6 and 36.5, respectively). The highest frequency of H-Ig was observed between 1.5 and 3.5 months after transplantation. H-Ig of the IgG1 and IgG2 subclasses were most frequent in all groups during the first 3.5 months. Later, H-Ig belonging to the IgM class also appeared in somewhat higher numbers. H-Ig of the IgA class was a very rare finding at any time. These results indicate that the presence of the thymus, but not necessarily of the spleen, is an important factor in the regulation of the immunoglobulin heterogeneity during the reconstitution of the immune system in lethally irradiated and bone marrow reconstituted mice.

Animals↗