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J Radl

Publications and source records attributed to J Radl.

At least 55 records · Page 3Linked to original sources
PubMed1991

Both IgA subclasses are reduced in parotid saliva from patients with AIDS.

Secretory IgA (SIgA), the isotypes IgA1 and IgA2, and IgM were measured by ELISA in stimulated parotid saliva from patients with AIDS (n = 16), subjects with asymptomatic HIV infection (n = 28), and HIV-seronegative healthy controls (n = 19). SIgA was significantly reduced in the AIDS group (10.4 micrograms/ml) compared with the asymptomatic HIV-infected subjects (17.1 micrograms/ml) and the controls (23.0 micrograms/ml). This decrease comprised both IgA1 and IgA2 to a similar extent on a relative basis. The SIgA decrease in AIDS patients was in striking contrast to their serum IgA level, which was significantly increased (6.9 g/l) compared with the asymptomatic HIV-infected subjects (2.9 g/l) as well as the controls (2.8 g/l). Low parotid output of SIgA in patients with HIV infection was associated with low numbers of CD4+ lymphocytes in peripheral blood as well as the presence of oral infections. The parotid output of IgM was similar in all groups. A low level of SIgA in the external secretions of patients with AIDS may well contribute to their frequent mucosal infections of opportunistic microorganisms.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Cellular origins of human polymeric and monomeric IgA: enumeration of single cells secreting polymeric IgA1 and IgA2 in peripheral blood, bone marrow, spleen, gingiva and synovial tissue.

Using modified ELISA and spot-ELISA, which permit the parallel determination of heavy chain subclass and the presence of covalently linked J chain, we analysed IgA found in cell culture supernatants or secreted by individual cells from peripheral blood, spleen, bone marrow, gingiva and synovial tissue, with respect to its polymeric or monomeric IgA form (pIgA, mIgA) and IgA1 or IgA2 subclass. The ELISA for determination of J chain in tissue culture supernatants was specific and highly sensitive (detection limit in pg). The results demonstrated that IgA1-producing cells predominated in the tissues examined, and that J chain could be detected in association with the majority of IgA1 and IgA2 secreted by individual cells. With respect to the frequency of cells secreting polymeric, J chain-containing IgA, only 20-30% of cells from the bone marrow were engaged in the synthesis of PIgA. In other tissues the frequency of cells secreting pIgA1 and pIgA2 was considerably higher. Peripheral blood mononuclear cells secreting pIgA2 were easily inducible during stimulation with T cell-dependent pokeweed mitogen, whereas Epstein-Barr virus-transformed cells secreted preferentially mIgA1. When the frequencies of pIgA-, pIgA1- or pIgA2-secreting cells (determined by spot-ELISA technique) from different tissues were correlated with the proportion of pIgA to mIgA (and IgA subclasses) secreted in tissue culture supernatants, data obtained suggest that many individual IgA-producing cells could be engaged in simultaneous secretion of mIgA and pIgA.

Adult↗
PubMed1991

Immune regulation of mouse 5T2 multiple myeloma. I. Immune response to 5T2 MM idiotype.

The transplantable murine multiple myelomas (MM) of the 5T series originated spontaneously in the aging C57BL/KaLwRij mice. These murine malignancies offer an excellent model for experimental studies on different aspects of the human disease. With the aim to look for new treatment modalities, the influence of idiotype-specific immune response on the 'take' and the development of the 5T2 MM was studied. In the first experiment, long-lasting subcutaneous immunizations of syngeneic mice with the 5T2 MM immunoglobulin (Ig) showed a dose dependent anti 5T2 MM Ig idiotype-specific response. The majority of the optimally immunized mice showed no 'take' or they had a prolonged survival after intravenous inoculation with the 5T2 MM cells. All control mice, nonimmunized or immunized with an irrelevant 5T14 MM Ig, developed 5T2 MM with a typical lethal course. In the second experiment, delayed type hypersensitivity (DTH) reaction to the 5T2 MM idiotype was studied. Subcutaneous immunizations of syngeneic mice with 5T2 MM Ig or with 5T2 MM bone marrow cells resulted in a specific DTH reaction 48 hours after challenge with 5T2 MM bone marrow cells. No DTH reaction was obtained when intravenous immunization was used. These results indicate that 5T2 MM is sensitive to idiotype-specific immune regulation; they constitute a basis for further studies on treatment of already established MM in vivo.

Animals↗
PubMed1991

Immune regulation of 5T2 mouse multiple myeloma. II. Immunological treatment of 5T2 MM residual disease.

The transplantable murine 5T2 multiple myeloma (MM) has been shown to be sensitive to idiotype-specific immunity, provided the recipient mice were immunized before transplantation. In the present study, anti-idiotype treatment was initiated after inoculation of the mice with 5T2 MM cells. Since in MM the serum idiotype concentration is far too high for anti-idiotype antibodies to reach the target cells, reduction of the MM to a minimal residual disease should be performed before. Intravenous (i.v.) or intraperitoneal (i.p.) administration of allogeneic (BALB/c) monoclonal anti-5T2 MM idiotype antibodies 3 days after i.v. infusion of the 5T2 MM cells into the mice, i.e. before 5T2 MM idiotype was serologically detectable, prevented the development of 5T2 MM in the majority of the animals. All mice that had not been treated with the anti-idiotype antibody became seropositive for 5T2 MM idiotype after 6 weeks. When mice with clearly developed 5T2 MM were treated with cyclophosphamide in order to obtain substantial tumor reduction, subsequent i.v. treatment with anti-5T2 MM idiotype antibodies resulted in prevention of myeloma growth in most animals. Injection of the antibody i.p. was, however, less effective. All mice that had been treated with cyclophosphamide only became seropositive for 5T2 MM and died. The results of these experiments demonstrated that passive anti-idiotype treatment of 5T2 MM is successful if the tumor mass is very small. The effector mechanisms of this treatment has to be investigated.

Animals↗
PubMed1990

Immunoblotting techniques for the detection of low level homogeneous immunoglobulin components in serum.

Because of the increasing demand for simple and reliable techniques for the detection of low concentrations of paraproteins against a highly heterogeneous serum background, two techniques were investigated for their sensitivity: isoelectric focusing (IEF) and Wieme high resolution electrophoresis, each with subsequent blotting by diffusion. The techniques were compared using isolated mouse monoclonal antibodies (mAb) of known concentration and specificity. Wieme electrophoresis in combination with immunoblotting (IBL) or antigen-specific immunoblotting (ABL) has a detection limit of 100 ng/ml and 10 ng/ml, respectively. For IEF in combination with IBL or ABL these limits were 1000 and 30 ng/ml, respectively. For ABL, polyvinylidene difluoride (PVDF) and nylon-supported nitrocellulose (NSNC) membranes gave similar detection limits, although for IBL, PVDF is preferred to NSNC. While IEF is essential for investigating the spectrum of the antibody repertoire. Wieme electrophoresis is the most powerful technique for the detection of homogeneous immunoglobulin components (H-Ig). After separation of the proteins. IBL is fast, simple and sensitive enough for routine detection and characterization of H-Ig. However, when the antibody specificity is known, ABL should be chosen for its superior sensitivity.

Animals↗
PubMed1990

Monoclonal gammopathies in human aging: increased occurrence with age and correlation with health status.

To determine the incidence of monoclonal gammopathies (MG) in relation to the aging process as such, and to evaluate the influence of disease on the occurrence of MG, we studied 439 elderly subjects aged 75-84 years. These individuals were categorized into 4 groups on the basis of their health status. There was a group of "optimally healthy" elderly, a group of "apparently healthy" residents of homes for the aged, a group of geriatric outpatients and a group of randomly chosen inpatients from a general hospital. Whereas no MG were detected in a control group of healthy young subjects aged 25-34 years, the frequency of MG in the aged groups ranged from 11% in the "optimally healthy" aged group to 38% in the inpatients group. In a tentative classification according to possible cause, most of the MG belonged to the pathogenetic category of immunodeficiency. There was a clear association of the occurrence of monoclonal gammopathies of this category with the health status.

Adult↗
PubMed1990

Age-related monoclonal gammapathies: clinical lessons from the aging C57BL mouse.

In this article the long-held notion that benign monoclonal gammapathy (BMG) is a premalignant stage in the development of multiple myeloma (MM) is attacked. Jiri Radl argues that clinical and experimental observations indicate that they are separate entities which may be distinguished in the laboratory and which should be managed in radically different ways.

Aging↗
PubMed1990

The 5T mouse multiple myeloma model: absence of c-myc oncogene rearrangement in early transplant generations.

Consistent chromosomal translocations involving the c-myc cellular oncogene and one of the three immunoglobin loci are typical for human Burkitt's lymphoma, induced mouse plasmacytoma (MPC) and spontaneously arising rat immunocytoma (RIC). Another plasma cell malignancy, multiple myeloma (MM), arising spontaneously in the ageing C57BL/KaLwRij mice, was investigated in order to see whether the MM cells contain c-myc abnormalities of the MPC or RIC type. Rearrangement of the c-myc oncogene was found in the bone marrow cells only in 5T2 MM transplantation line in a mouse of the 24th generation and in none of the seven other MM of the 5T series which were of earlier generations. Since the mouse 5T MM resembles the human MM very closely, including the absence of consistent structural c-myc oncogene abnormalities, it can serve as a useful experimental model for studies on the aetiopathogenesis of this disease.

Animals↗
PubMed1990

Do infections induce monoclonal immunoglobulin components?

The incidental finding of monoclonal immunoglobulin components (MC) in some infections prompted us to study this phenomenon more systematically. Using isoelectric focusing with immunoblotting (detection limit for MC 0.1 mg/ml), the following infections were studied for the presence of MC: visceral leishmaniasis, cytomegalovirus (CMV) infection, echinococcosis and infectious mononucleosis. MC were found in 16 of 20 leishmania patients and in eight of 18 CMV patients, but in only one of 20 echinococcosis patients and in none of 30 infectious mononucleosis patients. The MC were mostly transient, where tested. A minority of the MC found in the leishmaniasis patients was shown to bind to leishmania antigens. The specificity of the majority of the MC remains unknown. Further study is required to explain the high incidence of MC in CMV infection and visceral leishmaniasis.

Adolescent↗
PubMed1990

Site of catabolism of autologous and heterologous IgA in non-human primates.

Because of similarities between the human and monkey immune systems, we considered the monkey a suitable model for studies on the catabolism of various molecular forms of IgA, for which little information is available. The residualizing label dilactitol-[125I]tyramine was coupled to monkey (Macaca fuscata) IgA and IgG, as well as to human monomeric and polymeric myeloma IgA1 and IgA2 proteins. When labelled proteins were injected intravenously into monkeys, the non-metabolizable radioiodinated tracer accumulated at the cellular site of protein degradation, allowing identification of the catabolic sites. To determine the uptake of injected proteins by various tissues, monkeys were sacrificed 6-7 days after injection of labelled proteins, when blood-associated radioactivity was less than or equal to 10% of the injected dose, as measured by plasma clearance. When monkey or human monomeric IgA, as well as human polymeric IgA, irrespective of subclass, was administered to monkeys, the liver showed the greatest tissue uptake relative to total dose injected and to organ weight, and the highest acid soluble radioactivity (degraded protein). Although both hepatocytes and non-parenchymal liver cells were involved in IgA uptake, the hepatocytes were more active. Therefore, it appears that the liver is the major site of uptake and catabolism of IgA in monkeys and possibly in humans.

Animals↗
PubMed1989

Terasaki-ELISA for murine IgE-antibodies. I. Quality of the detecting antibody: production and specificity testing of antisera specific for IgE.

In order to develop an ELISA for the quantitative determination of murine IgE, antisera specific for murine IgE were prepared in the goat and rabbit. As immunogen, monoclonal IgE antibody mixtures of several allotypically different hybridomas were used. Before use, these antibodies were purified employing procedures that allow maximum recovery of binding activity. The goat and rabbit mouse epsilon chain-specific antisera were adsorbed on normal mouse serum. The purified antisera were found to be free of allotypic activity. However, immunoadsorption on NMS could not always remove contaminating anti-idiotypic antibodies. Repeated adsorptions with monoclonal antibodies of different isotypes carrying a similar idiotype were necessary to remove all detectable anti-idiotypic activity. Only after these precautions were the antisera suitable for detecting IgE molecules on nitrocellulose blots as well as for quantitating circulating IgE antibodies (ELISA) and IgE-secreting cells (plaque assay and reverse ELISA plaque assay). The purity and reactivity of several commercially available anti-IgE preparations were tested in similar types of specificity assays. Since the specificity of antibodies used in ELISA determines the monospecificity of the assay, retesting for contaminating cross-reactivities in commercial preparations was shown to be necessary.

Animals↗
PubMed1989

Monoclonal gammopathies in children.

Over a 10-year period sera of 4000 pediatric patients were subjected to agar gel electrophoresis and immunoelectrophoresis. Retrospective examination of the electrophoresis patterns indicated that single or multiple homogeneous immunoglobulin components were present in sera of 155 children (3.9%). They were most frequently found in patients suffering from primary and secondary immunodeficiency diseases, hematological malignancies, autoimmune diseases, and severe aplastic anemia. Follow-up analysis revealed that most of these monoclonal gammopathies were transient. The monoclonal gammopathies in the serum of 79 patients were identified by immunoblotting for class and light-chain isotypes. A marked absence of IgA monoclonal gammopathies and a predominance of monoclonal gammopathies of the lambda light-chain isotype were found. Most of the B-cell mono- or oligoclonal proliferations in children can probably develop due to a disturbance in the regulatory T-cell function.

Child↗
PubMed1989

IgA antibodies against phenolic glycolipid I from Mycobacterium leprae in serum of leprosy patients and contacts: subclass distribution and relation to disease activity.

The anti-PGL-I IgA response against phenolic glycolipid I (PGL-I) a specific surface antigen of Mycobacterium leprae, was demonstrated to be essentially of the IgA1 subclass in sera from leprosy patients and contacts. Anti-PGL-I IgA1 mean levels were found to increase significantly from the tuberculoid toward the lepromatous pole of the leprosy disease spectrum, thus resembling the predominating anti-PGL-I IgM response. Furthermore, anti-PGL-I IgA1 values were shown to increase significantly with increasing bacillary load, measured as bacillary index (BI) from skin biopsies. However, a number of BI negative leprosy patients recorded elevated anti-PGL-I IgA1 levels possibly reflecting a persistence of disease activity. Three of 28 household or family contacts of leprosy patients were detected seropositive for anti-PGL-I IgA1. Thus, our results suggest that anti-PGL-I IgA1 may be considered as an additional parameter for the early detection of infection with M. leprae.

Antibodies, Bacterial↗
PubMed1989

Elevated production of polymeric and monomeric IgA1 by the bone marrow in IgA nephropathy.

In bone marrow cultures of 15 patients with primary IgA nephropathy we found significantly (P = 0.02) increased synthesis of both monomeric and polymeric IgA1 compared to 23 controls, by using high performance liquid chromatography (HPLC) fractionation of culture supernatants. The relative contribution of polymeric to total IgA1 produced was not different for the two groups. Two-color immunofluorescence studies of the percentage of bone marrow IgA1 plasma cells able to bind secretory component in vitro showed no difference between patients and controls. In the sera of patients with primary IgA nephropathy the relative contribution of IgA1 polymers to total IgA1 was also similar to controls. These results indicate that in IgA nephropathy, the increased IgA production in the bone marrow is restricted to the IgA1 subclass. The production of both monomeric and polymeric IgA1 is increased in patients during a quiescent phase of the disease.

Adult↗
PubMed1989

Simultaneous expression of cytoplasmic IgM and IgG in plasma cells in a patient with IgG paraproteinaemia.

A dual expression of IgM and IgG was found in the cytoplasm of nearly all plasma cells in the bone marrow from a patient with an IgG1 paraprotein in the serum. These cells were morphologically and immunologically mature plasma cells. They lacked the B-cell markers surface Ig, CD19 and HLA-Dr, and were positive for HAN-PC1 and CD38. The cells were weakly positive for anti-J-chain and did not bind secretory component, indicating that the IgM was monomeric or aberrant. These findings show that class switch by deletion of DNA regions in mature plasma cells is not obligatory for the secretion of immunoglobulin classes other than IgM.

Aged↗
PubMed1989

Antibodies to a short synthetic peptide related to the hinge segment of human IgG3 recognizes thermally or fixative induced conformational changes in the human IgG3 molecule.

A synthetic decapeptide (SP) was used to produce a murine monoclonal antibody specific for the human IgG3 molecule. Recognition of the IgG3 determinant is heat- and fixation-sensitive in ELISA and immunoenzyme cytology, respectively. The antibody specifically recognizes a sequence from the hinge region of IgG3, but only when subtle alterations in the conformation are induced by mild heating (greater than 40 degrees) and subsequent stabilization by means of electrostatic interactions in solid-phase assays or by fixation with formalin acetic acid mercury chloride. The structure of the human IgG3 molecule is especially sensitive to microenvironmental influences, as can be concluded from its behaviour under various physicochemical conditions. To this, we add that the immunogenic determinants in the structure of relatively flexible parts of this protein can be severely altered by the routine application of fixation methods. It is shown that these changes can also be of importance in the recognition of antigen by monoclonal antibodies.

Antibodies, Monoclonal↗