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Biomedical subjects

L Hammarström

Publications and source records attributed to L Hammarström.

At least 199 records · Page 11Linked to original sources
PubMed1990

Transcription, translation and secretion of both IgA subclasses in polyclonally activated human lymphocytes.

To analyze human IgA subclass-specific mRNA we have developed RNA probes for quantitation of alpha 1 and alpha 2 heavy chain constant region genes by solution hybridization. Under our assay conditions, we can detect as little as 3 pg of specific mRNA and there is less than 2% cross-reactivity between the two IgA subclasses. Using this method, the relative proportions of IgA1 and IgA2 mRNA in pokeweed mitogen (PWM)-stimulated cells were found to be 66% and 34%, respectively, while in the Epstein-Barr virus (EBV)-stimulated cells they were 77% and 23%, respectively. Cytoplasmic staining of the plasma cells and determination of IgA subclass distribution by flow cytometry revealed an almost even distribution of the two IgA subclasses as induced by both activators. The culture supernatant contained 72% IgA1 and 28% IgA2 after PWM stimulation, while EBV stimulation induced 85% IgA1 and 15% IgA2. This report thus describes a method for the quantitative analysis of IgA subclass-specific mRNA. Furthermore, we present evidence that in response to in vitro stimulation of peripheral blood lymphocytes by polyclonal activators the IgA-producing B cells not only synthesize both isotypes but also have the potential to secrete them.

Antibodies, Monoclonal↗
PubMed1990

Periapical lesions of mandibular bone: difficulties in early diagnostics.

It is often difficult to establish a correct diagnosis on the basis of initial clinical and roentgenologic symptoms in mandibular bone disease. In this paper these problems are discussed, and some suggestions are made to overcome them. The discussion is based on cases of osteogenic sarcoma, histiocytic lymphoma, and chronic osteomyelitis. The patients were a boy and two middle-aged women, all of them with primary clinical symptoms of pain and swelling, diffuse roentgenologic changes in mandibular bone, uncertain response to treatment, and an unusual progress of the disease.

Adult↗
PubMed1990

Response to tetanus toxoid immunization after allogeneic bone marrow transplantation.

An ELISA was used to study long-term immunity and immunization responses to tetanus toxoid in 48 bone marrow transplant recipients. Among patients who were seropositive to tetanus before transplant, 51% had lost their seropositivity 1 year later. All patients who were not reimmunized with tetanus toxoid were seronegative 2 years after transplant. All patients who were seronegative before transplant remained seronegative 1 year later regardless of the donor's serologic status. There was no difference in the ability to remain seropositive to tetanus toxoid between patients with and without chronic graft-versus-host disease. Of 21 patients immunized with one dose of tetanus toxoid 1 year after transplant, 14 were seronegative at the time of immunization (response rate, 64%). At 1 year after immunization, 7 remained seropositive. Ten patients were reimmunized with two doses of tetanus toxoid. All responded and 90% remained seropositive 1 year later. When 21 patients were primarily immunized with three doses of tetanus toxoid, all patients seronegative at immunization responded and all tested patients remained seropositive 2 years later. The immunization responses were significantly superior in patients receiving three doses compared with those who received one. Reimmunization with tetanus toxoid of long-term survivors after marrow transplant seems necessary. A three-dose immunization schedule is recommended to obtain an adequate immune response.

Antibodies, Bacterial↗
PubMed1990

Development of IgA deficiency after bone marrow transplantation. The influence of acute and chronic graft-versus-host disease.

Serum IgA levels were monitored at 3, 6, 12, and 24 months after BMT in 131 allogeneic and 3 syngeneic bone marrow transplant recipients. In general, IgA levels were low during the first 6 months and did not return to normal levels until 1-2 years after transplantation. Children (less than 15 years) had lower IgA levels at 3 and 6 months post-BMT compared to the adults (P less than 0.05), but donor age had no influence on the recipient IgA levels after BMT. Patients receiving either methotrexate or cyclosporine alone for GVHD prophylaxis had markedly lower IgA levels compared to those given a combination of these two drugs or patients transplanted with T-cell-depleted marrow (P less than 0.001). Mean IgA levels in patients without or with grade I acute GVHD were within the normal range at 3, 6, 12, and 24 months after BMT (greater than 0.3 g/L), although approximately 20% of the patients in each group showed low IgA levels (less than or equal to 0.3 g/L) early after transplantation. Patients with grade II or III acute GVHD had significantly lower values from 3 months up to 2 years after transplantation (P less than 0.01). Patients with chronic GVHD had significantly lower IgA levels 1 and 2 years after BMT compared to patients without chronic GVHD (P less than 0.005). Severe acute GVHD, particularly when followed by chronic GVHD, seems to be the main reason for low IgA levels, while other factors such as CMV infection or donor status may also contribute to the development of IgA deficiency after BMT.

Acute Disease↗
PubMed1990

Aberrant IgG subclass distribution to measles in healthy seropositive individuals, in patients with SSPE and in immunoglobulin-deficient patients.

Sera from healthy seropositive donors, patients with acute measles, subacute sclerosing panencephalitis, common variable immunodeficiency, and CH gene deletions were analysed for anti-measles IgG1-4. Compared with other anti-viral immune responses of IgG1 and IgG3, an unusual predominance of specific IgG1 prevailed; only four out of a total of 68 patients showed anti-measles IgG3. Of the 17 healthy, measles seropositive serum donors, all showed specific IgG1, none showed IgG3 and six had IgG4. Eight out of 10 patients with SSPE showed an anti-measles IgG1 and IgG4 response while IgG3 was not seen. The IgG1 and IgG4 subclass patterns had some exceptions. Anti-measles IgG3 was found in five out of five patients with deletion of the gamma-1 encoding gene segments and in four out of 15 patients with recent measles antigen stimulation. The subclass pattern was suggested to reflect the immunological compromise associated with measles infections.

Adolescent↗
PubMed1990

Frequencies of interleukin-5 mRNA-producing cells in healthy individuals and in immunoglobulin-deficient patients, measured by in situ hybridization.

Interleukin-5 (IL-5) has previously been demonstrated to enhance immunoglobulin synthesis, especially IgA. Thus, it could be hypothesized that a defect production of IL-5 may cause immunoglobulin deficiency. We have analysed the frequency of IL-5 mRNA-producing cells in healthy adults and in patients with common variable immunodeficiency or selective IgA deficiency. Unstimulated lymphocytes were rarely found to synthesize IL-5 as measured by in situ hybridization. However, pokeweed mitogen and several other activating ligands induced the synthesis of IL-5 mRNA in peripheral blood and spleen lymphocyte cultures. After pokeweed mitogen activation, the number of IL-5 mRNA-producing cells most often peaked on day 3 with a maximal frequency of around 1-2% of mononuclear cells. In a kinetic study we were unable to detect any peak frequency differences between healthy controls (mean 0.44%) and 20 patients (mean 0.58%). Thus, although IL-5 has been reported to be an important regulator of IgA synthesis, a defect production does not seem to be the underlying mechanism in human immunoglobulin deficiency.

Adult↗
PubMed1990

Early antibody responses in human schistosomiasis.

Early diagnosis is important when handling patients with acute schistosomiasis. This state is usually more severe in travellers and tourists than in the immune, resident patients. With increased travelling to areas endemic for schistosomiasis, a tool is needed to solve the problem of differential diagnosis due to the non-specific symptoms of the early stages of the disease. Early appearance of antibodies against excretory/secretory antigens of the intestinal tract in the adult worm was seen in six individuals recently infected with Schistosoma mansoni, using an indirect immunofluorescence technique. The antibodies were of IgM, IgG and IgA classes, and of the IgG1, IgG3 and IgA1 subclasses as detected by ELISA using an antigen preparation of adult worm. On immunoblots, using a freeze-dried adult worm antigen, IgG1 and IgG3 antibodies recognized antigens of 32-35 kD. Antibodies against these antigens could thus be a marker of early infection in previously non exposed visitors to endemic areas.

Adult↗
PubMed1990

RFLP of human immunoglobulin genes.

Human immunoglobulin chains are encoded by variable, diversity, joining and constant gene segments localized on chromosomes 2, 22 (light chains) and 14 (heavy chains). An extensive genetic polymorphism exists as revealed by restriction fragment length polymorphism of the different genes. These new markers allow a more precise delineation of the evolution of the immune system and of genes linked to disease susceptibility.

Genes, Immunoglobulin↗
PubMed1990

[Production of antibodies with the aid of genetic technology].

During the past decade we have witnessed a rapid development of methods for the production of monoclonal antibodies with predefined specificity. These antibodies are now regularly being used both for diagnostic and therapeutic purposes. The first antibodies thus produced were mainly from cell lines generated by fusion of a mouse B lymphocyte with a given specificity with a mouse myeloma line. Efforts have lately been made also to make cell lines producing human antibodies either by immortalizing human cells or by "humanizing" mouse antibodies. The latter has recently been accomplished by genetic engineering. In these experiments the entire variable region of a mouse antibody or the hypervariable regions only (complementarity determining regions) have been grafted onto human constant region genes thus creating chimeric antibodies. Fragments of antibodies with retained binding properties have also been generated and some of these have been effectively produced in bacteria, allowing large scale production. Bifunctional antibodies have also been created with success and have been applied in different systems. The ease with which antibodies with desired specificities can now be designed and produced will form the beginning of a new era in immunology with a potential that we can not as yet foresee.

Animals↗
PubMed1989

Molecular and serologic analysis of IgG1 deficiency caused by new forms of the constant region of the Ig H chain gene deletions.

Selective IgG1 deficiency is a rare disease. We report a familial form of IgG1 deficiency, in which IgG1 was undetectable in a 5-yr-old girl with a history of asthma and respiratory tract infections. Her father had an IgG1 level that was one-third of the mean amount found in normal healthy controls. The defect in the proband was caused by a homozygous deletion of the structural gene for C gamma 1. A Southern blot analysis demonstrated that the maternal haplotype contained a deletion encompassing C gamma 1, C psi epsilon 1, C alpha 1, C psi gamma, and C gamma 2, whereas the deletion on the paternal haplotype was confined to the C gamma 1 gene. Neither of these deletions has previously been reported. IgG1 normally constitutes the dominant isotype for antibodies directed against protein Ag, including viral proteins. We have analyzed the immune response to a number of different protein and polysaccharide Ag in the patient and her parents. In the proband, antiviral antibodies were restricted to the IgG3 and IgG4 subclasses. However, the total amount of IgG directed against several viruses was below the concentration found in normal seropositive individuals. The father and the paternal grandfather, both with low serum IgG1 levels, also had asthma, thus indicating a possible causal relationship.

Adult↗
PubMed1989

Interleukin 4 induces synthesis of IgE and IgG4 in human B cells.

Interleukin (IL)4 has been shown to regulate the IgG subclasses and induce IgE production in splenic mouse B cells. Here we show that IL4 and phorbol 12-myristate 13-acetate (PMA) induce, on a per cell basis, very high IgE secretion in purified human B cells by using a mouse thymoma (EL4) co-culture method. In addition, a marked increase in the number of IgG4-producing cells was also observed. Furthermore, IL2 could synergize with IL4 and PMA in the production of IgE. By using limiting dilution analysis, a considerable increase in the precursor frequency for IgE was found when IL4 and PMA were added to cultures as compared to cultures with PMA only. This indicates that IL4 induces an isotype switch in human B cells.

Antibody Formation↗
PubMed1989

Immunoglobulin levels in saliva in individuals with selective IgA deficiency: compensatory IgM secretion and its correlation with HLA and susceptibility to infections.

Total levels of IgA, IgM, and IgG were measured in unstimulated whole saliva and serum from 63 individuals with selective IgA deficiency. Values were compared with the incidence of upper respiratory tract infections, antibiotic treatments (necessitated by upper respiratory tract infection), and HLA antigens. A statistically significant increase in salivary IgM and IgG levels was noted in individuals with selective IgA deficiency compared to healthy normal individuals. Healthy individuals with selective IgA deficiency did not have increased concentrations of salivary IgM compared to infectious-prone patients. Nor was there any correlation found between proneness to infections and HLA antigens or between salivary IgM or IgG levels and HLA antigens in this patient material.

Disease Susceptibility↗
PubMed1989

Antinuclear and related autoantibodies in sera of healthy subjects with IgA deficiency.

The sera of 49 healthy IgA-deficient (SIgAD) subjects were evaluated for the presence of autoantibodies directed against 10 different nuclear and cytoskeletal antigens, as well as for the presence of the common lupus anti-DNA idiotype (16/6 Id). Twenty-nine sera were from IgG subclass-deficient subjects (4 = IgG2, 25 = IgG3), and 25 from normal healthy subjects, used as controls. The incidence of antinuclear but not anti-cytoskeletal antibodies were found to be significantly greater in the SIgAD group, as compared to the IgG-deficient subjects and the normal controls. Overall, 39% of SIgAD sera demonstrated polyreactivity, namely reactivity against more than one nuclear antigen. The incidence of specific antibody detection ranged from 37% against cardiolipin to 12% against RNP in the IgA-deficient group, albeit not with statistical significance in all cases when compared to the control group. Isotype evaluation of the antinuclear and related antibodies in the SIgAD group showed a greater tendency towards IgG. This increased incidence of autoantibody production in SIgAD may preceed the development of an overt autoimmune disease in the future.

Agammaglobulinemia↗
PubMed1989

A proliferative inflammation in the mandible caused by implantation of an infected dental root. A possible experimental model for chronic osteomyelitis.

In order to provide a better understanding of the reactions of bone affected by an infectious stimulus, infected dental roots were implanted into the mandibular bone of 5 monkeys (Macaca fascicularis). The roots were infected by micro-organisms belonging to the monkeys' oral plaque flora. Following an observation period of 6 months, the monkeys were sacrificed. The mandibles were dissected. Radiographs were taken and then the mandibles were prepared for histology. In the mandibles where the infected roots had been implanted, advanced inflammatory changes were seen. Bacteria, however, were only found within the implanted roots, not in the surrounding tissue in spite of a heavy inflammatory reaction. The interaction between infection and inflammation is discussed on the basis of these observations. The role of possible neural transmittor substances in the pathogenesis of the inflammatory disease is also discussed. The signs and symptoms of the proliferative inflammatory changes provoked in this experiment are compared to those of chronic osteomyelitis.

Animals↗
PubMed1989

Influence of granulation tissue, dental calculus and contaminated root cementum on periodontal wound healing. An experimental study in monkeys.

The rôle of gingival granulation tissue, dental calculus and contaminated root cementum in marginal periodontal formation of new attachment was studied experimentally after chemical conditioning of the root surfaces of premolars and molars in 8 monkeys. Each treatment procedure was carried out in 4 monkeys. The other 4 monkeys served as controls. A morphometrical method was used to evaluate the results. It was concluded that a significant amount of new attachment including formation of new adhering cementum will result only on chemically-conditioned cementum surfaces. Small amounts of calculus or granulation tissue left in situ do not seem to influence healing, provided the cementum is left intact after chemical cleansing.

Alveolar Process↗
PubMed1989

Type-specific anti-pneumococcal antibody subclass response to vaccination after splenectomy with special reference to lymphoma patients.

The IgG and IgA antibody subclass responses to pneumococcal polysaccharide antigens type 6A and 19F were studied after immunization with a 14-valent vaccine (Pneumovax, MSD), in 53 splenectomized patients (11 Hodgkin's disease, 13 nonHodgkin's lymphoma (NHL), 9 immune haemolytic anaemia or idiopathic thrombocytopenia purpura and 20 posttraumatic splenectomized patients) and 18 non-splenectomized controls. The antibodies were mainly restricted to the IgG2 and IgA2 subclasses. NHL patients had lower pre-vaccination values to the studied antigens and lower antibody response to vaccination than the other patient groups in which the antibody responses did not differ from those of controls. 1 vaccinated NHL patient experienced two episodes of pneumococcal septicaemia, both occurring after chemotherapy which abolished the previously normal IgG2 antibody levels to the pneumococcal antigens. It is concluded that the antibody response to 6A and 19F antigens after pneumococcal vaccination is not reduced in splenectomized patients but is impaired in immunodeficiency states associated with B-cell lymphoma and treatment with cytostatic drugs.

Adolescent↗