The effects of FK 506 on cytokine production are dependent on the mode of cell activation.
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Biomedical subjects
Publications and source records attributed to J Andersson.
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Fibreoptic bronchoscopy with bronchoalveolar lavage (BAL), transbronchial lung biopsy (TBB) and brushing was performed, in 134 episodes of pulmonary disease in 118 compromised patients. Sixty eight of the patients were infected with immunodeficiency virus type 1 (HIV-1), 18 were renal and pancreas transplant recipients, 7 were liver and 15 were bone marrow transplant recipients, and 10 patients were undergoing immunosuppressive and/or cytotoxic drug therapy. Pneumocystis carinii (PC) was the predominant pathogen in HIV-1 infected patients. It was considered to be the aetiological cause of pneumonia in 54/82 (66%) episodes of lung complications noted in these patients. Cytomegalovirus (CMV) was the most common micro-organism in transplant recipients. CMV pneumonia was diagnosed in 22/42 episodes of pulmonary disease in these patients. CMV was detected by bronchoscopy procedures at a relatively high frequency of 36/82 (44%) episodes in HIV-1 infected patients. However, after analysis of clinical information, cultures from leucocytes and autopsy findings, CMV seemed to be involved in the pathogenicity of pneumonia in only two out of the 36 patients. Bacterial aetiology, including mycobacterial agents, was unusual, but was the major cause of pulmonary infections in 6/10 episodes in patients undergoing extensive immunosuppressive and/or cytotoxic drug therapy. Bronchoscopy was helpful in establishing correct aetiology in 98/134 (73%) episodes of pulmonary disease. Growth of Candida albicans and bacteria should always be viewed sceptically because of the possibility of contamination from colonization in the upper respiratory tract.
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Two different lines of C57BL/6 mice (IgHb) carrying complete rearranged mu chain genes from BALB/c (IgMa) were analyzed for the expression and secretion of endogenous as well as transgenic immunoglobulins at the level of single cells. Quantitation of B cells expressing endogenous IgMb by cytofluorometry, limiting dilution analyses of clonal precursors and secretory cell assays revealed a marked selective expansion, activation and terminal differentiation of those cells producing endogenous immunoglobulins. Thus, the very infrequent IgMb-bearing B cells produced in bone marrow of transgenic mice accumulate in spleen, where they are activated and account for roughly half of all natural immunoglobulin-secreting cells. These observations indicate that mu-transgenic mice are valuable in studies of the antibody repertoire selection operating in unprimed animals but their use could be misleading in the analyzing "monoclonal" immune system.
The production of interleukin 2 (IL 2), IL 4 and interferon-gamma (IFN-gamma) by in vitro activated unselected human blood mononuclear cells was studied at a single-cell level. Individual lymphokine-synthesizing cells were identified by intracellular immunofluorescent staining using cytokine-specific monoclonal or polyclonal antibodies. Cultures from adult blood donors revealed a biphasic kinetic production pattern for IL 2 and IFN-gamma with peaks occurring 4-6 and 24-30 h after initiation of the cultures. Approximately 20%-40% of the lymphocytes produced IL 2 and IFN-gamma. In contrast, only 1%-3% of the lymphocytes synthesized IL 4 with maximal frequency after 6 h of culture. CD4+ as well as CD8+ T cells contributed to the synthesis of all three lymphokines studied. CD4+CD45R- T cells were the major producers of IL 2 and IL 4, while CD8+CD45R- T cells were the most common phenotype of IFN-gamma-synthesizing cells. By performing two-color immunofluorescence studies we observed that among IL 4-producing cells every second one made simultaneously IL 2 and every fourth one made IFN-gamma. Mononuclear cells from umbilical cord blood could be stimulated to make IL 2 to the same extent as cells from adult blood donors. No IL 4 production and a strikingly reduced frequency of IFN-gamma producers were noted in cell cultures from neonates. IL 2, IL 4 and IFN-gamma accumulated in the Golgi system, which resulted in a characteristic morphology of the staining, eliminating problems with evaluation of background signals.
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To diagnose infectious mononucleosis caused by Epstein-Barr virus (EBV), a peptide from the EBV nuclear antigen (EBNA) 1 (p107) and an EBNA 2 peptide (polyproline) were used as antigens in enzyme-linked immunosorbent assays for IgG and IgM. Well-characterized serum samples (360) from healthy individuals and patients with EBV or cytomegalovirus infections were examined. The p107 IgG and IgM assays were also tested with serum from 1000 patients with suspected EBV-related disorders. The p107 and polyproline IgG assays were 100% specific for EBV seropositivity. Low p107 IgG titers (less than 1000) were found in 98% of patients with EBV infectious mononucleosis but also in 18% of patients with other diseases. A p107-to-polyproline IgG ratio of less than 1 was 98% specific for EBV infectious mononucleosis; sensitivity was 86%. In EBV capsid antigen-IgG seropositive patients, a p107 IgG titer of less than 1000 together with a p107 IgG-to-IgM ratio of less than 1 was 98% sensitive and specific for EBV infectious mononucleosis. Thus, this ratio appears adequate to measure EBNA antibodies for diagnosis of EBV mononucleosis.
Immunoglobulin G antibody titers to human herpesvirus 6 (HHV-6), measles virus, and cytomegalovirus (CMV) were examined in serum samples from 31 patients with Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM). Sera were drawn sequentially from the same patients less than or equal to 7 days until 3 years after onset of IM. In seropositive patients, there was a significant decrease with time after IM of the immunoglobulin G titers to the three viruses in the majority of patients; HHV-6 IgG titers decreased in 80%, measles virus IgG titers decreased in 75%, and CMV IgG titers decreased in 67%. Four patients contracted CMV infection during the observation period after IM. In these, HHV-6 IgG titers increased, while EBV and measles virus IgG titers remained essentially stationary. Polyclonal B-cell stimulation during IM is suggested to augment antiviral titers in general, but the increases of HHV-6 IgG titers during EBV and CMV infections may also be due to selective stimulation of memory B cells by related antigens or to reactivation of HHV-6 during infection with these herpesviruses.
The materno-fetal transfer of methionine in the Rhesus monkey was investigated using positron emission tomography, a non-invasive in vivo tracer technique based on short-lived radionuclides. A bolus dose of [11CH3]-l-methionine was administered intravenously and the radioactivity concentrations in the placenta, the fetus and the maternal arterial blood were measured as functions of time and fitted to an equation derived from a four compartment model of the feto-placental complex. Rate constants were calculated describing maternal placental blood flow, the transfer of [11CH3]-l-methionine to the placental tissue and the fetus. The transfer rate of methionine to the fetus was estimated as 0.8-1.5 nmol/min/g placenta and was similar to the transfer to the placental tissue. An approximate blood flow through the intervillous space of 128 ml/min was found. The correlation between placental transfer to the fetus and the maternal blood flow in the intervillous space was low.
We wish to report a 76-year-old woman with 2 episodes of meningitis related to the intake of trimethoprim. On both occasions the patient demonstrated encephalitic symptoms and a pathological electroencephalogram with cerebral function disturbances. A similar case with encephalitic symptoms due to trimethoprim has not been reported earlier.
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Epstein-Barr virus infection (EBV) was discovered 25 years ago in tumour cells from Burkitt's lymphoma. EBV causes infectious mononucleosis and contributes to the pathogenesis of Burkitt's lymphoma and nasopharyngeal cancer. Atypical courses of the primary infection are attracting increasing attention and may present problems of diagnosis at the same time as no clear diagnostic or laboratory-based definition of the reactivation of this herpes virus is available. The article reports on the clinical course, the diagnosis, and the possibilities of treatment.
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