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Biomedical subjects

G V Alm

Publications and source records attributed to G V Alm.

At least 55 records · Page 3Linked to original sources
PubMed1989

Appearance of interferon-alpha in serum and signs of reduced immune function in pigs after transport and installation in a fattening farm.

Pigs were transported from several breeding facilities at the age of 10-12 weeks and regrouped in a fattening farm, specialized in breeding pigs for subsequent slaughter. Blood samples were obtained from the animals just before transport and daily for 17 days after installation in the fattening farm. On each occasion a group of ten animals (170 animals in total) was sampled. The levels of interferon-alpha (IFN-alpha) in serum were measured as antiviral activity in a cytopathic effect inhibition assay. Beginning at day 4 after installation, a significant proportion of sera contained IFN-alpha, with the highest incidence of IFN-alpha positive animals (25%) and IFN-alpha titers on days 5-10. This indicates a high frequency of viral infections in the animals. The in vitro ability of peripheral blood mononuclear leukocytes (PBMCs) to produce IFN-alpha after stimulation by glutaraldehyde-fixed pseudorabies virus-infected PK15 cells and their proliferative response to the T-cell mitogen leukoagglutinin (LA) was also monitored. There was a significant, but moderate decrease in the ability of PBMCs to produce IFN-alpha during the observation period. In contrast, the response to the mitogen LA decreased markedly during the first 5 days, and thereafter remained at the same low level. The proliferative response to LA was significantly lower for PBMCs from serum of IFN-alpha-positive than from IFN-alpha-negative animals. These impaired PBMC responses could indicate a stress-induced immune depression, possibly contributing to the high incidence of viral infections.

Animal Husbandry↗
PubMed1989

Characterization of the blood mononuclear leucocytes producing alpha interferon after stimulation with herpes simplex virus in vitro, by means of combined immunohistochemical staining and in situ RNA-RNA hybridization.

A procedure is described for combined immunohistochemical staining and in situ RNA-RNA hybridization of human peripheral blood mononuclear leucocytes (PBMC). These cells were first stimulated in vitro by herpes simplex virus (HSV)-infected fibroblasts and after 6 h fixed and stained with a panel of antibodies against differentiation antigens. Alpha interferon (IFN-alpha)-producing cells (IPC) were identified by in situ hybridization by means of a 35S-labelled IFN-alpha 2 cRNA probe. The IPC were infrequent, one in 200-5000 PBMC, but heavily labelled with the cRNA probe. They lacked antigens typical of T and B lymphocytes, and were also essentially negative for the Leu-M5 antigen, present on a majority of monocytes. However, 50% of IPC expressed OKM5 antigens, corresponding to the thrombospondin receptor. The IPC lacked the antigens present on null lymphocytes detected by OKT16, but most of them expressed HLA-DR, -DP and -DQ antigens. The IPC may represent a small subpopulation in the monocyte/macrophage lineage, resembling cells described as antigen presenting and stimulators of autologous mixed lymphocyte reactions. Alternatively, they constitute a subpopulation among the null lymphocytes.

Antibodies, Monoclonal↗
PubMed1989

Interferons.

The interesting and complex biology of the interferon (IFN) system is briefly reviewed. Some encouraging results from the application of IFNs to therapy of human disease, as well as therapeutic problems are also pointed out. It is likely that increased knowledge of the functions of the IFN system will facilitate development of more efficient therapeutic strategies, involving e.g., mobilization of the patient's own ability to produce IFN, new combination therapies and circumvention of side effects such as development of antibodies neutralizing IFNs and autoimmunity.

Humans↗
PubMed1989

Development of neutralizing interferon antibodies after treatment with recombinant interferon-alpha 2b in patients with malignant carcinoid tumors.

Human leukocyte interferon (IFN) as well as recombinant (r)IFN-alpha 2b have demonstrated significant antitumor effects in patients with malignant carcinoid tumors, with objective response rates of about 50%. The development of anti-IFN-alpha 2b antibodies has been investigated in 20 patients treated with rIFN-alpha 2b. Three different assays have been used, one neutralization assay and two immunoassays. Increased titers of anti-IFN antibodies were obtained with all three assays in 3 patients (15%). Concomitantly with the development of neutralizing IFN antibodies, a loss of antitumor activity was observed in 2 patients. Neutralizing IFN antibodies may occur as soon as within 3 months of treatment with recombinant IFN-alpha 2b. The frequency of neutralizing IFN antibodies and their clinical significance need to be explored further. Standardized and relevant methods for antibody determinations also must be established.

Aged↗
PubMed1988

Different induction patterns of mRNA for IFN-alpha and -beta in human mononuclear leukocytes after in vitro stimulation with herpes simplex virus-infected fibroblasts and Sendai virus.

Human peripheral blood mononuclear leukocytes (PBL) were stimulated in vitro by HSV type 1-infected glutaraldehyde-fixed fibroblasts, or Sendai virus (SV). The PBL containing mRNA for IFN-alpha 2 or -beta 1 were clearly identified by RNA-RNA in situ hybridization by using 35S-labeled alpha 2- and beta 1-probes. Although the two inducers gave similar levels of IFN in the culture medium (about 20 U/10(4) PBL), the patterns of expression of mRNA at the cellular level differed. The HSV induced only IFN-alpha mRNA in the PBL, with a lag of 1 to 2 h, and with a peak frequency of about 10 labeled cells/10(4) PBL at 6 h. Grain counts were high, the majority of cells having more than 50 grains. They were morphologically medium to large lymphocytes. The HSV-infected glutaraldehyde-fixed fibroblasts therefore induce IFN-alpha 2 mRNA in infrequent but highly efficient PBL, each cell capable of producing as much as 2 antiviral units of IFN-alpha. In contrast, SV induced both IFN-alpha 2 and -beta 1 mRNA in PBL, and without clear lags. IFN-beta 1 mRNA-positive PBL peaked somewhat earlier (4 h) than cells containing IFN-alpha 2 mRNA (6 h), and their mean frequencies were approximately 80 and 60/10(4) PBL, respectively, in a panel of PBL from six blood donors. Grain counts were lower than with the HSV inducer, the majority of cells having less than 50 grains, and most labeled cells were morphologically monocytes. The frequency of labeled PBL rapidly decreased with increasing culture time with both the SV and HSV inducers, was low at 12 h and almost absent at 24 h.

Cell Transformation, Viral↗
PubMed1988

Determination of herpes simplex virus-induced alpha interferon-secreting human blood leucocytes by a filter immuno-plaque assay.

A filter immuno-plaque assay was developed which detects alpha interferon (INF-alpha)-secreting human peripheral blood leucocytes (PBL). Polyclonal anti-IFN-alpha antibodies were fixed to the nitrocellulose membrane bottoms of 96-well Millititer plates, which also contained monolayers of glutaraldehyde-fixed human WISH amnion cells infected by Herpes simplex virus type 1 (HSV). Such cells are potent IFN inducers and during a 16 h cocultivation with PBL, IFN-alpha was absorbed by the membrane-bound polyclonal antibodies around IFN-alpha-secreting cells. This IFN-alpha was detected with murine monoclonal antibodies against IFN-alpha and peroxidase-labelled antibodies against murine immunoglobulin, using diaminobenzidine as substrate. Distinctly stained plaques were seen, the frequency of which gave a minimal estimate of approximately 10 IFN-alpha-producing cells in 10(4) PBL (range in 12 blood donors 2.95-25.1). Fewer plaques than expected were seen at low PBL numbers per culture, one explanation being that cell interactions then limit the IFN-alpha response. The immuno-plaque assay should be useful in further studies of the cellular basis of the IFN-alpha response.

Enzyme-Linked Immunosorbent Assay↗
PubMed1987

Lymphokines in the regulation of immune responses.

Lymphokines are polypeptide factors produced by lymphocytes and other leukocytes, which modulate leukocyte activities in immune responses. Some of the more important lymphokines are reviewed in detail, with emphasis on those that have been cloned. These include interferon -alpha and -beta, interferon gamma, interleukin 2, interleukin 1, tumor necrosis factor and lymphotoxin, B lymphocyte growth factors, hemopoietic growth factors, and others.

Antibody Formation↗
PubMed1985

Human peripheral blood null lymphocytes stimulated by Staphylococcus aureus Cowan I produce atypical acid-labile interferon in vitro.

Peripheral blood mononuclear leucocytes (PBLs) stimulated in vitro by heat-killed formaldehyde-fixed Staphylococcus aureus Cowan I (SACoI) produced acid-labile alpha interferon (IFN-alpha) and, to various extents, also IFN-gamma. The IFN producers resided in nylon wool-nonadherent cells, and monocytes suppressed SACoI-induced IFN responses. Further separation of nonadherent PBLs in accordance with expression of surface antigenic markers was performed with a 'panning' technique. The SACoI induced production of IFN in cells that carried neither surface immunoglobulins nor OKT3-defined antigens. These cells were also characterized as OKM1- and OKT10-negative. In contrast, cells with natural killer (NK) activity against K562 erythroleukaemia cells were located in both OKM1- and OKT10-positive and -negative cells. At centrifugation on Percoll density gradients, cells with NK activity and IFN response against SACoI were recovered from light gradient fractions that contained mainly large granular lymphocytes (LGL). Furthermore, the IFN producers were enriched by removal of sheep erythrocyte-rosetting T cells from the Percoll fractions. These SACoI-induced IFN-producing PBLs are LGL but lack certain antigens that are frequently found on NK cells.

Antibodies, Monoclonal↗
PubMed1985

Treatment of therapy-resistant Sézary syndrome with Cyclosporin-A: suppression of pruritus, leukaemic T cell activation markers and tumour mass.

A patient with Sézary's syndrome resistant to conventional therapy was successfully treated with Cyclosporin-A (CyA) for 14 months. Pre-treatment in vitro studies showed that the leukaemic T cells were sensitive to therapeutic concentrations of CyA. The patient's pruritus disappeared promptly after 2 d of treatment. The positive effect of CyA on the pruritus was related to the dose and plasma concentrations of the drug. Analysis of leukaemic cell surface markers using monoclonal antibodies showed that episodes of pruritus were correlated with the appearance of cells expressing the T cell "activation" markers interferon- gamma (IFN-gamma) and HLA-DR. This indicated that CyA may control pruritus by suppressing the production/release of lymphokines. Immunohistochemical staining of repeated skin biopsies demonstrated a reduction of infiltrating T cells. Clinically, this was correlated with an improved skin status and a partial regress of palpable lymph node size. Apart from an initial reversible drop in the circulating helper/suppressor T cell ratio, the number of circulating Sézary cells was unaltered during CyA treatment. After 5 months, higher doses of CyA were needed to control symptoms, and this was correlated wit with partial drug resistance also in vitro.

Aged↗
PubMed1985

Defective leukocyte interferon response in children with recurrent infections accompanied by arthralgia.

Children with recurrent and/or unusually severe infections were investigated for possible defects in the interferon (IFN)-natural killer (NK) cell system. Two series, each of 13 children, were examined, one in 1982 and one in 1983. Healthy children, seven in 1982 and eight in 1983, served as controls. Peripheral blood mononuclear leukocytes were examined for IFN production induced by the IFN-alpha inducers Sendai virus and Escherichia coli and by the IFN-gamma inducers Concanavalin A and Lens culinaris lectin. None of these inducers discriminated patients from controls. However, the bacteria Staphylococcus aureus Cowan I (SACol), inducers of atypical IFN in null lymphocytes, yielded significantly lower IFN production in infection-prone children than in controls, particularly in children with recurrent infections accompanied by arthralgia. No differences in basal NK activity or in the in vitro enhancement of such activity by IFN-alpha were found between patients and controls.

Bacterial Infections↗
PubMed1985

Inverse relationship between interferon production by mononuclear leucocytes and oxidative metabolism of neutrophil granulocytes in infection prone children.

The ability of neutrophil granulocytes (PMN) from 15 infection prone children to produce luminol enhanced chemiluminescence (CL) was disturbed to varying extents in eight patients, two of whom were diagnosed as having chronic granulomatous disease (CGD). The ability of peripheral blood mononuclear leucocytes (PBL) to produce interferons (IFN) was normal, as tested with the inducers Sendai virus, E. coli, concanavalin A and L. culinaris lectin. However, the IFN response to the inducer S. aureus Cowan I (SACoI) was decreased in patients with normal CL and tended to be increased in those with decreased CL. There was a significant inverse relation between the CL of PMN and the SACoI-induced IFN responses by PBL of the patients. A regulatory effect of products of oxidative metabolism on SACoI-induced IFN production is therefore suggested. Patients, including those with CGD and controls showed similar basal and in vitro IFN enhanced natural killer (NK) activity of PBL against K-562 erythroleukaemia cells.

Cells, Cultured↗
PubMed1984

Interferon production in children with undue susceptibility to infections.

The interferon-producing ability of peripheral blood mononuclear leukocytes obtained from children with undue susceptibility to infections was investigated. Patients were grouped according to three clinical patterns, i.e. children with mainly upper respiratory tract infections, with lower respiratory tract infections and with frequent middle ear infections. There was no evidence of impaired mean interferon-alpha responses to the inducers Sendai virus and beta-hemolytic Group G streptococci in patients compared with control children, and there were no differences in this respect between the patient subgroups. A tendency to increased Concanavalin A-induced interferon-gamma production was seen in patients, particularly those with middle ear infections. Leukocytes from patients displayed a higher proliferative response to the T cell mitogens Concanavalin A and Lens culinaris lectin. In a minority of patients (5/28) reproducibly low interferon responses to Sendai virus were found but only one of these patients showed a response below the -2 SD limit for the control group. The results therefore indicate no major defects in the interferon responses of infection-prone children, and at the most suggest that a minority of such patients may be low responders to a viral interferon inducer.

Cells, Cultured↗
PubMed1983

Properties of human natural interferon-producing cells stimulated by tumor cell lines.

Human peripheral blood mononuclear leukocytes cocultured with WISH human amnion cells or K562 tumor cells rapidly produce interferon-alpha (IFN). In the present report we characterize the IFN-producing cells (IPC) in this system by cell separation procedures, including panning with different monoclonal antibodies. Two types of cells which were responsible for the IFN production could be identified. The first IPC was classified as monocyte/macrophage because it was present in plastic-adherent cells and apparently carried the OKM1 antigenic marker. T and B lymphocytes were not involved in the IFN production. The second type of IPC was nylon wool-nonadherent, sheep erythrocyte rosette-negative, at least partly Fc receptor-negative and resided in light Percoll density gradient fractions. The natural killer activity and IFN-producing capacity was studied in such cells fractionated by the panning technique, utilizing HNK-1, OKT10 and OKM1 antibodies. When WISH and K562 were used as IFN inducers, HNK-1+ and OKT10+ cells with lytic activity against K562 produced little or no IFN. The IPC were instead confined to HNK-1- and OKT10- cells. With cells fractionated with respect to the OKM1 antigen, natural killer activity against K562 and WISH cells and IFN production stimulated by K562 cells resided in the OKM1+ cells. In marked contrast, cells producing IFN in response to WISH cells were OKM1-. The results therefore demonstrate a dissociation between natural killer cells against tumor cells and IPC stimulated by the same targets, suggesting that for at least certain targets/inducers they may represent distinct entities.

Antibodies, Monoclonal↗
PubMed1983

Plasmodium falciparum parasites induce interferon production in human peripheral blood 'null' cells in vitro.

Human peripheral blood mononuclear cells were found to produce interferon (IFN) when stimulated by free P. falciparum parasites in vitro. On the other hand parasite-infected, intact erythrocytes were unable to induce IFN synthesis. When the IFN was characterized according to sensitivity to anti-IFN-alpha antibodies and pH 2 treatment it was found to consist of IFN-alpha. Cell fractionation procedures and analysis of each cell fraction with regard to natural killer (NK) cell activity and IFN-producing capacity revealed that both activities were confined to the same cell fraction. The possible relevance of the IFN-NK cell system in malaria is discussed.

Cell Separation↗
PubMed1983

Characterization of interferons induced by bacteria and interferon-producing leukocytes in human peripheral blood.

All of 23 different preparations of formaldehyde-fixed and heat-killed bacteria induced the appearance of high levels of interferon (IFN) in cultures of human peripheral blood mononuclear leukocytes. Some bacteria induced peak IFN titers after 24 h of culture, whereas other bacteria showed maximal titers on culture days 2 to 3. The IFN displayed various properties. One type, which appeared early during the cultures, had characteristics of IFN-alpha, being resistant to pH 2 treatment but neutralized by antibodies to IFN-alpha. A second type, which appeared later, on culture days 2 to 3, resembled IFN-gamma in being sensitive to pH 2 treatment but resistant to anti-IFN-alpha antibodies. A third type, which appeared to be sensitive to both pH 2 and antibody treatment, was interpreted as atypical IFN-alpha. The application of cell fractionation procedures indicated that nonadherent, predominantly Fc receptor-bearing, non-T, non-B cells were producers of IFN-alpha as defined by its antigenic properties. They copurified approximately with cells carrying natural killer activity toward human erythroid leukemia K562 cells. Some bacteria apparently also stimulated T lymphocytes to produce material with properties of IFN-gamma.

Antibodies, Viral↗
PubMed1983

Evaluation of the natural killer cell-interferon system in patients with mid-gut carcinoid tumours treated with leucocyte interferon.

Nine patients with mid-gut carcinoid tumours received leucocyte interferon (IFN) i.m. daily for 90 days. Six patients clearly ameliorated in symptoms typical of the carcinoid syndrome (flushing, diarrhoea, asthma) which correlated with reduced serum levels of tumour related polypeptides and urinary output of 5-hydroxyindole acetic acid (5-HIAA). Before IFN treatment, peripheral blood mononuclear leucocytes (PBLs) from carcinoid patients showed markedly deficient production of pH 2 labile IFN-alpha in response to Staphylococcus aureus Cowan I (SACoI) in vitro. In contrast, IFN-alpha responses to the inducers Sendai virus and beta-haemolytic streptococcus group G and IFN-gamma responses to Lens culinaris lectin and concanavalin A were normal. Also, basal and in vitro IFN enhanced natural killer (NK) cell activity and T cell mitogen-induced cell proliferation were similar in patients and controls. During 90 days of IFN therapy, SACoI-induced IFN responses became entirely undetectable. There were transient declines at 1 and 30 days in IFN responses to the other IFN inducers, of mitogen-induced lymphocyte proliferation and of basal NK activities. The increments of NK cell activities after in vitro IFN exposure were clearly decreased in IFN treated patients, suggesting in vivo activation of these cells. Thus, the results demonstrate one remarkable abnormality in carcinoid patients: a deficient IFN response to SACoI and a clear influence of IFN therapy on several parameters of the IFN-NK system.

Aged↗
PubMed1982

Limiting dilution analysis of human peripheral blood mononuclear leukocytes that react to human amnion cells and protect these against viral challenge.

Human peripheral blood mononuclear leukocytes (PBL) cocultured with WISH human amnion cells rapidly produced alpha-type interferon (IFN-alpha) and in an IFN-dependent manner protected the WISH cells against the cytopathic effects caused by vesicular stomatitis virus. When the number of PBL per WISH cell monolayer culture was diluted out using multiple WISH microtiter plate cultures for each PBL dilution, the protection of the WISH cultures appeared as an all-or-none phenomenon. Thus, at one small mean number of PBL per culture, some cultures were protected against the virus, while others were not. Limiting dilution analysis, with plot of the logarithm of the fraction of nonprotected WISH cell cultures at each PBL dilution against the mean number of PBL per culture, yielded straight lines with an intercept on the ordinate close to 1. This indicated a single-hit event due to the function of a single type of limiting "protecting unit". The frequency of this limiting unit in the PBL population could reproducibly be determined for an individual blood donor. For a limited number of different blood donors it ranged from 1/400 to 1/3000. These minimal frequency estimates were considerably increased (40-300%) after 3 h preincubation of PBL with IFN-alpha. Two major alternatives were considered with regard to the nature of the limiting protecting units. They were either IFN-producing cells operating alone, or they were inducer-type cells that possibly used IFN as a mediator to activate protecting cells present in excess in the coculture system. The second possibility was favored, and the relation of the protecting cell type to the natural killer cell system is discussed herein.

Amnion↗