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Biomedical subjects

F Miedema

Publications and source records attributed to F Miedema.

212 records · Page 12Linked to original sources
PubMed1984

Both Fc receptors and lymphocyte-function-associated antigen 1 on human T gamma lymphocytes are required for antibody-dependent cellular cytotoxicity (killer cell activity).

A monoclonal antibody, designated CLB-LFA-1/1, directed to the human lymphocyte-function-associated antigen 1 (LFA-1) was raised by immunization of mice with the peripheral blood lymphocytes of a T gamma lymphocytosis patient. The monoclonal antibody was selected by inhibition of the natural killer cell and the antibody-dependent killer cell activity of the patient's T gamma lymphocytes. In addition, the monoclonal antibody was shown to inhibit the cytotoxic activity of T cell clones specific for either class I or class II HLA molecules. The antigen recognized by CLB-LFA-1/1 consisted of three polypeptide chains with molecular weights of 180 000 (alpha), 155 000 and 94 000 (beta). The antibody reacted with T cells, B cells, monocytes and granulocytes, and stained normal T gamma cells and T gamma cells of patients with T gamma lymphocytosis two- to threefold stronger than normal T cells. It was shown that LFA-1 and the Fc receptor on T gamma cells did not comodulate and it is therefore concluded that Fc receptors and LFA-1 are independent membrane structures, both required for the killer cell activity of T gamma cells.

Antibodies, Monoclonal↗
PubMed1984

Regulatory activity of neoplastic T cells in Sezary syndrome on in vitro immunoglobulin production.

Functional activities and surface markers of the neoplastic T cells of three patients with Sézary syndrome were studied and compared with the functional activities of OKT4+ and OKT8+ T-cell subsets from healthy donors. The neoplastic T cells of the patients had the following marker phenotype: OKT1+3+4+6-8-11+17+I1-M1-3A1-. In contrast to healthy donor OKT4+ T cells, none of the neoplastic T cells had significant helper activity on pokeweed-mitogen-driven Ig synthesis. In one patient the neoplastic T cells suppressed pokeweed-mitogen-driven Ig synthesis. The suppression by the patient cells did not require the presence of radiosensitive OKT4+ suppressor-inducer cells in the culture. It is concluded that OKT4+8-3A1- neoplastic T cells from Sézary-syndrome patients lacking helper activity are more common than previously thought and that in some cases the OKT4+8-3A1- Sézary cells can mediate suppressor activity.

Antibodies, Monoclonal↗
PubMed1984

Functional properties of neoplastic T cells in adult T cell lymphoma/leukemia patients from the Caribbean.

The neoplastic T cells from five patients with adult T cell lymphoma/leukemia (ATLL), born in the Caribbean, were studied with respect to immunoregulatory activity on pokeweed mitogen (PWM) driven immunoglobulin (Ig) synthesis as well as surface-marker phenotypes with monoclonal antibodies. The neoplastic T cells in all patients had an OKT1+4+8-11+M1-I1-3A1- phenotype, but differed in the reactivity with OKT3. None of the patients' cells exerted helper activity on PWM-induced Ig synthesis. The neoplastic cells of three patients had suppressor activity on PWM-induced Ig synthesis. All patients were positive for human T cell leukemia/lymphoma virus (HTLV) or had antibodies against HTLV antigens. It has previously been shown that the neoplastic cells in Japanese ATLL patients and in patients from the Caribbean are indistinguishable by morphology and marker phenotype. We now show them to be also similar with respect to their functional properties.

Adult↗
PubMed1983

Vaccine potential of meningococcal group C polysaccharide-tetanus toxoid conjugate.

The antibody response in mice to Neisseria meningitidis (meningococcal) group C polysaccharide could be modified by its conjugation to proteins, i.e. tetanus toxoid. Whereas the pure polysaccharide behaved as a T-independent antigen, the polysaccharide-protein conjugate was clearly a T-dependent antigen, as shown by the pronounced IgG response after the first dose and by the booster effect after the second dose. In comparison, group C polysaccharide-outer membrane protein complexes isolated from the cell-free culture liquid of a meningococcal culture induced only a low level of IgG antibodies. Conjugation did not result in a reversion of tetanus toxoid to toxin. Tetanus toxoid present in the conjugate was as immunogenic as tetanus vaccine.

Animals↗
PubMed1983

Preparation and physicochemical and immunological characterization of polysaccharide-outer membrane protein complexes of Neisseria meningitidis.

A crude complex containing group C polysaccharide, outer membrane proteins, and lipopolysaccharide (LPS) was isolated from the cell-free culture liquid of Neisseria meningitidis serogroup C, serotype 2a. Group C polysaccharide and LPS were removed from this complex, resulting in an outer membrane complex and a purified complex, respectively. Analysis by electron microscopy showed the outer membrane origin of the crude complex and the outer membrane complex, whereas such a structure was absent in the purified complex. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns of the three complexes were identical. Pyrolysis-mass spectrometry data correlated well with those obtained by the biochemical assays and suggested a low LPS content in the purified complex and a low polysaccharide content in the outer membrane complex. The purified complex was shown to be nonpyrogenic and could be prepared with the same yield as that of purified polysaccharide. The immunogenic activities of the complexes were studied in mice. The antibodies were measured by the enzyme-linked immunosorbent assay; and the bactericidal antibody assay. All complexes induced immunoglobulin G antibodies to group C polysaccharide as well as to the serotype antigen, although the removal of polysaccharide and LPS resulted in a reduction of the immunogenic activities of outer membrane complex and purified complex, respectively. A second dose of all complexes produced a clear booster effect of both antibody responses. The antibodies were bactericidal.

Animals↗
PubMed1983

Preparation and immunochemical characterization of meningococcal group C polysaccharide-tetanus toxoid conjugates as a new generation of vaccines.

Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugates have been prepared by using high-molecular-weight polysaccharide and purified tetanus toxoid and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide as a coupling reagent. The influence of three conditions of preparation was studied. Biochemical assays, the enzyme-linked immunosorbent assay, and isopycnic CsCl gradient ultracentrifugation have been used to characterize the conjugates. The polysaccharide-to-protein ratios of the various conjugate preparations showed differences. The ability of the group C polysaccharide component to react with specific antibodies was reduced, whereas most of the tetanus toxoid seemed to be hidden by the polysaccharide. The composition of the conjugate was not homogeneous, and at least 10% of free polysaccharide was present. Thermostability in lyophilized condition in the presence of lactose was excellent.

Animals↗
PubMed1983

Immunological evaluation of meningococcal group C polysaccharide-tetanus toxoid conjugate in mice.

Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugate was prepared to obtain the polysaccharide component in a thymus-dependent form and to preserve the immunogenic properties of the tetanus toxoid component. Biochemical and immunochemical analyses of this conjugate revealed that (i) it was composed of equal amounts of polysaccharide and protein; (ii) the antigenic activity of the polysaccharide component was greatly reduced; (iii) it contained about 10% free polysaccharide; (iv) the composition was not homogeneous; and (v) only 5% of the tetanus toxoid component was present at the surface of the conjugate molecules. In this study, the influence of these characteristics on the antibody response to both components in mice was investigated. The dose-response relationship, the persistence of antibodies, a possible antigenic competition, and the specificities of the antibodies induced were also studied. Our data suggest that the conjugate behaves as a pronounced thymus-dependent antigen, that the tetanus toxoid component is more immunogenic at lower dosages (0.8 and 20 ng) than equivalent doses of tetanus vaccine, that the presence of free polysaccharide does not influence the induction of antibodies to polysaccharide by the conjugate, and that no antibodies to new structures in the conjugate are induced. These characteristics favor the application of this conjugate as a vaccine for human use.

Animals↗
PubMed1982

Functional properties of T cells in patients with chronic T gamma lymphocytosis and chronic T cell neoplasia.

The expanded T cell populations of 10 patients with either T gamma lymphocytosis (five patients) or proven chronic T cell malignancy (five patients) were analyzed with respect to functional activity in vitro, including proliferative responses to mitogens, cytotoxic activity (killer [K] and natural killer [NK] cell activity), and regulatory activity on pokeweed mitogen- (PWM) induced immunoglobulin (Ig) synthesis (help and suppression) in comparison with marker phenotypes. In each of the five patients with T gamma lymphocytosis, only one out of three functionally distinct cell types was found: T gamma-K cells, T gamma-S cells, or T gamma-NK/K cells, which mediated K-cell activity, suppressive activity, and both NK and K cell activity, respectively. An expanded T gamma-K cell population was demonstrated in three patients with neutropenia with or without recurrent infections. T gamma-S cells were found in a patient with severe hypogammaglobulinemia, and T gamma-NK/K cells in one patient with asymptomatic lymphocytosis. T gamma-K and T gamma-S cells had a similar surface-marker profile (E+ or E-, Fc gamma+, OKT1-3+4-8+I1-M1-), whereas that of T gamma-NK/K cells was different (E+, Fc gamma+, OKT1-3-4-8-I1+M1+). Longitudinal studies of three untreated patients with T gamma-K lymphocytosis showed that the abnormalities were persistent but not progressive. In contrast, five patients with chronic T cell malignancy (two with T-CLL, two with cutaneous T cell lymphoma [CTCL], and one with T-PLL) all had progressive disease. The neoplastic cells in these cases were E+, Fc gamma-OKT1+4+6- with variable expression of the OKT3 and OKT8 markers. The only functional activity observed in these cells was suppressive activity by OKT3-4+8- cells from a patient with CTCL.

Adult↗
PubMedDate not supplied

Interference with HIV-induced syncytium formation and viral infectivity by inhibitors of trimming glucosidase.

Human immunodeficiency virus (HIV), the causative agent of AIDS, infects human lymphocytes and monocytes. An interaction between the viral envelope gp 120 and CD4 protein is required to initiate an infectious cycle. HIV infection in vitro induces syncytium formation by cell-to-cell fusion; this aspect of viral cytopathogenicity is even more dependent on gp120-CD4 interactions. That gp120 is extremely heavily glycosylated (31-36 N-linked glycans per molecule), suggests involvement of N-linked glycans in the gp120-CD4 interaction. We therefore investigated the effects of castanospermine, 1-deoxynojirimycin (dNM) and 1-deoxymannojirimycin (dMM), three trimming glycosidase inhibitors which perturb N-linked glycan structure, on induction of the formation of syncytium between HIV-infected and CD4-expressing cells. The glucosidase inhibitors castanospermine and dNM, but not the mannosidase inhibitor dMM, inhibited syncytium formation and interfered with infectivity. The potential of glucosidase inhibitors as anti-HIV therapeutic agents deserves further investigation, especially because dNM and related compounds show little toxicity in vitro and in vivo.

1-Deoxynojirimycin↗
PubMedDate not supplied

IgG antibodies to HTLV-III associated antigens in patients with AIDS and at risk for AIDS in The Netherlands.

Thirty-nine homosexual males, 11 of whom suffered from AIDS and 13 from Lymphadenopathy Syndrome (LAS), 18 healthy hemophiliacs and 12 healthy blood donors, not belonging to any AIDS risk group, were tested for IgG antibodies to Human T-lymphotropic retrovirus type III (HTLV-III) by indirect immunofluorescence. All tested people were from the area of Amsterdam or from elsewhere in The Netherlands. Five of 11 AIDS patients, 8 of 13 LAS patients and 5 of 15 healthy homosexuals had antibodies to HTLV-III. Five of 18 healthy hemophiliacs were seropositive for HTLV-III. None of the 12 blood donors was seropositive for HTLV-III.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Withdrawing treatment from the hopelessly ill. Part 1: The ethical case.

The ICU exists so that critically ill patients can receive highly technical, specialized care which will support physiologic function until recovery can occur. When the patient cannot sustain life without the assistance of technology, and recovery is known to be unlikely, withdrawal of treatment may be appropriate. Nonetheless, withdrawal of life-sustaining treatment is often complex ethically and emotionally. The following case submitted by a DCCN reader illustrates the challenge of treatment withdrawal issues in critical care.

Aged↗