PubMed Health⌕ Search

Biomedical subjects

J Roder

Publications and source records attributed to J Roder.

87 records · Page 5Linked to original sources
PubMed1980

Chédiak-Higashi gene in humans I. Impairment of natural-killer function.

Natural-killer (NK)-cell function was profoundly depressed in donors homozygous for the Chediak-Steinbrinck-Higashi syndrome (C-HS) gene when compared with age- and sex-matched normals. This apparent defect was not simply a result of a delayed response because little cytolysis was evident in kinetics experiments even after 24 h of incubation. NK cells from C-HS donors failed to lyse adherent (MDA, CEM, and Alab) or nonadherent (K562 and Molt-4) tumor cell lines or nontransformed human fetal fibroblasts. Therefore, the apparent C-HS defect was not a result of a shift in target selectivities. In addition, the depressed reactivity did not appear to be a result of suppressor cells or factors because: (a) enriched NK populations (nonadherent lymphocytes bearing receptors for the Fc portion of IgG) from C-HS donors were low in NK-cell function, (b) C-HS mononuclear cells did not inhibit the cytotoxicity of normal cells in coculture experiments, and (c) cells from the C-HS donors remained poorly reactive even after culture for up to 7 d. The nature of the defective NK activity in C-HS patients is not clear but may lie within the lytic mechanism rather than at the level of the recognition structure or population size because the frequency of target-binding cells was normal. In vitro NK activity could be partially restored by interferon treatment. Combined with the results presented in the following paper (4), these observations suggest that the C-HS gene causes a selective immunodeficiency disorder, mainly involving NK cells. This finding, in conjunction with the high incidence of spontaneous possibly malignant, lymphoproliferative disorders in these patients, may have important implications regarding the theory of immune surveillance mediated by NK cells.

Adult↗
PubMed1980

Chédiak-Higashi gene in humans. II. The selectivity of the defect in natural-killer and antibody-dependent cell-mediated cytotoxicity function.

Antibody-dependent cell-mediated cytolysis (ADCC) of human tumor cells by FcR(+) nonadherent effector lymphocytes as well as natural killer (NK) activity was markedly impaired in Chediak-Steinbrinck-Higashi Syndrome (C-HS) patients. Compared to a more than 400-fold defect in NK activity in terms of lytic units, the abnormal ADCC response in C-HS donors was 24-fold below normal suggesting a partial but not complete overlap of lymphocytes or lytic mechanisms responsible for ADCC and NK. The ADCC mechanism against erythrocyte targets, however, was normal, thereby suggesting a qualitative difference in these two forms of ADCC. Other effector-cell functions against tumor-cell targets were normal as measured by (a) spontaneous cytolysis mediated by monocytes, (b) spontaneous cytostasis mediated by neutrophils, and (c) lectin-dependent cytolysis mediated by neutrophils. Although one C-HS patient was low in lectin-dependent cytolysis mediated by lymphocytes, the other C-HS patient was normal, thereby suggesting that cytolytic T function was not linked to the NK-ADCC defect. In addition, the proliferative response to T-dependent mitogens was also relatively normal. These results, combined with other studies showing normal cell-mediated and humoral immunity in these same patients, suggest that patients with C-HS have an immunodeficiency which is selective for NK and ADCC activity.

Adult↗
PubMed1980

Demonstration of natural antibodies in normal rabbit serum with similar specificity pattern as mouse natural killer cells.

Normal rabbit sera (NRS) obtained from noninbred animals were shown to contain antibody to YAC-1, a mouse lymphoma, in a complement-dependent 51Cr release assay. A positive correlation was found between the sensitivity to lysis by NRS antibody and the susceptibility to lysis by mouse natural killer (NK) cells when 7 mouse tumors and 1 guinea pig hepatoma were tested in both assay systems. This correlation was further established with a quantitative absorption assay in which NRS was absorbed with various mouse tumors and subsequently tested for cytotoxicity against YAC-1, the most NRS- and NK-sensitive tumor. A striking positive correlation appeared between the capacity to absorb the NRS anti-YAC-1 activity and the NK sensitivity of various mouse tumors to CBA spleen cells. Thymocytes from strain A/Sn mice less than 2 weeks old absorbed a substantial amount of the NRS anti-YAC-1 activity; these cells were also sensitive to mouse NK cytolysis, whereas thymocytes from older mice lacked both properties. These natural rabbit antibodies could not "arm" peripheral blood lymphocytes in the rabbit because 1) the peripheral blood lymphocytes from these animals used as serum donors showed only low cytotoxic activity in an NK assay against NK-sensitive mouse tumors, and 2) no positive correlation appeared between the levels of cytolytic activity and the levels of natural serum antibodies observed in the rabbits. The present data suggest that natural antibodies in NRS showed the same specificity pattern for mouse tumors displayed by mouse NK cells.

Age Factors↗
PubMed1979

Promonocytes have the functional characteristics of natural killer cells.

Promonocytes isolated from a 5-day-old L-fibroblast-conditioned liquid bone marrow culture show strong NK cell cytotoxicity. They kill YAC target cells in a short-term 125IUDR-release assay whereas P815 targets are unaffected. This NK-like cytotoxicity is enhanced in the presence of interferon preparations. Morphologically, these promonocytes resemble a medium size lymphocyte with a high nucleus to cytoplasma ratio, they are nonadherent, nonphagocytic, and negative in nonspecific esterase staining. Promonocytes are precursor cells from macrophages, which have not yet developed the typical macrophage criteria. Within 24 to 48 hr they mature to adherent macrophages. We have shown previously, that the same promonocytes have the capacity to perform K cell killing of antibody-coated tumor target cells. The cytotoxic effector functions of promonocytes are abolished when the cells are treated with the alloantimacrophage serum Mphi 1.2 plus rabbit C. The relationship or similarity between K cells, NK cells and promonocytes is discussed.

Animals↗
PubMed1978

[Detection of human proteins in the epoxy housing of implanted cardiac pacemakers (author's transl)].

On cardiac pacemakers with epoxy resin encapsulation of a certain type which had been implanted in humans for a considerable time, sessile human proteins were detected in the epoxy by means of immunofluorescence microscopy. These proteins are not extractable from shavings of the epoxy casing using the method described, as was shown by two different methods. The results of LOWRY's test on the eluate are invalid, because we assume that extractable amino groups are responsible for the positive results.

Amino Acids↗
PubMedDate not supplied

Modification in framework region I results in a decreased affinity of chimeric anti-TAG72 antibody.

A mouse/human chimeric B72.3P-1-6 antibody was produced by construction of a novel expression vector mpSV2neo-EP2-V-Crl containing the same gene fragments as the expression vector mpSV2neo-EP1-V-Crl (Xiang J., Roder J. and Hozunni N., submitted to Molec. Immun., 1991) except the promoter (P2) fragment in which the translation start codon ATG is retained. The expression vector was transfected into a heavy chain loss mutant cell line, B72.3M1. The translation of the chimeric heavy chain may start at the exogenous start codon ATG within the P2 fragment, which is 27 base pairs upstream of the endogenous start codon ATG in B72.3 heavy chain V region cDNA fragment, leading to an alteration in leader sequence cleavage sites and the formation of chimeric heavy chain with an elongation in the FR1 region. Chimeric B72.3P-1-6 antibody retained binding specificity to TAG72 antigen, but showed an eight-fold decrease in binding affinity to TAG72 compared with chimeric B72.3-1-3 antibody. This suggests that residues in FRI contribute to the correct folding of the antibody binding region of the B72.3 antibody.

Amino Acid Sequence↗
PubMedDate not supplied

Gene rearrangement in cells with natural killer activity and expression of the beta-chain of the T-cell antigen receptor.

The mammalian host defence system can be divided broadly into adaptive and non-adaptive immunity. Adaptive immunity is acquired and is mediated by B and T lymphocytes. Non-adaptive immunity is mediated in part by a small subclass of heterogeneous peripheral blood mononuclear cells. This population, termed null cells, consists of haematopoietic precursors and cells mediating natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC). NK cells are a class of non-adherent, non-phagocytic, rapidly cytotoxic lymphocytes which can efficiently lyse a wide variety of tumour cells, virally infected cells and immature cell types of normal origin. Despite the broad range of targets, only a limited number of specificities are thought to be involved in target-cell recognition. Morphologically, NK cells are large granular lymphocytes, but they have been shown to exhibit cell-surface markers characteristic of both T cells and monocytes, raising doubt over their lineage. The recent cloning of the beta-chain of the T-cell antigen receptor has now allowed us to investigate whether some NK cells are T-cell-related. We have examined rearrangement and expression of the beta-chain of the T-cell receptor in cloned murine NK cell lines and fresh murine NK cell populations, and our results support the hypothesis that a subpopulation of NK cells is related to T cells and provide basis for examining whether some NK activity is mediated by a small number of T-cell receptors.

Animals↗
PubMedDate not supplied

Overexpression of a calcium-binding protein, S100 beta, in astrocytes alters synaptic plasticity and impairs spatial learning in transgenic mice.

Recent evidence suggests that slowly propagating Ca2+ waves from astrocytes can modulate the function of neurons. Altering astrocytic calcium processes in vivo may therefore affect neuronal and behavioral phenotypes. Previously, we generated transgenic mice that overexpress an astrocytic calcium-binding protein, S100 beta. Immunocytochemistry and in situ hybridization showed elevated expression in the astrocytes of the hippocampus and other brain regions. Neurons in the hippocampus were negative for S100 beta. In this paper we analyze the hippocampal electrophysiology and learning properties of mice from two transgenic lines. Significant differences were found between the hippocampal slices of normal and transgenic mice in their response to high frequency (100 Hz) stimulation. The overall distribution of post-tetanic excitatory postsynaptic potentials (EPSP) of the slices from the transgenic mice was shifted significantly toward smaller values to a degree that 25% of slices exhibited depression. The altered hippocampal neurophysiology was accompanied by an impairment in a hippocampal-dependent learning task. Transgenic mice showed significant impairment in a spatial version of the Morris water maze, however, they performed normally in non-spatial tasks. Probe trials showed that transgenic mice, though significantly impaired, also acquired spatial information. The results suggested that the impairment was not due to motor dysfunction, impaired vision or motivation of the transgenic mice, findings compatible with a possible hippocampal mechanism. We conclude that overexpression of S100 beta in astrocytes impairs, but does not abolish, the ability to solve a spatial task, and it leads to a significantly decreased post-tetanic potentiation in the hippocampal slice. We hypothesize that the changes are due to calcium mediated processes. Our results support the notion that astrocytes are involved in higher brain functions.

Animals↗
PubMedDate not supplied

Selective abolition of the NMDA component of long-term potentiation in mice lacking mGluR5.

The mechanisms underlying the differential expression of long-term potentiation (LTP) by AMPA and NMDA receptors, are unknown, but could involve G-protein-linked metabotropic glutamate receptors. To investigate this hypothesis we created mutant mice that expressed no metabotropic glutamate receptor 5 (mGluR5), but showed normal development. In an earlier study of these mice we analyzed field-excitatory postsynaptic potential (fEPSPs) in CA1 region of the hippocampus and found a small decrease; possibly arising from changes in the NMDAR-mediated component of synaptic transmission. In the present study we used whole-cell patch clamp recordings of evoked excitatory postsynaptic currents (EPSCs) in CA1 pyramidal neurons to identify the AMPAR- and NMDAR-mediated components of LTP. Recordings from control mice following tetanus, or agonist application (IS, 3R-1-amino-cyclopentane 1,3-dicarboxylic acid) (ACPD), revealed equal enhancement of the AMPA and NMDA receptor-mediated components. In contrast, CA1 neurons from mGluR5-deficient mice showed a complete loss of the NMDA-receptor-mediated component of LTP (LTP(NMDA)), but normal LTP of the AMPA-receptor-mediated component (LTP(AMPA)). This selective loss of LTP(NMDA) was seen in three different genotypic backgrounds and was apparent at all holding potentials (-70 mV to +20 mV). Furthermore, the LTP(NMDA) deficit in mGluR5 mutant mice could be rescued by stimulating protein kinase C (PKC) with 4beta-phorbol-12,13-dibutyrate (PDBu). These results suggest that PKC may couple the postsynaptic mGluR5 to the NMDA-receptor potentiation during LTP, and that this signaling mechanism is distinct from LTP(AMPA). Differential enhancement of AMPAR and NMDA receptors by mGluR5 also supports a postsynaptic locus for LTP.

Animals↗