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Biomedical subjects

H Hirschberg

Publications and source records attributed to H Hirschberg.

At least 55 records · Page 3Linked to original sources
PubMed1988

Comparison of in vitro glioma cell cytotoxicity of LAK cells from glioma patients and healthy subjects.

Peripheral blood mononuclear cells from 11 glioma patients and 11 healthy control subjects were cultured in medium containing recombinant interleukin-2 for a period of 5 days. The cytotoxicity of these lymphokine-activated killer (LAK) cells was tested on chromium-51-labeled freshly prepared allogeneic glioblastoma cells, and on the cell lines K562 (natural killer cell (NK)-sensitive) and Daudi (NK-resistant). Peripheral blood mononuclear cells from all subjects showed high levels of cytotoxicity against these targets. There was no significant difference between the patients and the control group when LAK cytotoxicity was compared. Thus, although glioma patients are known to have depressed immunological reactivity, the cytotoxic capacity of LAK cells derived from glioma patients is similar to that of LAK cells from healthy control subjects. However, the glioma patients had significantly reduced numbers of mononuclear cells in their peripheral blood, possibly due to steroid treatment. Therefore, the volume of blood required to generate the same number of LAK cells was approximately three times larger from the glioma patients than from control subjects.

Adult↗
PubMed1987

Radioimmunoassay in microtiter plates. A convenient method for determining bound radiolabelled ligand.

A radioimmunoassay was performed in the wells of casein-coated microplates employing 125I-labelled sheep anti-human second antibody. The antigen-antibody complexes were thereafter dislodged from the well walls using the detergent sodium dodecyl sulfate (SDS) and the entire contents of the wells were simultaneously absorbed into 48 cellulose acetate-absorbing cartridges. All 48 cartridges were transferred to counting vials and the radioactivity determined by standard gamma counting techniques. The particular advantage of the method described here is the ease with which the supernatants can be collected and transferred to counting vials with minimal handling of radioactive samples.

Animals↗
PubMed1987

C-reactive protein levels in the differential diagnosis of brain abscesses.

C-reactive protein (CRP) is a protein found in plasma at elevated concentrations during acute or chronic infections. As an aid in the differential diagnosis between brain tumor and abscess, the CRP levels were measured in 20 patients with intracranial mass lesions and the appearance of ring-like contrast enhancement on computerized tomography (CT) scans. In nine of these patients, the final diagnosis was abscess, based on either biopsy of the mass (eight patients) or the clinical course (one patient). In seven of the nine patients, there was a significant increase in CRP levels in two consecutive measurements. In particular, patients with cerebritis who were examined early in the course of the disease and who showed nonspecific CT scans exhibited extremely high levels of CRP. Two patients had no measurable CRP activity although they both had brain abscesses. In 12 patients harboring either gliomas or metastatic intracerebral tumors, CRP levels were significantly lower than those found in patients with brain abscesses but were nevertheless higher compared to those of a group of patients with benign tumors. It is concluded, therefore, that the measurement of CRP can have some value in the differential diagnosis between brain abscess and brain tumor. The measurement technique is inexpensive and is available in the clinical laboratories of most hospitals with a neurosurgical department.

Adolescent↗
PubMed1985

Characterization of Chlamydia trachomatis serotypes by human T-lymphocyte clones.

T cells primed to Chlamydia trachomatis serotypes A, F, and K were cloned by limiting dilution. All T-lymphocyte clones obtained reacted only with C. trachomatis antigens. The proliferative capacity of 89 clones was studied with autologous non-T cells as antigen-presenting cells and the chlamydia serotypes A, B, D, F, K, and LGV-2 as antigens. Most of the clones reacted to several of the chlamydia strains, indicating common antigenic determinants. Other T-cell clones reacted with only a few serotypes. On the basis of the proliferation of the T-cell clones to the chlamydia strains and to interleukin-2, different reactivity patterns were obtained, which possibly can be used to differentiate among the chlamydia strains.

Chlamydia trachomatis↗
PubMed1984

Inhibition of the antigen activated T cell response by methylprednisolone is caused by inhibition of interleukin-2 (IL-2) production.

A mechanism by which the steroid methylprednisolone inhibits the T cell proliferation normally seen in antigen driven cultures was investigated. At methylprednisolone concentrations less than 10 micrograms ml-1 inhibition of cellular proliferation was almost exclusively via the inhibition of the production of interleukin-2 by activated T cells. The steroid seemed to inhibit IL-2 production directly and not via reduced sensitivity to interleukin-1 by IL-2 producer T cells, or reduced IL-1 production by the antigen presenting monocytes. At methylprednisolone concentrations of greater than 10 micrograms ml-1 direct inhibition of the T cell receptor to antigen complexes presented by cooperating monocytes seemed the most likely explanation. T cells in the presence of antigen and monocytes and MP concentrations of greater than 10 micrograms ml-1 did not produce IL-2 and were incapable of expressing IL-2 receptors. The inhibiting effects of methylprednisolone therefore are via several mechanisms depending on the concentration of the steroid employed.

Antigens↗
PubMed1984

The effect of short-term corticosteroid incubation on the alloactivating and antigen-presenting capacity of human epidermal Langerhans cells.

The effects of short-term incubation with hydrocortisone and methylprednisolone on the alloactivating capacity and the ability of human epidermal Langerhans cells and peripheral blood monocytes to induce antigen (PPD)-specific T-lymphocyte responses were investigated. The Langerhans cells and the monocytes were treated with different concentrations of the steroids before being added to allogeneic T lymphocytes, and before, after or simultaneously with, pulsing with PPD. Neither steroid inhibited the alloactivating capacity of the Langerhans cells, but a dose-dependent reduction of the stimulatory capacity of antigen-pulsed Langerhans cells and monocytes was obtained with methylprednisolone. Hydrocortisone had inhibitory effects only at high concentration. The inhibition appeared to be due to suppression of the presentation of PPD in immunogeneic form to sensitized T cells.

Cell Survival↗
PubMed1984

Lack of cell-mediated cytotoxicity towards Chlamydia trachomatis infected target cells in humans.

Induction of cell-mediated cytotoxicity towards Chlamydia trachomatis infected target cells was studied in humans. PHA-derived lymphoblasts, infected with inactivated or virulent LGV-2 chlamydial particles, were used as target cells. Chlamydial primed T cell blasts or specific, cloned T cells were used as effector cells. A highly sensitive 18 hours lytic assay employing 111In-labelled target cells was used. Specific cytotoxicity towards C. trachomatis infected target cells in humans could not be detected. This was the case regardless of the origin of the effector cells or the various protocols tested. However, this assay was capable of yielding significant positive results with effector cells primed to alloantigens. We conclude that cell-mediated cytotoxicity towards bacterial infected target cells probably does not play a major role.

Antigens, Bacterial↗
PubMed1983

Cell mediated lympholysis; a modified technique using 111indium-oxine-labelled targets.

The isotope 51Cr generally used in the cell mediated lympholysis (CML) assay suffers from the disadvantage of low specific activity, poor incorporation and high spontaneous release, limiting the CML assay to 4-6 h. We have labelled PHA derived human lymphoblasts with the isotope 111indium (using 111indium-oxine) and evaluated these cells as targets in CML. The level of 111In-oxine incorporation decreased rapidly in the presence of serum; in the absence of serum approximately 85% of the available isotope in the supernatant was incorporated into the blasts. Under the labelling conditions used, spontaneous release was 1.6-2%/h on average allowing an effector phase of 18 h. About 5-8% of the released isotope was reutilized by the effector cells during an 18 h incubation period. Extending the CML assay from 6 to 18 h greatly increased the cytotoxicity. At an effector to target ratio of 25:1, the average per cent specific release increased from 15 to 50%. The use of 111In-oxine labelled targets in the CML therefore increases the sensitivity of the test and allows fewer effector and target cells to be used as compared with 51Cr techniques.

Chromium Radioisotopes↗
PubMed1983

Donor-specific decreased cell-mediated cytotoxicity in recipients of well functioning, one HLA haplotype-mismatched kidney allografts.

Patients with well functioning kidney grafts from one HLA haplotype-mismatched related donors were studied 2 to 10 years after transplantation. No direct cell-mediated lympholysis (CML) toward donor cells was found. After in vitro sensitization in mixed lymphocyte culture, the recipient effector cells were not able to significantly kill donor target cells at an effector to target cell ratio of 50:1, while the HLA-A,B,D/DR-identical sibling of the recipient could generate strong cytotoxicity toward the donor at similar effector to target cell ratios. Nevertheless, the patient developed strong cytotoxicity toward third-party targets. Our findings indicate in vivo depletion of cytotoxic cells with specificity for donor antigens. No correlation between the mixed lymphocyte culture (MLC) response and the ability to generate cytotoxic cells could be found in recipient-donor combinations. In looking for in vivo generated suppressor cells toward the donor, a moderate suppression was found in three of six patients studied.

Cytotoxicity, Immunologic↗
PubMed1983

Cell-mediated cytotoxicity toward the donor in patients with well-functioning kidney grafts. Possible mechanism of specifically reduced cytotoxic response.

Patients with well-functioning kidney allografts from one-HLA-haplotype--mismatched related donors have strongly reduced donor-specific cell-mediated cytotoxicity 2-10 years after having received their grafts. This could also be demonstrated in secondary in vitro cell-mediated lympholysis (CML). Even though secondary donor-specific CML did not exceed 10% at an effector-to-target cell ratio of 50:1, specific lysis of donor target cells increased significantly with increasing effector cell concentrations. The weak cytotoxicity toward the donor could be enhanced neither through pool-cell stimulation nor by adding exogenous Interleukin 2 (IL-2) during the induction phase. Furthermore, growth factors were produced in the cultures during the induction of cytotoxic cells in concentrations comparable to those of the sibling control. Thus no evidence could be obtained that lack of IL-2 was causing the decreased cytotoxicity in these patients. Our studies indicate that in vivo depletion of cytotoxic cells with high lytic efficiency is probably the reason for the strongly reduced donor-specific cytotoxicity.

Cytotoxicity, Immunologic↗
PubMed1983

HLA-DR3- and HLA-DR7-restricted T-cell hyporesponsiveness to gluten antigen: a clue to the aetiology of coeliac disease?

Coeliac disease (CD) is strongly associated with the human class-II HLA determinants HLA-DR3 and -DR7. We investigated the relative frequency of gluten-reactive T cells from DR3- or DR7-positive. CD patients and healthy controls who were heterozygous at the DR locus. We found a consistently and significantly lower frequency of gluten-reactive T cells when the antigen was presented by monocytes in conjunction with DR3 or DR7 than in conjunction with the other DR determinant of the T-cell donor. In contrast, the frequency of reactive T cells in these donors to other antigens was not reduced in conjunction with DR3 or DR7. These results indicate a specific immunoregulatory function associated with class-II HLA molecules. The reduced frequency of gluten-reactive T cells in association with HLA-DR3 or -DR7 may be directly involved in the development of CD.

Antigens↗
PubMed1983

HLA-D restriction of antigen-specific proliferative T cell responses. Inhibitory activity of antisera against HLA determinants or stimulatory antigen.

The specificity of the inhibitory activity of anti HLA-DR antisera on the proliferative response of human T cells to soluble antigens has been recently challenged. Furthermore, there are conflicting reports about the effect of antisera to the stimulatory antigen. Therefore, we investigated the inhibitory activity of different antisera on the proliferative response of T lymphocytes from sensitized donors to the antigens HSV and PPD. Alloantisera to DR specificities shared between antigen presenting cells (APC) and T cells displayed a strong inhibitory activity: alloantisera to HLA-DR specificities expressed only by APC or the T cell donor displayed lower or no inhibitory activity. Monoclonal antibodies to monomorphic determinants of HLA-DR molecules were inhibitory, but only when used at a high concentration. Antisera to HLA-ABC molecules and to HSV displayed little if any inhibition. These findings provide further evidence that the HLA-DR molecules as such in the APC membrane, which were also present during initial sensitization, are restriction elements for T cells.

Animals↗
PubMed1983

Effect of methylprednisolone on human lymphocytes primed to alloantigens.

Human lymphocytes were primed in mixed lymphocyte cultures (MLC) in the presence of the corticosteroid methylprednisolone (MP). The generation of proliferative-, cytotoxic- and suppressor cells after specific restimulation of the cultures was studied. Low doses of MP strongly inhibited the generation of secondary proliferative and cytotoxic cells. MP did not render these cells permanently unresponsive, as lymphocytes primed in the presence of MP as were still able to respond to the original stimulators in a primary fashion. In contrast, doses of MP as high as 10 micrograms/ml which are well above clinical levels, had no inhibitory effect on the induction of suppressor cells in these cultures. Our results indicate therefore, that steroids may prevent priming of specific cytotoxic and proliferative T cells, without inhibiting the induction of suppressor lymphocytes in secondary allogeneic cultures.

Cytotoxicity, Immunologic↗
PubMed1982

HLA antigens on glioma cells from short term cultures.

Biopsied tumor cells from astrocytoma-bearing patients were grown in primary culture for 3-5 days. Both low and high grade tumors were represented in the study. The cultured cells could be shown to express the HLA-A and -B antigens using a multispecific allo-antiserum and a rabbit anti-beta-2 microglobulin antibody. The tumor cells were negative for the HLA-DR determinants when tested with either a rabbit anti-Ia-like antisera or specific anti-HLA-DR allo-antisera. They also failed to stimulate allogeneic lymphocytes in primary mixed lymphocyte-tumor cell cultures but moderately stimulated autologous lymphocytes from the tumor-bearing patient in most of the combinations tested.

Astrocytoma↗
PubMed1982

Histocompatibility antigens on astrocytoma cells.

Biopsies tumour cells from astrocytoma-bearing patients were grown in primary culture for 3-5 days. Both low and high grade tumours were represented in the study. The cultured cells could be shown to express the HLA-A and -B antigens using a multispecific allo-antiserum and a rabbit anti-beta-2 microglobulin antibody. The tumour cells were negative for the HLA-DR determinants when tested with either rabbit anti-Ia-like antisera or specific anti-HLA-DR allo-antisera. They also failed to stimulate allogeneic lymphocytes in primary mixed lymphocyte-tumour cell cultures but stimulated lymphocytes primed to tumour cells in vitro. The tumour cells were also capable of stimulating autologous lymphocytes from the tumour-bearing patient in most of the combinations tested.

Astrocytoma↗