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Biomedical subjects

H H Peter

Publications and source records attributed to H H Peter.

At least 307 records · Page 17Linked to original sources

Studies of the producer cell of interferon in human lymphocyte cultures.

The producer cells of interferon were studied in human leucocyte cultures stimulated by a variety of stimulants, including phytohemagglutinin (PHA), pokeweed mitogen (PWM), Corynebacterium parvum (CP) and Herpes Simplex Virus (HSV). When the cells were fractionated by the use of neuraminidase-treated sheep red blood cells (SRBC), the T cell population responded with interferon production to PHA and PWM but not to CP or HSV. However, the non-T population showed a vigorous response to the latter two stimuli. In contrast, nylon column eluate cells enriched for T cells responded well to CP and HSV with production of interferon. To resolve these contradictory data, we have used combinations of techniques. Nylon column eluate cells were further separated by SRBC and it was found that the nylon non-adherent rosetting cell did not produce interferon in response to HSV or CP whereas the nylon-nonadherent non-rosetting cell did. In additional experiments more elaborate techniques were used. Leucocytes were treated by plastic adherence and iron filings, passed over a nylon column and subsequently over an Ig-anti-Ig column, and then rosetted with SRBC. Again only the non-rosetting population produced interferon. In parallel experiments the capacity of the different cell populations to lyse three types of target cells in a chromium release assay as a test for "natural killer" (NK) cell activity was investigated. There was some correlation between interferon production and NK cell activity. Thus, our data indicate that interferon is produced by non-T, non-B cells, possibly by cells related to NK cells.

Cells, Cultured↗

[Effector function of acute leukemias in "spontaneous" (SCMC) and antibody dependent cellular cytotoxicity-tests (ADCC) (author's transl)].

Blood lymphocytes from 13 untreated acute leukemia patients, 3 pre-leukemias 3 immunoblastic lymphadenopathias and one infectious mononucleosis showed significantly lower spontaneous (SCMC) and antibody-dependent cellular cytotoxicity (ADCC) against 51Cr-labeled allogeneic melanoma cells of the IGR3 cell line than effector lymphocytes from 20 age- and sex matched control persons. While control lymphocytes exhibited the highest cytotoxic activity after depletion of mononuclear phagocytes (Fraction FFF), followed by the "Ficoll" purified Fraction F and defibrinated whole blood, the reverse was true for acute leukemias: here, the highest cytotoxicity was found in whole blood followed by the lymphocyte fractions F and FFF. Comparatively high cytotoxicity was found with two leukemia patients who had received blood transfusions the day before testing. During the course of an acute erythroleukemia chemotherapy drastically reduced SCMC and ADCC activities. A therapeutical splenectomy, on the other hand, did not affect cellular cytotoxicity in the case of a hairy cell leukemia. The angioimmunoblastic lymphadenopathies showed strikingly high percentages of EA- and EAC-rosettes forming cells and showed a marked increase of SCMC and ADCC activities after elimination of mononuclear phagocytes from the effector cell population.

Acute Disease↗

[Imprint cytology of axillary lymph nodes in breast neoplasms for intraoperative rapid diagnosis].

A total of 385 lymph nodes of patients suffering from breast cancer were examined intraoperatively for the presence of metastases. We applied imprint cytology and stained using the "Diff-Quick" set (3 times 30 seconds). The percentage of correct identifications following instant cytological examination amounted to 94.5 if compared with subsequent paraffin histology. The 21 diagnostic failures were composed of 3 false negative and 18 false positive results. These data make the advantages for routine clinical application quite obvious.

Axilla↗

Immunological and functional characteristics of peripheral blood and synovial fluid lymphocytes from patients with rheumatoid arthritis.

Spontaneous (SCMC) and antibody dependent cellular cytotoxicity (ADCC); mitogenic responsiveness (PHA, Con A, PPD, dextran and pokeweed) as well as lymphocyte subpopulations (E-, EA-, EAC-rosettes, S-Ig) were studied simultaneously in peripheral blood (PBL) and synovial fluid lymphocytes (SFL) of fifteen patients with rheumatoid arthritis. Marked differences were observed in the cytotoxic activity of SFL and PBL. Whereas SCMC activity of SFL was always significantly elevated above the cytotoxic levels of PBL, the reverse was true for the ADCC reaction; here, 50% of the patients showed a decreased cytotoxicity of SFL compared to PBL. Synovial fluid neutrophils (SFN) were found to be inactive in both cytotoxic assays. No differences were found in ADCC activity of PBL between normal controls and RA patients. In SCMC assays a significantly increased activity of control PBL was only observed at L/T ratios of 100:1. Overnight incubation of PBL from RA patients and normal controls resulted in a marked decrease in SCMC and, to a smaller extent, in ADCC activity. SFL from three out of four patients lost less SCMC activity after overnight incubation than the corresponding PBL. In one patient even an increased activity in both cytotoxic systems was obtained. Regarding lymphocyte populations, T-cells were significantly decreased in PBL of RA patients. With the exception of a significantly lowered percentage of C3 receptor positive cells in SFL, no significant differences were recorded in the lymphocyte distribution between the patients' PBL and SFL. In the RA patients, the response to T-cell mitogens was significantly depressed in SFL while PPD and pokeweed reactivity was equal to that of PBL.

Adult↗

Influence of continuous-flow blood separator leucophoresis on in vitro functions of human lymphocytes.

The influence of continuous-flow blood separator leucophoresis on these in vitro functions of human lymphocytes was studied. In ten separation experiments, lymphocyte functions were examined in the presence and absence of mononuclear phagocytes before, during and at the end of continuous flow leucophoresis. Cell surface markers and effector functions in spontaneous cell-mediated cytotoxicity (SCMC) and antibody-dependent cellular cytotoxicity (ADCC) assays did not change significantly under the conditions of leucophoresis. By contrast, separator lymphocytes exhibited a significantly increased mitogenic response to pokeweed mitogen and PPD. Removal of mononuclear phagocytes corrected for this phenomenon. PHA and Con A responses were not affected by leucophoresis, nor was the number of circulating haemopoietic stem cells (CFU-C) significantly altered during a 4 hr continuous flow blood separator run.

Antibody-Dependent Cell Cytotoxicity↗

IgG4 subclass in malignant melanoma.

Three hundred and ninety-seven sera from 185 melanoma patients were studied. These sera were classified into three groups according to stage of disease. An alteration in the level of the IgG4 subclass was found. It was related to the dissemination of disease. The percentage of abnormalities (either increased or decreased levels of IgG4) was more frequent in patients with stage II and III diseases (55 and 53%, respectively) than in patients with stage I(19%). The higher frequencies of high titers of IgG4 were essentially detected in advanced disease. The biologic significance of the increase of IgG4 in melanoma remains obscure. The increase may be related to the development of facilitating antibodies of the IgG4 subclass.

Female↗

Inhibition of spontaneous and antibody-dependent cellular cytotoxicity by sera and isolated antiglobulin preparations from rheumatoid arthritis patients.

Using sera from patients with rheumatoid arthritis and antiglobulin preparations obtained from such sera, inhibition of human lymphocyte cytotoxicity in antibody-dependent (ADCC) and spontaneous cell-mediated cytotoxicity (SCMC) reactions against an allogeneic melanoma cell line (IGR3) has been demonstrated. Fractionation of effector cell preparations indicated that Fc-receptor-bearing lymphocytes were operative in both reactions. Removal of phagocytic and adherent cells from the effector cell population resulted in more pronounced inhibition of SCMC and ADCC reactions by rheumatoid sera. The results indicate that antiglobulin preparations from human sera containing rheumatoid factor activity can effectively block the cytotoxic activity of Fc-receptor-bearing effector lymphocytes (K cells) in vitro. On analogy with the inhibition of ADCC and SCMC reactions by immune complexes and aggregated IgG, antiglobulin complexes present in the antiglobulin preparations are responsible for this effect.

Adult↗

Human peripheral blood "null-lymphocytes", a highly enriched pool for granulocytic stem cells (CFU-C).

A "Null"-lymphocyte preparation containing a high concentration of granulocytic stem cells (CFU-C) was isolated from human peripheral blood. 3 lymphocyte purification procedures were shown to produce an enrichment of CFU-C: 1. Removal of mononuclear phagocytes by iron phagocytosis and plastic adherence procedures. 2. Passage through Ig anti-Ig columns. 3. Removal of E-rosette-forming T cells. A combination of all 3 purification steps resulted in a 30- to 40-fold enrichment of CFU-C in the final "Null"-lymphocyte population as compared to the initial lymphocyte fraction isolated by Ficoll-Urografin density gradient centrifugation.

Animals↗

Estimation of T- and K-cell activity in the peripheral blood of sarcoidosis patients.

Depressed ADCC activity was found in sarcoidosis patients in clinical Stage II when whole blood was used as the effector cell pool. Whole blood in Stage I patients as well as purified peripheral lymphocytes of sarcoidosis patients did not reveal a diminished cytotoxic activity. Stimulation experiments with PHA, Con A, and PPD in two different concentrations resulted in a normal PHA response, a significantly decreased Con A response (regardless of the clinical stage of the patients), and a significantly decreased PPD responsiveness of peripheral lymphocytes in Stage II patients, respectively. Regarding the distribution of peripheral B and T lymphocytes, only a significantly depressed T-cell number in Stage I sarcoidosis patients was observed. Peripheral cells forming EA and EAC rosettes and staining for membrane-bound immunoglobulins were within normal ranges. Serum antibody titers to different herpes viruses, including Epstein-Barr virus, were found not to be elevated. Twenty percent of sarcoidosis patients showed anti-immunoglobulins in their sera specific for the Fc and Fab fragment.

Adult↗

Antibody-dependent cellular cytotoxicity and B-and T-cell activity in the peripheral blood of myasthenia gravis patients.

Antibody-dependent cellular cytotoxicity (ADCC) was found to be significantly decreased in whole blood as well as in purified lymphocyte preparations from myasthenia gravis patients. Decreased ADCC was found not to correlate with the clinical classification nor with the therapy regimen, including immunosuppressive agents. PHA, Con A, and PPD responsiveness of peripheral blood lymphocytes was normal. Likewise no significant decrease was observed in the T-and B-cell distribution in the peripheral blood.

Adult↗

Spontaneous cytotoxicity (SCMC) of normal human lymphocytes against a human melanoma cell line: a phenomenon due to a lymphotoxin-like mediator.

Spontaneous cell-mediated cytotoxicity (SCMC) of normal human lymphocytes against various allogenic tumor cell lines has recently been identified as a non-T lymphocyte function. In this study evidence is presented that SCMC against a human melanoma cell line (IGR3) involves a nonspecific lymphotoxin-like mediator(s) (LT), which is rapidly produced by lymphocytes that are retained on IgG-anti-IgG columns. LT was shown to inhibit in 48-hr cultures the DNA synthesis of growing IGR3 and HeLa cell monolayers. Furthermore, in short term 51Cr-release assays using IGR3 target cells, LT increased strongly the SCMC of normal allogeneic lymphocytes, although it exhibited little cytotoxicity by itself in this assay. LT was detectable in cell-free supernatants harvested after 6 hr from co-cultures of IGR3 melanoma cells and normal effector lymphocytes, but not in supernatants from melanoma cells alone or lymphocytes alone. Lymphocyte preparations that had been passed through IgG-anti-IgG columns had lost the capacity to generate LT and were poor effectors in SCMC. However, in the presence of LT, a small proportion of null cells, which pass through IgG-anti-IgG columns, was capable of inducing strong SCMC. Absorption of the supernatants, containing LT activity, with an insolubilized rabbit-anti-human IgG antiserum did not remove the mediator, suggesting that it is not an immunoglobulin.

Antibody Specificity↗

Spontaneous and antibody-dependent cellular cytotoxicity in melanoma patients and healthy control presons.

Spontaneous cell-mediated cytotoxicity (SCMC) and antibody-dependent cellular cytotoxicity (ADCC) against 51Cr labeled allogeneic target cells of a human melanoma cell line (IGR3) were determined with purified effector lymphocytes and defibrinated whole blood from 14 melanoma patients and 13 healthy control persons. Peripheral blood lymphocytes were isolated by Ficoll gradient centrifugation (fraction F); subsequently the phagocytic and adherent cells were removed and the supernating cell population (fraction fff) was passaged through IgG anti-IgG columns to obtain a B cell free lymphocyte suspension (fraction fff-c). cells from the 3 lymphocyte fractions and from defibrinated whole blood were simultaneously tested for cytotoxic activity against unsensitized IGR3 target cells (SCMC assay) and IGR3 cells perviously sensitized with a rabbit anti-melanoma IgG (ADCC assay). Dose-response curves were established with all lymphocyte fractions and with whole blood. The following results were obtained. 1. With all lymphocyte fractions tested, ADCC was approximately 15 time higher than SCMC, whereas with whole blood, the difference tended to be less pronounced. 2. Elimination of phagoctic and adherent cells had no significant effect on SCMC and ADCC. 3. Passage over IgG anti-IgG columns drastically reduced cytotoxicity in both assays without, however, completely abolishing it. 4. The only difference seen between lymphocyte cytotoxicity of melanoma patients and control persons was a slight, but non-significant depression of SCMC and ADCC in melanoma patients. The results confirm and extend our previous report that SCMC against an allogeneic tumor cell-line is due to not-specific "Null" or "K" cell-activity rather than to specific T cell cytotoxicity. In one experiment freshly explanted melanoma cells were labeled with 51Cr and reacted wiht autologous blood and purified lymphocyte fractions. It was found that cellular cytotoxicity depending on serum factors (ADCC) was an effective lytic mechanism, whereas T cell-mediated cytotoxicity could not be demonstrated.

Adult↗

Gm(1) and Gm(2) immunoglobulin allotypes in patients with malignant melanoma.

Gm allotype markers were determined in sera from 71 melanoma patients and 400 control persons. There was no significant difference between both groups in Gm distribution. The results were compared to a recent report. Furthermore, in 25 malanoma patients the capacity of serum to interfere with cell-mediated cytotoxicity (CMC) of autologous lymphocytes was determined and related to the Gm allotype.

Cell Line↗