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Biomedical subjects

H H Peter

Publications and source records attributed to H H Peter.

At least 271 records · Page 15Linked to original sources
PubMed1985

Relationship between intensity of infection and immunomodulation in human schistosomiasis. I. Lymphocyte subpopulations and specific antibody responses.

Cellular and humoral immune responsiveness in 44 Sudanese children with schistosomiasis was studied and related to the intensity of infection. The parasite load was quantitated by accurate assessment of the excretion of ova of S. mansoni and S. haematobium in stool and urine, respectively. Lymphocyte subpopulations (T3+, T4+, T8+, TAC+, HNK1+, Ia+, SIg+, LGL+, ANAE+) as well as specific IgE and IgG antibodies to adult schistosome antigens were determined. The relationships existing between intensity of infection and cellular and humoral immune responsiveness revealed a distinct pattern of anti-parasite immunity: The percentage of pan-T cells (T3+) and the T helper (T4+):T suppressor (T8+) ratio were inversely correlated to the intensity of infection. In contrast, the percentage of T suppressor cells positively correlated to the parasite load. Ia+, TAC+, HNK1+ and T4+ cell counts did not show a significant relationship to worm burden. Specific IgE and IgG antibodies to S. mansoni and S. haematobium adult worm antigen clearly increased with the parasite load. The dichotomy of decreased T cell parameters and increased antibody response in heavily infected individuals represents a unique feature in helminthic infections.

Antibody Formation↗
PubMed1985

Relationship between intensity of infection and immunomodulation in human schistosomiasis. II. NK cell activity and in vitro lymphocyte proliferation.

Natural killer (NK) cell activity against K-562 targets and lymphoproliferative responses to Con A, interleukin-2 (IL-2) and Con A + IL-2 were examined in a group of 41 Sudanese children suffering from schistosomiasis mansoni and haematobium. The results were correlated to the intensity of infection as determined by enumeration of parasite ova in urine and stool. NK cell activity measured at three effector to target cell ratios was significantly depressed in the patient group as compared to a German control group. Impairment of NK cell activity showed a direct relationship with the patients' parasite load. Furthermore lymphoproliferation to Con A, IL-2 and Con A + IL-2 was depressed in the group of patients. Interestingly the costimulation effect of IL-2 expressed as coefficient of delta ct/min(Con A + IL-2)/delta ct/minCon A correlated significantly to the intensity of infection suggesting that lymphocytes from heavily infected patients were defective in producing appropriate amounts of IL-2 in response to Con A. Our findings support the concept that heavy infections with S. mansoni and/or S. haematobium induce a peculiar dichotomy of cellular and humoral immune parameters. Whereas T cell-dependent cellular immune responsiveness and NK cell function decrease with increasing worm burden specific IgE and IgG antibody responses increase.

Cells, Cultured↗
PubMed1984

Immunoreconstitution in severe combined immunodeficiency after transplantation of HLA-haploidentical, T-cell-depleted bone marrow.

Immunological reconstitution by transplantation of HLA-haploidentical, paternal bone marrow was attempted in four infants with severe combined immunodeficiency who lacked HLA-identical donors. To prevent graft-versus-host disease, T lymphocytes were removed from the grafts by agglutination with soybean agglutinin and rosette formation with sheep red blood cells. None of the patients received conditioning treatment before transplantation. Normal, donor-derived cellular immune functions developed in all four patients within several months of transplantation. Threatening complications of graft-versus-host reactions were not seen. All four patients remain in excellent health 12-15 months after discharge home, with persisting normal T-cell functions.

Bone Marrow↗
PubMed1984

Sézary syndrome with hyposplenism.

Phenotypic, functional and clinical analysis of two patients with Sezary Syndrome are presented. Both patients had an elevated lymphocyte count with the helper/inducer cell phenotype by analysis with monoclonal antibodies (OKT3+, T4+, T6-, T8-, M1-), had the characteristic cerebriform nucleus of Sezary cells, and were Fc-IgG receptor negative. The functional tests revealed no proliferative, cytotoxic or immunoregulatory activity of patient E.P.'s leukemic cells, while the lymphocytes of patient A.N. responded to mitogen stimulation and had helper cell capacity in pokeweed mitogen driven B cell differentiation and maturation. Both patients presented skin involvement, pruritus, hepatomegaly and patient E.P. showed generalized lymphadenopathy. The spleen size of patient A.N. was below the normal range with an estimated spleen weight of approximately 160 g (normal 180-229 g). Patient E.P. had an extremely small spleen size with an estimated weight of approximately 20 g as shown by abdominal sonography and spleen scintigraphy and had Howell-Jolly bodies within the erythrocytes. The size of the spleen in various other diseases with T cell proliferations is discussed with respect to the possible proliferative centers of the various T-cell subpopulations.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1984

Analysis of T-cell cultures and clones from a patient with classic rheumatoid arthritis--evidence for the existence of autoreactive T-cell clones in blood and synovial fluid.

Using lectin-free IL-2 as the only initial stimulus, bulk cultures and T-cell clones were established from synovial fluid (SFL) and peripheral blood lymphocytes (PBL) of a patient with rheumatoid arthritis (RA). The cloning efficiency of growing bulk cultures was 3%-4% as evaluated by Poisson statistics and was not enhanced by the addition of autologous synovial fluid or serum. The majority of the cloned T cells expressed the OKT8+ phenotype; several clones were OKT4+ and one clone expressed OKT8+ and OKT4+ antigens. None of the cloned T cells exhibited high NK or lectin-dependent cytotoxicity, although bulk cultures had high NK activity. In primed lymphocyte typing responses, bulk cultures and two T-cell clones established from rheumatoid SFL and PBL showed consistent autoreactivity, which we have never before observed with MLC-derived bulk cultures and T cell clones. One of the autoreactive rheumatoid T-cell clones (B25) was found to provide strong helper activity to autologous B cells in the absence of mitogen. Attempts to reveal reactivity of RA-derived T-cell clones to microbial antigens have so far only been successful with Mycoplasma pneumoniae preparations. Careful analysis of this reactivity revealed, however, that Mycoplasma pneumoniae induces a stimulator cell-dependent mitogenic effect rather than an antigen-specific MHC-restricted T-cell proliferation.

Antigens, Bacterial↗
PubMed1984

The effect of BM 12.531 (azimexon) on natural killer cell activity in myeloma patients.

The 2-cyanaziridin derivative, azimexon (E), has previously been shown to have certain immunomodulatory properties. In particular, the induction of leukocytosis, the stimulation of delayed-type hypersensitivity reactions and the synergistic effect of azimexon and antibiotics in the control of lethal bacterial and fungal infections in mice prompted us to test azimexon as an adjuvant to chemotherapy in 14 myeloma patients. In a randomized double-blind cross-over study 3 X 600 mg of azimexon were added to one of two consecutive, identical chemotherapy courses consisting of melphalan/prednisone (MP) or vincristine/cyclophosphamide/melphalan/prednisone (VCMP). Chemotherapy was given during days 1-4 and azimexon or placebo were added on days 6, 10 and 14. Blood counts and natural killer (NK) cell testing were performed on days 0 and 21 of each course. With the exception of a transient taste irritation in two patients, azimexon caused no subjective side-effects. White blood cell counts were not altered by the drug; red blood cells and hemoglobin showed a borderline depression after azimexon. NK activities measured against three target cell lines (K562, IGR3, L1210) tended to increase after azimexon treatment. When added in vitro to NK assays azimexon caused a slight increase of NK activity at concentrations of 0.01-0.25 mu/ml, whereas concentrations above 1 microgram/ml were inhibitory. The increase of NK activity by azimexon was not due to the induction of interferon in the effector lymphocyte population.

Adjuvants, Immunologic↗
PubMed1984

Comparison of the inhibitory activity of seven anti-T8 antibodies on specific cellular cytotoxicity.

To evaluate the functional significance of the T-cell membrane structure recognized by OKT8 or Leu2a, seven different monoclonal antibodies, reacting with different epitopes of this 76 KD big membrane structure, were evaluated for their ability to alter specific cell mediated lympholysis after a mixed leukocyte reaction. The stimulated effector cells were first incubated with a monoclonal antibody, washed and then tested for their cytotoxicity. Those antibodies, which react with a highly trypsin-sensitive region of the T8 glycoprotein, were the most effective inhibitors of the cytotoxicity (T811, FK18). Those antibodies, which react with a relative trypsin-resistant region (OKT8, Leu2a, WT82, WT85) or with a trypsin-sensitive epitope (WT81), which is in a close neighborhood to WT82 or WT85, appear to be able to block the cytotoxicity only in certain effector/target cell combinations. The data suggest that different regions of the T8 glycoprotein are involved in the specific cytotoxic reactions, and that the involvement of certain epitopes may depend on the effector/target cell combination.

Antibodies, Monoclonal↗
PubMed1984

Interleukin-1-like activity constitutively generated by Hodgkin derived cell lines. I. Measurement in a human lymphocyte co-stimulator assay.

Culture supernatants (CS) from Hodgkin derived cell lines have previously been shown to contain colony stimulating activity (CSF) for human cord blood cells, fetal bone marrow and fetal liver cells. In this study 3-day CS from four Hodgkin lines (L428, L538, L540, L591) and two sublines (L428KS, L428KSA) were examined for interleukin (IL) activity. None of the tested CS supported the growth of an IL-2 dependent murine T-cell line, suggesting that the Hodgkin lines do not produce significant amounts of IL-2. When crude 3-day CS from the various lines were assayed for IL-1-activity in the conventional murine thymocyte costimulator assay no or only borderline IL-1-activity was detectable. However, concentrated CS from L428KS exhibited IL-1-activity also in this assay as did lipopolysaccharide (LPS) induced human IL-1. Surprisingly, crude 3-day CS from all Hodgkin cell lines were capable of fully replacing the accessory cell requirement in ConA-induced lymphoproliferation assays of heavily monocyte-depleted human blood lymphocytes. The monocyte-depleted lymphocyte populations were obtained by 1 X g sedimentation at a sedimentation rate of 30.2 to 38.8 mm/hr (fraction IIIa and IIIb). These cells responded poorly to the T-cell mitogen ConA at 10 micrograms/ml and produced no IL-2. Addition of irradiated, autologous monocytes or of CS from the various Hodgkin cell lines quantitatively restored the ConA responsiveness and induced significant IL-2 production in the monocyte-depleted lymphocyte population, suggesting that Hodgkin lines constitutively secrete IL-1 or IL-1-like activity. A preliminary biochemical characterization (heat and pH stability, molecular weight range of 13-24 KD) supports the notion that the accessory cell replacing activity present in CS of Hodgkin cell lines is a type of human IL-1.

Animals↗
PubMed1984

In vivo effects of interleukin 2 on lymphocyte subpopulations in a patient with a combined immunodeficiency.

This report describes a clinical trial with Interleukin 2 (IL-2) on a 17-month old male child with combined immunodeficiency (Nezelof's syndrome). IL-2 was prepared from conditioned media of phytohemagglutinin-stimulated leukocytes from buffy coats. The purification of IL-2 involved chromatography on Matrex Blue A sepharose and gel filtration chromatography. The preparation was free of macrophage cytotoxicity factor, macrophage migration inhibition factor and colony-stimulating factor. It contained negligible activity of interferon-gamma. IL-2 activity was adjusted to 1600 U/ml, which corresponds to about 0.8 micrograms homogeneous IL-2/ml. The patient was treated over a 50-day period with a total dose of 20,000 U IL-2, which was injected subcutaneously. IL-2 was well tolerated. Within 3 weeks, the treatment led to a normalization of a lymphocytosis which had prevailed for the previous 3 months. A pronounced eosinophilia also improved but did not reach normal levels. The most striking effect was a normalization of the OKT4+/OKT8+ ratio with a concomitant relative increase in OKT3+ cells in the peripheral blood. No effects were seen on E rosette formation, B cell counts or serum Ig levels. Also NK or ADCC activity remained high, as before the treatment. Infectious episodes and requirement for antibiotic treatment were less frequent during IL-2 therapy. Some effects of IL-2 were transient, e.g., the counts of OKT4+ and OKT3+ cells which returned to pathological values a few weeks after the treatment was discontinued.

Humans↗
PubMed1984

Numerical and functional alterations of lymphocytes in human schistosomiasis.

Peripheral blood mononuclear cells from 29 Sudanese children heavily infected with Schistosoma haematobium and S. mansoni were examined for lymphocyte subpopulations, for mitogen responsiveness in the absence and presence of interleukin-2 (IL-2), and for natural killer (NK) cell activity. The nutritional status was assessed by anthropometric and biochemical measurements. In comparison with a group of healthy Caucasian individuals the children with schistosomiasis showed a profound alteration of their cellular immune variables, reflecting a severe acquired immunodeficiency syndrome. The T-cell compartment, in particular the OKT4+ helper/inducer subset, was numerically reduced at the expense of an increased B-cell compartment. The patients' OKT4/OKT8 ratios were significantly diminished (median, 1.2; 95% confidence limits, 0.8-1.7) corresponding to a decreased responsiveness to the T-cell mitogen concanavalin A. Since addition of exogeneous IL-2 significantly enhanced the patients' lymphocyte proliferation in response to Con A, a defective IL-2 production was assumed to be at the origin of the impaired mitogenic response in chronic schistosomiasis. With regard to NK cell activity, most patients' lymphocytes failed to mediate significant cytotoxicity against the K562 target cell line, although normal percentages of cells with the NK phenotype (HNK-1+) were present. The results are discussed in view of immunological alterations seen in other parasitic infections with a heavy parasitic load.

Child↗
PubMed1984

[Lymphokine production in vitro by blood lymphocytes from patients with a defective or hyperactive immune system].

Blood lymphocytes from 8 patients with common variable immunodeficiency (CVID), 5 patients with signs of polyclonal activation of the immune system (1 SLE, 3 AILAP, 1 NHL) and 6 patients with various granulomatous diseases were examined for their capacity to produce lymphokines in vitro. Lymphocytes from 16 healthy individuals served as controls. To induce interleukin-2 (IL-2) and gamma-interferon (gamma-IFN) production lymphocytes were stimulated for 24 hrs with ConA or PHA or for 72 hrs with ConA + PMA + urea. alpha-IFN production was induced with Herpes simplex virus I (HSV) and the mycoplasma infected murine leukemia line L1210. Cell-free culture supernatants were harvested and IL-2 activity was determined by means of its growth promoting activity for a murine T-cell line (M-2). IFN activities were measured in a conventional virus plaque reduction assay. Besides lymphokine production the isolated cells were also examined for lymphocyte markers, mitogen responsiveness and NK activity. As compared to the control group, CVID lymphocytes exhibited a slightly enhanced IFN production and a moderately reduced IL-2 production. Three day preincubation in FCS containing medium enhanced the IL-2 production of control and patient lymphocytes. By contrast, preincubation of lymphocytes in medium supplemented with autologous serum no longer enhanced IL-2 production of CVID lymphocytes whereas it still did so for control lymphocytes. A striking finding was the impairment of IL-2 and IFN production in cultures of lymphocytes from patients with a polyclonally activated immune system. Notably lymphocytes from the three patients with angioimmunoblastic lymphadenopathy (AILAP) failed to produce significant amounts of lymphokines. Patients with granulomatous diseases (3 Morbus Behçet, 1 tuberculosis, 2 chronic granulomatous diseases) showed little alterations of their lymphokine production capacity. The results are compared with other lymphocyte parameters and are discussed in view of recent reports in the literature on lymphokine production in various diseases.

Adult↗
PubMed1984

[Terminal B-cell maturation and immunoglobulin synthesis in vitro in primary and secondary immune deficiencies].

Peripheral blood lymphocytes (PBL) from patients with various forms of primary and secondary immunodeficiencies and from 30 healthy control persons were examined for their capacity to show terminal B-cell maturation and immunoglobulin (Ig) synthesis in vitro following pokeweed mitogen (PWM) stimulation. PBL were cultured for 9 days with or without PWM and the percentages of B-cells or plasma cells with strongly positive cytoplasmic Ig (CIg+) were determined by indirect immunofluorescence on methanol fixed cytocentrifuged lymphocyte smears. In addition, newly synthesized IgA, IgG and IgM was measured in the cell free culture supernatant by means of a sensitive microplate ELISA. In 29 out of 30 control cultures the proportion of CIg+-cells increased markedly following 9-day stimulation with PWM. CIg+-cells and newly synthesized Ig were significantly correlated. In a group of 18 patients with common variable immunodeficiency (CVID) maturation to CIg+-cells was greatly impaired and the in vitro production of IgA and IgG was reduced. Two infants with severe combined immunodeficiency (SCID) failed to produce Ig prior to and following haplo-identical bone marrow transplantation despite the presence of immature B-cells. A heterogeneous group of secondary immunodeficiencies showed different forms of an impaired terminal B-cell maturation and a reduced capacity to synthesize Ig in vitro. The described PWM culture techniques in combination with the evaluation of CIg+-cells and the measurement of newly synthesized Ig in the culture supernatant proved to be a reliable in vitro correlate for terminal B-cell maturation and represent an important tool for the classification of humoral immunodeficiencies.

Adolescent↗
PubMed1984

[Melanoma metastasis in the neck region with unknown primary tumor].

In 4-8% of all melanoma patients, a lymph node metastasis develops as the first manifestation of the disease, whereas a primary lesion cannot be found. The latter may have been surgically removed already years ago, may be located at an occult place or - as it is especially characteristic for melanoma - may have vanished spontaneously due to a specific immunological mechanism. Such spontaneous tumour regression, which, for instance, becomes recognisable by the development of a halonaevus or an asymmetrical vitiligo, does not imply an improvement of the individual prognosis. However, present knowledge suggests that in patients with unknown primary lesion neither an adjuvant chemotherapy nor immunotherapy can be recommended, if the metastasis has been surgically removed completely. Additional radiotherapy does also not appear to be indicated. Only a short-interval follow-up remains important.

Adolescent↗
PubMed1983

[Iron chelation. Biological significance and medical application].

Iron, an essential element for all aerobic organisms, exists in a very insoluble form under physiological conditions. Therefore, most microorganisms secrete iron chelating compounds called siderophores which are able to sequester ferric ions from the environment. A vast number of such compounds has been isolated from cultures of microorganisms and tested for enhancement of iron excretion in experimental animals. Only one compound, deferrioxamine B, has been shown to be clinically effective and well tolerated in humans suffering from chronic iron overload. However, this drug can only be administered successfully by injection or slow infusion. In spite of considerable research it has not been possible to overcome this drawback by developing suitable formulations or derivatives which are orally active. Deferri-ferrithiocin, a novel type of siderophore, has recently been isolated from a streptomyces culture. This substance is well absorbed orally and has been shown to enhance the excretion of ferric ion in iron loaded rats. Further investigations are now necessary to establish acute toxicity levels and longterm tolerability before efficacy tests in man can be planned. Other recent developments in the field of metal chelation include experimental studies using deferrioxamine for the treatment of conditions resulting from toxic levels of iron or aluminium in chronically dialyzed patients. In addition, attempts are being made to administer chelation therapy in the treatment of various infections and chronic inflammation, as well as other conditions linked with disorders of iron metabolism.

Animals↗
PubMed1983

NK cell function in severe combined immunodeficiency (SCID): evidence of a common T and NK cell defect in some but not all SCID patients.

The immunologic work-up of eight infants with the clinical diagnosis of severe combined immunodeficiency (SCID) was performed with special emphasis on natural killer (NK) cell function and ontogeny. Contrary to previous reports, our study shows that not all SCID patients lack NK activity; some may even express very high NK- and antibody-dependent cellular cytotoxicity (ADCC). The present group of eight SCID infants was homogeneous with respect to normal levels of the purine metabolism enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP). They all had low serum Ig levels and were defective for specific antibody formation against BSA and diphtheria toxin (DiT). None of the infants' peripheral blood mononuclear cells (PBMC) proliferated significantly upon in vitro stimulation with PHA, concanavalin A (Con A), pokeweed mitogen (PWM), and irradiated allogeneic lymphocytes. Seven of eight patients, however, responded significantly to mitogenic factors present in a lectin-free interleukin 2 (IL 2) preparation, and two exhibited a positive costimulation as well with simultaneous exposure to IL 2 + Con A. The lymphocyte marker analysis revealed high percentages of OKT10+ cells in seven of eight infants, whereas peripheral T cells (OKT3+) with suppressor/killer (OKT8+) or helper/inducer (OKT4+) phenotypes were abnormally low in all infants with one exception. The PBMC of two patients formed low to normal percentages of E rosettes but expressed no B cell markers (B-/SCID). The six other infants had high percentages of B cells (B+/SCID) but lacked E rosette-forming cells. High NK and ADCC activity was found in the two B-/SCID patients. The B+/SCID infants either totally lacked NK and ADCC function (four of six) or expressed low to normal NK activity together with some T cell markers as revealed by monoclonal antibody staining but not by E rosette formation (two of six). From the data presented, an ontogenic model is proposed that assumes the status of an independent cell lineage in between T cells and monocytes for human NK cells, or that places these cells in close proximity to early differentiation steps of the T cell lineage. In any case, NK cell function clearly constitutes an additional parameter of heterogeneity in the immunologic analysis of SCID.

Adenosine Deaminase↗