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Biomedical subjects

G Sieber

Publications and source records attributed to G Sieber.

At least 19 recordsLinked to original sources
PubMed1992

[Clinical aspects, pathophysiology, therapy and expert evaluation of splenectomy].

Splenectomy increases on principle and for life the risk to die of a foudroyant postsplenectomy infection, the so called OPSI-syndrome. The main factors determining the frequency of the OPSI-syndrome are the age at time of operation and the indication for splenectomy. Postsplenectomy infection is mostly caused by pneumococci. In general the important pathophysiological factors are a lack of filtration capacity, a decreased opsonisation activity and a deficiency of early immunoglobulin production. The increased risk of children is probably caused by a physiologically reduced immune response and a cumulation of primary infections. In the foudroyant course of postsplenectomy infection therapy is mostly taken not in time, and mortality ranges between 50 and 80%. For this reason it is necessary to stress prophylaxis as: antibiotics, vaccination, autotransplantation and preserving surgery. The effectivity and application of these prophylactic measurements are clearly limited. Therefore it is very important to inform all patients and their parents about the low, but lifelong risk of infection following splenectomy in order to begin the antibiotic therapy as soon as possible even in cases of banal infections. In expert opinion about the loss of spleen the real situation of the splenectomized individual has to be regarded in making very precise analysis of the course of disease. This has to be done in considering the branch of insurance ordering the opinion (legal accident insurance, legal pensions insurance, social compensation law, private accident or life insurance). If infections or other illness often appear after splenectomy, these have to recognized as resulting impairment, provided that other causes have been excluded. In uncomplicated course it is not justified to suppose disability only by immanent risk.

Expert Testimony↗
PubMed1989

Immunosuppressive effects of recombinant interferon-alpha during long-term treatment of cancer patients.

Interferons (IFN) are known to modulate immune responses in an either stimulatory or inhibitory manner. Most of the knowledge about immunomodulatory activities of IFN comes from investigations of IFN effects on cells in vitro. This study examines the influence which long-term treatment with recombinant interferon-alpha 2 exerts on immune functions in cancer patients. Serial in vitro immune function studies of peripheral blood mononuclear cells were done to determine parameters of B-cell and T-cell functions as well as natural killer (NK)-cell activity. The authors detected profound suppression of in vitro immunoglobulin synthesis and lymphocyte proliferation as well as depression of NK-cell activity during IFN treatment. All suppressed immune functions normalized on discontinuation of IFN therapy. The authors conclude from these observations that, apart from their beneficial effects, IFN produce substantial immunosuppression.

Drug Administration Schedule↗
PubMed1988

Abnormalities of B cell activation and immunoregulation in patients with chronic inflammatory liver diseases.

The immunoglobulin production capacities of peripheral blood lymphocytes obtained from patients with various chronic inflammatory liver diseases and from normal individuals were compared. Using a reverse hemolytic plaque assay, immunoglobulin-secreting cells (ISC) were counted immediately after isolation (immediate ISC) and again after 6-day, in vitro cultivation without stimulant (spontaneous ISC) or in the presence of pokeweed mitogen, PWM (PWM-induced ISC). An increased number of immediate ISC were observed in patients with chronic active hepatitis (CAH) of the autoimmune type (n = 7) or with CAH type B (n = 32), probably reflecting a defect of the in vivo suppressor cell system as previously demonstrated. In vitro preincubation of cells with 5 x 10(-8) M prednisolone reduced the increase in the number of immediate ISC in patients with CAH of the autoimmune type. On the other hand, lymphocytes obtained from patients with CAH-type NANB (n = 9) and with primary biliary cirrhosis (PBC) (n = 12) showed an impaired capacity to generate ISC upon stimulation with PWM. Spontaneous ISC from patients' lymphocytes were not significantly different from those of normal individuals. Using allogeneic co-cultures with lymphocytes from normal individuals and from patients with CAH NANB hepatitis or primary biliary cirrhosis, we observed no increase in suppressor cell activity. Therefore, the diminished responses to PWM are probably attributable to an alteration in the peripheral helper T-cell compartment.

Antibody Formation↗
PubMed1988

Modulation of immune functions by long-term treatment with recombinant interferon-alpha 2 in a patient with hairy-cell leukemia.

Serial in vitro immune function studies of peripheral blood mononuclear cells (PBMC) were carried out during the long-term treatment with recombinant interferon-alpha 2 (IFN-alpha 2) in a patient with hairy-cell leukemia (HCL). Parameters of B- and T-cell functions as well as NK-cell activity were determined. Treatment with IFN-alpha 2 is associated with temporary and long-term depression of some immune functions, but can also normalize immune responses: in vitro-induced immunoglobulin synthesis, which was normal at diagnosis, was inhibited during the first weeks of IFN therapy but subsequently rose to normal levels. Lymphocyte proliferative responses to mitogens and antigens that were markedly reduced pretherapeutically were further depressed by IFN treatment but, with the exception of pokeweed mitogen (PWM)-induced responses, normalized completely by the 15th to 17th week of treatment. Cocultivation of PBMC with monocytes from normal individuals enhanced depressed lymphocyte proliferative responses. NK-cell activity, which was low at diagnosis, did not rise to the normal range during IFN treatment, but rapidly normalized when IFN therapy was stopped. A discussion is presented on the implications of the alteration of immune functions by treatment with IFN.

Antibody Formation↗
PubMed1986

Chronic myelocytic leukemia as a second neoplasia in the course of chronic lymphocytic leukemia. Case report and review of the literature.

A patient with chronic lymphocytic leukemia developed Ph1-positive chronic myelocytic leukemia after a 6-yr course of CLL. Chemotherapy for CLL consisted of chlorambucil and steroids, later vincristine and bleomycin; after resistance to these agents, cyclophosphamide, vincristine and prednisolone were applied. When CML was diagnosed, we found two morphologically distinct populations of malignant cells in the bone marrow; the Ph1-chromosome was identified, and immunological surface marker studies also demonstrated two distinct malignant cell populations. Up to now, only five cases of CML have been reported following CLL and one case accompanying it. Three patients were treated with cytostatic drugs, one patient by total body irradiation and two patients received no therapy. At present, it is not clear whether the development of CML during CLL represents a therapy-induced complication or an increased susceptibility to second malignancies due to the leukemic process itself or possibly to immunological deficiencies in CLL. Since two patients received no treatment for CLL, previous therapy does not seem to be a prerequisite for the development of CML.

Aged↗
PubMed1985

Impaired B lymphocyte reactivity in patients after radiotherapy.

The effect of therapeutic irradiation upon B lymphocyte function was investigated in patients with various malignancies. The test system used was a reverse hemolytic plaque assay, which made it possible to study the activation and differentiation of B lymphocytes into immunoglobulin-secreting cells (ISC). Peripheral blood lymphocytes from normal individuals and patients before and after radiotherapy were stimulated in vitro with the polyclonal B cell activator pokeweed mitogen, and the number of ISC was estimated. B cell reactivity was markedly reduced in those patients who had received irradiation within the last six months. In patients in whom radiotherapy had been terminated more than 12 months before the lymphocytes were tested, B cell reactivity was comparable to that of patients prior to radiotherapy. By means of marker analyses, there was a reduction of B lymphocytes and T lymphocytes in the peripheral blood with a preponderance of T helper cells. Several mechanisms--e.g., reduced or defective B cell differentiation, altered regulatory T-helper or suppressor cell function or activation of suppressive monocytes--could be responsible for impaired B cell reactivity after radiotherapy.

Adult↗
PubMed1985

Abnormalities of B-cell activation and immunoregulation in splenectomized patients.

Using a reverse hemolytic plaque assay as the effector system, we studied B-lymphocyte function in 12 patients after posttraumatic splenectomy, as well as in 25 normal individuals. The time interval between the splenectomy and the immunological studies varied between 2 days and 7 years. Compared to normal individuals, the splenectomized patients had markedly elevated numbers of spontaneous immunoglobulin-secreting cells (ISC) and severely decreased responses to the polyclonal activator pokeweed mitogen. A tendency towards normalization of these abnormalities, especially the high spontaneous ISC levels, could be observed during the time interval extending up to 7 years after splenectomy. In order to characterize the mechanism responsible for the altered immune response in splenectomized patients, co-culture experiments with unseparated and separated lymphocytes were performed. These revealed an impaired T-helper cell capacity as well as an intrinsic B-cell defect. Marker analyses with monoclonal antibodies revealed normal proportions with the exception of OKT 4 positive and B 1 positive cells that identify T-helper/inducer and peripheral B-cells respectively. We conclude that immune dysfunction in peripheral blood lymphocytes of splenectomized patients involves mainly the B-cell as well as the T-helper/inducer-cell population.

Adult↗
PubMed1985

Chronic lymphocytic leukemia B-lymphocytes forming SRBC-rosettes not due to an anti-SRBC activity of monoclonal surface immunoglobulin.

A case of chronic lymphocytic leukemia is described in which large numbers of peripheral blood lymphocytes expressed immunoglobulin on their membrane and rosetted spontaneously with sheep red blood cells (SRBC) at 4 degrees C. They also showed weak staining with a heterologous antiserum against T-cells as well as with a monoclonal antibody (OKT11) with specificity for an epitope associated with the SRBC-receptor, but failed to react with other T-lineage-restricted monoclonal antibodies. The B-cell origin of the leukemic cells was documented by the presence of light-chain-restricted monoclonal surface immunoglobulin, reactivity with various monoclonal anti-B-cell reagents, presence of Ia-like antigens, their capability to synthesize intracytoplasmic immunoglobulin on exposure to phorbol ester TPA, their lack of response to T-cell mitogen PHA, and their inability to help or suppress the allogeneic B-cell response upon PWM stimulation. Extensive blocking studies with both specific antisera and Forsmann antigen-rich guinea pig kidney extracts, which did not prevent SRBC-rosetting, lend support to the hypothesis that SRBC-rosette formation in this case was not attributable to an anti-SRBC affinity of the surface immunoglobulin on the cells. This case will be discussed in relation to the recent finding of SRBC-rosette expression on some cultured chronic lymphocytic leukemia B-lymphocytes.

Aged↗
PubMed1985

[Characterization of the leukemic cell population in a patient with T-ALL at disease beginning and in recurrence: parallel changes in phenotypic and functional behavior].

The phenotypic and functional characteristics of the leukemic cells from one patient with a suppressor T-ALL were studied. At the time of diagnosis a high proportion of OKT8 positive (suppressor/cytotoxic) cells were identified which mediated strong suppressor activity to the differentiation of allogenic B-cells. A complete remission of 12 months duration was achieved by chemotherapy. In the relapse the marker analysis showed a dramatic decrease of the OKT8 positive cell fraction. Functionally the suppressor activity was completely lost indicating a close correlation between phenotype and functional activity also in a leukemic cell population.

Adult↗
PubMed1985

Coincident change of cellular function and phenotype in the course of a suppressor T cell acute lymphocytic leukaemia.

The phenotypic and functional characteristics of the leukaemic cells from one patient with T suppressor ALL were studied at the time of diagnosis and in relapse. At the time of diagnosis, the phenotype corresponded to the intermediate stage between the cortical and medullary phases of normal thymocyte differentiation with a high proportion of T8+ cells (E-R+, TdT+, C3bR-, T3-, T4-, T6+, T8++, T10+). Functionally, the cells did not respond to mitogens but mediated strong suppressor activity to allogeneic B-cells, as measured in a reversely haemolytic plaque test. Clinically, the patient exhibited the uncommon feature of hypogammaglobulinaemia. Induction therapy led to complete remission, which continued for 12 months. In the relapse, the phenotype remained essentially stable except for a dramatic decrease of the T8+ cell fraction and an increase of the T10+ cell fraction. Functionally, the suppressor activity was completely lost, indicating a close correlation between phenotype and functional activity in this leukaemic cell population.

Adult↗
PubMed1979

Activation of human lymphocyte subpopulations by protein A from Staphylococcus aureus bacteria.

Cowan I strain Staphylococcus aureus bacteria were found to be mitogenic for human peripheral and cord blood lymphocytes. Experiments with lymphocyte supopulations otained by nylon wool filtration and/or E-rosette separation revealed that T-lymphocytes are the main target cells, whereas isolated B cells did not respond significantly. Further experiments suggested that B cells could be activated in the presence of mitomycin-treated T cells. Null cell-enriched lymphocyte suspensions could be stimulated by Con A but not by the bacteria or by PHA.

B-Lymphocytes↗