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Biomedical subjects

C Huber

Publications and source records attributed to C Huber.

At least 271 records · Page 15Linked to original sources
PubMed1989

Acute effects of single doses of recombinant interferon-gamma on blood cell counts and lymphocyte subsets in patients with advanced renal cell cancer.

The object of this study was to investigate the effects of different single doses of recombinant interferon-gamma (rIFN-gamma) on white blood cell counts, differential blood counts, and the relative composition of T-cell subsets in the peripheral blood of cancer patients. Sixteen patients suffering from metastasizing renal cell carcinoma received 10, 100, or 500 micrograms of rIFN-gamma three times at weekly intervals. After a therapy-free interval of 2 weeks, the next dose level was applied. The order of dose levels was assigned randomly to each patient. White blood cells, differential blood counts, and the number of Leu1, Leu3, Leu2a, Leu7, and HLA DR+ cells were measured immediately before and at 4, 24, 48, 72, 96, and 168 h after the administration of single doses of rIFN-gamma. Results indicated that white blood cells were transiently removed from the blood circulation after administration of IFN-gamma. Monocytes, HLA DR+ cells, and Leu7+ cells were reduced to below 50% of pretreatment values 4 h after application of the cytokine. CD8+ cells and granulocyte counts declined to approximately 70% of pretreatment values 24 h after IFN therapy. The preferential reduction of CD8+ lymphocytes resulted in a temporary increase of the T4/T8 ratio in these patients.

Adult↗
PubMed1989

Studies of the mechanism of tolerance induced by short-term immunosuppression with cyclosporine in high-risk corneal allograft recipients. I. Analysis of CTL precursor frequencies.

Transplantation of unmatched allogeneic corneas into highly vascularized recipient eyes under the cover of short-term immunosuppression with cyclosporine enables permanent engraftment. The aim of this study was to further elucidate the mechanism(s) underlying this tolerant state. In eight "high-risk" cornea recipients the clone sizes of donor-specific and third-party reactive cytotoxic T cell precursors were assessed by limiting dilution analyses before and at three and six months after transplantation. Acquired allograft tolerance in these patients was not accompanied by clonal reduction of donor-specific CTL-p, whereas in the case of an irreversible rejection the donor-specific CTL pool size was significantly enlarged. This donor-specific CTL-p increase could already be seen two months before clinical manifestation. These patterns differed from that of tolerant renal transplant patients, in whom marked and donor-specific reduction of CTL-p was observed. During rejection identical patterns with increasing donor-specific CTL-p frequencies were seen in both groups of patients. We conclude that induction of tolerance by short-term CsA to unmatched cornea grafts is not caused by clonal reduction of the effector precursor cell pool.

Adult↗
PubMed1989

Release of interleukin 2 and gamma interferon by peripheral mononuclear cells in human Schistosoma mansoni infection normalizes after chemotherapy.

Interleukin 2 (IL-2) and gamma interferon (IFN-gamma) were determined in supernatants of mitogen- and antigen-driven cell cultures from patients with hepatosplenic or intestinal schistosomiasis. Skin reactivity was tested using a panel of eight recall antigens. Results were compared with those of uninfected local controls. In both schistosomiasis groups, IL-2 activity was reduced before treatment. In less than one third of the patients, schistosomal antigens elicited detectable IL-2 activity. IFN-gamma production was reduced more severely in hepatosplenic cases, in particular after stimulation by anti-CD3 monoclonal antibodies. After anti-schistosomal therapy with praziquantel, mitogen-induced IL-2 and IFN-gamma activities became normal within 3 months in intestinal schistosomiasis, and within 6 months in the hepatosplenic patient group. Results of in vivo delayed-type hypersensitivity tests paralleled those of in vitro lymphokine production. In conclusion, evidence is presented for severe, antigen-unspecific suppression of lymphokine production and skin reactivity against recall antigens. Anti-parasitic chemotherapy is shown to reverse the impairment of cell-mediated immune responses at the cytokine level.

Adolescent↗
PubMed1989

Three ophthalmological instruments: the rotating contact glass holder, the cutying forceps and the diamond cystotome.

Three new ophthalmological instruments are described: a rotating contact glass holder for easier control of the three-mirror Goldmann or other diagnostic contact lens which must be rotated on the eye; a suture-tying forceps combined with a sapphire blade, combining the tying and cutting functions in one instrument and a diamond cystotome for anterior capsulectomy with a cutting edge of unequalled sharpness.

Microsurgery↗
PubMed1989

Successful treatment of metastatic renal cell carcinoma with a biologically active dose of recombinant interferon-gamma.

We tested the clinical efficacy of a biologically active dose (BAD) of interferon (IFN)-gamma for treatment of progressive renal cell carcinoma (RCC). Twenty-two RCC patients with disease progression subsequent to nephrectomy were entered on a phase II clinical trial. During an initial dose-finding phase, biochemical responses to repeated once-weekly subcutaneous injections of 10, 100, or 500 micrograms of recombinant IFN-gamma were tested in 16 patients. Results indicated that 100 micrograms IFN-gamma applied once weekly was biologically active with induction of serum beta 2-microglobulin and neopterin. Such a dose induced a nearly maximum response of both markers lasting more than 4 days. This dose was also associated with minimal side effects. A dose of 100 micrograms IFN-gamma given once weekly was, therefore, subsequently given weekly for long-term treatment. During a median time of therapy of 10 months (range, 2 to 32 months) two complete (CR; 20+, 20+ months) and four partial tumor responses (PR; 6+, 7+, 8+, 24+ months) were seen (30% CR plus PR; 95% confidence limits, 12% to 54%) among 20 patients evaluable for response. Patients with refractory disease had significantly lower IFN-gamma-induced increments of serum beta 2-microglobulin than those who achieved clinical remission or stable disease.

Adult↗
PubMed1989

Lymphokine overproduction in severe aplastic anemia is not related to blood transfusions.

The production of interferons (IFNs), IFN-gamma, tumor necrosis factors (TNFs) and TNF-alpha (TNF-alpha) by peripheral blood mononuclear cells (PBMNCs) of untransfused and transfused, but otherwise untreated patients with severe aplastic anemia (SAA) was determined using bioassays and immunoassays. In untransfused and pretransfused SAA patients, spontaneous and lectin-induced production of these cytokines by PBMNCs was strongly enhanced. Cytokine production in untransfused SAA patients did not differ from that in pretransfused patients. Similar relative frequencies of activated (HLA-DR+) lymphocyte subpopulations present in the PBMNCs demonstrated cytokine overproduction per cells. Cytokine production was studied in three SAA patients before and after blood cell transfusions. Spontaneous and lectin-induced production of these cytokines was abnormally high and unaffected by blood transfusions. In another patient exhibiting abnormal cytokine production, the hematopoietic response to cyclosporin-A in vivo was accompanied by normalization of cytokine production in vitro. We conclude that overproduction of IFN-gamma and TNF-alpha by lectin-stimulated PBMNCs is an intrinsic abnormality of SAA unrelated to blood transfusions. Normalization of production of IFN-gamma and TNF-alpha accompanying a clinical response to cyclosporin-A may cautiously be taken as further evidence suggesting a pathogenetic role of cytokine overproduction in SAA.

Anemia, Aplastic↗
PubMed1989

The importance of patient monitoring in clinical cytokine trials: use of serum markers to define biologically active doses.

Due to their pleiotropic activities, network-like interactions, unknown mode of action and peculiar pharmacokinetics, the in vivo application of cytokines in clinical therapy studies is a difficult task. This paper deals with two therapeutic strategies which imply either maximum tolerated or biological active doses of human recombinant cytokines. Evidence is presented that the serum markers beta-2-microglobulin, which relates to HLA-AB antigen biosynthesis, and neopterin, which relates to macrophage activation, are useful response parameters for the definition of biological activity of IFN-alpha and IFN-gamma. Defined by such means, biological active doses are shown to be considerably less toxic than maximum tolerated doses, but are equally or more effective in the treatment of certain malignant disease states.

Biomarkers↗
PubMed1989

Neopterin excretion after liver transplantation and its value in differential diagnosis of complications.

The aim of this study was to investigate patterns and clinical utility of a neopterin marker in liver allograft recipients. Urinary neopterin levels were studied in 59 transplant patients daily until discharge. During the early postoperative period (days +1 to +20) neopterin excretion exhibited a liver-specific pattern that clearly differed from that seen in renal and bone marrow transplant recipients. Neopterin concentrations increased and reached peak values on day +7. The height of this early peak varied in context with complications such as infection or rejection, and was correlated with an unfavorable prognosis. In contrast to the early phase, no liver-specific pattern was observed after day 20. As seen in all other transplant patient populations, values normalized in patients with an uncomplicated course but again increased during infection or rejection episodes. Neopterin levels were particularly high during CMV infection, and their increments were directly related to the severity of CMV disease. The neopterin marker, although not specific, enables discrimination between patients with a complicated and uncomplicated clinical course. High neopterin values early after transplantation are associated with unfavorable prognosis and correlate with an increased risk of developing CMV disease.

Biopterins↗
PubMed1988

abl oncogene expression in non-Hodgkin lymphomas: correlation to histological differentiation and clinical status.

Eight reactive lymphatic tissues, 166 cases of non-Hodgkin lymphomas (NHL) and 11 cases of multiple myeloma were investigated for expression of the c-abl protein using the poly-clonal anti-abl antibody 4411 and an indirect peroxidase technique. In selected cases the results were compared to those obtained with a second polyclonal and 2 monoclonal anti-abl antibodies. In 7 cases, Northern blot analysis of abl-mRNA was performed in parallel. In reactive lymphatic tissues, cells positive for the 4411 antibody were confined to the B-cell areas, i.e., to the mantle zone and parts of the germinal center. In NHL, a positive staining of the cell membrane was predominantly detectable in lymphomas putatively originating in the germinal center or mantle zone (in particular in centrocytic NHL), independent of their proliferative activity. Clinically, 7 out of 8 abl-positive cases of chronic lymphocytic leukemia (CLL) had a more aggressive course of disease, whereas "progressive disease" occurred in only 7 out of 19 c-abl antigen-negative cases. When the clinical status of 78 patients with NHL and 11 patients with multiple myeloma was related to c-abl expression, c-abl-positivity was mostly confined to patients in advanced tumor stages [p less than 0.001 (NHL)].

Animals↗
PubMed1988

Latex immunoassay of serum alpha-fetoprotein using polyethylene glycol pretreatment.

A latex particle immunoassay has been developed for the determination of serum alpha-fetoprotein. The assay consists of incubating the serum sample for 30 min at 50 degrees C with latex particles coated with anti-alpha-fetoprotein immunoglobulin, then quantifying the remaining unagglutinated particles with an optical particle counter. The assay is fully automated with a sampling rate of 40/h. The interference from rheumatoid factor is eliminated by precipitation with polyethylene glycol (7% final concentration). The alpha-fetoprotein standard curve, prepared in a human serum matrix, extends from 0.5 to 32 micrograms/l. Because sera are diluted ten-fold, the limit of detection of the assay lies around 5 micrograms/l. Coefficients of variation ranged from 4 to 15% and the recovery of alpha-fetoprotein tested on eight normal sera and four sera containing rheumatoid factor averaged 102.2% (SD = 13.2). The correlation coefficient between latex immunoassay and radioimmunoassay, calculated from the assay of 138 samples was 0.98.

Humans↗
PubMed1988

IFN-mediated induction of MHC antigen expression on human keratinocytes and its influence on in vitro alloimmune responses.

The MHC Ag expression on the surface of keratinocytes is altered after treatment with IFN. IFN-gamma induces, as expected, a strong increase in class I MHC Ag expression as well as de novo expression of class II MHC Ag, whereas IFN-alpha 2 only slightly increases class I MHC Ag and does not induce keratinocytes to express class II MHC Ag. We used untreated and IFN-pretreated keratinocytes as stimulators and also as targets to study whether IFN-induced MHC Ag changes would alter the immunogenicity of keratinocytes in alloimmune responses. It was found that class II MHC Ag-carrying keratinocytes were unable to induce the proliferation of resting lymphocytes, but did stimulate T blasts. Untreated keratinocytes were virtually resistant to the lysis by classical CTL but became susceptible after exposure to IFN-gamma, but not IFN-alpha 2 at physiologic doses. These data demonstrate mechanisms by which the release of IFN-gamma might contribute to the development of disease such as the graft vs host disease.

Cell Division↗
PubMed1988

Cytomegalovirus infection.

Interest has focused on cytomegalovirus (CMV) infections during recent years for two reasons: First, the number of immunocompromised patients with CMV infections has risen continuously and, secondly, recent advances in basic research have clarified some of the mechanisms of persistent and recurrent CMV infection. Three different clinical pictures can arise with CMV infection. In healthy individuals most of the CMV infections are not clinically apparent. In immunocompromised patients CMV causes a wide spectrum of diseases and is one of the predominant causes of death in AIDS patients and bone marrow transplant recipients. The most important problem for public health associated with CMV are connatal and perinatal CMV infections. Progress has been made with treatment of CMV infection in immunocompromised patients with inhibitors of viral replication.

Acquired Immunodeficiency Syndrome↗
PubMed1988

The biology of interferon actions.

The interferons comprise a group of proteins which were first identified by their ability to protect cells against virus infections. They are synthesized and secreted by a variety of cell types in response to various inducers and exert their effects in vivo by interaction with specific cellular receptors. In this sense the interferons are analogous to polypeptide hormones. In recent years it has become clear that the interferons are capable of influencing cellular physiology and behavior in a number of ways. Their effects include antiviral actions, inhibition of cell growth and proliferation, regulation of the expression of specific genes, modulation of cell differentiation and activation of various cell types in the immune system. This review aims to summarize the current state of biology of interferon actions with special emphasis on the hemopoetic system.

Animals↗
PubMed1988

Interferon-alpha-2 in the treatment of idiopathic myelofibrosis.

We investigated the effect of human recombinant DNA-derived IFN-alpha-2 given in a dose of 1-2 X 10(6) units daily by subcutaneous injection to five patients with advanced idiopathic myelofibrosis (IM). Transfusion dependent anemia and symptomatic splenomegaly were taken as inclusion criteria for this pilot study. Two patients succumbed, one and three months after starting interferon-treatment because of pneumonia and traumatic cranial injury, respectively. While on IFN-treatment no improvement of cytopenia or reduction of splenomegaly was seen in four of the patients. In one patient, however, the requirement for erythrocyte transfusions decreased from 5 to 1.7 monthly upon IFN-treatment. After two, four and six months respectively IFN-treatment had to be stopped in these cases because of progressive thrombocytopenia and/or neutropenia. These observations suggest, that IFN-alpha might be of only marginal value in the treatment of advanced idiopathic myelofibrosis.

Aged↗
PubMed1988

The different effect of alpha and gamma interferons and interleukin 2 on the expression of CD2, CD3, CD4 and CD8 antigens in comparison to histocompatibility antigens of human lymphocytes.

The effects of alpha- and gamma-interferons (IFN-alpha, -gamma) and of interleukin 2 (IL-2) on the expression of certain differentiation antigens were compared with those of major histocompatibility antigens on human lymphocytes. IFN-gamma and IFN-alpha in high doses significantly increased the expression of T11 (CD2) differentiation antigen, but did not affect the expression of T4 (CD4), T8 (CD8), T3 (CD3) and Leu-7 antigens (HNK-1). Both natural and recombinant IFN-alpha and -beta apparently increased the expression of HLA-ABC antigens and of beta-2 microglobulin (beta 2m) after 16 h incubation. The amount of HLA-DR antigen, however, doubled in a few hours following IFN-gamma treatment. IL-2 affected the expression of CD2 and CD8 antigens only marginally, but did not affect that of CD3 and Leu-7; however, it strongly enhanced the expression of HLA-ABC, HLA-DR, and beta 2m antigens.

Antigens, Differentiation↗
PubMed1988

Comparative study of alloimmune reactions induced by leukocyte and platelet transfusions in humans: characteristic changes of activation markers, gamma interferon, and FcR blocking antibody production.

This study was undertaken to define immune responses induced by leukocyte and platelet transfusions. We offer evidence that activation by alloimmunization with intravenously administered "buffy coat" cells results in immune alterations similar to the early rejection episodes following kidney transplantation. Thus, IL-2 and HLA-DR expression increased on PBL 2 and 3 days after antigen exposure and paralleled elevations of IFN-gamma, neopterin, and beta 2 microglobulin levels. No significant changes were detected in the number of T-cell subpopulations. Alloimmunization by purified platelets alone that express only class I MHC antigens failed to induce the above alteration, even after repeated exposure. Repeated alloimmunization with "buffy coat" cells or isolated platelets stimulated a progressive increase up to 100% blocking activity on EA rosette formation. We conclude that the expression of activation markers on PBL and the production of IFN gamma and neopterin reflect the early phase of alloimmune response induced by leukocytes. This type of alloactivation is not a prerequisite for the development of FcR-blocking antibody, which is produced after pure platelet transfusion as well.

Binding, Competitive↗