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Biomedical subjects

W Fierz

Publications and source records attributed to W Fierz.

At least 19 recordsLinked to original sources
PubMed1992

T cell clones with normal or defective O-galactosylation from a patient with permanent mixed-field polyagglutinability.

To delineate the extent of O-galactosyltransferase deficiency within the lymphoid lineage, monoclonal antibody specific for the Thomsen-Friedenreich (TF) antigen (Gal beta 1----3GalNAc alpha 1-O-Ser/Thr) and its precursor the Tn antigen (GalNAc alpha 1-O-Ser/Thr) were applied to the flow cytometric analysis of peripheral blood lymphocytes from a patient with permanent mixed-field polyagglutinability (PMFP). We show that only a minor population of 4% expressed the Tn antigen which is in contrast to 93% of the patient's erythrocytes carrying the defect. Tn+ lymphocytes mainly belonged to the CD3+ subset, but were also CD19+ or CD16+. Both Tn+ and TF+ T cell clones from patient R. R. were established and shown to belong to the CD4+ or CD8+ antigenic subset. Three glycosyltransferase activities were determined in lysates from these clones: all Tn+ clones were deficient in UDP-Gal: GalNAc alpha 1-O-Ser/Thr beta 1----3 galactosyltransferase (beta 3Gal-T) activity; by contrast this activity was present in all lysates from TF-expressing clones. UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase (GalNAc-T) and UDP-Gal: GlcNAc-R beta 1----4 galactosyl-transferase (beta 4Gal-T) exhibited similar activities in both Tn+ and TF+ T cell clones. As a consequence of defective O-galactosylation in Tn+ T cells, cell surface sialic acid of Tn+ clones was reduced by greater than 50% when compared to TF+ clones as demonstrated by sialic acid-specific labeling using fluoresceinated Limax flavus agglutinin(LA) and flow cytometry. The Tn phenotype of T cell clones was stable for more than 1 year of continuous expansion in vitro. These data demonstrate that in PMFP, T cells may also be affected by the O-galactosyltransferase deficiency which is accompanied by a substantial loss of cell surface sialic acid. However, the frequency of Tn+ lymphocytes in peripheral blood from patient R.R. was strikingly low. These T cell clones should be useful to study the defect at a genetic level and the importance of O-linked carbohydrates for proper T cell function.

Agglutination↗
PubMed1992

Immunization-induced decrease of the CD4+:CD8+ ratio in cats experimentally infected with feline immunodeficiency virus.

In a previous experiment a group of 15 specified pathogen free (SPF) cats were experimentally infected with a Swiss isolate of feline immunodeficiency virus (FIV). A group of 15 SPF cats served as FIV negative controls. Nine cats of each group were vaccinated with a recombinant feline leukemia virus (FeLV) vaccine, six cats in each group with a placebo vaccine. All vaccinated cats developed high antibody titers to FeLV and were protected against subsequent FeLV challenge infection. In both control groups five of six cats became persistently infected with FeLV. Unexpectedly, the primary immune response to the vaccine antigen was significantly higher in the FIV positive group than in the FIV negative. The secondary response was stronger in the FIV negative cats. The goal of the present investigation was to further study the immune response in these 30 cats. They were immunized twice with the synthetic peptide L-tyrosine-L-glutamic acid-poly(DL-alanine)-poly(L-lysine) (TGAL) 21 days apart. Blood samples were collected on four occasions during the immunization process. They were tested for antibodies to TGAL, complete blood cell counts and CD4+, CD8+ and pan-T-lymphocyte counts. The following observations were made: (1) in contrast to the FeLV vaccine experiment, the primary immune response to TGAL was not significantly stronger in the FIV positive cats when tested by enzyme-linked immunosorbent assay (2). The absolute size of the CD4+ lymphocyte population was distinctly smaller in the FIV positive than in the FIV negative cats. The lowest CD4+ values were found in the dually FIV/FeLV infected cats. (3) A population of CD8+ lymphocytes was identified that was characterized by a distinctly weaker fluorescence. The size of this population increased in FIV positive and decreased in FIV negative cats during the TGAL immunization experiment. (4) The CD4+:CD8+ ratio increased in FIV negative cats during TGAL immunization from 1.9 to 2.3. In contrast, in FIV positive animals the CD4+:CD8+ ratio decreased significantly from 1.9 to 1.3 during the same period. From these and earlier data it was concluded that in short-term FIV infection the immune response to T-cell dependent antigens may be increased over that of the controls. Immune suppression develops gradually with duration of the infection. The significant drop of the CD4+:CD8+ ratio over a 5 week immunization period suggests that antigenic stimulation may accelerate the development of immune suppression in FIV positive cats. If this is a general feature, FIV infection may provide a particularly interesting model for studying the pathogenesis of AIDS.

Amino Acid Sequence↗
PubMed1991

Clinical and immune modulatory effects of alternative weekly interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma and melanoma.

The clinical and immune modulatory effects of interleukin-2 (IL-2) and interferon (INF) alfa-2a were examined in a phase II study in patients with metastatic renal cell carcinoma (six patients) and melanoma (eight patients). Treatment consisted in IL-2 3 MU/m2 continuous infusion days 1-4 and INF alfa-2a 6 MU/m2 subcutaneously day 1 and 4, both given on alternate weeks. Tumour response was assessed after four cycles of treatment or earlier, if necessary. Patients with stable disease or response were to be continued for another nine cycles or up to disease progression. The 14 patients received a total of 60 cycles of treatment. Major toxicities (WHO Grade III/IV) were fever, capillary leak syndrome with hypotension, nausea and vomiting, erythema with pruritus, leuco- and thrombopenia and sepsis with staphylococcus aureus. Five of 14 patients (36%) developed a self limiting autoimmune thyroiditis with HLA-DR expression on thyrocytes. Long term treatment toxicity was moderate with an average weight loss of 5% and an average fall in Karnofsky index of 10% compared to baseline. No responses were seen in renal cell carcinoma, two patients with melanoma had a partial and two a minor response with a duration of 1-7 months. Serial measurements of immune modulatory parameters showed a functional response to treatment with an increase of NK- and LAK-activity during the first two cycles, followed by a plateau and decrease during the third and fourth cycles. These findings were paralleled by a successive decline in treatment induced INF gamma response. These findings suggest, that alternative weekly treatment with IL-2 and INF alfa-2a results in an exhaustion of lytic capacity of NK- and LAK-cells and an attenuation of secondary cytokine release.

Adult↗
PubMed1991

Chronic relapsing experimental allergic neuritis induced by repeated transfer of P2-protein reactive T cell lines.

Chronic relapsing experimental allergic neuritis (crEAN) was induced by repeated transfers of P2-protein reactive T lymphocyte lines. Clinically, each intravenous transfer of P2-reactive T cells induced a relapse of the disease with weight loss and flaccid paresis of the hindlimbs followed by recovery. After multiple transfers, recovery from disease was incomplete, leading to increasing neurological deficit during the remissions. The pathology of the lesions during exacerbations was characterized by massive inflammation in the peripheral nervous system, associated with extensive endoneurial oedema, nerve fibre destruction and wallerian degeneration. Selective primary demyelination and remyelination was found in the minority of affected nerve fibres. No onion bulbs were present in chronic lesions. In the central nervous system partial degeneration of the posterior columns reflected the extent of wallerian degeneration in the peripheral nerves and spinal roots. In addition, during stages of active disease some T lymphocytes and upregulation of Ia antigen expression were found in the spinal cord.

Animals↗
PubMed1991

Poor antibody response after tetanus and pneumococcal vaccination in immunocompromised, HIV-infected patients.

Ten patients with symptomatic HIV infection (six with ARC, four with AIDS) received tetanus and 23-valent pneumococcal vaccination. Anti-tetanus IgG and IgM, and anti-pneumococcal IgG against all 23 capsular types of the vaccine were measured on days 0, 11, 17, 30, and 90. Anti-pneumococcal IgG were simultaneously determined in two plasma pools of 100 healthy unimmunized blood donors and of 112 healthy adults who had previously received a 14-valent pneumococcal vaccination. Peak IgG responses to both vaccines were observed on day 17; thereafter, the antibody levels gradually fell again. Anti-tetanus IgG rose from 0.6 U/ml (geometric mean) to 2.0 U/ml on day 17. Anti-tetanus IgM remained unchanged. Anti-pneumococcal IgG increased only by 1.14-fold compared with pre-vaccination levels (geometric mean of IgG rises against all 23 polysaccharides in 10 patients), and exceeded the upper 95% limit of unvaccinated blood donors in only 30 out of 230 specimens. Pre-vaccination levels for pneumococcal type-specific IgG were significantly higher in HIV-infected patients compared with the pool of unimmunized healthy controls, possibly indicating a higher rate of previous pneumococcal infections in HIV-seropositive subjects. However, post-pneumococcal vaccination levels were significantly lower in HIV-infected patients than in the pool of healthy controls. The increase in anti-tetanus IgG significantly correlated with the level of CD4 lymphocytes and with in vitro lymphocyte proliferation by pokeweed mitogen (5 micrograms/ml) and phytohaemagglutinin (2.5 micrograms/ml), confirming a particularly low vaccination response in patients who were severely immunocompromised.

AIDS-Related Complex↗
PubMed1990

[The effect of rejection crises and immunosuppressive therapy on the lymphocyte subpopulations of patients after kidney transplantation].

The lymphocyte subsets in the peripheral blood were examined 3 times a week in 17 patients receiving a cadaveric renal allograft using 2-color flow cytometry and several combinations of monoclonal antibodies. Patients who experienced a rejection crisis (n = 12) had a significantly higher CD4/CD8-ratio (2.72 +/- 1.26 mean +/- SD) than patients with stable graft function (1.76 +/- 1.33, p less than 0.05). 9/12 patients showed 0-3 days prior to the rejection episode an increase of the CD4/CD8- ratio (greater than or equal to 0.5) and/or a high ratio (greater than or equal to 2.5) with a decrease following antirejection therapy. The activation markers HLA-DR and IL-2 receptor on T cells were increased only during 3/12 rejection episodes. Patients with rejections resistant to prednisone pulse therapy (n = 6) had significantly more lymphocytes/mm3 in the peripheral blood (1111.7 +/- 597.5) than successfully treated patients (n = 6, 336.7 +/- 196.0, p less than 0.02). Antirejection therapy with prednisone pulses and/or antithymocyte globuline resulted in a significant decrease of T lymphocytes (CD3+) with a selective reduction of T helper/inducer cells (CD4+). 6 months after renal transplantation the patients had a higher percentage of suppressor/cytotoxic cells (CD8+) compared to the pretransplant values (26.3 +/- 10.9% vs 17.7 +/- 6.2%, p less than 0.02) and blood donors (16.3 +/- 6.2%, p less than 0.01). Furthermore the percentage of T helper cells (CD4+/CD28-) was significantly higher and the T suppressor-inducer cells (CD4+/CD28+) were significantly lower compared to the controls. Serial flow cytometric determinations of lymphocyte subsets in renal allograft recipients may be helpful in some cases although rejection episodes could not be predicted in the individual patient.

Adult↗
PubMed1990

The role of interferon-gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system.

The role of interferon-gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system was investigated. Administration of rat recombinant interferon-gamma markedly augmented both myelin-induced and T-cell line-mediated experimental autoimmune neuritis. Conversely, in vivo application of a monoclonal antibody to interferon-gamma suppressed the disease. Clinical and electrophysiological findings were corroborated by semiquantitative morphometric analysis. Mechanisms responsible for the enhancing effects of interferon-gamma include upregulation of major histocompatibility complex class II antigen expression in the nerve lesion, increased cellular influx of T cells and macrophages, and heightened macrophage activity with enhanced release of toxic oxygen species. These observations establish a pivotal role of the cytokine interferon-gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system.

Animals↗
PubMed1989

[The natural history and laboratory parameters of HIV infection].

Since 1983 the morbidity and mortality rates as well as results of haematological, immunological and (later) HIV serological tests were recorded prospectively for 497 HIV-positive patients during 1837 clinic visits at least twice within at most six months for a median period of observation of 18 months (range 6-64 months). The rate of progression to a higher stage was calculated according to the method of Kaplan-Meier. The rate for asymptomatic patients was 16% after one and 33% after two years; for patients with persisting generalized lymphadenopathy it was 13% and 21%, respectively, for those with AIDS-related complex 28% and 47%, respectively, and for those with AIDS 33% and 82%, respectively. As for results of laboratory tests, patients with progressive disease had significantly lower titres of anti-HIV nuclear antibodies, as well as a higher incidence of HIV-p24 antigen. Haemoglobin levels, platelet and lymphocyte counts and number of CD-4-positive lymphocytes were significantly lower, Neopterin and beta 2-microglobulins higher (P less than 0.01).

AIDS-Related Complex↗
PubMed1989

Suppression of P2-T cell line-mediated experimental autoimmune neuritis by interleukin-2 receptor targeted monoclonal antibody ART 18.

The monoclonal antibody ART 18 directed to the rat interleukin-2 receptor (IL-2 R) was administered to Lewis rats immediately prior to and/or on consecutive days after adoptive transfer of autoreactive P2-T line lymphocytes. The effects of ART 18 and sham treatment on the development of adoptive transfer--experimental autoimmune neuritis (AT-EAN) were assessed by clinical inspection, serial electrophysiological monitoring, and semiquantitative histomorphological analysis. Early injection of ART 18 suppressed AT-EAN while treatment after appearance of clinical signs did not. Since the IL-2 R is expressed exclusively on proliferating T cells activated by antigen, the in vivo application of an IL-2 R-targeted monoclonal antibody allows for more selective immunosuppression of experimental autoimmune disease of the peripheral nervous system than has previously been achieved.

Animals↗
PubMed1989

[Immunologic changes and infection in severely injured patients].

The severity of major surgery determines the extent of immunodeficiency which follows. The most pronounced immunodepression is found after severe blunt trauma; in polytraumatized patients the alterations of many measured parameters correlate with the injury severity score (ISS) i.e. with the severity of the injuries. Infection is also followed by many changes in the immune response. A score including serum concentrations of IgA, beta 2-microglobulin and percentage of monocytes was found to be predictive for the first 3 days after trauma with regard to subsequent occurrence of infection. In the first post-trauma day the lymphocyte-monocyte ratio correlates with the probability of survival or death by infection. Pneumonia occurred in 47% and septicemia in 22% of 150 polytraumatized patients ventilated artificially for more than 24 hours. The first signs of these infections were already present during the first 5 days, i.e. in the period of the most severe immunodeficiency. The preliminary results of a pilot study with immunomodulation by thymopentin are encouraging and show a significant decrease in the frequency of infections.

Humans↗
PubMed1989

Cerebrospinal fluid immunoglobulins and multiple sclerosis. Correspondence with magnetic resonance imaging and visually evoked potential changes.

The clinical (disability) and paraclinical (visually evoked potential [VEP]/magnetic resonance imaging [MRI]) data of patients with definite or probable multiple sclerosis (MS) were compared with their cerebrospinal fluid (CSF) immunoglobulins taken within the same period of time. For patients with definite diagnosis by the Schumacher criteria (n = 61) we found significant correlations between CSF immunoglobulin content (absolute gamma-globulin value [aggv]) and quantified MRI factors (r = .47), between aggv and the sum of VEP latencies of both eyes (r = .53), and also between MRI and VEP changes (r = .62). This was not true for the patients with a probable MS diagnosis and for patients with first attacks. No correlations were evident between aggv and disability status or duration of the illness. The results give support to recent neuropathologic and experimental findings in animals indicating close pathogenic connections between CSF immunoglobulins and demyelination in MS.

Adolescent↗
PubMed1989

Electrophysiological investigations in adoptively transferred experimental autoimmune encephalomyelitis in the Lewis rat.

Lewis rats with experimental autoimmune encephalomyelitis transferred adoptively with myelin basic protein-specific T line cells (AT-EAE) were studied clinically, electrophysiologically, and histologically. Injection with 5 x 10(6) line cells induced EAE with a rapidly developing tetraplegia after a latent period of 4 days. Electrophysiological testing revealed a profound slowing of afferent conduction within the dorsal column of the spinal cord, and conduction abnormalities in the spinal roots. Injection with a lower cell dose of 1 x 10(6) T line cells caused only moderate clinical signs paralleled by milder conduction slowing and conduction failure. Light microscopy showed marked inflammation with infiltration of mononuclear cells and some demyelination throughout the spinal cord and roots. Inflammation and demyelination were dose dependent and the caudal parts of the spinal cord were more affected than the cranial parts. The peripheral nerves were free of electrophysiological and morphological alterations. Systemic treatment with 4-aminopyridine accelerated and partially restored conduction in the dorsal columns and roots, while increasing the body temperature had a detrimental effect, suggesting demyelination as a prominent pathophysiological mechanism. These findings show that in AT-EAE in Lewis rats the dysfunction of the central nervous system and of spinal roots is cell dose dependent, that the peripheral nervous system distal to the spinal roots is spared, and suggest that paranodal demyelination is an important pathogenic mechanism.

4-Aminopyridine↗
PubMed1989

[Immunosuppression caused by surgery and severe trauma].

The present prospective study was performed to describe physiological immunosuppressive effects dependent on minor surgical interventions and an immunodeficiency syndrome after major surgery and severe trauma. Parameters of cellular and humoral immunity were monitored in 64 patients of the Department of Surgery of the University Hospital Zurich preoperatively and on days 1, 2, 3 and 4 after selective surgery or polytrauma. 22 patients were multiply traumatized (mean ISS 34.7 +/- 13), 14 patients underwent Y-grafting of the abdominal aorta, 11 resection of colorectal carcinoma, 8 cholecystectomy and 9 inguinal herniotomy. There could be seen a decrease of parameters of cellular immunity (absolute lymphocyte count, CD-4-/CD-8-cell-ratio and release of IL2-receptors), a decrease of humoral defense (immunoglobulins and complement factors) and an increase of macrophage activation (serum levels of neopterin).

Humans↗
PubMed1988

[HIV serological parameters in the prognosis and follow-up assessment of an HIV infection].

53 individuals negative for anti-HIV by screening test and 79 individuals positive for anti-HIV were prospectively surveyed for clinical progression and by quantitatively measuring anti-p24 (antibodies against an HIV core protein), anti-gp41 (antibodies against an HIV surface protein) and HIV-(p24) antigen. The patients were classified into four categories of HIV-markers: 1. Anti-p24 in high concentrations, HIV-Ag negative, 2. anti-p24 in high concentrations, HIV-Ag positive (most often transitory only), 3. anti-p24 absent/deficient, HIV-Ag negative and 4. anti-p24 absent/deficient and HIV-AG positive. Within a minimum of 18 months, 4 of the 53 (8%) initially anti-HIV negative individuals contracted HIV infection. 17 of the 79 (22%) initially anti-HIV positive individuals showed disease progression. 8 of the patients in category 4 already had AIDS when entering the study, and 3 of the 6 (5%) remaining patients of this category developed AIDS. Amongst the 19 patients in the third category 2 individuals (11%) developed AIDS and in a further 5 (26%) individuals the disease progressed but in no case to AIDS. None of the patients of the categories 1 and 2 developed AIDS but 2 of the 10 (20%) individuals in the second category and 3 of the 29 (10%) in the first category showed disease progression but not to AIDS. In conclusion, the quantitative measurement of anti-p24 and of HIV-Ag affords prognostic pointers for the clinical outcome of HIV infection.

AIDS-Related Complex↗
PubMed1988

Cyclosporine versus azathioprine in the long-term treatment of multiple sclerosis--results of the German multicenter study.

In a double-blind controlled trial of 194 patients with clinically definite active multiple sclerosis, 98 were randomized to treatment with cyclosporine (CyA, 5 mg/kg/day), and 96 to treatment with azathioprine (Aza, 2.5 mg/kg/day). Eighty-five patients in the CyA group and 82 in the Aza group completed a treatment period of 24 to 32 months in accordance with the study protocol. No significant differences could be detected between the two treatment groups at the end of the trial. Assessment was done by serial quantitative neurological examinations and Kurtzke's Expanded Disability Status Scale. Frequency of relapse and patient self-evaluation also failed to show significant differences. Overall deterioration observed in both groups during the trial was only minor. The incidence of side effects in the CyA group was more than two times that in the Aza group. We conclude that CyA as a single agent cannot be the drug of final choice in long-term immunosuppressive treatment of relapsing-remitting and relapsing-progressive multiple sclerosis.

Adolescent↗