[So-called cellulitic heavy legs].
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Biomedical subjects
Publications and source records attributed to C Huber.
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This study aimed to evaluate the molecular weight distribution patterns and the quantitative expression of surface glycoproteins (S-GP) of various differentiation stages of human leucocytes. S-GP were first exposed by treatment with neuraminidase; subsequently they were labelled by galactose-oxidase treatment followed by reduction with 3H-sodium borohydride. Labelled S-GP were separated on polyacrylamide gels in the presence of SDS and were visualized by means of fluorography. A total of 8 major S-GP bands with apparent molecular weights of 230 000, 215 000, 200 000, 185 000, 175 000, 150 000, 125 000 and 110 000 daltons were identified. All of these S-GP were already expressed at the level of pluripotent myelopoietic stem cells but different in their relative expression during further cellular maturation.
Large granular lymphocytes (LGL) represent a morphologically distinct and new population of mononuclear blood cells. In normals on average 12% of their peripheral blood mononuclear cells exhibit morphological features of LGL. In this article we summarize experimental evidence suggesting that LGL represent the effectors of spontaneous cell mediated cytotoxicity responses in normal as well as in diseased states. This conclusion is based on two main findings: 1. the frequency of LGL correlates with the capacity to mediated spontaneous cell mediated cytotoxicity when pooled data of normal controls were analyzed, as well as when different density fractions or organs from one and the same individual were compared. 2. disease associated reduction in the numbers of LGL is invariably accompanied by an impaired spontaneous cytotoxicity. It thus appears that evaluation of LGL by morphological means represents a new way to assess spontaneous cell mediated cytotoxicity responses.
In this review evidence is summarized indicating that the pteridine compound, neopterin represents a new and clinically useful biochemical tool to detect activated T-lymphocytes. T-cells stimulated in vivo or in vitro by allogeneic or virally or chemically modified autologous cells produce large amounts of this molecule. Other mononuclear blood cells, in contrast, lack this capacity. These findings suggested that evaluation of neopterin levels might represent a means for the biochemical monitoring of disease states mediated by or associated with activated T-cells. Our clinical data obtained on patients suffering from allograft rejection, viral disease, or autoimmune states strongly support this concept.
This article describes the successful treatment of a patient with postpartum haemolytic uraemic syndrome by means of plasmopheresis. Also discussed are problems of the differential diagnosis and current therapeutic concepts of this rare syndrome.
Thalamic projections of the pallidum and the deep cerebellar nuclei were studied by unitary recordings as well as field potential analysis in the thalamus of squirrel monkeys (Saimiri Sciureus) under sodium pentobarbital anesthesia. Stimulation of the pallidum produced a positive field potential preceded by incoming afferent fiber volleys in the thalamus. Spontaneous discharges of thalamic neurons were suppressed during this positive potential corresponded to that of the hyperpolarizing potential. The hyperpolarization was presumed to be a monosynaptic inhibitory post synaptic potential by the short synaptic delay (about 0.5--0.7 ms) and responsiveness to high frequency stimulation (over 150 Hz). The positive field potential on stimulation of the external pallidal segment was distributed in L.po (VA) and the reticular thalamic nucleus around L.po, whereas that on stimulation of the internal segment was in V.o.a (the anterior basal part of VL) and in Z.o (upper part of VL). The projection of the external segment appeared to be less dense than that of the internal segment. The projection of deep cerebellar nuclei was situated in V.o.a, V.o.p (posterior part of basal part of VL), V.o.i (VLm), the intralaminar nucleus (CL), and some part of V. im (the rostral part of VPLo). Projections of the interpositus and dentate nuclei were distributed in a more anterior part than those of the fastigial nucleus. A certain topographical arrangement of the projections of these three nuclei was found in V.o.p, V.o.i and V.im. No significant overlap was detected between pallidum and the deep cerebellar nuclei within the thalamus.
Large granular lymphocytes (LGL) represent a morphologically distinct mononuclear cell type. In healthy individuals an average of 12.5 +/- 5.2% of peripheral mononuclear cells exhibit this morphology. Structurally they are characterized by azurophilic granules, light cell density, low surface adherence and expression of Fc-IgG receptors. Functional analyses on LGL suspensions enriched by means of density gradient fractionation and adherence procedures included testing of T-cell and monocyte-specific in vitro reactions as well as evaluation of their natural cytotoxicity (NC). Results indicated a close correlation between the percentages of LGL and the capacity to bind and to lyse NC-susceptible tumor targets. In agreement with others we would thus conclude that LGL embrace the majority of NK-effector cells. The morphological definition of LGL provides an additional tool for the clinical evaluation of this cell mediated immune reactivity.
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The use of daily urinary neopterin evaluation to detect immunological complications has been tested in 96 consecutive cadaveric kidney recipients, three liver recipients, and one pancreas recipient. In 29 of these patients an immunologically uncomplicated posttransplant course was associated with stable or low neopterin levels, or both. In only 5% of daily determinations on these patients were increasing or high neopterin levels seen. On the other hand, major immunological complications, such as acute rejection episodes (38 cases), viral infections (17 cases), or both problems (8 cases), were preceded by increasing or high neopterin levels or both--on the average by one day. Withdrawal of cyclosporine was also found to be followed by increase of urinary neopterin levels. Neopterin evaluation enabled reliable and accurate prediction of immunological complications in 95% of patients with acute rejections and in 100% of patients with viral infections. It thus appears that daily assessment of urinary neopterin levels represents a useful tool for biochemical detection of immunological complications in allograft recipients.
A 70-year-old woman developed typical clinical symptoms of pure red cell anemia (PRCA) following a history of rheumatoid arthritis (RA). The patient's bone marrow erythropoietic progenitors cells were cloned in a micro agar culture system several times over a period of 11 months, revealing a diminished frequency of bone marrow erythroblasts paralleled by a markedly reduced number of CFU-e and BFU-e in vitro. No inhibitory activity in the patient's IgG fraction could be detected either by preincubation with IgG and/or rabbit complement, or in the continuous presence of IgG. Depletion of T lymphocytes from the patient's bone marrow cells led to an improved in vitro erythroid proliferation. Cytostatic therapy with cyclophosphamide clinically induced a marked increase in the bone marrow erythroblast and reticulocyte number, correlated in vitro by normalization of CFU-e levels and increase in the number of BFU-e. Nevertheless, BFU-e values never attained normal levels, which could be attributed to a reduced stem cell pool resulting from previous therapy with cyclophosphamide and/or antirheumatic drugs. Two independent factors, a reduced pool of committed stem cells as well as an autoimmune cell-mediated suppression, may both contribute to the pathomechanism of the disease in this patient.
Neopterin excretion in urine of patients with AIDS was measured by high pressure liquid chromatography. Urinary neopterin levels in patients with generalized lymphadenopathy, which is considered to be part of the spectrum of AIDS, as well as in severe AIDS cases were significantly elevated, compared to normal controls. This finding may prove useful as a screening test for donors of blood products in order to prevent transmission of AIDS by this route.
We present evidence that most T cells proliferating in response to autologous SRBC-separated NT cells are not specific for autoantigens but for antigens derived from xenogeneic sources. The conclusion was based on the following three observations: First, we found that NT cells isolated in the absence of xenoproteins by means of density gradient centrifugation on Percoll only weakly stimulated autologous T cells. NT cells isolated by the above method in the absence of xenogeneic determinants readily acquired stimulatory capacity after brief exposure to either SRBC or FCS. Secondly, restimulation of T memory cells generated in 1 degree AMLR against SRBC-separated autologous NT cells was exclusively seen when NT cells exposed to or separated with xenoproteins were used for restimulation. Thirdly, T memory cells generated against SRBC-separated autologous NT cells were specifically restimulated by autologous Percoll-separated NT cells which had been pulsed with a variety of xenogeneic mammalian sera. These xenogeneic determinants were preferentially recognized in context with autologous HLA-DR+ cells. From these findings and from our previous results which indicated an absolute requirement of HLA-DR+-adherent NT cells, we conclude that human AMLR primarily does not represent an autoantigen but a xenoantigen response which is genetically restricted by the HLA-DR type of the antigen-presenting cell.
Evidence is presented that activation of T cells by allogeneic or modified autologous cells leads to the specific production of two distinct molecular compounds of the PT class. One of these two PT has previously been identified as neopterin. The structure of the other is still under investigation. This conclusion was based on the following findings: a) In vitro both PT were produced by T cells proliferating in response to HLA incompatible allogeneic or to autologous EB-virus-transformed or TNP-haptenized cells. b) In vitro stimulation of T cells with mitogenic lectins or protein antigens, of macrophages with zymosan-complement, of B cells with PWM or EB-virus, and of NK effector cells with tumor targets failed to induce comparable release of these PT. c) In vivo increased amounts of both PT were excreted via the urine during allograft rejection and viral infections. It thus appears that the production of these PT is primarily a feature of activated T cells involved in the control of self integrity.
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We present evidence that most T cells proliferating in response to autologous sheep erythrocyte (SRBC)-separated non-T cells (NT) cells are not specific for autoantigens but for antigens derived from xenogeneic sources. The conclusion was based on the following three observations. First, we found that NT cells isolated in the absence of xenoproteins by means of density gradient centrifugation on Percoll only weakly stimulated autologous T cells. Because this weak proliferation could not be expanded in restimulation experiments, its significance as an immune recognitive event remains questionable. NT cells isolated by the above method in the absence of xenogeneic determinants readily acquired stimulatory capacity after brief exposure to either SRBC or fetal calf serum. Second, restimulation of T memory cells generated in 1 degree autologous mixed lymphocyte reaction (AMLR) against SRBC-separated autologous NT cells was exclusively seen when NT cells exposed to or separated with xenoproteins were used for restimulation. Third, T memory cells generated against SRBC-separated autologous NT cells were specifically restimulated by autologous Percoll-separated NT cells that had been pulsed with a variety of xenogeneic mammalian sera. These xenogeneic determinants were preferentially recognized in context with autologous HLA-DR+ cells. From these findings and from our previous results that indicated an absolute requirement of HLA-DR+-adherent NT cells (8), we conclude that human AMLR primarily does not represent an autoantigen but a xenoantigen response that is genetically restricted by the HLA-DR type of the antigen-presenting cell.
Large granular lymphocytes from normal human blood were enriched by centrifugation on discontinuous Percoll density gradients. Their capacity for natural killing, but not for phagocytosis of yeast cells, was demonstrated. Large granular lymphocytes are characterized in electron microscopy by their fine structure, especially by typical granules and by inclusions of tubular structures in a parallel array. Their lymphocyte nature is supported by activity of acid-alpha-naphthyl acetate esterase and by the absence of myelo-peroxidase (POX) and of macrophage POX. The Fc gamma receptor of their cell membrane is marked by soluble POX-anti-POX-complexes; labeled parts of their membrane are not incorporated into the cytoplasm as in monocytes.
The aim of this study was to analyze the density distribution patterns of subsets of normal human lymphocytes. Density distribution was assessed by equilibrium centrifugation on linear polysucrose-metrizoat gradients. Results of the analyses of various subsets of lymphoid cells differing in their degree of cellular maturation and functional activation suggested that their distribution patterns are determined by three independent factors: the derivation, the stage of differenciation and the functional activity.