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Biomedical subjects

K Wagner

Publications and source records attributed to K Wagner.

At least 217 records · Page 12Linked to original sources
PubMed1992

[Immunosuppression after organ transplantation].

Immunosuppression after organ transplantation is based on pharmacologic interventions using steroids, azathioprin, sandimmun and anti-T-cell-globulins. During the induction-period the use of a high-dose combination-therapy guaranties a low incidence of rejection episodes. However infective complications may predominate. In the long-term phase the results of different immunosuppressive protocols are similar in respect to patient- and graft survival. This circumstance promotes the possibility to perform an individualised immunosuppression, which compiles to the personal demands of the graft recipient.

Graft Rejection↗
PubMed1992

Cutaneous histopathologic, immunohistochemical, and clinical manifestations in patients with hemophagocytic syndrome. Military Medical Consortium for Applied Retroviral Research (MMCARR).

BACKGROUND AND DESIGN: The hemophagocytic syndrome (HPS) is characterized by fever, wasting, generalized lymphadenopathy, hepatosplenomegaly, and pancytopenia, often with associated coagulopathy. The most common cutaneous manifestations are panniculitis and purpura. Cytophagic histiocytic panniculitis fits within the spectrum of HPS, and the most consistent histopathologic feature in HPS is a proliferation of mature histiocytes that exhibit prominent erythrophagocytosis and cytophagocytosis. The clinical spectrum, the underlying causes, and the histopathologic features found in HPS are broad. The characteristic phagocytic histiocytes seen in HPS have been confused with malignant histiocytes in the past, but are now known to be reactive. The clinical findings, histologic, and immunohistochemical features of 10 cases of HPS with cutaneous lesions were reviewed. Immunohistochemical markers included KP-1, beta F-1, UCHL-1, L-26, MAC-387, factor XIIIa, and S100 protein. RESULTS: The HPS was associated with T-cell lymphoma and/or viral infection. Most biopsy specimens showed edema and hemorrhage with a lymphohistiocytic infiltrate and prominent histiocytic cells showing erythrophagocytosis and, in some cases, cytophagocytosis. The histiocytic cells showed positive reactions for KP-1 and negative reactions for the lymphoid markers. In all cases the lymphoid cells showed a mixed pattern with most cells positive for beta F-1 and UCHL-1, and a small percentage positive for L-26. CONCLUSION: In HPS, the prominent phagocytic histiocytes are reactive and are stimulated by T-cell lymphocytes, either neoplastic or in response to viral infection. Many of the findings in the HPS may also be due directly or indirectly to cytokines produced by proliferating T-cell lymphocytes and/or reactive phagocytic histiocytes.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Determination of the tyrosine phosphorylation sites of the nicotinic acetylcholine receptor.

The peripheral nicotinic acetylcholine receptor (nAChR) is phosphorylated on tyrosine residues in vivo and in vitro at a high stoichiometry. We have previously reported that this tyrosine phosphorylation occurs on the beta, gamma, and delta subunits of the receptor and is implicated in both the modulation of the function of the receptor and localization of the receptor at the synapse. The specific tyrosine residue of each subunit which is phosphorylated is now identified. The endogenously phosphorylated nAChR from the electric organ of Torpedo californica was phosphorylated to maximal stoichiometry in vitro exclusively on tyrosine residues as indicated by phosphoamino acid analysis. Two-dimensional phosphopeptide maps of thermolysin limit digests of the isolated phosphorylated subunits indicated that each subunit is phosphorylated at a single site. To determine the site of tyrosine phosphorylation of the beta, gamma, and delta subunits, phosphorylated subunits were isolated and digested with trypsin. A single phosphotyrosine containing peptide from each subunit was purified by antiphosphotyrosine antibody affinity chromatography and reverse phase high performance liquid chromatography. The purified phosphopeptides were subjected to sequential Edman degradation and sequence analysis. Comparison of the phosphopeptide sequence data with the deduced amino acid sequence of each subunit indicated that Tyr-355 of beta, Tyr-364 of gamma, and Tyr-372 of delta are the sites of in vitro and in vivo tyrosine phosphorylation of the nAChR. Identification of these sites should facilitate further studies of the role of tyrosine phosphorylation in the regulation of receptor function.

Amino Acid Sequence↗
PubMed1991

A sensitive and efficient induction system for murine IgE. Single cell analysis at the clonal level.

A culture system is described which permits the analysis of IgE expression by single murine cells within clones of B cells. The system is based on the use of a CB5.1 stroma cell line as a feeder which optimally supports the IL-4-induced switch to IgE of LPS-stimulated B cells in culture. In this system 100 U/ml IL-4 induces the switch to IgE, in 3-5% of B cells and the switch frequency to IgG1 was as high as 2%. Five ng IgE or 12 ng IgG1 were produced per clone containing on average 13-15 PFC. The detection of single IgE secreting B cells was possible due to two newly developed, highly specific rat anti-mouse IgE antibodies used in a sandwich-ELISA. The frequency of IgE-secreting B cells was enhanced 2.5 times when the fibroblastoid CB5.1 cells rather than thymocytes were used as feeder cells. CB5.1 cells supported the differentiation of B cells to IgM-PFC almost as well as rat thymocytes (which have, to date, been used as the standard feeder layer) whereas the amount of secreted IgG1 was about 3 times lower than in thymocyte cultures. Optimal switching to IgE occurred at concentrations of IL-4 which were 10-fold lower than that required for IgG1 expression, a situation quite opposite to that observed in the rat thymocyte-supported culture system. In confirmation of established data the switch of B cells to IgE or IgG1 occurred randomly. The advantages of CB5.1 cells as feeder cells are (1) the use of a homogeneous and defined cell line, (2) their limited release of defined lymphokines (IL-6 and GM-CSF), and (3) the low degradation and consumption of cytokine factors. The combination of the CB5.1 cell line with a highly specific IgE ELISA assay made it possible to analyse the appearance of IgE producing cells within a developing B cell clone.

Animals↗
PubMed1991

[Pneumatosis coli--a rare complication of cytostatic therapy].

Recurring paroxysmal abdominal pain developed in a 19-year old woman suffering from acute lymphatic T-cell leukaemia, during induction chemotherapy with cyclophosphamide, cytarabine and mercaptopurine. Both the plain radiograph and CT of the abdomen showed pathognomonic intramural gas accumulations and free air below the right diaphragm, pointing to pneumatosis coli. There was marked pancytopenia (leucocytes 800/microliters,haemoglobin 7.6 g/dl, thrombocytes 10,000/microliters). Whereas the abdominal pain subsided rapidly under oxygen therapy and liquid nourishment, the radiological changes receded gradually. However, fever and diarrhoeas occurred subsequently. Fever persisted for 3 weeks despite treatment with antibiotics (three times 60 mg/d gentamicin, three times 2 g/d mefoxitin and three times 500 mg/d metronidazole, and later 30 mg/d amphotericin B) and subsided only after completion of the induction chemotherapy and an increase of leucocyte count.

Adult↗
PubMed1991

[New triterpenoids saponins from Helianthus annuus].

Three new bisdesmosidic triterpenoid saponins, helianthoside 1(1), 2(2), and 3(3), were isolated from the flowers of Helianthus annuus L. and a new monodesmoside 4 was isolated after the cleavage of the ester-glycosidic linkages of 2 and 3. The structures of the compounds were elucidated by 13C-NMR, FAB-MS, GC/EI-MS of partially methylated alditol acetates and degradation methods.

Carbohydrate Sequence↗
PubMed1991

Cutaneous lesions of listeriosis in a newborn.

Although HIV-infected patients are commonly infected by organisms that require an intact T cell immune system for control or eradication, there are some exceptions. The intracellular pathogen Listeria monocytogenes is one such organism. Listeriosis occurs primarily in neonates, elderly patients, patients on immune suppressive medications, cancer patients, and during pregnancy. However, listeriosis is an uncommon opportunistic infection in HIV-infected patients. We report a case of listeriosis with cutaneous lesions in a neonate born to an HIV-infected woman.

Humans↗
PubMed1991

New concepts of IgE regulation.

B cell switch to IgE expression is mediated by IL-4 and is regarded as a T helper cell-related phenomenon. In this overview we describe that IgE switch can also be induced by mast cell/basophil like cells (from splenic non-B, non-T cells), activated by IgE receptor cross-linking and/or IL-3 which results in IL-4 production by these cells. Furthermore, activated mast cells produce their own growth factors, IL-3 and GM-CSF. Thus, activation of mast cells can provoke an ongoing local allergic reaction as long as antigen confrontation is maintained, a process which is sustained by further IgE production as well as renewal of mast cells. It is furthermore demonstrated that in certain established immune situations the IgE response may become independent of IL-4, namely in the spontaneous in vitro IgE expression of cells from atopic individuals as well as in an in vitro antigen-induced secondary IgE response of spleen cells derived from previously immunized mice. Thus, IgE-switched B cells may persist in vivo and may represent a pool of potentially IgE-producing cells. Finally, a selective inhibition of the IgE response is described in vitro and in vivo by the use of so-called non-anaphylactic monoclonal anti-IgE antibodies. Such antibodies bind to surface IgE+ B cells, but not to IgE-sensitized mast cells, and thereby inhibit IgE responses. Non-anaphylactic antibodies blocked the binding of allergen-specific IgE to mast cells by competing with the Fc epsilon on these cells. As a consequence they do not induce but rather prevent allergen-induced mediator release by mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Influence of the calcium antagonist nitrendipine on the hepatotoxic effect of cyclosporine A.

Calcium antagonists have a protective effect on different forms of nephrotoxicity due to cyclosporine A (CsA). The objective of the present study was to examine the influence of a calcium antagonist on the liver function in CsA-treated patients after kidney transplants. Different quantitative liver function tests were performed in six patients before and 3 months after administration of the calcium antagonist nitrendipine. Indocyanine green clearance (ICG-Cl) as a marker for hepatic blood flow and excretion showed a significant increase under nitrendipine. In addition, there was an improvement of the galactose elimination capacity. Although nitrendipine and lidocaine are both metabolized by the cytochrome P system, there was no reduction in lidocaine clearance. These results suggest an improvement of liver function under nitrendipine. Whether these findings alone are the expression of an improved liver blood flow or whether there is an additional hepatoprotective characteristic of the calcium antagonist nitrendipine cannot be determined.

Cyclosporine↗
PubMed1991

The effect of race on waiting time in two urban emergency departments.

This study examines the relation between patient race and waiting time in two urban Emergency Departments, located in the northeastern United States. Consecutive patients presenting with lacerations make up the subjects in the study. In order to control for the effect of disease severity, we restricted the sample to patients presenting with small, single lacerations requiring sutures. Patients who were intoxicated, had experienced syncope, had been involved in motor vehicle accidents, or who required tests or consultation were excluded. Taking socio-demographic (age, sex, insurance status) and clinical variables (location of laceration, time of day, day of week) into account, we found no substantial difference in total time spent in the Emergency Departments between whites and non-whites.

Attitude of Health Personnel↗
PubMed1990

[Prevalence, causes and effects of increased iron storage in patients with kidney transplantation].

Patients on chronic hemodialysis often need blood transfusions due to erythropoietin deficiency. Even after successful kidney transplantation iron overload may persist. Former histological studies have revealed siderosis of the liver in 69% of all patients whose serum ferritin was above 1100 ng/ml. The aim of the present study was to evaluate the influence of iron overload on liver function. In 146 symptom free patients with renal allografts serum ferritin was determined to detect possible iron overload. Serum ferritin between 4 and 5480 ng/ml were found (women: 358.7 +/- 105.3; men 282.4 +/- 63.3 ng/ml; x +/- SEM). Twelve patients (8.1%) had ferritin levels higher than 1100 ng/ml. These twelve patients as well as another group of eight patients with renal allografts whose serum ferritin was known to be higher than 1100 ng/ml were included for further evaluation. Their data were matched and compared with those of a control group also patients with renal allograft (same age and sex) whose serum ferritin was lower than 1100 ng/ml. Transaminases (SGPT 22.6 +/- 3.6 vs. 15.4 +/- 6.0 U/l; SGOT 14.7 +/- 2.0 vs. 13.0 +/- 4.8 U/l) and plasma glucose (90.5 +/- 7.1 vs. 76.8 +/- 3.7 mg/dl) were found to be significantly higher (p less than 0.05) in patients with serum ferritin levels above 1100 ng/ml. Elevated transaminases were significantly more frequent in patients with high serum ferritin (9 vs. 2; p less than 0.02) as compared with the control. Ferritin levels significantly correlated with the number of preceding blood transfusions (p less than 0.002). Hbs-persistence was detected in six out of 20 patients with high ferritin levels but only in one out of 20 in the control group (p less than 0.05) whereas anti-Hbs prevalence was not different in the two groups. These data indicate that chronic iron overload should be considered as a possible cause of chronic liver disease in patients with renal allografts.

Adolescent↗
PubMed1990

An in vitro murine model of a penicillin specific IgE anamnestic response.

A new murine model system was developed to study hapten specific IgE anamnestic antibody forming cell (AFC) responses induced in vitro. BALB/c mice injected intraperitoneally with BPO-KLH (10 micrograms) in aluminum hydroxide gel (alum) on day 0 and 21 were killed on day 42. Spleen cells (4 X 10(7] were cultured for 0-8 days in the presence of BPO-KLH (0.25-2500 ng/ml), after which the numbers of BPO specific IgE AFC were enumerated in an ELISPOT assay at 37 degrees C using BPO-BSA coated plates. Peak BPO specific IgE anamnestic AFC responses (approximately 40 AFC/10(7) cultured cells) occurred when cells were cultured with 100 ng/ml BPO-KLH for 5 days; peak BPO specific IgG1 and IgA responses (approximately 3000 and approximately 280 AFC/10(7) cultured cells) were detected one day earlier with the same antigen concentration. No ELISPOTs of any isotype were detected if: cells were cultured in the absence of specific antigen; cells from alum treated or unsensitized mice were used; assay wells were coated with BSA alone; isotype specific antibodies were omitted; or assays were performed in the presence of cycloheximide or at 4 degrees C. Cellular interactions in IgE anamnestic AFC responses were studied using the newly developed model system. We found that these responses were partially T cell independent, and that spleens from sensitized and unsensitized adult mice, as well as neonatal mice, contained cells which suppressed these responses.

Animals↗
PubMed1990

The human pregnancy-specific glycoprotein genes are tightly linked on the long arm of chromosome 19 and are coordinately expressed.

The pregnancy-specific glycoprotein (PSG) genes encode a group of proteins which are found in large amounts in placenta and maternal serum. In situ hybridization analyses of metaphase chromosomes reveal that all the human pregnancy-specific glycoprotein (PSG) genes are located on the long arm of chromosome 19 (19q13.2-13.3), overlapping the region containing the closely-related carcinoembryonic antigen (CEA) gene subgroup. Higher resolution analyses indicate that the PSG genes are closely linked within an 800kb SacII restriction endonuclease fragment. This has been confirmed through restriction endonuclease mapping and DNA sequence analyses of isolated genomic clones, which show that at least some of these genes are located in very close proximity. Further, these studies have helped to identify a new member of the PSG gene subfamily (PSG7). DNA/RNA hybridization analyses, using gene-specific oligonucleotide probes based on published sequences, showed that five from six PSG genes tested are coordinately transcribed in the placenta. Due to the close proximity of these genes and their coordinated expression pattern, common transcriptional regulatory elements may exist.

Base Sequence↗
PubMed1990

Simultaneous production of interleukin 2, interleukin 4 and interferon-gamma by activated human blood lymphocytes.

The production of interleukin 2 (IL 2), IL 4 and interferon-gamma (IFN-gamma) by in vitro activated unselected human blood mononuclear cells was studied at a single-cell level. Individual lymphokine-synthesizing cells were identified by intracellular immunofluorescent staining using cytokine-specific monoclonal or polyclonal antibodies. Cultures from adult blood donors revealed a biphasic kinetic production pattern for IL 2 and IFN-gamma with peaks occurring 4-6 and 24-30 h after initiation of the cultures. Approximately 20%-40% of the lymphocytes produced IL 2 and IFN-gamma. In contrast, only 1%-3% of the lymphocytes synthesized IL 4 with maximal frequency after 6 h of culture. CD4+ as well as CD8+ T cells contributed to the synthesis of all three lymphokines studied. CD4+CD45R- T cells were the major producers of IL 2 and IL 4, while CD8+CD45R- T cells were the most common phenotype of IFN-gamma-synthesizing cells. By performing two-color immunofluorescence studies we observed that among IL 4-producing cells every second one made simultaneously IL 2 and every fourth one made IFN-gamma. Mononuclear cells from umbilical cord blood could be stimulated to make IL 2 to the same extent as cells from adult blood donors. No IL 4 production and a strikingly reduced frequency of IFN-gamma producers were noted in cell cultures from neonates. IL 2, IL 4 and IFN-gamma accumulated in the Golgi system, which resulted in a characteristic morphology of the staining, eliminating problems with evaluation of background signals.

Adult↗
PubMed1990

Pharmacokinetic interaction between cyclosporin and diltiazem.

Previous reports have indicated that administration of the calcium antagonist diltiazem results in major changes in the pharmacokinetics of cyclosporin A (CyA). A new clinical trial was undertaken in 22 renal transplant patients receiving a constant dose of cyclosporin to further explore this interaction. Coadministration of diltiazem for one week produced an increase in the blood concentration of CyA and its metabolites 17 and 18 in almost all patients, but no increase in CyA metabolites 1 and 21. The mean whole blood CyA trough level determined by HPLC rose from 117 ng.ml-1 to 170 ng.ml-1 after one week on diltiazem, and the mean trough level of metabolite 17 rose similarly from 184 ng.ml-1 before to 336 ng.ml-1. Based on experiments with microsomes from human liver the effect of diltiazem was due to noncompetitive inhibition of CyA-metabolism by diltiazem, and the increased concentration of metabolite 17 might have been due to stronger inhibition of its secondary metabolism steps.

Adult↗