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Biomedical subjects

M Trendelenburg

Publications and source records attributed to M Trendelenburg.

At least 19 recordsLinked to original sources
PubMed2003

Autoantibodies against complement receptor 1 (CD35) in SLE, liver cirrhosis and HIV-infected patients.

The acquired loss of CR1 (CD35) on erythrocytes in specific autoimmune diseases and chronic infections may be due to autoAb against CR1. An ELISA using rCR1 was established to measure antiCR1 IgG autoAb. Plasma containing alloAb to polymorphism on CR1 (Knops blood group Ab) reacted strongly against rCR1 and were used as positive controls. AntiCR1 Ab was found in 3/90 (3.5%) plasma samples from healthy blood donors. The binding of these Ab was not inhibited by high salt concentrations. AntiCR1 Ab were present in the IgG fractions of plasma, and they bound to rCR1 on Western Blot. Affinity chromatography on rCR1-sepharose depleted the plasma of antiCR1, and the acid-eluted fractions contained the antiCR1 Ab. An increased frequency of antiCR1 autoAb was found in patients with SLE (36/78; 46%), liver cirrhosis (15/41; 36%), HIV infection (23/76; 30%) (all P < 0.0001), and in patients with anticardiolipin Ab (4/21; 19%, P < 0.01) multiple sclerosis (7/50; 14%, P < 0.02), and myeloma (autoAb (8/56; 14%, P < 0.02), but not in those with acute poststreptococcal glomerulonephritis (1:32; 3%). Because C1q binds to CR1, antiC1q Ab were analysed in the same patients. There was no correlation between levels of antiC1q and antiCR1 autoAb. In HIV patients, levels of antiCR1 did not correlate with low CR1 levels expressed on erythrocytes or soluble CR1 in plasma. The binding of antiCR1 autoAb to rCR1 fixed on ELISA plates was not inhibited by soluble rCR1 or by human erythrocyte CR1, in contrast to alloAb and one SLE serum, which induced partial blockade. Thus, antiCR1 autoAb recognize mostly CR1 epitope(s) not present on the native molecule, suggesting that they are not directly involved in the loss of CR1. Rather antiCR1 autoAb might indicate a specific immune response to denatured CR1.

Autoantibodies↗
PubMed2001

Disseminated scabies evolving in a patient undergoing induction chemotherapy for acute myeloblastic leukaemia.

We report on a 34-year-old refugee from the Balkans presenting with a generalized papular rash during induction chemotherapy for acute myeloblastic leukaemia (AML M4eo). This rash appeared on day 5 of the chemotherapy and was diagnosed as disseminated scabies. It was successfully treated with a combination of oral ivermectin and topical lindane. Scabies disappeared completely despite ongoing neutropenia and other severe infectious complications. Disseminated scabies should be included in the differential diagnosis of rash in severely immunosuppressed patients coming from poor housing conditions.

Adult↗
PubMed2001

Anti-C1q antibodies may help in diagnosing a renal flare in lupus nephritis.

It is still uncertain which, if any, immunologic parameters may help diagnose a renal flare of lupus nephritis. Anti-C1q antibody (Ab) titers have been elevated in patients with lupus with renal involvement, but little information is available on whether the titers are different in quiescent and active phases of lupus nephritis. In this study, we compared anti-C1q Ab titers with other serological test results in 48 patients with biopsy-proven lupus nephritis to assess which parameter could offer the best reliability for differentiating between quiescent and active phases of lupus nephritis. Serum C3 and C4 levels, as well as anti-double-stranded DNA, antiendothelial cell, anti-C1q, and antiphospholipid Ab titers, were evaluated in patients with quiescent renal disease (38 samples) and those with clinical evidence of renal activity (23 samples). Only anti-C1q Ab titers correlated with active renal disease in both univariate (P < 0.0001) and multivariate analysis (P < 0.0001), with a sensitivity of 87% and a specificity of 92%. In six patients, immunologic parameters were measured serially. In all patients, the high anti-C1q Ab titers returned to normal values after treatment-induced remission. The other serological parameters did not show a significant association with renal disease activity. In patients with biopsy-proven lupus nephritis, anti-C1q Ab titers appear to be strongly related to renal disease activity. Their measurement may be useful for confirming the diagnosis of renal flares of lupus nephritis.

Adult↗
PubMed2000

[New physiopathological findings in paraproteinemias].

Apart from their antigen-recognising function, immunoglobulins have other physicochemical properties. The best described is cryoprecipitation of monoclonal and/or polyclonal immunoglobulins. The cryoprecipitation phenomenon is unique for each cryoglobulin, and depends on the intrinsic properties of the monoclonal immunoglobulin, the protein environment, temperature and the surrounding ionic concentrations. The complement activating properties of monoclonal immunoglobulins are also unique. We have described a series of monoclonal immunoglobulins which are able to activate the classical pathway of complement without the formation of antigen/antibody complexes. Analysis of the properties of these monoclonal immunoglobulins suggests new therapeutic strategies in oncology. Monoclonal chimeric antibodies, combining antibody specific against tumour antigens and strong complement activation, may be more damaging to tumor cells than currently used antibodies.

Complement Pathway, Classical↗
PubMed2000

[Apoptosis and C1q: possible explanations for the pathogenesis of systemic lupus erythematosus].

Dysregulation of apoptosis may play a major role in the pathogenesis of systemic lupus erythematosus (SLE). A defective clearance of apoptotic cells or inappropriately high rates of apoptosis may lead to a pathologic accumulation of abnormal cell material with a secondary autoimmune response. Experimental findings in apoptotic keratinocytes and C1q knock-out mice suggest an important role of C1q in the clearance of apoptotic cell material. In addition, there are several links between C1q and SLE: Most the patients with C1q deficiency develop a SLE-like syndrome. SLE itself often causes secondary C1q deficiency and autoantibodies to C1q are detected in almost all patients with active lupus nephritis. These observations suggest a central role of C1q in apoptosis and in the pathogenesis of SLE.

Animals↗
PubMed1999

Monomeric complement-activating IgG paraproteins.

Three patients presented a unique syndrome of recurrent panniculitis with an IgGkappa paraprotein and depletion of the early components of the classical pathway of complement. The IgGkappa paraproteins were monomers with a normal structure, and with no evidence for aggregation, as assessed by electron microscopy and ultracentrifugation. Both heavy and light chains were of normal molecular size (SDS-PAGE), and the paraproteins were not heavily glycosylated. However, the paraproteins from all three patients had unusual features that included abnormal behavior on gel filtration chromatography and a heavy chain of high pI. When analyzed by fast protein liquid chromatography (Superdex 200), elution of the paraproteins was retarded, particularly when the ionic strength was increased. This retardation was partially reversed in 20% alcohol, and fully reversed in 6 M guanidine-HCl. Neither anti-C1 inhibitor nor anti-C1q autoantibodies were found in any of the patients' sera. However, the paraproteins bound to the globular heads of C1q at normal ionic strength. They activated C4 in normal human serum, but not in C1q-deficient serum. Activation led to the formation of C1s-C1 inhibitor complexes. Taken together, the data suggest that the unusual paraproteins have the capacity to bind C1q, which then leads to activation of C1. The ability of these paraproteins to activate C1, in spite of their being soluble monomers, is likely to be related to their unique physicochemical features.

Chromatography, Gel↗
PubMed1999

Concomitant blockade of P2X-receptors and ecto-nucleotidases by P2-receptor antagonists: functional consequences in rat vas deferens.

In order to assess the consequences of a concomitant blockade of P2X-receptors and ecto-nucleotidases, effects of 13 P2-receptor antagonists were investigated on contractions of the rat vas deferens elicited by alpha,beta-methylene ATP (alpha,beta-MeATP) and ATP and on the removal of ATP from the incubation medium by vas deferens tissue. Increasing concentrations of all antagonists reduced and finally abolished contractions elicited by alpha,beta-MeATP (3 microM), with IC50-values ranging from 1.1 to 100 microM. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonate (PPADS), 6-azophenyl-4-amino-5-hydroxy-naphthalene-1,3-disulphonate (NH02), 4,4'-diisothiocyanatostilbene-2,2'-disulphonate (DIDS) and uniblue A also progressively reduced and finally abolished contractions elicited by ATP (1 mM). 8,8'-[Carbonylbis(imino-3, 1-phenylenecarbonyl-imino)]-bis-(1,3,5-naphthalenetrisulphonate ) (NF023), suramin, pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (iso-PPADS), trypan blue and reactive blue 19, in contrast, caused only partial blockade, by 34-43% maximally; reactive blue 2 and reactive red 2 had no effect; and 6,6'-(1,1'-biphenyl-4,4'-diylbisazo)-bis-4-amino-5-hydroxy-naphtha lene-1,3-disulphonate (NH01) and Evans blue even enhanced the response to ATP. For antagonists causing full or partial inhibition, the IC50-values against ATP were close to those against alpha,beta-MeATP. All antagonists attenuated the removal of ATP, with IC25%-values ranging from 0.8 microM to >320 microM. The results confirm the frequent combination, in one antagonist molecule, of P2-receptor blockade and blockade of ecto-nucleotidases. This dual action underlies the effect of such compounds on contractions of the vas deferens elicited by ATP which, for certain substances (e.g., suramin, reactive blue 2), can be explained by a simple model in which the antagonist simultaneously blocks the degradation of ATP and a single contraction-mediating receptor (P2X1). Several observations, however, do not conform with this model, and the existence of multiple contraction-mediating receptors for ATP or multiple, pharmacologically distinct ecto-nucleotidases has to be considered.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1999

Hepatitis virus-related and ethanol-induced chronic liver disease with or without cryoglobulins--is there a difference concerning clinical or laboratory manifestation?

Mixed cryoglobulinemia is frequent in southern Europe and attributed to hepatitis C infection. We analyzed prevalence and clinical symptoms of mixed cryoglobulinemia in our region among patients with chronic hepatitis C (n = 29) and B (n = 7) in comparison to alcoholic liver cirrhosis without evidence of hepatitis virus infection (n = 10). Cryoglobulinemia was found in 13/29 patients with hepatitis C (11 type III, one type I1-III and one type II), 2/7 with hepatitis B (one type II, one type III) and 4/10 with alcoholic liver cirrhosis (one type II, three type III). Patients with moderate active hepatitis had more type II than type III cryoglobulins. Concerning clinical symptoms, only sicca syndrome was more frequent in patients with hepatitis C. Rheumatoid factor (RF) and immune globulin M (IgM) levels were higher in hepatitis C than in the other groups. Renal disease was rare in all but not different between the groups. Mixed cryoglobulinemia in hepatitis C (and B) is most frequently of type III. Patients with hepatitis C had the same prevalence of cryoglobulins as patients with alcoholic liver cirrhosis. Cryoglobulins had no influence on clinical syndromes or organ damage.

Adolescent↗
PubMed1999

Hypocomplementemic urticarial vasculitis or systemic lupus erythematosus?

The 2 patients presented here showed the typical signs of hypocomplementemic urticarial vasculitis syndrome (HUVS). During follow-up, there was an inverse correlation between anti-C1q autoantibody titer and C1q antigen concentration in serum in both patients over a period of 2 years. The first patient had nephritis characterized by immune deposits in glomeruli and around the tubules. The histological findings, C1q deposits, and presence of tubuloreticular inclusions in capillary endothelial cells suggested a disease process identical to systemic lupus erythematosus (SLE). The second patient, after a lag phase of 2 years, fulfilled a fourth American College of Rheumatology criteria for SLE when she developed anti-double-stranded DNA antibodies. HUVS and SLE overlap, and the criteria for identifying HUVS as an entity distinct from SLE are lacking.

Adult↗
PubMed1998

Correction of spurious blood cell counts in a patient with cryoglobulinemia reversed by the use of citrate-anticoagulated blood.

Cryoglobulins may interfere with automated cell counting when proteins precipitate or blood cells aggregate. This results in spurious platelet or leukocyte counts, false values for red blood cell parameters and abnormal scattergrams. Usually it can be reversed by warming blood specimens to 37 degrees C. We describe the case of a 63-year-old woman with autoimmune disease in whom the diagnosis of cryoglobulinemia was suspected due to typical changes in blood cell counts. Artifacts were resistant to warming of the sample to 37 degrees C in both EDTA- and heparin-anticoagulated blood specimens. In contrast, the use of citrate as anticoagulant allowed correct measurements. This case underlines the role of assessment of blood counts in the detection of cryoglobulinemia. Correct measurements of automated blood counts in cryoglobulinemia may depend on the use of alternative anticoagulants.

Anticoagulants↗
PubMed1997

The human papillomavirus type 16 E7 protein is associated with the nucleolus in mammalian and yeast cells.

In this study we show, by immunofluorescence and electron microscopy immuno-gold labelling, that the major transforming protein of Human Papillomavirus type 16 E7 is associated with the nucleolus of cells derived from the HPV16-positive cervical carcinoma line CaSki. The E7 nucleolar staining appeared to be cell cycle dependent, being considerably reduced in the G2 phase. The total level of the protein in the cell, however, remained constant during all phases. We also show that the cellular protein Rb1, which is targeted by E7, is localised in the nucleus and nucleolus in CaSki cells. Thus, it is possible that the presence of E7 in the nucleolus correlates with a hypothetical function(s) of Rb1 in this particular intranuclear compartment. The nucleolar localisation of HPV16 E7 protein was also observed in the fission yeast Schizosaccharomyces pombe, suggesting that a targeting mechanism of HPV16 E7 protein into the nucleolus is common to both mammalian and yeast systems. Nucleolar localisation of HPV16 E7 protein may be independent from Rb1 since no Rb1 related proteins have been identified in fission yeast.

Antibodies, Monoclonal↗
PubMed1997

Use of a mass-thickness marker to estimate systematic errors and statistical noise in the detection of phosphorus by electron spectroscopic imaging.

The element signal obtained from electron-energy-filtered micrographs depends on the systematic error in calculating the background and on the noise in the background-corrected image. Both systematic error and statistical fluctuation of the background can be assessed experimentally with a specimen that combines the element-containing feature with a mass-thickness marker. The approach is described for the mapping of phosphorus in turnip yellow mosaic viruses prepared on a supporting carbon film of variable thickness. The thickness modulations are produced by the additional deposition of heat-evaporated carbon through a second grid used as a mask. The three-window power-law method and the two-window difference method are compared. With the three-window power-law method, the mass-thickness modulations of the marker are still visible in the map, indicating a systematic error for the calculated background. In addition, the intensity profile over the area of the thick carbon film is broader than in the map corrected by the two-window method, indicating a higher level of noise. With the two-window difference method, mass-thickness contrast was practically eliminated due to an improved protocol that uses the mass-thickness marker to calculate the scaling factor: instead of scaling the grey-level of a single background feature, the pre-edge image is scaled to the contrast of the marker area in the image acquired at the element-specific energy loss.

Electron Probe Microanalysis↗
PubMed1995

Microchip implant system used for animal identification in laboratory rabbits, guineapigs, woodchucks and in amphibians.

Traditional methods for animal identification have a number of drawbacks. We evaluated a new system for individual identification using microchip implants in rabbits, guineapigs, woodchucks (Marmota monax) and amphibians (Xenopus laevis, Pleurodeles waltlii). Implantation procedure and long-term observations are described. Microchip implants proved to be a practicable and reliable system for animal identification without obvious adverse effects. The applicability of electronic animal identification in comparison with common methods and with regard to animal welfare and legal aspects is discussed.

Amphibians↗