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Biomedical subjects

S Horn

Publications and source records attributed to S Horn.

At least 19 recordsLinked to original sources
PubMed1992

Use of a molecularly cloned human SS.B antigen to detect anti-SS.B antibodies.

The aim of this study was to examine the utility of diagnostic assays based on recombinant SS.B/La (rSS.B). Using this antigen, we have developed an ELISA and an immunoblot and compared these recombinant antigen-based assays with traditional thymus extract-based counterimmunoelectrophoresis (CIEP). Using the recombinant ELISA, the incidence of anti-SS.B in 184 normal blood donors was 2.2% (four sera). These four sera were all low titre, i.e., 3-5 SD above the mean. Of 38 sera positive for anti-SS.B by CIEP, 37 were positive in both recombinant assays (97.4% concordance). Anti-SS.B titre in CIEP correlated strongly with results of the rSS.B-based ELISA, but the ELISA was 3,000-fold more sensitive. In an analysis of 152 autoimmune sera containing anti-DNA, anti-RNP, anti-centromere, anti-SS.A/Ro or anti-cardiolipin, all of which were negative for anti-SS.B/La by CIEP, the recombinant assays detected 17 new anti-SS.B positives. These positive results were found only in sera which had previously been characterised by CIEP as anti-SS.A/Ro positive. Anti-SS.B/La antibodies detected by recombinant SS.B assays were found to be highly predictive of primary Sjögren's syndrome. Our results show that rSS.B can have an important role in the design of sensitive and specific assays for anti-SS.B. The diagnostic significance of anti-SS.B/La as a guide to primary Sjögren's syndrome is not diminished by the increased sensitivity of recombinant SS.B assays.

Antibodies, Antinuclear↗
PubMed1991

Phagocytosis of phenylhydrazine oxidized and G-6-PD-deficient red blood cells: the role of cell-bound immunoglobulins.

In this study, the role of Igs in the recognition and removal of oxidatively damaged human red blood cells (RBCs) was investigated. Phagocytosis of normal RBCs exposed to the oxidative hemolytic agent phenylhydrazine (Phz) and of glucose-6-phosphate dehydrogenase (G6PD)-deficient RBCs by murine macrophages was examined. A 40-fold increase in phagocytosis of RBCs treated with 3 mmol/L Phz was obtained both in the absence and presence of autologous serum, indicating that binding of autologous antibodies to the oxidized cells is not essential for phagocytosis. Yet, a basal number of IgG molecules was found to be present on the RBCs, as determined both by binding of 125I protein A and fluorescein isothiocyanate-antihuman Ig to the cells. Macrophage Fc receptors were found to be involved in the recognition of the RBCs, because phagocytosis was partially inhibited by incubating macrophages with bovine serum albumin (BSA) anti-BSA complexes, aIg (aggregated Igs), and anti-Fc receptor II monoclonal antibodies. Galactose/mannose inhibited phagocytosis of oxidized RBCs additively to aIg. Because phagocytosis was decreased when Phz-RBCs were incubated with F(ab')2 fragments of antihuman antibodies, it is suggested that the basal amount of Igs bound to the cells plays a role in the recognition of Phz-RBCs. G6PD-deficient RBCs were recognized and phagocytosed by murine macrophages without preexposure to oxidants in vitro (mean of 19 RBCs/100 macrophages). This phagocytosis was not affected by the addition of serum and was inhibited by incubating macrophages with galactose/mannose and the various Fc receptor blockers. A positive correlation between hemoglobin content and the number of cell-bound Igs to each patient erythrocytes was found. These results support the involvement of both an Fc and a lectin-like macrophage receptor in the recognition and phagocytosis of Phz-oxidized and G6PD-deficient RBCs and suggest opsonization as a possible physiologic process for the removal of severe damaged RBCs.

Anemia↗
PubMed1991

Characterization of the binding domains on platelet glycoproteins Ib-IX and IIb/IIIa complexes for the quinine/quinidine-dependent antibodies.

Sera of 12 patients with quinine/quinidine-induced thrombocytopenia showed drug-dependent antibody binding to glycoprotein (GP) Ib-IX complex. The reaction with GPIb-IX complex of 11 of these 12 sera was strongly inhibited by the complex-specific monoclonal antibodies (MoAbs) AK1 and SZ1. The exception was a quinine-induced serum designated BU. The reaction of the six quinidine-induced sera was also partially blocked by an anti-GPIX MoAb, FMC25. Only 3 of the 12 patient sera showed drug-dependent antibody binding to GPIIb/IIIa, which was strongly inhibited by the anti-GPIIIa MoAb 22C4, and the anti-GPIIb alpha MoAb SZ22. With detergent-solubilized Serratia metalloprotease-treated platelets, quinine/quinidine-induced sera, except BU, immunoprecipitated a membrane-bound proteolytic fragment of GPIb-IX complex. In contrast, BU immunoprecipitated glycocalicin and a 40-Kd peptide tail fragment of GPIb alpha from the cell supernatant. Using purified GPIb-IX complex or its components as the target antigen, all the quinine-induced sera, except BU, immunoprecipitated GPIb-IX complex but failed to immunoprecipitate GPIb, GPIX, or the complex reformed from GPIb and GPIX. The quinidine-induced sera strongly immunoprecipitated purified GPIb-IX complex, weakly immunoprecipitated purified GPIX and the recombined complex, but did not immunoprecipitate purified GPIb. The combined data suggest that one quinine-dependent antibody (BU) recognizes an epitope in the peptide tail region of GPIb alpha and the other five quinine-dependent antibodies react with a complex-specific epitope on the membrane-associated region of GPIb-IX complex, whereas each of the six quinidine-induced sera contain two drug-dependent antibodies, one reactive with the GPIb-IX complex-specific epitope and the other reactive with GPIX. The binding domain(s) on GPIIb/IIIa for the quinine/quinidine-dependent antibodies appear to be sterically close to the epitopes for 22C4 and SZ22.

Antibodies↗
PubMed1991

Odorant signal termination by olfactory UDP glucuronosyl transferase.

The onset of olfactory transduction has been extensively studied, but considerably less is known about the molecular basis of olfactory signal termination. It has been suggested that the highly active cytochrome P450 monooxygenases of olfactory neuroepithelium are termination enzymes, a notion supported by the identification and molecular cloning of olfactory-specific cytochrome P450s (refs. 13-16). But as reactions catalysed by cytochrome P450 (refs 17, 18) often do not significantly alter volatility, lipophilicity or odour properties, cytochrome P450 may not be solely responsible for olfactory signal termination. In liver and other tissues, drug hydroxylation by cytochrome P450 is frequently followed by phase II biotransformation, for example by UDP glucuronosyl transferase (UGT), resulting in a major change of solubility and chemical properties. We report here the molecular cloning and expression of an olfactory-specific UGT. The olfactory enzyme, but not the one in liver microsomes, shows preference for odorants over standard UGT substrates. Furthermore, glucuronic acid conjugation abolishes the ability of odorants to stimulate olfactory adenylyl cyclase. This, together with the known broad spectrum of drug-detoxification enzymes, supports a role for olfactory UGT in terminating diverse odorant signals.

Amino Acid Sequence↗
PubMed1991

Oxidative stress in newborn erythrocytes.

Phenylhydrazine (PHZ) exposure is used to study in vitro red cell aging mechanisms dependent on Hb oxidation. The effect of PHZ on normal neonatal red blood cells was studied in unseparated blood and after separation into light and heavy cells. PHZ caused more extensive morphologic changes in neonatal than in adult red blood cells. PHZ exposure of neonatal cells caused less reduced glutathione depletion than in adult cells. Although we found the same total amount of oxidized Hb in both cells, a well-defined oxidation product of Hb was demonstrated by Mössbauer spectra only in neonatal cells. This oxidation product was not methemoglobin but a trivalent, high-spin iron compound. All neonatal cell populations were more sensitive to PHZ than were adult ones, as demonstrated by the presence of Heinz bodies at low PHZ concentration, which did not affect adult cells. These studies demonstrate greater sensitivity of neonatal cells to PHZ in all density-separated populations.

Adult↗
PubMed1991

[Clinical experiences with Wegener's granulomatosis from the nephrologic viewpoint].

Immunosuppressive treatment with cyclophosphamide and prednisolone has markedly improved the prognosis of Wegener's granulomatosis (WG). In patients with WG the detection of anti-neutrophil-cytoplasmic autoantibodies (ANCA or ACPA) has become an important parameter to confirm or even routinely establish the diagnosis of WG over the past few years. From 1985 to 1990 we observed and treated 12 patients (5 males and 7 females) aged 14-64 years (mean 41.1 years) with WG. In the same time span an analysis of 35 patients with rapidly progressive glomerulonephritis showed that the octiology was idiopathic in the majority of cases (54.3%), but nevertheless 8 cases (22.8%) were caused by WG. In 9 out of 10 cases the ANCA test was positive; whereas in 8 out of 10 cases we found a close correlation between the serum level of ANCA and disease activity. However, extraordinarily high serum levels (titres up to 1:2560) were recorded in one patient with WG without any clinical symptoms, whilst another patient with severe symptoms of WG showed a titre of only 1:5. 10 out of 12 patients were successfully brought to remission under cyclophosphamide-cortisone treatment. 4 out of 10 patients with renal insufficiency have been retained on the chronic haemodialysis regimen. 2 patients, aged 31 and 51 years, died within 2-5 months after the onset of clinical symptoms of WG.

Adolescent↗
PubMed1990

A lectin-like receptor on murine macrophage is involved in the recognition and phagocytosis of human red cells oxidized by phenylhydrazine.

Phenylhydrazine (Phz) is a powerful hemolytic agent which has several effects on both normal and G6PD deficient red blood cells (RBCs). We have studied the mechanism of removal of Phz-damaged human RBCs by murine macrophages. Phagocytosis of Phz-treated RBCs was found to be 50 RBCs/100 mac as compared to 2 RBCs/100 mac of the controls. EGTA and sodium azide inhibited the phagocytosis, indicating a requirement for both calcium ions and energy. Incubation of macrophages with sugars such as D-galactose or D-mannose reduced phagocytosis of Phz-treated RBCs by up to 60%, indicating the involvement of a macrophage lectin-like receptor in the recognition of Phz-treated RBCs. The presence of serum in the phagocytosis assay did not affect either phagocytosis of Phz-treated RBCs or inhibition by sugars. beta-Galactosidase, but not neuraminidase, treatment of RBCs caused a significant inhibition in phagocytosis of Phz-treated RBCs. These results suggest that galactosyl residues are exposed on RBC membrane during oxidation, probably not as a result of desialization. We conclude that Phz-treated RBCs are detected as damaged cells mainly due to sugar changes on their membrane, which are directly recognized by lectin-like receptors on the macrophages.

Animals↗
PubMed1990

[Color-coded duplex sonography and the resistive index in dysfunctional kidney transplants].

In a prospective analysis we performed 182 colour duplex US studies in 60 patients with renal transplants to determine the effects of different causes of graft dysfunction on the resistive index (RI) and the colour imaging pattern of the transplant arteries. Allografts with normal function, cyclosporin toxicity, cytomegaly infection, acute tubular necrosis, glomerulonephritis and postoperative functional nephrotoxicity showed normal RI (less than 0.7) and normal pattern of the arteries in colour duplex. Grafts with acute and chronic rejection, obstructive uropathy and arteriolosclerosis showed significant elevated RI and in colour duplex always a characteristic blinking of the arteries and a numerical reduction of the peripheral arteries. It seems that the assessment of an increase of vascular impedance is possible also with colour duplex US.

Adult↗
PubMed1990

Setting payment rates for capitated systems: a comparison of various alternatives.

Numerous proposals have been suggested to revise the current adjusted annual per capita cost (AAPCC) method for paying HMOs in the Medicare program. Several evaluations of the various alternatives conclude that including a prior utilization variable is the most promising alternative. In this paper, using statistical and other criteria, we compare the current AAPCC method with three different prior utilization models. The results suggest that all three prior utilization models can predict expenditures for either individuals or a group--drawn from a cross section and a risk selected sample of aged Medicare beneficiaries--more accurately than the AAPCC method. Of the three prior utilization measures, Payment Amount for Capitated Systems (PACS) predicts actual expenditures most accurately.

Capitation Fee↗
PubMed1989

Retraction.

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Retraction Notice↗
PubMed1987

Tumor necrosis factor (TNF)-alpha but not TNF-beta induces secretion of colony stimulating factor for macrophages (CSF-1) by human monocytes.

Tumor necrosis factor (TNF)-alpha has been identified as a major inducer of colony stimulating factor (CSF)-secretion by human vascular endothelial cells and fibroblasts. In the present study we assessed the capacity of TNFs to induce release of CSF-1 from highly purified peripheral blood monocyte preparations. Whereas monocytes do not accumulate CSF-1 messenger (m)RNA constitutively and consequently do not produce CSF-1 protein, CSF-1 mRNA and protein secretion became detectable, when monocytes were cultured in the presence of TNF-alpha, that was synergistically enhanced by interferon-gamma (IFN-gamma). However, under identical experimental conditions TNF-beta failed to induce monocyte CSF-1 synthesis. Cultures of monocytes in the presence of TNF-beta before addition of TNF-alpha abolished the CSF-1 inducing capacity of TNF-alpha, suggesting that TNF-beta may act as antagonist to TNF-alpha for CSF-1 production. These data point out a previously unrecognized function of TNF-alpha to modulate CSF-1 release by monocytes and demonstrate disparate biological properties of different TNF species in hematopoiesis.

Colony-Forming Units Assay↗