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Biomedical subjects

J J Morgenthaler

Publications and source records attributed to J J Morgenthaler.

At least 37 records · Page 2Linked to original sources
PubMed1989

Inhibition by immunoglobulins of Staphylococcus aureus adherence to fibronectin-coated foreign surfaces.

Recent data suggest that fibronectin may favor Staphylococcus aureus infection by promoting attachment to either injured tissues or implanted foreign bodies. Using a previously described in vitro assay, we show that promotion of S. aureus adherence by surface-bound fibronectin, adsorbed on polymethylmethacrylate (PMMA) coverslips, is antagonized by antistaphylococcal antibodies present in immunoglobulin G (IgG) purified from human plasma. Among the different organisms tested, the protein A-deficient strain Wood 46 of S. aureus was the most strongly inhibited by purified IgG or whole serum dose-dependently. Bacterial adherence was not influenced by preincubating fibronectin-coated PMMA with either purified IgG or whole serum. However, inhibition of bacterial adherence was directly related to the extent of IgG binding to S. aureus Wood 46. When F(ab')2 fragments of purified IgG were tested in the adherence assay, they could also reduce the interaction between S. aureus Wood 46 and fibronectin-coated PMMA. Two other staphylococcal strains were also tested in the adherence inhibition assay: Whereas the protein A-rich strain Cowan I of S. aureus was moderately inhibited by purified IgG or whole serum, S. epidermidis KH 11 was not at all inhibited by IgG which bound poorly to the bacterial cells. This study has demonstrated that bacterial coating by humoral factors, and specifically IgG, may influence significantly subsequent adherence of S. aureus to surface-bound fibronectin.

Bacterial Adhesion↗
PubMed1989

Inactivation of viruses and safety of stable plasma products.

The safety of blood or plasma derived products with respect to the transmission of viruses has various aspects, one of them being the methods that may be used for inactivating viruses during processing of plasma products. In industry, the most important methods are heating in solution (pasteurization) or in the lyophilized state and treatment with solvents and detergents (S/D treatment). Both S/D treatment and pasteurization produce safe products. However, ethanol fractionation by itself may result in virus-safe preparations, since this procedure chemically inactivates viruses and also partitions viruses away from fractions that are subsequently used therapeutically.

Blood Preservation↗
PubMed1988

Fibronectin-cleaving activity in bronchial secretions of patients with cystic fibrosis.

In cystic fibrosis, colonization of the airways with Pseudomonas aeruginosa follows colonization with Staphylococcus aureus and is related to accelerated deterioration of pulmonary function. Because P. aeruginosa adheres better to cell surfaces devoid of fibronectin, we searched for fibronectin-cleaving activity in bronchial secretions and saliva from 24 patients with cystic fibrosis who were followed up for 4.5 y and from two control groups. Proteolytic activity against 125I-labeled fibronectin was continuously present in cystic fibrosis bronchial secretions; significantly higher fibronectin-cleaving activity was found in older vs. younger patients, in patients with advanced disease stages determined by a five-stage scoring system, and in those colonized with P. aeruginosa. The fibronectin-cleaving activity was due to neutrophil elastase and cathepsin G. Cystic fibrosis bronchial secretions had proteolytic activity against surface fibronectin of airway mucosal cells. Thus fibronectin-cleaving activity of bronchial secretions rather than of saliva may favor P. aeruginosa colonization of the upper respiratory tract in individuals with cystic fibrosis.

Adolescent↗
PubMed1988

Inactivation and partition of human immunodeficiency virus during Kistler and Nitschmann fractionation of human blood plasma.

We studied the inactivation of the etiologic agent of the acquired immunodeficiency syndrome, human immunodeficiency virus, in the course of the Kistler and Nitschmann cold ethanol fractionation of human blood plasma. By measuring reverse transcriptase activity and viral infectivity, we have shown that the virus load is reduced by a factor of 10(4) during the initial and at least a factor of 10(6) during the subsequent steps of the fractionation procedure. This loss of virus may be observed in the absence or in the presence of antibodies against human immunodeficiency virus and is due to a combination of chemical inactivation, physical partition, and injury caused by repeated freezing and thawing. The laboratory data therefore further confirm epidemiological studies which indicate that immunoglobulin preparations obtained by ethanol fractionation do not transmit human immunodeficiency virus.

Chemical Fractionation↗
PubMed1987

Two monoclonal antibodies that discriminate between allelic variants of human low density lipoprotein.

Human low density lipoprotein shows a genetic polymorphism, the so-called Ag-system. it consists of 5 pairs of allelic epitopes, x/y, al/d, c/g, t/z, and h/i, which are localized on apolipoprotein B. We have generated a large number of monoclonal antibodies against low density lipoprotein. Two of them, D2E1 and H11G3, recognize epitopes related to this genetic polymorphism. Direct ELISA and ELISA inhibition experiments with different low density lipoproteins of known phenotype showed that D2E1 is directed against the allelic epitope c and H11G3 against d. The two antibodies were used for the characterization of low density lipoprotein in sera from different blood donors and the results compared to those obtained by passive hemagglutination using human allotypic anti-sera. Sera from homo- or heterozygous donors (which display the relevant epitope) could be distinguished from the sera of homozygous donors (which lack the epitope) with the monoclonal antibodies described.

Alleles↗
PubMed1987

Fibronectin in pemphigus.

In the skin organ culture model of pemphigus, fibronectin concentrations of 300 and 500 micrograms/ml inhibited pemphigus plasma-induced acantholysis and intraepidermal binding of the pemphigus antibodies examined by direct immunofluorescence. A direct interaction of fibronectin with pemphigus antibodies could not be demonstrated by chromatography of pemphigus plasma on immobilized fibronectin or by incubation with fibronectin and subsequent precipitation with antifibronectin. We then measured fibronectin concentrations in the plasma of 15 patients suffering from various types of pemphigus and presenting different activities of their disease. Immunoreactive fibronectin levels in untreated patients with active disease were generally in the low normal or even clearly in the subnormal range. They had the tendency to decrease when the disease subsided during therapy with high doses of glucocorticoids, sometimes in combination with azathioprine. The fibronectin concentration in the blister fluid of a patient with acute, untreated pemphigus vulgaris was similar to that in a plasma sample taken at the same time. Skin biopsies of pemphigus patients exhibited an essentially normal fibronectin pattern in direct immunofluorescence. We discuss a possible protective role of fibronectin in pemphigus e.g., by reducing the permeability for pemphigus antibodies in the dermal-epidermal junction zone.

Acantholysis↗
PubMed1985

Purified fibronectin administration to patients with severe abdominal infections. A controlled clinical trial.

Subnormal plasma fibronectin (Fn) levels are found in patients with severe abdominal infections (SAI). The repletion of Fn has been postulated to have therapeutic benefit by virtue of its opsonic, reticuloendothelial system (RES) stimulating effects. A controlled, prospective trial of Fn administration was performed in patients with SAI to assess its use as an adjunct to standard procedures of intensive care. Thirty-three SAI patients were given daily doses of 0.8 g of purified Fn on days 1-5 following admission to the ICU, whereas 34 control patients received no Fn. All patients received the clinical care, antibiotics, and pharmacologic agents appropriate to their individual needs. The admission status and laboratory profiles of the two patient groups (+ and -Fn) were comparable on admission to the study. No side effects of the Fn preparation were observed. As judged by subgroup averages, the Fn replacement regimen was effective in elevating Fn levels to within normal range from day 2 onwards, as measured by immunological and functional assays. The estimated intravascular recovery of Fn averaged 82% in those patients who survived, yet only 52% in the nonsurvivors. Ultimate hospital mortality was 9/33 (27.3%) in the +Fn group versus 13/34 (38.2%) in the -Fn group (p = 0.244, Fisher's exact test). Although ultimate mortality was not significantly changed by the administration of Fn, the Fn treated patients appeared to survive longer than did the control patients. This trend was confirmed through the analysis of expected survival curves (D = 3.12, 0.1 greater than p greater than 0.05). When compared to the survivors, the ultimate nonsurvivors entered the study with statistically higher group averages of bilirubin and creatinine concomitant with lower averages of Fn, antithrombin III, C4, C3, C3b-INH, and transferrin. These differences persisted throughout the 11-day monitoring period; differences between survivors and nonsurvivors with respect to platelets, plasminogen, B-1-H, alpha-2-macroglobulin, and prealbumin appeared during the same period. Dramatic differences between the +Fn and -Fn treatment groups were not seen. Other than Fn, the Fn recipients only developed higher levels of the acute phase reactants C4, C3b-INH, B-1-H and alpha-1-antitrypsin (p less than 0.05) than did their non-Fn treated counterparts. In the present study, we again found a highly significant pattern of correlations between the absolute levels as well as the changes of Fn and other plasma proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗
PubMed1985

Influence of heparin and calcium chloride on assay, stability, and recovery of factor VIII.

The influence of heparin alone or in conjunction with calcium chloride on the coagulation assay for factor VIII, on the stability of factor VIII in blood and in plasma, and on the recovery of factor VIII in cryoprecipitate and in an intermediate purity concentrate was investigated. A stabilizing effect of heparin and calcium on factor VIII activity in blood and plasma could be confirmed. We were, however, unable to make use of the higher activity that can, under certain circumstances, be recovered in the cryoprecipitates; this was mainly due to the poor solubility of cryoprecipitates prepared from heparinized blood. Heparin (or the absence of a calcium chelator) also interferes with the recovery of plasma components other than factor VIII.

Calcium Chloride↗
PubMed1984

Foreign body infection: role of fibronectin as a ligand for the adherence of Staphylococcus aureus.

Foreign bodies made of polymethylmethacrylate coverslips were implanted subcutaneously into guinea pigs, were explanted four weeks later, and were tested for in vitro adherence of Staphylococcus aureus strain Wood 46. In the presence of serum, the level of staphylococcal adherence to explanted coverslips was 20 times higher than that of adherence to unimplanted coverslips. Adherence to explanted coverslips was caused by fibronectin deposits on the foreign body surface and was inhibited in a dose-related fashion by specific antibodies to fibronectin.

Adhesiveness↗
PubMed1984

Isolation of fibronectin under mild conditions.

Fibronectin was isolated from human blood plasma by affinity chromatography on immobilized Physiogel, a plasma expander made by chemical degradation of gelatin. Binding of fibronectin to Physiogel is weaker than to gelatin; elution could therefore be performed under rather mild conditions: at pH 6.5 and 30 degrees C. Loading of the sample at low temperature increases the capacity of the affinity column.

Chromatography, Affinity↗
PubMed1984

Adsorption of fibronectin onto polymethylmethacrylate and promotion of Staphylococcus aureus adherence.

Recent data suggest that fibronectin may favor Staphylococcus aureus infection by promoting attachment to either injured tissues or implanted foreign bodies. We studied the quantitative adsorption of fibronectin onto polymethylmethacrylate (PMMA) cover slips by using a 125I-labeled preparation of the purified plasma glycoprotein. Fibronectin in buffer solutions showed a high affinity to PMMA coverslips. Adherence of S. aureus Wood 46 was studied on PMMA pre-exposed to fibronectin, using an assay specifically adapted to the cover slip model. Whereas S. aureus adherence in an albumin-containing buffer was less than or equal to 10(3) CFU on control uncoated cover slips, adherence in the same medium increased up to maximum of 7.7 X 10(4) CFU on cover slips preincubated in a solution of fibronectin (125-micrograms/ml). At intermediate fibronectin concentrations, bacterial adherence was a linear function of both the quantity in solution and of the quantity adsorbed on the PMMA cover slips. The presence of human serum proteins, as represented by a fibronectin-depleted pool, essentially prevented adsorption of radiolabeled fibronectin on PMMA and subsequent bacterial adherence on the cover slips. Precoating of PMMA with denatured collagen resulted in increased fibronectin adsorption on PMMA, even in the presence of serum proteins, and S. aureus adherence was optimal on such surfaces. Collagen may therefore play a role as a cofactor contributing to S. aureus adherence onto fibronectin-coated substrata or foreign bodies.

Adhesiveness↗
PubMed1982

Chromatography of antihemophilic factor on diaminoalkane- and aminoalkane-derivatized Sepharose.

Antihemophilic factor was chromatographed on a homologous series of diaminoalkane- and aminoalkane-modified Sepharose beads. Both factor VIII procoagulant activity (VIII:C) and protein are retarded on these columns when compared to their elution on a column made of unmodified Sepharose. Longer chains bind VIII:C and protein more tightly than shorter chains. No bound activity could be eluted with ethylene glycol. Increasing ionic strength eluted VIII:C and protein from aminoalkane- as well as from alkane-Sepharose. It seems likely that hydrophobic, rather than ionic forces, are responsible for the binding of VIII:C to the latter carriers.

Chromatography, Agarose↗
PubMed1982

Characterization of various immunoglobulin preparations for intravenous application. I. Protein composition and antibody content.

In this comparative study we investigated 14 immunoglobulin (Ig) preparations for intravenous application; they were prepared by various manufacturers who used either placental or venous blood as the starting material. The pepsin- and plasmin-treated products and a preparation which, according to the manufacturer, was not degraded enzymatically, contained 17-86% of IgG split products. On the other hand, three chemically modified preparations, one preparation treated at pH 4, for products treated with poly(ethylene glycol) (PEG) and one preparation protected by albumin contained 90% or more of non-fragmented IgG. The IgG subclass distribution corresponded to the distribution of subclasses in normal serum only in the nonmodified and not enzymatically degraded preparations. All samples except one contained 0.1 mg/ml IgA or more, all contained only traces of IgM. No product had clinically relevant titers of irregular antibodies against erythrocyte antigens. The content of those antiviral and antibacterial antibodies that were tested for was similar in all preparations. Only the anti-HBs activity exhibited large variations. Some PEG-treated preparations showed an elevated prekallikrein activator (PKA) level, whereas all other preparations contained, if any, only traces of PKA.

ABO Blood-Group System↗